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  1. Neurochemical alterations associated with borderline personality disorder.

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    Atmaca, Murad; Karakoc, Tevfik; Mermi, Osman; Gurkan Gurok, M; Yildirim, Hanefi

    2015-01-01

    In neuroimaging on borderline personality disorder, prior studies focused on the hippocampus and amygdala, as mentioned above. However, no study investigated whether there were neurochemical changes in the patients with borderline personality disorder. Therefore, in the present study, we aimed to investigate neurochemical change of patients diagnosed with borderline disorder and hypothesized that neurochemicals would change in the hippocampus region of these patients. Seventeen patients and the same number of healthy control subjects were analyzed by using a 1.5 Tesla GE Signa Imaging System. N-acetylaspartate (NAA), choline compounds (CHO), and creatine (CRE) values of hippocampal region were measured. The mean NAA/CRE ratio in the hippocampus region was significantly reduced in the patients with borderline personality disorder compared to that of healthy control subjects, In addition, NAA/CHO ratio of the patients with borderline personality disorder was also significantly reduced when compared to that of healthy subjects. There was no difference in the ratio of CHO/CRE. In summary, we present evidence for reduced NAA in the patients with borderline personality disorder. © 2015, The Author(s).

  2. Thiamine Deficiency Induced Neurochemical, Neuroanatomical, and Neuropsychological Alterations: A Reappraisal

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    Raffaele Nardone

    2013-01-01

    Full Text Available Nutritional deficiency can cause, mainly in chronic alcoholic subjects, the Wernicke encephalopathy and its chronic neurological sequela, the Wernicke-Korsakoff syndrome (WKS. Long-term chronic ethanol abuse results in hippocampal and cortical cell loss. Thiamine deficiency also alters principally hippocampal- and frontal cortical-dependent neurochemistry; moreover in WKS patients, important pathological damage to the diencephalon can occur. In fact, the amnesic syndrome typical for WKS is mainly due to the damage in the diencephalic-hippocampal circuitry, including thalamic nuclei and mammillary bodies. The loss of cholinergic cells in the basal forebrain region results in decreased cholinergic input to the hippocampus and the cortex and reduced choline acetyltransferase and acetylcholinesterase activities and function, as well as in acetylcholine receptor downregulation within these brain regions. In this narrative review, we will focus on the neurochemical, neuroanatomical, and neuropsychological studies shedding light on the effects of thiamine deficiency in experimental models and in humans.

  3. Rapid recovery and altered neurochemical dependence of locomotor central pattern generation following lumbar neonatal spinal cord injury.

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    Züchner, Mark; Kondratskaya, Elena; Sylte, Camilla B; Glover, Joel C; Boulland, Jean-Luc

    2018-01-15

    were two main locomotor frequencies, but injured spinal cords exhibited a shift towards the higher frequency. Injury also altered the neurochemical dependence of locomotor CPG output, such that injured spinal cords, unlike control spinal cords, were incapable of generating low frequency rhythmic coordinated activity in the presence of NMDA and dopamine alone. Thus, the neonatal spinal cord also exhibits remarkable functional recovery after lumbar injuries, but the neurochemical sensitivity of locomotor circuitry is modified in the process. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

  4. Diphenyl ditelluride impairs short-term memory and alters neurochemical parameters in young rats.

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    Stangherlin, Eluza Curte; Rocha, João Batista Teixeira; Nogueira, Cristina Wayne

    2009-01-01

    The aim of this study was to investigate if maternal exposure to 0.03 mg/kg of diphenyl ditelluride (PhTe)2 during the first 14 days of lactational period in Wistar rats alters recognition memory and neurochemical parameters in young rats. Object recognition memory task, evaluation of synaptosomal [3H]glutamate uptake and release as well as cerebral Na+/K+ATPase activity were evaluated in 4 week-old rats. There were no significant specific overt signs of maternal intoxication. The body weight gain of rats was similar among groups. (PhTe)2-exposed group showed a significantly lower time exploring the novel object when compared to the performance of the control group in short-term memory (STM) test. In addition, (PhTe)2 significantly inhibited synaptosomal [3H]glutamate uptake and cerebral Na+/K+ATPase activity in animals. The synaptosomal [3H]glutamate release was similar between (PhTe)2 and control groups. In conclusion, the present study establishes that young rats presented cognitive impairment after exposure to (PhTe)2 via maternal milk, demonstrated by the performance of animals in object recognition memory task. The possible mechanism involved in (PhTe)2 action in memory of recognition might involve inhibition of cerebral Na+/K+ATPase activity and synaptosomal [3H]glutamate uptake.

  5. Neurochemical aspects of childhood autism

    NARCIS (Netherlands)

    R.B. Minderaa (Ruud)

    1985-01-01

    textabstractThe topic of this thesis is neurochemical aspects of infantile autism. The experimental work is centered around the most robust and consistant neurochemical finding in child psychiatry, namely that group mean whole blood serotonin (5-Hydroxytryptamine, 5-HT) values are

  6. Neurochemical Changes after Acute Binge Toluene Inhalation in Adolescent and Adult Rats: A High-Resolution Magnetic Resonance Spectroscopy Study

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    O'Leary-Moore, Shonagh K.; Galloway, Matthew P.; McMechan, Andrew P.; Irtenkauf, Susan; Hannigan, John H.; Bowen, Scott E.

    2009-01-01

    Inhalant abuse in young people is a growing public health concern. We reported previously that acute toluene intoxication in young rats, using a pattern of exposures that approximate abuse patterns of inhalant use in humans, significantly altered neurochemical measures in select brain regions. In this study, adolescent and young adult rats were exposed similarly to an acute (2 × 15 min), high dose (8000 − 12000 ppm) of toluene and high-resolution magic angle spinning proton magnetic resonance spectroscopy (HR-MAS 1H-MRS) was used to assess neurochemical profiles of tissue samples from a number of brain regions collected immediately following solvent exposure. The current investigation focused on N-acetyl-aspartate (NAA), choline-containing compounds, creatine, glutamate, GABA, and glutamine. Contrary to our predictions, no significant alterations were found in levels of NAA, choline, creatine, glutamate, or glutamine in adolescent animals. In contrast to these minimal effects in adolescents, binge toluene exposure altered several neurochemical parameters in young adult rats, including decreased levels of choline and GABA in the frontal cortex and striatum and lowered glutamine and NAA levels in the frontal cortex. One of the more robust findings was a wide-ranging increase in lactate after toluene exposure in adult animals, an effect not observed in adolescents. These age-dependent effects of toluene are distinct from those reported previously in juvenile rats and suggest a developmental difference in vulnerability to the effects of inhalants. Specifically, the results suggest that the neurochemical response to toluene in adolescents is attenuated compared to adults, and imply an association between these neurochemical differences and age-influenced differences in solvent abuse in humans. PMID:19628036

  7. Neurochemical dynamics of acute orofacial pain in the human trigeminal brainstem nuclear complex.

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    de Matos, Nuno M P; Hock, Andreas; Wyss, Michael; Ettlin, Dominik A; Brügger, Mike

    2017-11-15

    The trigeminal brainstem sensory nuclear complex is the first central relay structure mediating orofacial somatosensory and nociceptive perception. Animal studies suggest a substantial involvement of neurochemical alterations at such basal CNS levels in acute and chronic pain processing. Translating this animal based knowledge to humans is challenging. Human related examining of brainstem functions are challenged by MR related peculiarities as well as applicability aspects of experimentally standardized paradigms. Based on our experience with an MR compatible human orofacial pain model, the aims of the present study were twofold: 1) from a technical perspective, the evaluation of proton magnetic resonance spectroscopy at 3 T regarding measurement accuracy of neurochemical profiles in this small brainstem nuclear complex and 2) the examination of possible neurochemical alterations induced by an experimental orofacial pain model. Data from 13 healthy volunteers aged 19-46 years were analyzed and revealed high quality spectra with significant reductions in total N-acetylaspartate (N-acetylaspartate + N-acetylaspartylglutamate) (-3.7%, p = 0.009) and GABA (-10.88%, p = 0.041) during the pain condition. These results might reflect contributions of N-acetylaspartate and N-acetylaspartylglutamate in neuronal activity-dependent physiologic processes and/or excitatory neurotransmission, whereas changes in GABA might indicate towards a reduction in tonic GABAergic functioning during nociceptive signaling. Summarized, the present study indicates the applicability of 1 H-MRS to obtain neurochemical dynamics within the human trigeminal brainstem sensory nuclear complex. Further developments are needed to pave the way towards bridging important animal based knowledge with human research to understand the neurochemistry of orofacial nociception and pain. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Suicide: Neurochemical Approaches

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    Ritabrata Banerjee

    2013-10-01

    Full Text Available Despite the devastating effect of suicide on numerous lives, there is still a dearthof knowledge concerning its neurochemical aspects. There is increasing evidence that brain-derived neurotrophic factor (BDNF and Nerve growth factor (NGF are involved in the pathophysiology and treatment of depression through binding and activating their cognate receptors trk B and trk A respectively. The present study was performed to examine whether the expression profiles of BDNF and/or trk B as well as NGF and/or trk A were altered in postmortem brain in subjects who commitsuicide and whether these alterations were associated with specific psychopathologic conditions. These studies were performed in hippocampus obtained 21 suicide subjects and 19 non-psychiatric control subjects. The protein and mRNA levels of BDNF, trk B and NGF, trk A were determined with Sandwich ELISA, Western Blot and RT PCR respectively. Given the importance of BDNFand NGF along with their cognate receptors in mediating physiological functions, including cell survival and synaptic plasticity, our findings of reduced expression of BDNF, Trk B and NGF, Trk A in both protein and mRNA levels of postmortem brain in suicide subjects suggest that these molecules may play an important role in the pathophysiological aspects of suicidal behavior.

  9. Neurochemical enhancement of conscious error awareness.

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    Hester, Robert; Nandam, L Sanjay; O'Connell, Redmond G; Wagner, Joe; Strudwick, Mark; Nathan, Pradeep J; Mattingley, Jason B; Bellgrove, Mark A

    2012-02-22

    How the brain monitors ongoing behavior for performance errors is a central question of cognitive neuroscience. Diminished awareness of performance errors limits the extent to which humans engage in corrective behavior and has been linked to loss of insight in a number of psychiatric syndromes (e.g., attention deficit hyperactivity disorder, drug addiction). These conditions share alterations in monoamine signaling that may influence the neural mechanisms underlying error processing, but our understanding of the neurochemical drivers of these processes is limited. We conducted a randomized, double-blind, placebo-controlled, cross-over design of the influence of methylphenidate, atomoxetine, and citalopram on error awareness in 27 healthy participants. The error awareness task, a go/no-go response inhibition paradigm, was administered to assess the influence of monoaminergic agents on performance errors during fMRI data acquisition. A single dose of methylphenidate, but not atomoxetine or citalopram, significantly improved the ability of healthy volunteers to consciously detect performance errors. Furthermore, this behavioral effect was associated with a strengthening of activation differences in the dorsal anterior cingulate cortex and inferior parietal lobe during the methylphenidate condition for errors made with versus without awareness. Our results have implications for the understanding of the neurochemical underpinnings of performance monitoring and for the pharmacological treatment of a range of disparate clinical conditions that are marked by poor awareness of errors.

  10. Induction of gram-negative bacterial growth by neurochemical containing banana (Musa x paradisiaca) extracts.

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    Lyte, M

    1997-09-15

    Bananas contain large quantities of neurochemicals. Extracts from the peel and pulp of bananas in increasing stages of ripening were prepared and evaluated for their ability to modulate the growth of non-pathogenic and pathogenic bacteria. Extracts from the peel, and to a much lesser degree the pulp, increased the growth of Gram-negative bacterial strains Escherichia coli O157:H7, Shigella flexneri, Enterobacter cloacae and Salmonella typhimurium, as well as two non-pathogenic E. coli strains, in direct relation to the content of norepinephrine and dopamine, but not serotonin. The growth of Gram-positive bacteria was not altered by any of the extracts. Supplementation of vehicle and pulp cultures with norepinephrine or dopamine yielded growth equivalent to peel cultures. Total organic analysis of extracts further demonstrated that the differential effects of peel and pulp on bacterial growth was not nutritionally based, but due to norepinephrine and dopamine. These results suggest that neurochemicals contained within foodstuffs may influence the growth of pathogenic and indigenous bacteria through direct neurochemical-bacterial interactions.

  11. Behavioral, neurochemical, and electrophysiological changes in an early spontaneous mouse model of nigrostriatal degeneration.

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    Sgadò, Paola; Viaggi, Cristina; Pinna, Annalisa; Marrone, Cristina; Vaglini, Francesca; Pontis, Silvia; Mercuri, Nicola Biagio; Morelli, Micaela; Corsini, Giovanni Umberto

    2011-08-01

    In idiopathic Parkinson's disease, clinical symptoms do not emerge until consistent neurodegeneration has occurred. The late appearance of symptoms implies the existence of a relatively long preclinical period during which several disease-induced neurochemical changes take place to mask the existence of the disease and delay its clinical manifestations. The aim of this study was to examine the neurochemical, neurophysiological, and behavioral changes induced by the loss of nigrostriatal innervation in the En1+/-;En2-/- mouse, in the 10 months following degeneration, compared to En2 null mutant mice. Behavioral analysis (Pole-test, Beam-walking test, and Inverted grid test) and field potential recordings in the striatum indicated that loss of ~70% of nigrostriatal neurons produced no significant functional effects until 8 months of age, when En1+/-;En2-/- animals started to show frank motor deficits and electrophysiological alterations in corticostriatal plasticity. Similarly, alterations in dopamine homeostasis, dopamine turnover, and dopamine innervation were observed in aged animals compared to young En1+/-;En2-/- mice. These data suggests that in En1+/-;En2-/- mice nigrostriatal degeneration in the substantia nigra is functionally compensated.

  12. Investigation of spatial trends and neurochemical impacts of mercury in herring gulls across the Laurentian Great Lakes

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    Rutkiewicz, Jennifer [Department of Environmental Health Sciences, University of Michigan School of Public Health, 109 S. Observatory St, Ann Arbor, MI 48109 (United States); Scheuhammer, Anton; Crump, Doug; Jagla, Magdalena [Environment Canada, National Wildlife Research Centre, Carleton University, Ottawa, ON K1A 0H3 (Canada); Basu, Niladri, E-mail: niladri@umich.ed [Department of Environmental Health Sciences, University of Michigan School of Public Health, 109 S. Observatory St, Ann Arbor, MI 48109 (United States)

    2010-08-15

    Herring gulls (Larus argentatus) bioaccumulate mercury (Hg) but it is unknown whether they are exposed at levels of neurological concern. Here we studied brain tissues from gulls at five Great Lakes colonies and one non-Great Lakes colony during spring of 2001 and 2003. Total brain Hg concentrations ranged from 0.14 to 2.0 {mu}g/g (dry weight) with a mean of 0.54 {mu}g/g. Gulls from Scotch Bonnet Island, on the easternmost edge of the Great Lakes, had significantly higher brain Hg than other colonies. No association was found between brain Hg concentration and [3H]-ligand binding to neurochemical receptors (N-methyl-D-aspartate, muscarinic cholinergic, nicotinic cholinergic) or nicotinic receptor {alpha}-7 relative mRNA expression as previously documented in other wildlife. In conclusion, spatial trends in Hg contamination exist in herring gulls across the Great Lakes basin, and herring gulls accumulate brain Hg but not at levels associated with sub-clinical neurochemical alterations. - Spatial trends in brain mercury exist in herring gulls across the Laurentian Great Lakes though levels are not associated with neurochemical biomarkers.

  13. Investigation of spatial trends and neurochemical impacts of mercury in herring gulls across the Laurentian Great Lakes

    International Nuclear Information System (INIS)

    Rutkiewicz, Jennifer; Scheuhammer, Anton; Crump, Doug; Jagla, Magdalena; Basu, Niladri

    2010-01-01

    Herring gulls (Larus argentatus) bioaccumulate mercury (Hg) but it is unknown whether they are exposed at levels of neurological concern. Here we studied brain tissues from gulls at five Great Lakes colonies and one non-Great Lakes colony during spring of 2001 and 2003. Total brain Hg concentrations ranged from 0.14 to 2.0 μg/g (dry weight) with a mean of 0.54 μg/g. Gulls from Scotch Bonnet Island, on the easternmost edge of the Great Lakes, had significantly higher brain Hg than other colonies. No association was found between brain Hg concentration and [3H]-ligand binding to neurochemical receptors (N-methyl-D-aspartate, muscarinic cholinergic, nicotinic cholinergic) or nicotinic receptor α-7 relative mRNA expression as previously documented in other wildlife. In conclusion, spatial trends in Hg contamination exist in herring gulls across the Great Lakes basin, and herring gulls accumulate brain Hg but not at levels associated with sub-clinical neurochemical alterations. - Spatial trends in brain mercury exist in herring gulls across the Laurentian Great Lakes though levels are not associated with neurochemical biomarkers.

  14. Effect of Artificial Gravity: Central Nervous System Neurochemical Studies

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    Fox, Robert A.; D'Amelio, Fernando; Eng, Lawrence F.

    1997-01-01

    The major objective of this project was to assess chemical and morphological modifications occurring in muscle receptors and the central nervous system of animals subjected to altered gravity (2 x Earth gravity produced by centrifugation and simulated micro gravity produced by hindlimb suspension). The underlying hypothesis for the studies was that afferent (sensory) information sent to the central nervous system by muscle receptors would be changed in conditions of altered gravity and that these changes, in turn, would instigate a process of adaptation involving altered chemical activity of neurons and glial cells of the projection areas of the cerebral cortex that are related to inputs from those muscle receptors (e.g., cells in the limb projection areas). The central objective of this research was to expand understanding of how chronic exposure to altered gravity, through effects on the vestibular system, influences neuromuscular systems that control posture and gait. The project used an approach in which molecular changes in the neuromuscular system were related to the development of effective motor control by characterizing neurochemical changes in sensory and motor systems and relating those changes to motor behavior as animals adapted to altered gravity. Thus, the objective was to identify changes in central and peripheral neuromuscular mechanisms that are associated with the re-establishment of motor control which is disrupted by chronic exposure to altered gravity.

  15. Neuroprotective potential of curcumin in combination with piperine against 6-hydroxy dopamine induced motor deficit and neurochemical alterations in rats.

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    Singh, Shamsher; Kumar, Puneet

    2017-02-01

    6-hydroxy dopamine (6-OHDA) is a neurotoxin which on intranigral administration produces severe nigrostriatal damage with motor and cognitive deficit in animals. Curcumin (CMN) in combination with bioenhancer piperine (PP) in 6-hydroxydopamine-induced Parkinsonian rats was used to investigate the antioxidant, neuromodulatory and neuroprotective mechanisms. Hemi-Parkinson's rat model was developed with intranigral infusion of 6-OHDA (8 μg/2 μl, once, unilaterally), treatment with CMN (25 and 50 mg/kg) and combination of PP (2.5 mg/kg) with CMN (25 mg/kg) was given daily for 21 days starting from the 7th day after 6-OHDA infusion. The behavioral (locomotor, grip strength, and narrow beam walk) parameters were studied on weekly basis. On 22nd day, isolated brain preparations were subjected to biochemical (lipid peroxidation, glutathione, and nitrite), neuroinflammatory (IL-1β, IL-6, and TNF- α), and neurochemical (DA, NE, 5- HT, GABA, Glutamate, DOPAC, HVA, and 5-HIAA) analysis. Oral administration of CMN had significantly prevented behavioral, neuroinflammatory, and neurochemical changes and preserved the antioxidant potential of the nigrostriatum in rats treated with 6-OHDA. In the present study, PP and CMN had afforded a better neuroprotective effect compared to alone treatment on behavior, biochemical, neuroinflammatory, and neurochemical parameters in rats.

  16. Protective effect of gallic acid in experimental model of ketamine-induced psychosis: possible behaviour, biochemical, neurochemical and cellular alterations.

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    Yadav, Monu; Jindal, Deepak Kumar; Dhingra, Mamta Sachdeva; Kumar, Anil; Parle, Milind; Dhingra, Sameer

    2018-04-01

    Gallic acid has been reported to possess a number of psychopharmacological activities. These activities are attributed to the antioxidant potential due to the presence of phenolic moeity. The present study was carried out to investigate the protective effects of gallic acid in an experimental model of ketamine-induced psychosis in mice. Ketamine (50 mg/kg, i.p.) was used to induce stereotyped psychotic behavioural symptoms in mice. Behavioural studies (locomotor activity, stereotype behaviour, immobility duration and memory retention) were carried out to investigate the protective of gallic acid on ketamine-induced psychotic symptoms, followed by biochemical and neurochemical changes and cellular alterations in the brain. Chronic treatment with gallic acid for 15 consecutive days significantly attenuated stereotyped behavioural symptoms in mice. Biochemical estimations revealed that gallic acid reduced the lipid peroxidation and restored the total brain proteins. Furthermore, gallic acid remarkably reduced the dopamine levels, AChE activity and inflammatory surge (serum TNF-α), and increased the levels of GABA and increased glutathione in mice. The study revealed that gallic acid could ameliorate psychotic symptoms and biochemical changes in mice, indicating protective effects in psychosis.

  17. WINCS Harmoni: Closed-loop dynamic neurochemical control of therapeutic interventions

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    Lee, Kendall H.; Lujan, J. Luis; Trevathan, James K.; Ross, Erika K.; Bartoletta, John J.; Park, Hyung Ook; Paek, Seungleal Brian; Nicolai, Evan N.; Lee, Jannifer H.; Min, Hoon-Ki; Kimble, Christopher J.; Blaha, Charles D.; Bennet, Kevin E.

    2017-04-01

    There has been significant progress in understanding the role of neurotransmitters in normal and pathologic brain function. However, preclinical trials aimed at improving therapeutic interventions do not take advantage of real-time in vivo neurochemical changes in dynamic brain processes such as disease progression and response to pharmacologic, cognitive, behavioral, and neuromodulation therapies. This is due in part to a lack of flexible research tools that allow in vivo measurement of the dynamic changes in brain chemistry. Here, we present a research platform, WINCS Harmoni, which can measure in vivo neurochemical activity simultaneously across multiple anatomical targets to study normal and pathologic brain function. In addition, WINCS Harmoni can provide real-time neurochemical feedback for closed-loop control of neurochemical levels via its synchronized stimulation and neurochemical sensing capabilities. We demonstrate these and other key features of this platform in non-human primate, swine, and rodent models of deep brain stimulation (DBS). Ultimately, systems like the one described here will improve our understanding of the dynamics of brain physiology in the context of neurologic disease and therapeutic interventions, which may lead to the development of precision medicine and personalized therapies for optimal therapeutic efficacy.

  18. Unrequited: neurochemical enhancement of love.

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    Bamford, Rebecca

    2015-07-01

    I raise several concerns with Earp and colleagues' analysis of enhancement through neurochemical modulation of love as a key issue in contemporary neuroethics. These include: (i) strengthening their deflation of medicalization concerns by showing how the objection that love should be left outside of the scope of medicine would directly undermine the goal of medicine; (ii) developing stronger analysis of the social and political concerns relevant to neurochemical modulation of love, by exploring and suggesting possible counters to ways in which 'wellbeing' may be used as a tool of oppression; (iii) providing reasons to support a broad need for ecological investigation of, and indeed ecological education concerning, neurotechnology; (iv) suggesting ways in which philosophy, and the humanities more broadly, remain directly relevant to responding effectively to issues in contemporary neuroethics.

  19. Neurochemical characterization of the tree shrew dorsal striatum

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    MATTHEW W RICE

    2011-08-01

    Full Text Available The striatum is a major component of the basal ganglia and is associated with motor and cognitive functions. Striatal pathologies have been linked to several disorders, including Huntington's, Tourette's syndrome, obsessive-compulsive disorders and schizophrenia. For the study of these striatal pathologies different animal models have been used, including rodents and non-human primates. Rodents lack on morphological complexity (for example, the lack of well defined caudate and putamen nuclei, which makes it difficult to translate data to the human paradigm. Primates, and especially higher primates, are the closest model to humans, but there are ever-increasing restrictions to the use of these animals for research. In our search for a non-primate animal model with a striatum that anatomically (and perhaps functionally can resemble that of humans, we turned our attention to the tree shrew. Evolutionary genetic studies have provided strong data supporting that the tree shrews (Scadentia are one of the closest groups to primates, although their brain anatomy has only been studied in detail for specific brain areas. Morphologically, the tree shrew striatum resembles the primate striatum with the presence of an internal capsule separating the caudate and putamen, but little is known about its neurochemical composition. Here we analyzed the expression of calcium-binding proteins, the presence and distribution of the striosome and matrix compartments (by the use of calbindin, tyrosine hydroxylase and acetylcholinesterase immunohistochemistry, and the GABAergic system by immunohistochemistry against glutamic acid decarboxylase and Golgi impregnation. In summary, our results show that when compared to primates, the tree shrew dorsal striatum presents striking similarities in the distribution of most of the markers studied, while presenting some marked divergences when compared to the rodent striatum.

  20. Mercury Vapour Long-Lasting Exposure: Lymphocyte Muscarinic Receptors as Neurochemical Markers of Accidental Intoxication

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    E. Roda

    2016-01-01

    Full Text Available Introduction. Chronic poisoning may result in home setting after mercury (Hg vapours inhalation from damaged devices. We report a chronic, nonoccupational Hg poisoning due to 10-year indoor exposure to mercury spillage. Case Report. A 72-year-old man with polyneuropathy of suspected toxic origin. At hospitalization, toxicological clinical evaluations confirmed the altered neurological picture documented across the last decade. Periodic blood and urine Hg levels (BHg, UHg monitoring were performed from admission (t0, until 1 year later (t2, paralleled by blood neurochemical markers assessment, that is, lymphocytes muscarinic receptors (l-MRs. At t0: BHg and UHg were 27 and 1.4 microg/L, respectively (normal values: BHg 1–4.5; UHg 0.1–4.5, associated with l-MRs increase, 185.82 femtomoL/million lymphocytes (normal range: 8.0–16.0. At t1 (two days after DMSA-mobilization test, BHg weak reduction, paralleled by UHg 3.7-fold increase, was measured together with further l-MRs enhancement (205.43 femtomoL/million lymphocytes. At t2 (eight months after two cycles of DMSA chelating therapy ending, gradual improving of clinical manifestations was accompanied by progressive decrease of BHg and UHg (4.0 and 2.8 microg/L, resp. and peripheral l-MRs neurochemical marker (24.89 femtomoL/million lymphocytes. Conclusion. l-MRs modulatory effect supports their use as peripheral neurochemical marker in Hg poisoning diagnosis and chelation therapy monitoring.

  1. Caffeine triggers behavioral and neurochemical alterations in adolescent rats.

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    Ardais, A P; Borges, M F; Rocha, A S; Sallaberry, C; Cunha, R A; Porciúncula, L O

    2014-06-13

    Caffeine is the psychostimulant most consumed worldwide but concerns arise about the growing intake of caffeine-containing drinks by adolescents since the effects of caffeine on cognitive functions and neurochemical aspects of late brain maturation during adolescence are poorly known. We now studied the behavioral impact in adolescent male rats of regular caffeine intake at low (0.1mg/mL), moderate (0.3mg/mL) and moderate/high (1.0mg/mL) doses only during their active period (from 7:00 P.M. to 7:00 A.M.). All tested doses of caffeine were devoid of effects on locomotor activity, but triggered anxiogenic effects. Caffeine (0.3 and 1mg/mL) improved the performance in the object recognition task, but the higher dose of caffeine (1.0mg/mL) decreased the habituation to an open-field arena, suggesting impaired non-associative memory. All tested doses of caffeine decreased the density of glial fibrillary acidic protein and synaptosomal-associated protein-25, but failed to modify neuron-specific nuclear protein immunoreactivity in the hippocampus and cerebral cortex. Caffeine (0.3-1mg/mL) increased the density of brain-derived neurotrophic factor (BDNF) and proBDNF density as well as adenosine A1 receptor density in the hippocampus, whereas the higher dose of caffeine (1mg/mL) increased the density of proBDNF and BDNF and decreased A1 receptor density in the cerebral cortex. These findings document an impact of caffeine consumption in adolescent rats with a dual impact on anxiety and recognition memory, associated with changes in BDNF levels and decreases of astrocytic and nerve terminal markers without overt neuronal damage in hippocampal and cortical regions. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  2. Age-Related Neurochemical Changes in the Vestibular Nuclei

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    Paul eSmith

    2016-03-01

    Full Text Available There is evidence that the normal aging process is associated with impaired vestibulo-ocular (VOR and vestibulo-spinal reflexes, causing reduced visual acuity and postural instability. Nonetheless, the available evidence is not entirely consistent, especially with respect to the VOR. Some recent studies have reported that VOR gain can be intact even above 80 years of age. Similarly, although there is evidence for age-related hair cell loss and neuronal loss in Scarpa’s ganglion and the vestibular nucleus complex (VNC, it is not entirely consistent. Whatever structural and functional changes occur in the VNC as a result of aging, either to cause vestibular impairment or to compensate for it, neurochemical changes must underlie them. However, the neurochemical changes that occur in the VNC with aging are poorly understood because the available literature is very limited. This review summarises and critically evaluates the available evidence relating to the noradrenaline, serotonin, dopamine, glutamate, GABA, glycine, and nitric oxide neurotransmitter systems in the aging VNC. It is concluded that, at present, it is difficult, if not impossible, to relate the neurochemical changes observed to the function of specific VNC neurons and whether the observed changes are the cause of a functional deficit in the VNC or an effect of it. A better understanding of the neurochemical changes that occur during aging may be important for the development of potential drug treatments for age-related vestibular disorders. However, this will require the use of more sophisticated methodology such as in vivo microdialysis with single neuron recording and perhaps new technologies such as optogenetics.

  3. Age-Related Neurochemical Changes in the Vestibular Nuclei.

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    Smith, Paul F

    2016-01-01

    There is evidence that the normal aging process is associated with impaired vestibulo-ocular reflexes (VOR) and vestibulo-spinal reflexes, causing reduced visual acuity and postural instability. Nonetheless, the available evidence is not entirely consistent, especially with respect to the VOR. Some recent studies have reported that VOR gain can be intact even above 80 years of age. Similarly, although there is evidence for age-related hair cell loss and neuronal loss in Scarpa's ganglion and the vestibular nucleus complex (VNC), it is not entirely consistent. Whatever structural and functional changes occur in the VNC as a result of aging, either to cause vestibular impairment or to compensate for it, neurochemical changes must underlie them. However, the neurochemical changes that occur in the VNC with aging are poorly understood because the available literature is very limited. This review summarizes and critically evaluates the available evidence relating to the noradrenaline, serotonin, dopamine, glutamate, GABA, glycine, and nitric oxide neurotransmitter systems in the aging VNC. It is concluded that, at present, it is difficult, if not impossible, to relate the neurochemical changes observed to the function of specific VNC neurons and whether the observed changes are the cause of a functional deficit in the VNC or an effect of it. A better understanding of the neurochemical changes that occur during aging may be important for the development of potential drug treatments for age-related vestibular disorders. However, this will require the use of more sophisticated methodology such as in vivo microdialysis with single neuron recording and perhaps new technologies such as optogenetics.

  4. Neurochemical changes in the pericalcarine cortex in congenital blindness attributable to bilateral anophthalmia.

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    Coullon, Gaelle S L; Emir, Uzay E; Fine, Ione; Watkins, Kate E; Bridge, Holly

    2015-09-01

    Congenital blindness leads to large-scale functional and structural reorganization in the occipital cortex, but relatively little is known about the neurochemical changes underlying this cross-modal plasticity. To investigate the effect of complete and early visual deafferentation on the concentration of metabolites in the pericalcarine cortex, (1)H magnetic resonance spectroscopy was performed in 14 sighted subjects and 5 subjects with bilateral anophthalmia, a condition in which both eyes fail to develop. In the pericalcarine cortex, where primary visual cortex is normally located, the proportion of gray matter was significantly greater, and levels of choline, glutamate, glutamine, myo-inositol, and total creatine were elevated in anophthalmic relative to sighted subjects. Anophthalmia had no effect on the structure or neurochemistry of a sensorimotor cortex control region. More gray matter, combined with high levels of choline and myo-inositol, resembles the profile of the cortex at birth and suggests that the lack of visual input from the eyes might have delayed or arrested the maturation of this cortical region. High levels of choline and glutamate/glutamine are consistent with enhanced excitatory circuits in the anophthalmic occipital cortex, which could reflect a shift toward enhanced plasticity or sensitivity that could in turn mediate or unmask cross-modal responses. Finally, it is possible that the change in function of the occipital cortex results in biochemical profiles that resemble those of auditory, language, or somatosensory cortex. Copyright © 2015 the American Physiological Society.

  5. Effect of facial self-resemblance on the startle response and subjective ratings of erotic stimuli in heterosexual men.

    Science.gov (United States)

    Lass-Hennemann, Johanna; Deuter, Christian E; Kuehl, Linn K; Schulz, Andre; Blumenthal, Terry D; Schachinger, Hartmut

    2011-10-01

    Cues of kinship are predicted to increase prosocial behavior due to the benefits of inclusive fitness, but to decrease approach motivation due to the potential costs of inbreeding. Previous studies have shown that facial resemblance, a putative cue of kinship, increases prosocial behavior. However, the effects of facial resemblance on mating preferences are equivocal, with some studies finding that facial resemblance decreases sexual attractiveness ratings, while other studies show that individuals choose mates partly on the basis of similarity. To further investigate this issue, a psychophysiological measure of affective processing, the startle response, was used in this study, assuming that differences in approach motivation to erotic pictures will modulate startle. Male volunteers (n = 30) viewed 30 pictures of erotic female nudes while startle eyeblink responses were elicited by acoustic noise probes. The female nude pictures were digitally altered so that the face either resembled the male participant or another participant, or were not altered. Non-nude neutral pictures were also included. Importantly, the digital alteration was undetected by the participants. Erotic pictures were rated as being pleasant and clearly reduced startle eyeblink magnitude as compared to neutral pictures. Participants showed greater startle inhibition to self-resembling than to other-resembling or non-manipulated female nude pictures, but subjective pleasure and arousal ratings did not differ among the three erotic picture categories. Our data suggest that visual facial resemblance of opposite-sex nudes increases approach motivation in men, and that this effect was not due to their conscious evaluation of the erotic stimuli.

  6. Biochemical and neurochemical effects in rats following Iow-level chronic moniliformin mycotoxin treatment

    International Nuclear Information System (INIS)

    Adam, Y.M.; Abdel-Kader, S.M.

    2000-01-01

    An investigation was conducted to study the biochemical and neurochemical effects of moniliformin mycotoxins in rats. Moniliformin was extracted from fusarium oxysporum and injected intraperitoneally to male albino rats at a dose level 225 magaa g/kg (1/220 LD 5 0) daily for three weeks. The results. The results revealed a decrease in body weight of treated animals, in addition to alteration in the weights of some selected organs. A significant increase of serum ALT, AST and ALP were observed, indicating changes in liver function. Kidney function of treated rats as determined by alteration creatinine and blood urea also was affected. On the other hand the data obtained revealed a dramatic decrease in brain acetylcholinesterase activity. In addition, moniliformin exhibited alteration in the total content of catecholamines, dopamine (DA), norepinephrine (NE), serotonine (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), free inorganic phosphate (Pi) and gamma-aminobutyric acid (GABA) in rat brain of treated animals. Also, profound decline in serum testosterone level was observed. No pathological changes were detected. Hormonal assays were performed using radioimmunoassay techniques

  7. Altered Neurochemical Ingredient of Hippocampus in Patients with Bipolar Depression

    Directory of Open Access Journals (Sweden)

    Murad Atmaca

    2012-01-01

    Full Text Available Background. In a number of investigations, hippocampal neurochemicals were evaluated in the patients with bipolar disorder who were on their first episode or euthymic periods. However, we did not meet any investigation in which only patients with bipolar depression were examined. As a consequence, the objective of the present study was to examine both sides of hippocampus of patients with bipolar disorder in depressive episode and healthy controls using 1H-MRS. Methods. Thirteen patients with DSM-IV bipolar I disorder, most recent episode depressed, were recruited from the Department of Psychiatry at Firat University School of Medicine. We also studied 13 healthy comparison subjects who were without any DSM-IV Axis I disorders recruited from the hospital staff. The patients and controls underwent proton magnetic resonance spectroscopy (1H-MRS of their hippocampus. NAA, CHO, and CRE values were measured. Results. No significant effect of diagnosis was observed for NAA/CRE ratio. For the NAA/CHO ratio, the ANCOVA with age, gender, and whole brain volume as covariates revealed that the patients with bipolar depression had significantly lower ratio compared to healthy control subjects for right and for left side. As for the CHO/CRE ratio, the difference was statistically significant for right side, with an effect diagnosis of F = 4.763, P = 0.038, and was very nearly significant for left side, with an effect diagnosis of F = 3.732, P = 0.064. Conclusions. We found that the patients with bipolar depression had lower NAA/CHO and higher CHO/CRE ratios compared to those of healthy control subjects. The findings of the present study also suggest that there may be a degenerative process concerning the hippocampus morphology in the patients with bipolar depression.

  8. Antioxidant-Rich Fraction of Urtica dioica Mediated Rescue of Striatal Mito-Oxidative Damage in MPTP-Induced Behavioral, Cellular, and Neurochemical Alterations in Rats.

    Science.gov (United States)

    Bisht, Rohit; Joshi, Bhuwan Chandra; Kalia, Ajudhiya Nath; Prakash, Atish

    2017-09-01

    Parkinson's disease (PD) having a complex and multi-factorial neuropathology includes mainly the degeneration of the dopaminergic nigrostriatal pathway, which is a cumulative effect of depleted endogenous antioxidant enzymes, increased oxidative DNA damage, mitochondrial dysfunction, excitotoxicity, and neuroinflammation. The present study was designed to investigate the neuroprotective effect of a potent antioxidant from Urtica dioica in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of parkinsonism. MPTP was administered intranigrally for the induction of PD in male Wistar rats. Behavioral alterations were assessed in between the study period. Animals were sacrificed immediately after behavioral session, and different biochemical, cellular, and neurochemical parameters were measured. Intranigrally repeated administration of MPTP showed significant impairment of motor co-ordination and marked increase of mito-oxidative damage and neuroinflammation in rats. Intranigral MPTP significantly decreases the dopamine and its metabolites with impairment of dopaminergic cell density in rat brain. However, post-treatment with the potent antioxidant fraction of Urtica dioica Linn. (UD) (20, 40, 80 mg/kg) improved the motor function, mito-oxidative defense alteration significantly and dose dependently in MPTP-treated rats. In addition, the potent antioxidant fraction of UD attenuated the pro-inflammatory cytokines (TNF-α and IL-β) and restored the level of dopamine and its metabolites in MPTP-induced PD in rats. Moreover, minocycline (30 mg/kg) with lower dose of UD (20 mg/kg) had significantly potentiated the protective effect of minocycline as compared to its effect with other individual drug-treated groups. In conclusion, Urtica dioica protected the dopaminergic neurons probably by reducing mito-oxidative damage, neuroinflammation, and cellular alteration along with enhanced neurotrophic potential. The above results revealed that the antioxidant rich

  9. Brain region-specific perfluoroalkylated sulfonate (PFSA) and carboxylic acid (PFCA) accumulation and neurochemical biomarker responses in east Greenland polar bears (Ursus maritimus)

    DEFF Research Database (Denmark)

    Pedersen, Kathrine Eggers; Basu, Niladri; Letcher, Robert J.

    2015-01-01

    to bioaccumulate in lipid rich tissues of the brain among other tissues such as liver, and can reach high concentrations in top predators including the polar bear. PFCA and PFSA bioaccummulation in the brain has the potential to pose neurotoxic effects and therefore we conducted a study to investigate...... if variations in neurochemical transmitter systems i.e. the cholinergic, glutaminergic, dopaminergic and GABAergic, could be related to brain-specific bioaccumulation of PFASs in East Greenland polar bears. Nine brain regions from nine polar bears were analyzed for enzyme activity (monoamine oxidase (MAO...... regions, whereas GS activity was positively correlated with PFASs primarily in occipital lobe. Results from the present study support the hypothesis that PFAS concentrations in polar bears from East Greenland have exceeded the threshold limits for neurochemical alterations. It is not known whether...

  10. Convulsant activity and neurochemical alterations induced by a fraction obtained from fruit Averrhoa carambola (Oxalidaceae: Geraniales).

    Science.gov (United States)

    Carolino, Ruither O G; Beleboni, Renê O; Pizzo, Andrea B; Vecchio, Flavio Del; Garcia-Cairasco, Norberto; Moyses-Neto, Miguel; Santos, Wagner F Dos; Coutinho-Netto, Joaquim

    2005-06-01

    We obtained a neurotoxic fraction (AcTx) from star fruit (Averrhoa carambola) and studied its effects on GABAergic and glutamatergic transmission systems. AcTx had no effect on GABA/glutamate uptake or release, or on glutamate binding. However, it specifically inhibited GABA binding in a concentration-dependent manner (IC(50)=0.89muM). Video-electroencephalogram recordings demonstrated that following cortical administration of AcTx, animals showed behavioral changes, including tonic-clonic seizures, evolving into status epilepticus, accompanied by cortical epileptiform activity. Chemical characterization of AcTx showed that this compound is a nonproteic molecule with a molecular weight less than 500, differing from oxalic acid. This neurotoxic fraction of star fruit may be considered a new tool for neurochemical and neuroethological research.

  11. Behavioral metabolomics analysis identifies novel neurochemical signatures in methamphetamine sensitization

    Science.gov (United States)

    Adkins, Daniel E.; McClay, Joseph L.; Vunck, Sarah A.; Batman, Angela M.; Vann, Robert E.; Clark, Shaunna L.; Souza, Renan P.; Crowley, James J.; Sullivan, Patrick F.; van den Oord, Edwin J.C.G.; Beardsley, Patrick M.

    2014-01-01

    Behavioral sensitization has been widely studied in animal models and is theorized to reflect neural modifications associated with human psychostimulant addiction. While the mesolimbic dopaminergic pathway is known to play a role, the neurochemical mechanisms underlying behavioral sensitization remain incompletely understood. In the present study, we conducted the first metabolomics analysis to globally characterize neurochemical differences associated with behavioral sensitization. Methamphetamine-induced sensitization measures were generated by statistically modeling longitudinal activity data for eight inbred strains of mice. Subsequent to behavioral testing, nontargeted liquid and gas chromatography-mass spectrometry profiling was performed on 48 brain samples, yielding 301 metabolite levels per sample after quality control. Association testing between metabolite levels and three primary dimensions of behavioral sensitization (total distance, stereotypy and margin time) showed four robust, significant associations at a stringent metabolome-wide significance threshold (false discovery rate < 0.05). Results implicated homocarnosine, a dipeptide of GABA and histidine, in total distance sensitization, GABA metabolite 4-guanidinobutanoate and pantothenate in stereotypy sensitization, and myo-inositol in margin time sensitization. Secondary analyses indicated that these associations were independent of concurrent methamphetamine levels and, with the exception of the myo-inositol association, suggest a mechanism whereby strain-based genetic variation produces specific baseline neurochemical differences that substantially influence the magnitude of MA-induced sensitization. These findings demonstrate the utility of mouse metabolomics for identifying novel biomarkers, and developing more comprehensive neurochemical models, of psychostimulant sensitization. PMID:24034544

  12. Does facial resemblance enhance cooperation?

    Directory of Open Access Journals (Sweden)

    Trang Giang

    Full Text Available Facial self-resemblance has been proposed to serve as a kinship cue that facilitates cooperation between kin. In the present study, facial resemblance was manipulated by morphing stimulus faces with the participants' own faces or control faces (resulting in self-resemblant or other-resemblant composite faces. A norming study showed that the perceived degree of kinship was higher for the participants and the self-resemblant composite faces than for actual first-degree relatives. Effects of facial self-resemblance on trust and cooperation were tested in a paradigm that has proven to be sensitive to facial trustworthiness, facial likability, and facial expression. First, participants played a cooperation game in which the composite faces were shown. Then, likability ratings were assessed. In a source memory test, participants were required to identify old and new faces, and were asked to remember whether the faces belonged to cooperators or cheaters in the cooperation game. Old-new recognition was enhanced for self-resemblant faces in comparison to other-resemblant faces. However, facial self-resemblance had no effects on the degree of cooperation in the cooperation game, on the emotional evaluation of the faces as reflected in the likability judgments, and on the expectation that a face belonged to a cooperator rather than to a cheater. Therefore, the present results are clearly inconsistent with the assumption of an evolved kin recognition module built into the human face recognition system.

  13. Altered synaptic phospholipid signaling in PRG-1 deficient mice induces exploratory behavior and motor hyperactivity resembling psychiatric disorders.

    Science.gov (United States)

    Schneider, Patrick; Petzold, Sandra; Sommer, Angela; Nitsch, Robert; Schwegler, Herbert; Vogt, Johannes; Roskoden, Thomas

    2018-01-15

    Plasticity related gene 1 (PRG-1) is a neuron specific membrane protein located at the postsynaptic density of glutamatergic synapses. PRG-1 modulates signaling pathways of phosphorylated lipid substrates such as lysophosphatidic acid (LPA). Deletion of PRG-1 increases presynaptic glutamate release probability leading to neuronal over-excitation. However, due to its cortical expression, PRG-1 deficiency leading to increased glutamatergic transmission is supposed to also affect motor pathways. We therefore analyzed the effects of PRG-1 function on exploratory and motor behavior using homozygous PRG-1 knockout (PRG-1 -/- ) mice and PRG-1/LPA 2 -receptor double knockout (PRG-1 -/- /LPA 2 -/- ) mice in two open field settings of different size and assessing motor behavior in the Rota Rod test. PRG-1 -/- mice displayed significantly longer path lengths and higher running speed in both open field conditions. In addition, PRG-1 -/- mice spent significantly longer time in the larger open field and displayed rearing and self-grooming behavior. Furthermore PRG-1 -/- mice displayed stereotypical behavior resembling phenotypes of psychiatric disorders in the smaller sized open field arena. Altogether, this behavior is similar to the stereotypical behavior observed in animal models for psychiatric disease of autistic spectrum disorders which reflects a disrupted balance between glutamatergic and GABAergic synapses. These differences indicate an altered excitation/inhibition balance in neuronal circuits in PRG-1 -/- mice as recently shown in the somatosensory cortex [38]. In contrast, PRG-1 -/- /LPA 2 -/- did not show significant changes in behavior in the open field suggesting that these specific alterations were abolished when the LPA 2 -receptor was lacking. Our findings indicate that PRG-1 deficiency led to over-excitability caused by an altered LPA/LPA 2 -R signaling inducing a behavioral phenotype typically observed in animal models for psychiatric disorders. Copyright

  14. Early-onset behavioral and neurochemical deficits in the genetic mouse model of phenylketonuria.

    Science.gov (United States)

    Fiori, Elena; Oddi, Diego; Ventura, Rossella; Colamartino, Marco; Valzania, Alessandro; D'Amato, Francesca Romana; Bruinenberg, Vibeke; van der Zee, Eddy; Puglisi-Allegra, Stefano; Pascucci, Tiziana

    2017-01-01

    Phenylketonuria (PKU) is one of the most common human inborn errors of metabolism, caused by phenylalanine hydroxylase deficiency, leading to high phenylalanine and low tyrosine levels in blood and brain causing profound cognitive disability, if untreated. Since 1960, population is screened for hyperphenylalaninemia shortly after birth and submitted to early treatment in order to prevent the major manifestations of the disease. However, the dietetic regimen (phenylalanine free diet) is difficult to maintain, and despite the recommendation to a strict and lifelong compliance, up to 60% of adolescents partially or totally abandons the treatment. The development and the study of new treatments continue to be sought, taking advantage of preclinical models, the most used of which is the PAHenu2 (BTBR ENU2), the genetic murine model of PKU. To date, adult behavioral and neurochemical alterations have been mainly investigated in ENU2 mice, whereas there are no clear indications about the onset of these deficiencies. Here we investigated and report, for the first time, a comprehensive behavioral and neurochemical assay of the developing ENU2 mice. Overall, our findings demonstrate that ENU2 mice are significantly smaller than WT until pnd 24, present a significant delay in the acquisition of tested developmental reflexes, impaired communicative, motor and social skills, and have early reduced biogenic amine levels in several brain areas. Our results extend the understanding of behavioral and cerebral abnormalities in PKU mice, providing instruments to an early preclinical evaluation of the effects of new treatments.

  15. Multivoxel proton magnetic resonance spectroscopy detects thalamic neurochemical metabolic changes in patients with major depressive disorder

    Directory of Open Access Journals (Sweden)

    Rania E. Mohamed

    2017-06-01

    Conclusion: The multi-voxel 1H-MRS can provide an insight to the neurochemical metabolic changes occurring in both thalami in patients with MDD. Increased severity of depression is significantly related to these thalamic neurochemical changes.

  16. Linking Essential Tremor to the Cerebellum: Neurochemical Evidence.

    Science.gov (United States)

    Marin-Lahoz, Juan; Gironell, Alexandre

    2016-06-01

    The pathophysiology and the exact anatomy of essential tremor (ET) is not well known. One of the pillars that support the cerebellum as the main anatomical locus in ET is neurochemistry. This review examines the link between neurochemical abnormalities found in ET and cerebellum. The review is based on published data about neurochemical abnormalities described in ET both in human and in animal studies. We try to link those findings with cerebellum. γ-aminobutyric acid (GABA) is the main neurotransmitter involved in the pathophysiology of ET. There are several studies about GABA that clearly points to a main role of the cerebellum. There are few data about other neurochemical abnormalities in ET. These include studies with noradrenaline, glutamate, adenosine, proteins, and T-type calcium channels. One single study reveals high levels of noradrenaline in the cerebellar cortex. Another study about serotonin neurotransmitter results negative for cerebellum involvement. Finally, studies on T-type calcium channels yield positive results linking the rhythmicity of ET and cerebellum. Neurochemistry supports the cerebellum as the main anatomical locus in ET. The main neurotransmitter involved is GABA, and the GABA hypothesis remains the most robust pathophysiological theory of ET to date. However, this hypothesis does not rule out other mechanisms and may be seen as the main scaffold to support findings in other systems. We clearly need to perform more studies about neurochemistry in ET to better understand the relations among the diverse systems implied in ET. This is mandatory to develop more effective pharmacological therapies.

  17. Metabolomics reveals distinct neurochemical profiles associated with stress resilience

    Directory of Open Access Journals (Sweden)

    Brooke N. Dulka

    2017-12-01

    Full Text Available Acute social defeat represents a naturalistic form of conditioned fear and is an excellent model in which to investigate the biological basis of stress resilience. While there is growing interest in identifying biomarkers of stress resilience, until recently, it has not been feasible to associate levels of large numbers of neurochemicals and metabolites to stress-related phenotypes. The objective of the present study was to use an untargeted metabolomics approach to identify known and unknown neurochemicals in select brain regions that distinguish susceptible and resistant individuals in two rodent models of acute social defeat. In the first experiment, male mice were first phenotyped as resistant or susceptible. Then, mice were subjected to acute social defeat, and tissues were immediately collected from the ventromedial prefrontal cortex (vmPFC, basolateral/central amygdala (BLA/CeA, nucleus accumbens (NAc, and dorsal hippocampus (dHPC. Ultra-high performance liquid chromatography coupled with high resolution mass spectrometry (UPLC-HRMS was used for the detection of water-soluble neurochemicals. In the second experiment, male Syrian hamsters were paired in daily agonistic encounters for 2 weeks, during which they formed stable dominant-subordinate relationships. Then, 24 h after the last dominance encounter, animals were exposed to acute social defeat stress. Immediately after social defeat, tissue was collected from the vmPFC, BLA/CeA, NAc, and dHPC for analysis using UPLC-HRMS. Although no single biomarker characterized stress-related phenotypes in both species, commonalities were found. For instance, in both model systems, animals resistant to social defeat stress also show increased concentration of molecules to protect against oxidative stress in the NAc and vmPFC. Additionally, in both mice and hamsters, unidentified spectral features were preliminarily annotated as potential targets for future experiments. Overall, these findings

  18. Quantitative autoradiography of neurochemicals

    International Nuclear Information System (INIS)

    Rainbow, T.C.; Biegon, A.; Bleisch, W.V.

    1982-01-01

    Several new methods have been developed that apply quantitative autoradiography to neurochemistry. These methods are derived from the 2-deoxyglucose (2DG) technique of Sokoloff (1), which uses quantitative autoradiography to measure the rate of glucose utilization in brain structures. The new methods allow the measurement of the rate of cerbral protein synthesis and the levels of particular neurotransmitter receptors by quantitative autoradiography. As with the 2DG method, the new techniques can measure molecular levels in micron-sized brain structures; and can be used in conjunction with computerized systems of image processing. It is possible that many neurochemical measurements could be made by computerized analysis of quantitative autoradiograms

  19. Dysregulation of Brain Reward Systems in Eating Disorders: Neurochemical Information from Animal Models of Binge Eating, Bulimia Nervosa, and Anorexia Nervosa

    Science.gov (United States)

    Avena, Nicole M.; Bocarsly, Miriam E.

    2012-01-01

    Food intake is mediated, in part, through brain pathways for motivation and reinforcement. Dysregulation of these pathways may underlay some of the behaviors exhibited by patients with eating disorders. Research using animal models of eating disorders has greatly contributed to the detailed study of potential brain mechanisms that many underlie the causes or consequences of aberrant eating behaviors. This review focuses on neurochemical evidence of reward-related brain dysfunctions obtained through animal models of binge eating, bulimia nervosa, or anorexia nervosa. The findings suggest that alterations in dopamine (DA), acetylcholine (ACh) and opioid systems in reward-related brain areas occur in response to binge eating of palatable foods. Moreover, animal models of bulimia nervosa suggest that while bingeing on palatable food releases DA, purging attenuates the release of ACh that might otherwise signal satiety. Animal models of anorexia nervosa suggest that restricted access to food enhances the reinforcing effects of DA when the animal does eat. The activity-based anorexia model suggests alterations in mesolimbic DA and serotonin occur as a result of starvation coupled with excessive wheel running. These findings with animal models complement data obtained through neuroimaging and pharmacotherapy studies of clinical populations. Finally, information on the neurochemical consequences of the behaviors associated with these eating disorders will be useful in understanding these complex disorders and may inform future therapeutic approaches, as discussed here. PMID:22138162

  20. A diamond-based electrode for detection of neurochemicals in the human brain

    Directory of Open Access Journals (Sweden)

    Kevin E. Bennet

    2016-03-01

    Full Text Available Deep brain stimulation (DBS, a surgical technique to treat certain neurologic and psychiatric conditions, relies on pre-determined stimulation parameters in an open-loop configuration. The major advancement in DBS devices is a closed-loop system that uses neurophysiologic feedback to dynamically adjust stimulation frequency and amplitude. Stimulation-driven neurochemical release can be measured by fast-scan cyclic voltammetry (FSCV, but existing FSCV electrodes rely on carbon fiber, which degrades quickly during use and is therefore unsuitable for chronic neurochemical recording. To address this issue, we developed durable, synthetic boron-doped diamond-based electrodes capable of measuring neurochemical release in humans. Compared to carbon fiber electrodes, they were more than two orders-of-magnitude more physically-robust and demonstrated longevity in vitro without deterioration. Applied for the first time in humans, diamond electrode recordings from thalamic targets in patients (n=4 undergoing DBS for tremor produced signals consistent with adenosine release at a sensitivity comparable to carbon fiber electrodes.

  1. Neurochemical differences in learning and memory paradigms among rats supplemented with anthocyanin-rich blueberry diets and exposed to acute doses of 56Fe particles

    Science.gov (United States)

    Poulose, Shibu M.; Rabin, Bernard M.; Bielinski, Donna F.; Kelly, Megan E.; Miller, Marshall G.; Thanthaeng, Nopporn; Shukitt-Hale, Barbara

    2017-02-01

    The protective effects of anthocyanin-rich blueberries (BB) on brain health are well documented and are particularly important under conditions of high oxidative stress, which can lead to "accelerated aging." One such scenario is exposure to space radiation, consisting of high-energy and -charge particles (HZE), which are known to cause cognitive dysfunction and deleterious neurochemical alterations. We recently tested the behavioral and neurochemical effects of acute exposure to HZE particles such as 56Fe, within 24-48 h after exposure, and found that radiation primarily affects memory and not learning. Importantly, we observed that specific brain regions failed to upregulate antioxidant and anti-inflammatory mechanisms in response to this insult. To further examine these endogenous response mechanisms, we have supplemented young rats with diets rich in BB, which are known to contain high amounts of antioxidant-phytochemicals, prior to irradiation. Exposure to 56Fe caused significant neurochemical changes in hippocampus and frontal cortex, the two critical regions of the brain involved in cognitive function. BB supplementation significantly attenuated protein carbonylation, which was significantly increased by exposure to 56Fe in the hippocampus and frontal cortex. Moreover, BB supplementation significantly reduced radiation-induced elevations in NADPH-oxidoreductase-2 (NOX2) and cyclooxygenase-2 (COX-2), and upregulated nuclear factor erythroid 2-related factor 2 (Nrf2) in the hippocampus and frontal cortex. Overall results indicate that 56Fe particles may induce their toxic effects on hippocampus and frontal cortex by reactive oxygen species (ROS) overload, which can cause alterations in the neuronal environment, eventually leading to hippocampal neuronal death and subsequent impairment of cognitive function. Blueberry supplementation provides an effective preventative measure to reduce the ROS load on the CNS in an event of acute HZE exposure.

  2. Behavioral and Neurochemical Studies in Stressed and Unstressed Rats Fed on Protein, Carbohydrate and Fat Rich Diet

    Directory of Open Access Journals (Sweden)

    Samia Moin§, Saida Haider*, Saima Khaliq1, Saiqa Tabassum and Darakhshan J. Haleem

    2012-05-01

    Full Text Available Stress produces behavioral and neurochemical deficits. To study the relationship between adaptation to stress and macronutrient intake, the present study was designed to monitor the effects of different diets on feed intake, growth rate and serotonin (5-Hydroxytryptamine, 5-HT metabolism following exposure to restraint stress in rats. Rats were divided into four groups (n=12 as control, sugar, protein and fat rich diet fed rats. After 5 weeks of treatment animals of each group were divided into unrestrained and restrained animals (n=6. Rats of restrained group were given immobilization stress for 2 hours/day for 5 days. Food intake and growth rates of unrestrained and restrained rats were monitored daily. Rats were decapitated on 6th day to collect brain samples for neurochemical estimation. Results show that sugar diet fed rats produced adaptation to stress early as compared to normal diet fed rats. Food intake and growth rates of unrestrained and restrained rats were comparable on 3rd day in sugar diet fed rats and on 4th day in normal diet fed rats. Stress decreased food intake and growth rates of protein and fat treated rats. Repeated stress did not alter brain 5-HT and 5-HIAA levels of normal diet fed rats and sugar diet fed rats. Protein diet fed restrained rats showed elevated brain 5-HT levels. Fat diet fed restrained rats significantly decreased brain TRP and 5-HIAA levels. Finding suggested that carbohydrate diet might protect against stressful conditions. Study also showed that nutritional status could alter different behaviors in response to a stressful environment.

  3. Neurochemical metabolites in prefrontal cortex in patients with mild/moderate levels in first-episode depression

    Directory of Open Access Journals (Sweden)

    Sozeri-Varma G

    2013-08-01

    Full Text Available Gülfizar Sözeri-Varma,1 Nalan Kalkan-Oğuzhanoglu,1 Muharrem Efe,1 Yilmaz Kiroglu,2 Taçlan Duman11Department of Psychiatry, 2Department of Radiology, Faculty of Medicine, Pamukkale University, Denizli, TurkeyBackground: Previous studies have determined the neurochemical metabolite abnormalities in major depressive disorder (MDD. The results of studies are inconsistent. Severity of depression may relate to neurochemical metabolic changes. The aim of this study is to investigate neurochemical metabolite levels in the prefrontal cortex (PFC of patients with mild/moderate MDD.Methods: Twenty-one patients with mild MDD, 18 patients with moderate MDD, and 16 matched control subjects participated in the study. Patients had had their first episode. They had not taken treatment. The severity of depression was assessed by the Hamilton Rating Scale for Depression (HAM-D. Levels of N-acetyl aspartate (NAA, choline-containing compounds (Cho, and creatine-containing compounds (Cr were measured using proton magnetic resonance spectroscopy (1H-MRS at 1.5 T, with an 8-cm3 single voxel placed in the right PFC.Results: The moderate MDD patients had lower NAA/Cr levels than the control group. No differences were found in neurochemical metabolite levels between the mild MDD and control groups. No correlation was found between the patients’ neurochemical metabolite levels and HAM-D scores.Conclusion: Our findings suggest that NAA/Cr levels are low in moderate-level MDD in the PFC. Neurochemical metabolite levels did not change in mild depressive disorder. Our results suggest that the severity of depression may affect neuronal function and viability. Studies are needed to confirm this finding, including studies on severely depressive patients.Keywords: major depressive disorder, magnetic resonance spectroscopy, N-acetyl aspartate, creatine, choline

  4. Previous Ketamine Produces an Enduring Blockade of Neurochemical and Behavioral Effects of Uncontrollable Stress

    Science.gov (United States)

    Dolzani, Samuel D.; Tilden, Scott; Christianson, John P.; Kubala, Kenneth H.; Bartholomay, Kristi; Sperr, Katherine; Ciancio, Nicholas; Watkins, Linda R.; Maier, Steven F.

    2016-01-01

    Recent interest in the antidepressant and anti-stress effects of subanesthetic doses of ketamine, an NMDA receptor antagonist, has identified mechanisms whereby ketamine reverses the effect of stress, but little is known regarding the prophylactic effect ketamine might have on future stressors. Here we investigate the prophylactic effect of ketamine against neurochemical and behavioral changes that follow inescapable, uncontrollable tail shocks (ISs) in Sprague Dawley rats. IS induces increased anxiety, which is dependent on activation of serotonergic (5-HT) dorsal raphe nucleus (DRN) neurons that project to the basolateral amygdala (BLA). Ketamine (10 mg/kg, i.p.) administered 2 h, 1 week, or 2 weeks before IS prevented the increased extracellular levels of 5-HT in the BLA typically produced by IS. In addition, ketamine administered at these time points blocked the decreased juvenile social investigation produced by IS. Microinjection of ketamine into the prelimbic (PL) region of the medial prefrontal cortex duplicated the effects of systemic ketamine, and, conversely, systemic ketamine effects were prevented by pharmacological inhibition of the PL. Although IS does not activate DRN-projecting neurons from the PL, IS did so after ketamine, suggesting that the prophylactic effect of ketamine is a result of altered functioning of this projection. SIGNIFICANCE STATEMENT The reported data show that systemic ketamine, given up to 2 weeks before a stressor, blunts behavioral and neurochemical effects of the stressor. The study also advances understanding of the mechanisms involved and suggests that ketamine acts at the prelimbic cortex to sensitize neurons that project to and inhibit the DRN. PMID:26740657

  5. Pupillometry as a glimpse into the neurochemical basis of human memory encoding.

    Science.gov (United States)

    Hoffing, Russell Cohen; Seitz, Aaron R

    2015-04-01

    Neurochemical systems are well studied in animal learning; however, ethical issues limit methodologies to explore these systems in humans. Pupillometry provides a glimpse into the brain's neurochemical systems, where pupil dynamics in monkeys have been linked with locus coeruleus (LC) activity, which releases norepinephrine (NE) throughout the brain. Here, we use pupil dynamics as a surrogate measure of neurochemical activity to explore the hypothesis that NE is involved in modulating memory encoding. We examine this using a task-irrelevant learning paradigm in which learning is boosted for stimuli temporally paired with task targets. We show that participants better recognize images that are paired with task targets than distractors and, in correspondence, that pupil size changes more for target-paired than distractor-paired images. To further investigate the hypothesis that NE nonspecifically guides learning for stimuli that are present with its release, a second procedure was used that employed an unexpected sound to activate the LC-NE system and induce pupil-size changes; results indicated a corresponding increase in memorization of images paired with the unexpected sounds. Together, these results suggest a relationship between the LC-NE system, pupil-size changes, and human memory encoding.

  6. Modulatory effect of cilostazol on tramadol-induced behavioral and neurochemical alterations in rats challenged across the forced swim despair test

    Directory of Open Access Journals (Sweden)

    Noha M. Gamil

    2016-06-01

    Full Text Available Pain-associated depression is encountered clinically in some cases such as cancer, chronic neuropathy, and after operations. Tramadol is an opioid analgesic drug that may modulate monoaminergic neurotransmission by inhibition of noradrenaline and serotonin reuptake that may contribute to its antidepressant-like effects. Clinically, tramadol is used either alone or in combination with other NSAIDs in the treatment of cases associated with pain and depression, e.g. low back pain, spinal cord injury, and post-operative pain management. However, tramadol monotherapy as an antidepressant is impeded by severe adverse effects including seizures and serotonin syndrome. Interestingly, phosphodiesterase-III inhibitors demonstrated novel promising antidepressant effects. Among which, cilostazol was reported to attenuate depression in post-stroke cases, geriatrics and patients undergoing carotid artery stenting. Therefore, this study was carried out to investigate the possible antidepressant-like effects of tramadol and/or cilostazol on the behavioral level in experimental animals, and to examine the neurochemical and biochemical effects of tramadol, cilostazol and their combination in rats, in order to explore the probable mechanisms of action underlying their effects. To achieve our target, male albino mice and rats were randomly allocated into five groups and administered either vehicle for control, fluoxetine (20 mg/kg, p.o., tramadol HCl (20 mg/kg, p.o., cilostazol (100 mg/kg, p.o., or combination of both tramadol and cilostazol. At day 14, mice and rats were challenged in the tail suspension test and forced swim test, respectively. Rats were sacrificed and brains were isolated for determination of brain monoamines, MDA, NO, SOD, and TNF-α. The current results showed that concurrent administration of cilostazol to tramadol-treated animals modulated depression on the behavioral level, and showed ameliorative neurochemical and biochemical effects

  7. Resemblance and investment in children.

    Science.gov (United States)

    Dolinska, Barbara

    2013-01-01

    According to evolutionary explanations men hardly ever are absolutely certain about their biological fatherhood therefore they must seek various sources of information to subjectively establish whether they are the genetic fathers of the children they raise. Apicella and Marlowe (2004) showed that fathers who perceived greater similarity between their children and themselves were willing to invest more resources (e.g., time, money, care) in their offspring presumably because the perceived resemblance indicated to the fathers their genetic relatedness with their children. The present study extended the design of Apicella and Marlowe's original study and included both fathers and mothers as participants. Parents were recruited by a female confederate at the airport and at the railway station in Wroclaw (Poland). Multiple regression analyses showed that perceived resemblance predicted parental investment in the child for both men and women. The fact that mothers' declarations of investment in their children also depended on the perceived resemblance factor is not consistent with evolutionary formulations delineated by Apicella and Marlowe (2004; 2007). Future studies must resolve the issue of whether the resemblance-investment relation in fathers results from men relaying on child's resemblance to themselves as an indicator of their own biological paternity, or whether it results from the more parsimonious phenomenon that people in general are attracted more to other people who are similar to them.

  8. Attenuation of neurobehavioral and neurochemical abnormalities in animal model of cognitive deficits of Alzheimer's disease by fermented soybean nanonutraceutical.

    Science.gov (United States)

    Bhatt, Prakash Chandra; Pathak, Shruti; Kumar, Vikas; Panda, Bibhu Prasad

    2018-02-01

    The present study was performed to evaluate the efficacy of nanonutraceuticals (NN) for attenuation of neurobehavioral and neurochemical abnormalities in Alzheimer's disease. Solid-state fermentation of soybean with Bacillus subtilis was performed to produce different metabolites (nattokinase, daidzin, genistin and glycitin and menaquinone-7). Intoxication of rats with colchicine caused impairment in learning and memory which was demonstrated in neurobehavioral paradigms (Morris water maze and passive avoidance) linked with decreased activity of acetylcholinesterase (AChE). NN treatment led to a significant increase in TLT in the retention trials as compared to acquisition trial TLT suggesting an improved learning and memory in rats. Further, treatment of NN caused an increase in the activity of AChE (42%), accompanied with a reduced activity of glutathione (42%), superoxide dismutase (43%) and catalase (41%). It also decreased the level of lipid peroxidation (28%) and protein carbonyl contents (30%) in hippocampus as compared to those treated with colchicine alone, suggesting a possible neuroprotective efficacy of NN. Interestingly, in silico studies also demonstrated an effective amyloid-β and BACE-1 inhibition activity. These findings clearly indicated that NN reversed colchicine-induced behavioral and neurochemical alterations through potent antioxidant activity and could possibly impart beneficial effects in cognitive defects associated with Alzheimer's disease.

  9. Neurochemical phenotype of cytoglobin‑expressing neurons in the rat hippocampus

    DEFF Research Database (Denmark)

    Hundahl, Christian Ansgar; Fahrenkrug, Jan; Hannibal, Jens

    2014-01-01

    in a subpopulation of brain neurons. Recently, it has been shown that stress upregulates Cygb expression in the brain and the majority of neuronal nitric oxide synthase (nNOS)-positive neurons, an enzyme that produces NO, co-express Cygb. However, there are more neurons expressing Cygb than nNOS, thus a large number...... of Cygb neurons remain uncharacterized by the neurochemical content. The aim of the present study was to provide an additional and more detailed neurochemical phenotype of Cygb-expressing neurons in the rat hippocampus. The rat hippocampus was chosen due to the abundance of Cygb, as well as this limbic...... structure being an important target in a number of neurodegenerative diseases. Using triple immunohistochemistry, it was demonstrated that nearly all the parvalbumin- and heme oxygenase 1-positive neurons co-express Cygb and to a large extent, these neuron populations are distinct from the population...

  10. Dysregulation of brain reward systems in eating disorders: neurochemical information from animal models of binge eating, bulimia nervosa, and anorexia nervosa.

    Science.gov (United States)

    Avena, Nicole M; Bocarsly, Miriam E

    2012-07-01

    Food intake is mediated, in part, through brain pathways for motivation and reinforcement. Dysregulation of these pathways may underlay some of the behaviors exhibited by patients with eating disorders. Research using animal models of eating disorders has greatly contributed to the detailed study of potential brain mechanisms that many underlie the causes or consequences of aberrant eating behaviors. This review focuses on neurochemical evidence of reward-related brain dysfunctions obtained through animal models of binge eating, bulimia nervosa, or anorexia nervosa. The findings suggest that alterations in dopamine (DA), acetylcholine (ACh) and opioid systems in reward-related brain areas occur in response to binge eating of palatable foods. Moreover, animal models of bulimia nervosa suggest that while bingeing on palatable food releases DA, purging attenuates the release of ACh that might otherwise signal satiety. Animal models of anorexia nervosa suggest that restricted access to food enhances the reinforcing effects of DA when the animal does eat. The activity-based anorexia model suggests alterations in mesolimbic DA and serotonin occur as a result of restricted eating coupled with excessive wheel running. These findings with animal models complement data obtained through neuroimaging and pharmacotherapy studies of clinical populations. Information on the neurochemical consequences of the behaviors associated with these eating disorders will be useful in understanding these complex disorders and may inform future therapeutic approaches, as discussed here. This article is part of a Special Issue entitled 'Central Control of Food Intake'. Copyright © 2011 Elsevier Ltd. All rights reserved.

  11. Recent Advances in Mass Spectrometry for the Identification of Neuro-chemicals and their Metabolites in Biofluids.

    Science.gov (United States)

    Kailasa, Suresh Kumar; Wu, Hui-Fen

    2013-07-01

    Recently, mass spectrometric related techniques have been widely applied for the identification and quantification of neurochemicals and their metabolites in biofluids. This article presents an overview of mass spectrometric techniques applied in the detection of neurological substances and their metabolites from biological samples. In addition, the advances of chromatographic methods (LC, GC and CE) coupled with mass spectrometric techniques for analysis of neurochemicals in pharmaceutical and biological samples are also discussed.

  12. Neurochemical Correlates of Autistic Disorder: A Review of the Literature

    Science.gov (United States)

    Lam, Kristen S. L.; Aman, Michael G.; Arnold, L. Eugene

    2006-01-01

    Review of neurochemical investigations in autistic disorder revealed that a wide array of transmitter systems have been studied, including serotonin, dopamine, norepinephrine, acetylcholine, oxytocin, endogenous opioids, cortisol, glutamate, and gamma-aminobutyric acid (GABA). These studies have been complicated by the fact that autism is a very…

  13. Brain region-specific perfluoroalkylated sulfonate (PFSA) and carboxylic acid (PFCA) accumulation and neurochemical biomarker responses in east Greenland polar bears (Ursus maritimus).

    Science.gov (United States)

    Eggers Pedersen, Kathrine; Basu, Niladri; Letcher, Robert; Greaves, Alana K; Sonne, Christian; Dietz, Rune; Styrishave, Bjarne

    2015-04-01

    PFCA; rp=-0.40, p=0.003, ∑PFSA; rp=-0.37, p=0.007; n=52). AChE activity and D2 density were negatively correlated with single PFCAs in several brain regions, whereas GS activity was positively correlated with PFASs primarily in occipital lobe. Results from the present study support the hypothesis that PFAS concentrations in polar bears from East Greenland have exceeded the threshold limits for neurochemical alterations. It is not known whether the observed alterations in neurochemical signaling are currently having negative effects on neurochemistry in East Greenland polar bears. However given the importance of these systems in cognitive processes and motor function, the present results indicate an urgent need for a better understanding of neurochemical effects of PFAS exposure to wildlife. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Age-related changes of neurochemically different subpopulations of cardiac spinal afferent neurons in rats.

    Science.gov (United States)

    Guić, Maja Marinović; Runtić, Branka; Košta, Vana; Aljinović, Jure; Grković, Ivica

    2013-08-01

    This study investigated the effect of aging on cardiac spinal afferent neurons in the rat. A patch loaded with retrograde tracer Fast Blue (FB) was applied to all chambers of the rat heart. Morphological and neurochemical characteristics of labeled cardiac spinal afferent neurons were assessed in young (2 months) and old (2 years) rats using markers for likely unmyelinated (isolectin B4; IB4) and myelinated (neurofilament 200; N52) neurons. The number of cardiac spinal afferent neurons decreased in senescence to 15% of that found in young rats (1604 vs. 248). The size of neuronal soma as well as proportion of IB4+ neurons increased significantly, whereas the proportion of N52+ neurons decreased significantly in senescence. Unlike somatic spinal afferents, neurochemically different populations of cardiac spinal afferent neurons experience morphological and neurochemical changes related to aging. A major decrease in total number of cardiac spinal afferent neurons occurs in senescence. The proportion of N52+ neurons decreased in senescence, but it seems that nociceptive innervation is preserved due to increased proportion and size of IB4+ unmyelinated neurons. Copyright © 2013 Elsevier Inc. All rights reserved.

  15. Unique Behavioral and Neurochemical Effects Induced by Repeated Adolescent Consumption of Caffeine-Mixed Alcohol in C57BL/6 Mice.

    Directory of Open Access Journals (Sweden)

    Meridith T Robins

    Full Text Available The number of highly caffeinated products has increased dramatically in the past few years. Among these products, highly caffeinated energy drinks are the most heavily advertised and purchased, which has resulted in increased incidences of co-consumption of energy drinks with alcohol. Despite the growing number of adolescents and young adults reporting caffeine-mixed alcohol use, knowledge of the potential consequences associated with co-consumption has been limited to survey-based results and in-laboratory human behavioral testing. Here, we investigate the effect of repeated adolescent (post-natal days P35-61 exposure to caffeine-mixed alcohol in C57BL/6 mice on common drug-related behaviors such as locomotor sensitivity, drug reward and cross-sensitivity, and natural reward. To determine changes in neurological activity resulting from adolescent exposure, we monitored changes in expression of the transcription factor ΔFosB in the dopaminergic reward pathway as a sign of long-term increases in neuronal activity. Repeated adolescent exposure to caffeine-mixed alcohol exposure induced significant locomotor sensitization, desensitized cocaine conditioned place preference, decreased cocaine locomotor cross-sensitivity, and increased natural reward consumption. We also observed increased accumulation of ΔFosB in the nucleus accumbens following repeated adolescent caffeine-mixed alcohol exposure compared to alcohol or caffeine alone. Using our exposure model, we found that repeated exposure to caffeine-mixed alcohol during adolescence causes unique behavioral and neurochemical effects not observed in mice exposed to caffeine or alcohol alone. Based on similar findings for different substances of abuse, it is possible that repeated exposure to caffeine-mixed alcohol during adolescence could potentially alter or escalate future substance abuse as means to compensate for these behavioral and neurochemical alterations.

  16. Neurochemical Effects of Chronic Administration of Calcitriol in Rats

    Directory of Open Access Journals (Sweden)

    Pei Jiang

    2014-12-01

    Full Text Available Despite accumulating data showing the various neurological actions of vitamin D (VD, its effects on brain neurochemistry are still far from fully understood. To further investigate the neurochemical influence of VD, we assessed neurotransmitter systems in the brain of rats following 6-week calcitriol (1,25-dihydroxyvitamin D administration (50 ng/kg/day or 100 ng/kg/day. Both the two doses of calcitriol enhanced VDR protein level without affecting serum calcium and phosphate status. Rats treated with calcitriol, especially with the higher dose, exhibited elevated γ-aminobutyric acid (GABA status. Correspondingly, the mRNA expression of glutamate decarboxylase (GAD 67 was increased. 100 ng/kg of calcitriol administration also increased glutamate and glutamine levels in the prefrontal cortex, but did not alter glutamine synthetase (GS expression. Additionally, calcitriol treatment promoted tyrosine hydroxylase (TH and tryptophan hydroxylase 2 (TPH2 expression without changing dopamine and serotonin status. However, the concentrations of the metabolites of dopamine and serotonin were increased and the drug use also resulted in a significant rise of monoamine oxidase A (MAOA expression, which might be responsible to maintain the homeostasis of dopaminergic and serotonergic neurotransmission. Collectively, the present study firstly showed the effects of calcitriol in the major neurotransmitter systems, providing new evidence for the role of VD in brain function.

  17. Personality and neurochemicals in the human brain: A preliminary study using 1H MRS

    Institute of Scientific and Technical Information of China (English)

    XU Shiyong; PENG Danling; JIN Zhen; LIU Hongyan; YANG Jie

    2005-01-01

    To investigate the neuro-biological bases of introversion-extraversion personality traits, the concentra- tion of four neurochemicals (Cho, mI, α-Glx and NAA) in anterior cigulate gyrus between normal extroverts and introverts were examined using non-invasive 1H MRS technique. Our study revealed that introverts have significantly higher level of α-Glx, Cho and mI in the anterior cingulate gyrus than extroverts. This result provides new evidence that the anterior cingulate gyrus is related to personality traits partly in support of Eysenck's supposition that introverts have higher arousal level than extroverts. Moreover, this result offers neurochemical data for psychobiological theories of personality.

  18. Hippocampal neurochemical changes in senescent mice induced with chronic injection of D-galactose and NaNO₂: an in vitro high-resolution NMR spectroscopy study at 9.4T.

    Directory of Open Access Journals (Sweden)

    Yan Lin

    Full Text Available Proton magnetic resonance spectroscopy (¹H-MRS has been used to provide useful information about the neurochemical changes reflecting early pathological alterations in Alzheimer's disease (AD brain. In this study, we have longitudinally measured the hippocampal neurochemical profile in vitro in senescent mice induced with chronic injection of D-Galactose and NaNO₂, at different time point from day 30 to day 70 with a 10-day interval. Pathological brain alterations induced by D-Galactose and NaNO₂ were monitored through hematoxylin and eosin (HE staining, Congo red staining and bielschowsky silver staining, and the cognition deficits were assessed via Morris Water Maze (MWM test. This D-galactose and NaNO₂ treated mouse model, characterized by an early-onset memory dysfunction, a robust neuronal loss, amyloid plaques and neurofibrillary tangles in hippocampal subdivision, well mimics a prodromal Alzheimer's phenotype. Consistent with previously published in vivo ¹H MRS findings in human AD patients and AD transgenic mice, our in vitro ¹H MRS on the perchloric acid extractions of hippocampus in senescent mice observed significant decreases of N-acetylaspartate (NAA and Glutamate (Glu but an increase in Myo-inositol (mIns. Elevated mIns occurred prior to the reduction of NAA and Glu during the progression of aging. In addition, changes in mIns, NAA and Glu were found to precede pathological abnormalities. Overall, our in vitro findings in senescent mice validated the concept that hippocampal neurochemical alternations preceded the pathological changes of the brain, and could serve as potential markers of AD progression. Reductions of NAA and Glu can be interpreted in terms of neuronal degeneration and dysfunctions in glutamatergic activity that may contribute to the pathophysiological mechanisms underlying AD. Elevated mIns might be related to glial activation. Further experiments are needed to explore the potential value of mIns in the

  19. Piperine Augments the Protective Effect of Curcumin Against Lipopolysaccharide-Induced Neurobehavioral and Neurochemical Deficits in Mice.

    Science.gov (United States)

    Jangra, Ashok; Kwatra, Mohit; Singh, Tavleen; Pant, Rajat; Kushwah, Pawan; Sharma, Yogita; Saroha, Babita; Datusalia, Ashok Kumar; Bezbaruah, Babul Kumar

    2016-06-01

    The aim of the present study was to investigate the protective effects of curcumin alone and in combination with piperine against lipopolysaccharide (LPS)-induced neurobehavioral and neurochemical deficits in the mice hippocampus. Mice were treated with curcumin (100, 200, and 400 mg/kg, p.o.) and piperine (20 mg/kg, p.o.) for 7 days followed by LPS (0.83 mg/kg, i.p.) administration. Animals exhibited anxiety and depressive-like phenotype after 3 and 24 h of LPS exposure, respectively. LPS administration increased the oxido-nitrosative stress as evident by elevated levels of malondialdehyde, nitrite, and depletion of glutathione level in the hippocampus. Furthermore, we found raised level of pro-inflammatory cytokines (IL-1β and TNF-α) in the hippocampus of LPS-treated mice. Pretreatment with curcumin alleviated LPS-induced neurobehavioral and neurochemical deficits. Furthermore, co-administration of curcumin with piperine significantly potentiated the neuroprotective effect of curcumin. These results demonstrate that piperine enhanced the neuroprotective effect of curcumin against LPS-induced neurobehavioral and neurochemical deficits.

  20. Covertly active and progressing neurochemical abnormalities in suppressed HIV infection.

    Science.gov (United States)

    Cysique, Lucette A; Jugé, Lauriane; Gates, Thomas; Tobia, Michael; Moffat, Kirsten; Brew, Bruce J; Rae, Caroline

    2018-01-01

    To assess whether HIV-related brain injury is progressive in persons with suppressed HIV infection. Seventy-three HIV+ virally suppressed men and 35 HIV- men, screened for psychiatric and alcohol/drug use disorders, underwent neuropsychological evaluation and proton magnetic resonance spectroscopy ( 1 H-MRS) at baseline and after and 23 ± 5 months. 1 H-MRS included brain regions known to be vulnerable to HIV and aging: frontal white matter (FWM), posterior cingulate cortex (PCC), and caudate area (CA). Major brain metabolites such as creatine (Cr: marker of cellular energy), N -acetyl aspartate (NAA: marker of neuronal integrity), choline (marker of cellular membrane turnover), glutamate/glutamine (excitatory/inhibitory neurotransmitter), and myo -Inositol (mI: marker of neuroinflammation) were calculated with reference to water signal. Neurocognitive decline was corrected for practice effect and baseline HIV-associated neurocognitive disorder (HAND) status. Across the study period, 44% had intact cognition, 42% stable HAND (including the single case that improved), 10% progressing HAND, and 4% incident HAND. When analyzing the neurochemical data per neurocognitive trajectories, we found decreasing PCC Cr in all subgroups compared with controls ( p < 0.002). In addition, relative to the HIV- group, stable HAND showed decreasing FWM Cr, incident HAND showed steep FWM Cr reduction, whereas progressing HAND had a sharply decreasing PCC NAA and reduced but stable CA NAA. When analyzing the neurochemical data at the group level (HIV+ vs HIV- groups), we found stable abnormal metabolite concentrations over the study period: decreased FWM and PCC Cr (both p < 0.001), decreased PCC NAA and CA NAA (both p < 0.05) and PCC mI increase ( p < 0.05). HIV duration and historical HAND had modest effects on metabolite changes. Our study reveals covertly active or progressing HIV-related brain injury in the majority of this virally suppressed cohort, reflecting ongoing

  1. Comparison of Different Matrices as Potential Quality Control Samples for Neurochemical Dementia Diagnostics

    NARCIS (Netherlands)

    Lelental, Natalia; Brandner, Sebastian; Kofanova, Olga; Blennow, Kaj; Zetterberg, Henrik; Andreasson, Ulf; Engelborghs, Sebastiaan; Mroczko, Barbara; Gabryelewicz, Tomasz; Teunissen, Charlotte; Mollenhauer, Brit; Parnetti, Lucilla; Chiasserini, Davide; Molinuevo, Jose Luis; Perret-Liaudet, Armand; Verbeek, Marcel M.; Andreasen, Niels; Brosseron, Frederic; Bahl, Justyna M. C.; Herukka, Sanna-Kaisa; Hausner, Lucrezia; Froelich, Lutz; Labonte, Anne; Poirier, Judes; Miller, Anne-Marie; Zilka, Norbert; Kovacech, Branislav; Urbani, Andrea; Suardi, Silvia; Oliveira, Catarina; Baldeiras, Ines; Dubois, Bruno; Rot, Uros; Lehmann, Sylvain; Skinningsrud, Anders; Betsou, Fay; Wiltfang, Jens; Gkatzima, Olymbia; Winblad, Bengt; Buchfelder, Michael; Kornhuber, Johannes; Lewczuk, Piotr

    2016-01-01

    Background: Assay-vendor independent quality control (QC) samples for neurochemical dementia diagnostics (NDD) biomarkers are so far commercially unavailable. This requires that NDD laboratories prepare their own QC samples, for example by pooling leftover cerebrospinal fluid (CSF) samples.

  2. Cannabinoids for the Treatment of Schizophrenia? A Balanced Neurochemical Framework for Both Adverse and Therapeutic Effects of Cannabis Use

    Directory of Open Access Journals (Sweden)

    Carissa M. Coulston

    2011-01-01

    Full Text Available Recent studies have found that cannabinoids may improve neuropsychological performance, ameliorate negative symptoms, and have antipsychotic properties for a subgroup of the schizophrenia population. These findings are in contrast to the longstanding history of adverse consequences of cannabis use, predominantly on the positive symptoms, and a balanced neurochemical basis for these opposing views is lacking. This paper details a review of the neurobiological substrates of schizophrenia and the neurochemical effects of cannabis use in the normal population, in both cortical (in particular prefrontal and subcortical brain regions. The aim of this paper is to provide a holistic neurochemical framework in which to understand how cannabinoids may impair, or indeed, serve to ameliorate the positive and negative symptoms as well as cognitive impairment. Directions in which future research can proceed to resolve the discrepancies are briefly discussed.

  3. Neurochemical changes underpinning the development of adjunct therapies in recovery after stroke: A role for GABA?

    Science.gov (United States)

    Johnstone, Ainslie; Levenstein, Jacob M; Hinson, Emily L; Stagg, Charlotte J

    2017-01-01

    Stroke is a leading cause of long-term disability, with around three-quarters of stroke survivors experiencing motor problems. Intensive physiotherapy is currently the most effective treatment for post-stroke motor deficits, but much recent research has been targeted at increasing the effects of the intervention by pairing it with a wide variety of adjunct therapies, all of which aim to increase cortical plasticity, and thereby hope to maximize functional outcome. Here, we review the literature describing neurochemical changes underlying plasticity induction following stroke. We discuss methods of assessing neurochemicals in humans, and how these measurements change post-stroke. Motor learning in healthy individuals has been suggested as a model for stroke plasticity, and we discuss the support for this model, and what evidence it provides for neurochemical changes. One converging hypothesis from animal, healthy and stroke studies is the importance of the regulation of the inhibitory neurotransmitter GABA for the induction of cortical plasticity. We discuss the evidence supporting this hypothesis, before finally summarizing the literature surrounding the use of adjunct therapies such as non-invasive brain stimulation and SSRIs in post-stroke motor recovery, both of which have been show to influence the GABAergic system.

  4. Chronic marijuana smoke exposure in the rhesus monkey. IV: Neurochemical effects and comparison to acute and chronic exposure to delta-9-tetrahydrocannabinol (THC) in rats.

    Science.gov (United States)

    Ali, S F; Newport, G D; Scallet, A C; Paule, M G; Bailey, J R; Slikker, W

    1991-11-01

    THC is the major psychoactive constituent of marijuana and is known to produce psychopharmacological effects in humans. These studies were designed to determine whether acute or chronic exposure to marijuana smoke or THC produces in vitro or in vivo neurochemical alterations in rat or monkey brain. For the in vitro study, THC was added (1-100 nM) to membranes prepared from different regions of the rat brain and muscarinic cholinergic (MCh) receptor binding was measured. For the acute in vivo study, rats were injected IP with vehicle, 1, 3, 10, or 30 mg THC/kg and sacrificed 2 h later. For the chronic study, rats were gavaged with vehicle or 10 or 20 mg THC/kg daily, 5 days/week for 90 days and sacrificed either 24 h or 2 months later. Rhesus monkeys were exposed to the smoke of a single 2.6% THC cigarette once a day, 2 or 7 days a week for 1 year. Approximately 7 months after the last exposure, animals were sacrificed by overdose with pentobarbital for neurochemical analyses. In vitro exposure to THC produced a dose-dependent inhibition of MCh receptor binding in several brain areas. This inhibition of MCh receptor binding, however, was also observed with two other nonpsychoactive derivatives of marijuana, cannabidiol and cannabinol. In the rat in vivo study, we found no significant changes in MCh or other neurotransmitter receptor binding in hippocampus, frontal cortex or caudate nucleus after acute or chronic exposure to THC. In the monkey brain, we found no alterations in the concentration of neurotransmitters in caudate nucleus, frontal cortex, hypothalamus or brain stem.(ABSTRACT TRUNCATED AT 250 WORDS)

  5. SOME NEUROCHEMICAL DISTURBANCES IN MULTIPLE SCLEROSIS

    Directory of Open Access Journals (Sweden)

    Vladimir V. Markelov

    2006-04-01

    Full Text Available ABSTRACTThe data presented in this manuscript suggest a pivotal role of the central nervous system (CNS in the regulation of immune status. We describe here that some neurochemical disturbances may provoke development of various diseases including multiple sclerosis. Some theoretic and practical backgrounds, how to improve the multiple sclerosis sufferers and patients with other autoimmune disorders, are also given.RESUMENLos datos que presentamos en este manuscrito, sugieren un papel guia del sistema nervioso central (SNC en la regulación del estado inmune. Describimos aquí que varias alteraciones neuroquímicas pueden provocar el desarrollo de varias enfermedades, incluyendo esclerosis múltiple. También se comenta acerca del trasfondo teórico y práctico, y cómo mejorar a víctimas y pacientes con esclerosis múltiple y otras alteraciones autoinmunes.

  6. Large-scale neurochemical metabolomics analysis identifies multiple compounds associated with methamphetamine exposure.

    Science.gov (United States)

    McClay, Joseph L; Adkins, Daniel E; Vunck, Sarah A; Batman, Angela M; Vann, Robert E; Clark, Shaunna L; Beardsley, Patrick M; van den Oord, Edwin J C G

    2013-04-01

    Methamphetamine (MA) is an illegal stimulant drug of abuse with serious negative health consequences. The neurochemical effects of MA have been partially characterized, with a traditional focus on classical neurotransmitter systems. However, these directions have not yet led to novel drug treatments for MA abuse or toxicity. As an alternative approach, we describe here the first application of metabolomics to investigate the neurochemical consequences of MA exposure in the rodent brain. We examined single exposures at 3 mg/kg and repeated exposures at 3 mg/kg over 5 days in eight common inbred mouse strains. Brain tissue samples were assayed using high-throughput gas and liquid chromatography mass spectrometry, yielding quantitative data on >300 unique metabolites. Association testing and false discovery rate control yielded several metabolome-wide significant associations with acute MA exposure, including compounds such as lactate ( p = 4.4 × 10 -5 , q = 0.013), tryptophan ( p = 7.0 × 10 -4 , q = 0.035) and 2-hydroxyglutarate ( p = 1.1 × 10 -4 , q = 0.022). Secondary analyses of MA-induced increase in locomotor activity showed associations with energy metabolites such as succinate ( p = 3.8 × 10 -7 ). Associations specific to repeated (5 day) MA exposure included phosphocholine ( p = 4.0 × 10 -4 , q = 0.087) and ergothioneine ( p = 3.0 × 10 -4 , q = 0.087). Our data appear to confirm and extend existing models of MA action in the brain, whereby an initial increase in energy metabolism, coupled with an increase in behavioral locomotion, gives way to disruption of mitochondria and phospholipid pathways and increased endogenous antioxidant response. Our study demonstrates the power of comprehensive MS-based metabolomics to identify drug-induced changes to brain metabolism and to develop neurochemical models of drug effects.

  7. A neurochemical map of the developing amphioxus nervous system

    Directory of Open Access Journals (Sweden)

    Candiani Simona

    2012-06-01

    Full Text Available Abstract Background Amphioxus, representing the most basal group of living chordates, is the best available proxy for the last invertebrate ancestor of the chordates. Although the central nervous system (CNS of amphioxus comprises only about 20,000 neurons (as compared to billions in vertebrates, the developmental genetics and neuroanatomy of amphioxus are strikingly vertebrate-like. In the present study, we mapped the distribution of amphioxus CNS cells producing distinctive neurochemicals. To this end, we cloned genes encoding biosynthetic enzymes and/or transporters of the most common neurotransmitters and assayed their developmental expression in the embryo and early larva. Results By single and double in situ hybridization experiments, we identified glutamatergic, GABAergic/glycinergic, serotonergic and cholinergic neurons in developing amphioxus. In addition to characterizing the distribution of excitatory and inhibitory neurons in the developing amphioxus CNS, we observed that cholinergic and GABAergic/glycinergic neurons are segmentally arranged in the hindbrain, whereas serotonergic, glutamatergic and dopaminergic neurons are restricted to specific regions of the cerebral vesicle and the hindbrain. We were further able to identify discrete groups of GABAergic and glutamatergic interneurons and cholinergic motoneurons at the level of the primary motor center (PMC, the major integrative center of sensory and motor stimuli of the amphioxus nerve cord. Conclusions In this study, we assessed neuronal differentiation in the developing amphioxus nervous system and compiled the first neurochemical map of the amphioxus CNS. This map is a first step towards a full characterization of the neurotransmitter signature of previously described nerve cell types in the amphioxus CNS, such as motoneurons and interneurons.

  8. Neuroprotective and neurochemical properties of mint extracts

    DEFF Research Database (Denmark)

    López, Víctor; Martín, Sara; Gómez-Serranillos, Maria Pilar

    2010-01-01

    (A) receptor). Mentha x piperita and Mentha aquatica produced significant (p oxidative stress. All the plants exhibited antioxidant and MAO-A inhibitory activities, M. x piperita being the most active. M. aquatica showed the highest affinity to the GABA......Mints are aromatic plants with a tradition as medicinal remedies and culinary herbs. With the aim of investigating potential central nervous system (CNS) activities of traditional medicinal plants, four species and one hybrid of the genus Mentha (M. aquatica, M. longifolia, M. pulegium, M....... suaveolens and M. x piperita) were selected. Methanolic extracts of the plants were tested for protective effects against hydrogen-peroxide-induced toxicity in PC12 cells, antioxidant activity (by ABTS and X/XO methods) and neurochemical properties (MAO-A inhibition, AChE inhibition and affinity to the GABA...

  9. Prenatal cocaine exposure alters alpha2 receptor expression in adolescent rats

    Directory of Open Access Journals (Sweden)

    Silvers Janelle M

    2006-04-01

    Full Text Available Abstract Background Prenatal cocaine exposure produces attentional deficits which to persist through early childhood. Given the role of norepinephrine (NE in attentional processes, we examined the forebrain NE systems from prenatal cocaine exposed rats. Cocaine was administered during pregnancy via the clinically relevant intravenous route of administration. Specifically, we measured α2-adrenergic receptor (α2-AR density in adolescent (35-days-old rats, using [3H]RX821002 (5 nM. Results Sex-specific alterations of α2-AR were found in the hippocampus and amygdala of the cocaine-exposed animals, as well as an upregulation of α2-AR in parietal cortex. Conclusion These data suggest that prenatal cocaine exposure results in a persistent alteration in forebrain NE systems as indicated by alterations in receptor density. These neurochemical changes may underlie behavioral abnormalities observed in offspring attentional processes following prenatal exposure to cocaine.

  10. Neurochemical binding profiles of novel indole and benzofuran MDMA analogues.

    OpenAIRE

    Shimshoni, JA; Winkler, I; Golan, E; Nutt, D

    2016-01-01

    3,4-Methylenedioxy-N-methylamphetamine (MDMA) has been shown to be effective in the treatment of post-traumatic stress disorder (PTSD) in numerous clinical trials. In the present study, we have characterized the neurochemical binding profiles of three MDMA-benzofuran analogues (1-(benzofuran-5-yl)-propan-2-amine, 5-APB; 1-(benzofuran-6-yl)-N-methylpropan-2-amine, 6-MAPB; 1-(benzofuran-5-yl)-N-methylpropan-2-amine, 5-MAPB) and one MDMA-indole analogue (1-(1H-indol-5-yl)-2-methylamino-propan-1-...

  11. [Liesegang's rings resembling helminthiasis].

    Science.gov (United States)

    Zámecník, M; Riedl, I

    1996-12-01

    So called Liesegang's rings are lamellar corpuscles which develop after periodical precipitation of oversaturated solutions in gel medium. They can occur in cysts, closed cavities, inflammatory exudates and necroses. They resemble parasitic eggs, larvae or adult forms. A case of 28-year-old woman is presented with many Liesegang's rings in a stuff from dilated renal calyx. Their preliminary evaluation considered helminths, especially Dioctophyma renale.

  12. Differential Effects of Intrauterine Growth Restriction on the Regional Neurochemical Profile of the Developing Rat Brain.

    Science.gov (United States)

    Maliszewski-Hall, Anne M; Alexander, Michelle; Tkáč, Ivan; Öz, Gülin; Rao, Raghavendra

    2017-01-01

    Intrauterine growth restricted (IUGR) infants are at increased risk for neurodevelopmental deficits that suggest the hippocampus and cerebral cortex may be particularly vulnerable. Evaluate regional neurochemical profiles in IUGR and normally grown (NG) 7-day old rat pups using in vivo 1 H magnetic resonance (MR) spectroscopy at 9.4 T. IUGR was induced via bilateral uterine artery ligation at gestational day 19 in pregnant Sprague-Dawley dams. MR spectra were obtained from the cerebral cortex, hippocampus and striatum at P7 in IUGR (N = 12) and NG (N = 13) rats. In the cortex, IUGR resulted in lower concentrations of phosphocreatine, glutathione, taurine, total choline, total creatine (P regions. Persistent neurochemical changes may lead to cortex-based long-term neurodevelopmental deficits in human IUGR infants.

  13. A neurochemical closed-loop controller for deep brain stimulation: toward individualized smart neuromodulation therapies.

    Directory of Open Access Journals (Sweden)

    Peter Jonas Grahn

    2014-06-01

    Full Text Available Current strategies for optimizing deep brain stimulation (DBS therapy involve multiple postoperative visits. During each visit, stimulation parameters are adjusted until desired therapeutic effects are achieved and adverse effects are minimized. However, the efficacy of these therapeutic parameters may decline with time due at least in part to disease progression, interactions between the host environment and the electrode, and lead migration. As such, development of closed-loop control systems that can respond to changing neurochemical environments, tailoring DBS therapy to individual patients, is paramount for improving the therapeutic efficacy of DBS.Evidence obtained using electrophysiology and imaging techniques in both animals and humans suggests that DBS works by modulating neural network activity. Recently, animal studies have shown that stimulation-evoked changes in neurotransmitter release that mirror normal physiology are associated with the therapeutic benefits of DBS. Therefore, to fully understand the neurophysiology of DBS and optimize its efficacy, it may be necessary to look beyond conventional electrophysiological analyses and characterize the neurochemical effects of therapeutic and non-therapeutic stimulation. By combining electrochemical monitoring and mathematical modeling techniques, we can potentially replace the trial-and-error process used in clinical programming with deterministic approaches that help attain optimal and stable neurochemical profiles. In this manuscript, we summarize the current understanding of electrophysiological and electrochemical processing for control of neuromodulation therapies. Additionally, we describe a proof-of-principle closed-loop controller that characterizes DBS-evoked dopamine changes to adjust stimulation parameters in a rodent model of DBS. The work described herein represents the initial steps toward achieving a smart neuroprosthetic system for treatment of neurologic and

  14. Zebrafish Get Connected: Investigating Neurotransmission Targets and Alterations in Chemical Toxicity

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    Katharine A. Horzmann

    2016-08-01

    Full Text Available Neurotransmission is the basis of neuronal communication and is critical for normal brain development, behavior, learning, and memory. Exposure to drugs and chemicals can alter neurotransmission, often through unknown pathways and mechanisms. The zebrafish (Danio rerio model system is increasingly being used to study the brain and chemical neurotoxicity. In this review, the major neurotransmitter systems, including glutamate, GABA, dopamine, norepinephrine, serotonin, acetylcholine, histamine, and glutamate are surveyed and pathways of synthesis, transport, metabolism, and action are examined. Differences between human and zebrafish neurochemical pathways are highlighted. We also review techniques for evaluating neurological function, including the measurement of neurotransmitter levels, assessment of gene expression through transcriptomic analysis, and the recording of neurobehavior. Finally examples of chemical toxicity studies evaluating alterations in neurotransmitter systems in the zebrafish model are reviewed.

  15. Neurochemical Evidence of Potential Neurotoxicity After Prophylactic Cranial Irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Kalm, Marie, E-mail: marie.kalm@neuro.gu.se [Department of Clinical Neuroscience and Rehabilitation, Insitute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Gothenburg (Sweden); Abel, Edvard [Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy at the University of Gothenburg, Gothenburg (Sweden); Wasling, Pontus [Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Gothenburg (Sweden); Nyman, Jan [Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy at the University of Gothenburg, Gothenburg (Sweden); Hietala, Max Albert [Department of Neurology, Karolinska University Hospital, Stockholm (Sweden); Bremell, Daniel; Hagberg, Lars [Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg (Sweden); Elam, Mikael [Department of Clinical Neuroscience and Rehabilitation, Insitute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Gothenburg (Sweden); Blennow, Kaj [Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal (Sweden); Björk-Eriksson, Thomas [Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy at the University of Gothenburg, Gothenburg (Sweden); Zetterberg, Henrik [Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal (Sweden); UCL Institute of Neurology, London (United Kingdom)

    2014-07-01

    Purpose: To examine whether cerebrospinal fluid biomarkers for neuroaxonal damage, neuroglial activation, and amyloid β–related processes could characterize the neurochemical response to cranial radiation. Methods and Materials: Before prophylactic cranial irradiation (PCI) of patients with small cell lung cancer, each patient underwent magnetic resonance imaging of the brain, lumbar puncture, and Mini-Mental State Examination of cognitive function. These examinations were repeated at approximately 3 and 12 months after radiation. Results: The major findings were as follows. (1) Cerebrospinal fluid markers for neuronal and neuroglial injury were elevated during the subacute phase after PCI. Neurofilament and T-tau increased 120% and 50%, respectively, after PCI (P<.05). The same was seen for the neuroglial markers YKL-40 and glial fibrillary acidic protein, which increased 144% and 106%, respectively, after PCI (P<.05). (2) The levels of secreted amyloid precursor protein-α and -β were reduced 44% and 46%, respectively, 3 months after PCI, and the levels continued to decrease as long as 1 year after treatment (P<.05). (3) Mini-Mental State Examination did not reveal any cognitive decline, indicating that a more sensitive test should be used in future studies. Conclusion: In conclusion, we were able to detect radiation therapy–induced changes in several markers reflecting neuronal injury, inflammatory/astroglial activation, and altered amyloid precursor protein/amyloid β metabolism, despite the low number of patients and quite moderate radiation doses (20-30 Gy). These changes are hypothesis generating and could potentially be used to assess the individual risk of developing long-term symptoms of chronic encephalopathy after PCI. This has to be evaluated in large studies with extended clinical follow-up and more detailed neurocognitive assessments.

  16. Neurochemical Evidence of Potential Neurotoxicity After Prophylactic Cranial Irradiation

    International Nuclear Information System (INIS)

    Kalm, Marie; Abel, Edvard; Wasling, Pontus; Nyman, Jan; Hietala, Max Albert; Bremell, Daniel; Hagberg, Lars; Elam, Mikael; Blennow, Kaj; Björk-Eriksson, Thomas; Zetterberg, Henrik

    2014-01-01

    Purpose: To examine whether cerebrospinal fluid biomarkers for neuroaxonal damage, neuroglial activation, and amyloid β–related processes could characterize the neurochemical response to cranial radiation. Methods and Materials: Before prophylactic cranial irradiation (PCI) of patients with small cell lung cancer, each patient underwent magnetic resonance imaging of the brain, lumbar puncture, and Mini-Mental State Examination of cognitive function. These examinations were repeated at approximately 3 and 12 months after radiation. Results: The major findings were as follows. (1) Cerebrospinal fluid markers for neuronal and neuroglial injury were elevated during the subacute phase after PCI. Neurofilament and T-tau increased 120% and 50%, respectively, after PCI (P<.05). The same was seen for the neuroglial markers YKL-40 and glial fibrillary acidic protein, which increased 144% and 106%, respectively, after PCI (P<.05). (2) The levels of secreted amyloid precursor protein-α and -β were reduced 44% and 46%, respectively, 3 months after PCI, and the levels continued to decrease as long as 1 year after treatment (P<.05). (3) Mini-Mental State Examination did not reveal any cognitive decline, indicating that a more sensitive test should be used in future studies. Conclusion: In conclusion, we were able to detect radiation therapy–induced changes in several markers reflecting neuronal injury, inflammatory/astroglial activation, and altered amyloid precursor protein/amyloid β metabolism, despite the low number of patients and quite moderate radiation doses (20-30 Gy). These changes are hypothesis generating and could potentially be used to assess the individual risk of developing long-term symptoms of chronic encephalopathy after PCI. This has to be evaluated in large studies with extended clinical follow-up and more detailed neurocognitive assessments

  17. Effects of melatonin on aluminium-induced neurobehavioral and neurochemical changes in aging rats.

    Science.gov (United States)

    Allagui, M S; Feriani, A; Saoudi, M; Badraoui, R; Bouoni, Z; Nciri, R; Murat, J C; Elfeki, A

    2014-08-01

    This study aimed to investigate the potential protective effects of melatonin (Mel) against aluminium-induced neurodegenerative changes in aging Wistar rats (24-28months old). Herein, aluminium chloride (AlCl3) (50mg/kg BW/day) was administered by gavage, and melatonin (Mel) was co-administered to a group of Al-treated rats by an intra-peritoneal injection at a daily dose of 10mg/kg BW for four months. The findings revealed that aluminium administration induced a significant decrease in body weight associated with marked mortality for the old group of rats, which was more pronounced in old Al-treated rats. Behavioural alterations were assessed by 'open fields', 'elevated plus maze' and 'Radial 8-arms maze' tests. The results demonstrated that Mel co-administration alleviated neurobehavioral changes in both old and old Al-treated rats. Melatonin was noted to play a good neuroprotective role, reducing lipid peroxidation (TBARs), and enhancing enzymatic (SOD, CAT and GPx) activities in the brain organs of old control and old Al-treated rats. Mel treatment also reversed the decrease of AChE activity in the brain tissues, which was confirmed by histological sections. Overall, the results showed that Mel administration can induce beneficial effects for the treatment of Al-induced neurobehavioral and neurochemical changes in the central nervous system (CNS). Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Neurochemical Metabolomics Reveals Disruption to Sphingolipid Metabolism Following Chronic Haloperidol Administration.

    Science.gov (United States)

    McClay, Joseph L; Vunck, Sarah A; Batman, Angela M; Crowley, James J; Vann, Robert E; Beardsley, Patrick M; van den Oord, Edwin J

    2015-09-01

    Haloperidol is an effective antipsychotic drug for treatment of schizophrenia, but prolonged use can lead to debilitating side effects. To better understand the effects of long-term administration, we measured global metabolic changes in mouse brain following 3 mg/kg/day haloperidol for 28 days. These conditions lead to movement-related side effects in mice akin to those observed in patients after prolonged use. Brain tissue was collected following microwave tissue fixation to arrest metabolism and extracted metabolites were assessed using both liquid and gas chromatography mass spectrometry (MS). Over 300 unique compounds were identified across MS platforms. Haloperidol was found to be present in all test samples and not in controls, indicating experimental validity. Twenty-one compounds differed significantly between test and control groups at the p < 0.05 level. Top compounds were robust to analytical method, also being identified via partial least squares discriminant analysis. Four compounds (sphinganine, N-acetylornithine, leucine and adenosine diphosphate) survived correction for multiple testing in a non-parametric analysis using false discovery rate threshold < 0.1. Pathway analysis of nominally significant compounds (p < 0.05) revealed significant findings for sphingolipid metabolism (p = 0.015) and protein biosynthesis (p = 0.024). Altered sphingolipid metabolism is suggestive of disruptions to myelin. This interpretation is supported by our observation of elevated N-acetyl-aspartyl-glutamate in the haloperidol-treated mice (p = 0.004), a marker previously associated with demyelination. This study further demonstrates the utility of murine neurochemical metabolomics as a method to advance understanding of CNS drug effects.

  19. Neurochemical, morphologic, and laminar characterization of cortical projection neurons in the cingulate motor areas of the macaque monkey

    Science.gov (United States)

    Nimchinsky, E. A.; Hof, P. R.; Young, W. G.; Morrison, J. H.; Bloom, F. E. (Principal Investigator)

    1996-01-01

    The primate cingulate gyrus contains multiple cortical areas that can be distinguished by several neurochemical features, including the distribution of neurofilament protein-enriched pyramidal neurons. In addition, connectivity and functional properties indicate that there are multiple motor areas in the cortex lining the cingulate sulcus. These motor areas were targeted for analysis of potential interactions among regional specialization, connectivity, and cellular characteristics such as neurochemical profile and morphology. Specifically, intracortical injections of retrogradely transported dyes and intracellular injection were combined with immunocytochemistry to investigate neurons projecting from the cingulate motor areas to the putative forelimb region of the primary motor cortex, area M1. Two separate groups of neurons projecting to area M1 emanated from the cingulate sulcus, one anterior and one posterior, both of which furnished commissural and ipsilateral connections with area M1. The primary difference between the two populations was laminar origin, with the anterior projection originating largely in deep layers, and the posterior projection taking origin equally in superficial and deep layers. With regard to cellular morphology, the anterior projection exhibited more morphologic diversity than the posterior projection. Commissural projections from both anterior and posterior fields originated largely in layer VI. Neurofilament protein distribution was a reliable tool for localizing the two projections and for discriminating between them. Comparable proportions of the two sets of projection neurons contained neurofilament protein, although the density and distribution of the total population of neurofilament protein-enriched neurons was very different in the two subareas of origin. Within a projection, the participating neurons exhibited a high degree of morphologic heterogeneity, and no correlation was observed between somatodendritic morphology and

  20. Behavioral correlates of cerebrospinal fluid amino acid and biogenic amine neurotransmitter alterations in dementia.

    Science.gov (United States)

    Vermeiren, Yannick; Le Bastard, Nathalie; Van Hemelrijck, An; Drinkenburg, Wilhelmus H; Engelborghs, Sebastiaan; De Deyn, Peter P

    2013-09-01

    Behavioral and psychological signs and symptoms of dementia (BPSD) are a heterogeneous group of behavioral and psychiatric disturbances occurring in dementia patients of any etiology. Research suggests that altered activities of dopaminergic, serotonergic, (nor)adrenergic, as well as amino acid neurotransmitter systems play a role in the etiopathogenesis of BPSD. In this study we attempted to identify cerebrospinal fluid (CSF) neurochemical correlates of BPSD to provide further insight into its underlying neurochemical pathophysiological mechanisms. Patients with probable Alzheimer's disease (AD; n = 202), probable AD with cerebrovascular disease (n = 37), probable frontotemporal dementia (FTD; n = 32), and probable dementia with Lewy bodies (DLB; n = 26) underwent behavioral assessment and lumbar puncture. CSF levels of six amino acids and several biogenic amines and metabolites were analyzed using ultraperformance liquid chromatography with fluorescence detection and reversed-phase high-performance liquid chromatography with fluorescence detection. In the AD patients, CSF homovanillic acid/5-hydroxyindoleacetic acid (HVA/5HIAA) ratios correlated positively with anxieties/phobias, whereas CSF levels of taurine correlated negatively with depression and behavioral disturbances in general. In FTD patients, CSF levels of glutamate correlated negatively with verbally agitated behavior. In DLB patients, CSF levels of HVA correlated negatively with hallucinations. Several neurotransmitter systems can be linked to one specific behavioral syndrome depending on the dementia subtype. In addition to biogenic amines and metabolites, amino acids seem to play a major role in the neurochemical etiology of BPSD as well. Copyright © 2013 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

  1. Transplacental exposure to AZT induces adverse neurochemical and behavioral effects in a mouse model: protection by L-acetylcarnitine.

    Directory of Open Access Journals (Sweden)

    Anna Rita Zuena

    Full Text Available Maternal-fetal HIV-1 transmission can be prevented by administration of AZT, alone or in combination with other antiretroviral drugs to pregnant HIV-1-infected women and their newborns. In spite of the benefits deriving from this life-saving prophylactic therapy, there is still considerable uncertainty on the potential long-term adverse effects of antiretroviral drugs on exposed children. Clinical and experimental studies have consistently shown the occurrence of mitochondrial dysfunction and increased oxidative stress following prenatal treatment with antiretroviral drugs, and clinical evidence suggests that the developing brain is one of the targets of the toxic action of these compounds possibly resulting in behavioral problems. We intended to verify the effects on brain and behavior of mice exposed during gestation to AZT, the backbone of antiretroviral therapy during human pregnancy. We hypothesized that glutamate, a neurotransmitter involved in excitotoxicity and behavioral plasticity, could be one of the major actors in AZT-induced neurochemical and behavioral alterations. We also assessed the antioxidant and neuroprotective effect of L-acetylcarnitine, a compound that improves mitochondrial function and is successfully used to treat antiretroviral-induced polyneuropathy in HIV-1 patients. We found that transplacental exposure to AZT given per os to pregnant mice from day 10 of pregnancy to delivery impaired in the adult offspring spatial learning and memory, enhanced corticosterone release in response to acute stress, increased brain oxidative stress also at birth and markedly reduced expression of mGluR1 and mGluR5 subtypes and GluR1 subunit of AMPA receptors in the hippocampus. Notably, administration during the entire pregnancy of L-acetylcarnitine was effective in preventing/ameliorating the neurochemical, neuroendocrine and behavioral adverse effects induced by AZT in the offspring. The present preclinical findings provide a

  2. Detecting analogical resemblance without retrieving the source analogy.

    Science.gov (United States)

    Kostic, Bogdan; Cleary, Anne M; Severin, Kaye; Miller, Samuel W

    2010-06-01

    We examined whether people can detect analogical resemblance to an earlier experimental episode without being able to recall the experimental source of the analogical resemblance. We used four-word analogies (e.g., robin-nest/beaver-dam), in a variation of the recognition-without-cued-recall method (Cleary, 2004). Participants studied word pairs (e.g., robin-nest) and were shown new word pairs at test, half of which analogically related to studied word pairs (e.g., beaver-dam) and half of which did not. For each test pair, participants first attempted to recall an analogically similar pair from the study list. Then, regardless of whether successful recall occurred, participants were prompted to rate the familiarity of the test pair, which was said to indicate the likelihood that a pair that was analogically similar to the test pair had been studied. Across three experiments, participants demonstrated an ability to detect analogical resemblance without recalling the source analogy. Findings are discussed in terms of their potential relevance to the study of analogical reasoning and insight, as well as to the study of familiarity and recognition memory.

  3. Repeated, Intermittent Social Defeat across the Entire Juvenile Period Resulted in Behavioral, Physiological, Hormonal, Immunological, and Neurochemical Alterations in Young Adult Male Golden Hamsters

    Science.gov (United States)

    Yu, Wei-Chun; Liu, Ching-Yi; Lai, Wen-Sung

    2016-01-01

    The developing brain is vulnerable to social defeat during the juvenile period. As complements of human studies, animal models of social defeat provide a straightforward approach to investigating the functional and neurobiological consequences of social defeats. Taking advantage of agonist behavior and social defeat in male golden hamster, a set of 6 experiments was conducted to investigate the consequences at multiple levels in young adulthood resulting from repeated, intermittent social defeats or “social threats” across the entire juvenile period. Male hamsters at postnatal day 28 (P28) were randomly assigned to either the social defeat, “social threat”, or arena control group, and they correspondingly received a series of nine social interaction trials (i.e., either social defeat, “social threat”, or arena control conditions) from P33 to P66. At the behavioral level (Experiment 1), we found that repeated social defeats (but not “social threats”) significantly impacted locomotor activity in the familiar context and social interaction in the familiar/unfamiliar social contexts. At the physiological and hormonal levels (Experiments 2 and 3), repeated social defeat significantly enhanced the cortisol and norepinephrine concentrations in blood. Enlargement of the spleen was also found in the social defeat and “social threat” groups. At the immunological level (Experiment 4), the social defeat group showed lower levels of pro-inflammatory cytokines in the hypothalamus and hippocampus but higher concentration of IL-6 in the striatum compared to the other two groups. At the neurochemical level (Experiment 5), the socially defeated hamsters mainly displayed reductions of dopamine, dopamine metabolites, and 5-HT levels in the striatum and decreased level of 5-HT in the hippocampus. In Experiment 6, an increase in the spine density of hippocampal CA1 pyramidal neurons was specifically observed in the “social threat” group. Collectively, our

  4. Neurochemical mechanisms underlying responses to psychostimulants

    Energy Technology Data Exchange (ETDEWEB)

    Volkow, N.D.; Fowler, J.S.; Hitzemann, R.; Wang, G.J. [Brookhaven National Lab., Upton, NY (United States)]|[State Univ. of New York, Stony Brook, NY (United States)

    1994-11-01

    This study employed positron emission tomography (PET) to investigate biochemical and metabolic characteristics of the brain of individuals which could put them at risk for drug addiction. It takes advantage of the normal variability between individuals in response to psychoactive drugs to investigate relation between mental state, brain neurochemistry and metabolism and the behavioral response to drugs. We discuss its use to assess if there is an association between mental state and dompaminergic reactivity in response to the psychostimulant drug methylphenidate (MP). Changes in synaptic dopamine induced by MP were evaluated with PET and [11C]raclopride, a D{sub 2} receptor radioligand that is sensitive to endogenous dopamine. Methylpphenidate significantly decreased striatal [11C]raclopride binding. The study showed a correlation between the magnitude of the dopamine-induced changes by methylphenidate, and the mental state of the subjects. Subjects reporting high levels of anxiety and restlessness at baseline had larger changes in MP-induced dopamine changes than those that did not. Further investigations on the relation between an individual`s response to a drug and his/her mental state and personality as well as his neurochemical brain composition may enable to understand better differences in drug addiction vulnerability.

  5. The gyri of the octopus vertical lobe have distinct neurochemical identities.

    Science.gov (United States)

    Shigeno, Shuichi; Ragsdale, Clifton W

    2015-06-15

    The cephalopod vertical lobe is the largest learning and memory structure known in invertebrate nervous systems. It is part of the visual learning circuit of the central brain, which also includes the superior frontal and subvertical lobes. Despite the well-established functional importance of this system, little is known about neuropil organization of these structures and there is to date no evidence that the five longitudinal gyri of the vertical lobe, perhaps the most distinctive morphological feature of the octopus brain, differ in their connections or molecular identities. We studied the histochemical organization of these structures in hatchling and adult Octopus bimaculoides brains with immunostaining for serotonin, octopus gonadotropin-releasing hormone (oGNRH), and octopressin-neurophysin (OP-NP). Our major finding is that the five lobules forming the vertical lobe gyri have distinct neurochemical signatures. This is most prominent in the hatchling brain, where the median and mediolateral lobules are enriched in OP-NP fibers, the lateral lobule is marked by oGNRH innervation, and serotonin immunostaining heavily labels the median and lateral lobules. A major source of input to the vertical lobe is the superior frontal lobe, which is dominated by a neuropil of interweaving fiber bundles. We have found that this neuropil also has an intrinsic neurochemical organization: it is partitioned into territories alternately enriched or impoverished in oGNRH-containing fascicles. Our findings establish that the constituent lobes of the octopus superior frontal-vertical system have an intricate internal anatomy, one likely to reflect the presence of functional subsystems within cephalopod learning circuitry. © 2015 Wiley Periodicals, Inc.

  6. Carbon Nanofiber Electrode Array for Neurochemical Monitoring

    Science.gov (United States)

    Koehne, Jessica E.

    2017-01-01

    A sensor platform based on vertically aligned carbon nanofibers (CNFs) has been developed. Their inherent nanometer scale, high conductivity, wide potential window, good biocompatibility and well-defined surface chemistry make them ideal candidates as biosensor electrodes. Here, we report using vertically aligned CNF as neurotransmitter recording electrodes for application in a smart deep brain stimulation (DBS) device. Our approach combines a multiplexed CNF electrode chip, developed at NASA Ames Research Center, with the Wireless Instantaneous Neurotransmitter Concentration Sensor (WINCS) system, developed at the Mayo Clinic. Preliminary results indicate that the CNF nanoelectrode arrays are easily integrated with WINCS for neurotransmitter detection in a multiplexed array format. In the future, combining CNF based stimulating and recording electrodes with WINCS may lay the foundation for an implantable smart therapeutic system that utilizes neurochemical feedback control while likely resulting in increased DBS application in various neuropsychiatric disorders. In total, our goal is to take advantage of the nanostructure of CNF arrays for biosensing studies requiring ultrahigh sensitivity, high-degree of miniaturization, and selective biofunctionalization.

  7. Separate neurochemical classes of sympathetic postganglionic neurons project to the left ventricle of the rat heart.

    Science.gov (United States)

    Richardson, R J; Grkovic, I; Allen, A M; Anderson, C R

    2006-04-01

    The sympathetic innervation of the rat heart was investigated by retrograde neuronal tracing and multiple label immunohistochemistry. Injections of Fast Blue made into the left ventricular wall labelled sympathetic neurons that were located along the medial border of both the left and right stellate ganglia. Cardiac projecting sympathetic postganglionic neurons could be grouped into one of four neurochemical populations, characterised by their content of calbindin and/or neuropeptide Y (NPY). The subpopulations of neurons contained immunoreactivity to both calbindin and NPY, immunoreactivity to calbindin only, immunoreactivity to NPY only and no immunoreactivity to calbindin or NPY. Sympathetic postganglionic neurons were also labelled in vitro with rhodamine dextran applied to the cut end of a cardiac nerve. The same neurochemical subpopulations of sympathetic neurons were identified by using this technique but in different proportions to those labelled from the left ventricle. Preganglionic terminals that were immunoreactive for another calcium-binding protein, calretinin, preferentially surrounded retrogradely labelled neurons that were immunoreactive for both calbindin and NPY. The separate sympathetic pathways projecting to the rat heart may control different cardiac functions.

  8. Effect of chronic psychogenic stress on some behavioral and neurochemical characteristics of rats

    International Nuclear Information System (INIS)

    Danchev, N.D.; Rozhanets, V.V.; Val'dman, A.V.

    1986-01-01

    This paper studies the behavioral, somatic, and certain neurochemical parameters in rats under conditions of unavoidable chronic stress, according to Hecht et al. in a situation of possible avoidance, with the same total number of aversive stimuli. Specific binding of tritium-flunitrazepam and tritium-dihydroalprenolol was studied. The dissociatin constant and the maximal concentration of ligand-receptor complexes were determined in Scatchard plots by means of an HP-33E computer. The protein concentration in the samples was determined by Peterson's method

  9. Vanillin Attenuated Behavioural Impairments, Neurochemical Deficts, Oxidative Stress and Apoptosis Against Rotenone Induced Rat Model of Parkinson's Disease.

    Science.gov (United States)

    Dhanalakshmi, Chinnasamy; Janakiraman, Udaiyappan; Manivasagam, Thamilarasan; Justin Thenmozhi, Arokiasamy; Essa, Musthafa Mohamed; Kalandar, Ameer; Khan, Mohammed Abdul Sattar; Guillemin, Gilles J

    2016-08-01

    Vanillin (4-hydroxy-3-methoxybenzaldehyde), a pleasant smelling organic aromatic compound, is widely used as a flavoring additive in food, beverage, cosmetic and drug industries. It is reported to cross the blood brain barrier and also displayed antioxidant and neuroprotective activities. We previously reported the neuroprotective effect of vanillin against rotenone induced in in vitro model of PD. The present experiment was aimed to analyze the neuroprotective effect of vanillin on the motor and non-motor deficits, neurochemical variables, oxidative, anti-oxidative indices and the expression of apoptotic markers against rotenone induced rat model of Parkinson's disease (PD). Rotenone treatment exhibited motor and non-motor impairments, neurochemical deficits, oxidative stress and apoptosis, whereas oral administration of vanillin attenuated the above-said indices. However further studies are needed to explore the mitochondrial protective and anti-inflammatory properties of vanillin, as these processes play a vital role in the cause and progression of PD.

  10. Behavioral and neurochemical responses to 8-OH-DPAT in restrained and unrestrained animals treated with lithium carbonate in drinking water

    International Nuclear Information System (INIS)

    Naz, H.; Haleem, D.J.

    2012-01-01

    Lithium has been suggested for mood disorders and neurodegenerative diseases. Its ability to increase the gray matter and provision of protection against neuronal death makes it tempting to be marketed as brain food. Moreover it also ameliorates the effects of stress on brain dendrites; however lithium has a narrow therapeutic range. Brain serotonin (5-HT) neurotransmission may mediate the actions of lithium. Preclinical studies have shown that single restraint stress produces behavioral and neurochemical deficits. The present study was designed to investigate a potential role of Lithium in attenuation of stress induced behavioral and neurochemical deficits in rats. Moreover the study also monitored the esponsiveness of pre and post synaptic serotonin 1 A receptor following restraint and administration of lithium carbonate. Pre stress behavioral activities were monitored after 15 and 30 days of consumption of 0.1% lithium carbonate in drinking water while post stress were monitored on day 31. Pre and post synaptic 5-HT -1 A responsiveness was monitored by injecting 0.25mg/ml/kg of 8-OH-DPAT. Although lithium produced hypo activity but attenuated stress induced behavioral deficits. Whole brain neurochemical analysis revealed that its administration increased tryptophan, 5-HT and 5-Hydroindoleacetic acid (5-HIAA). 8-OH-DPAT elicited hyperactivity and fore paw treading were enhanced in lithium treated rats. Lithium induced pre synaptic changes together with the super sensitivity of post synaptic receptors may be able to produce antidepressant effect. (author)

  11. A High-Performance Application Specific Integrated Circuit for Electrical and Neurochemical Traumatic Brain Injury Monitoring.

    Science.gov (United States)

    Pagkalos, Ilias; Rogers, Michelle L; Boutelle, Martyn G; Drakakis, Emmanuel M

    2018-05-22

    This paper presents the first application specific integrated chip (ASIC) for the monitoring of patients who have suffered a Traumatic Brain Injury (TBI). By monitoring the neurophysiological (ECoG) and neurochemical (glucose, lactate and potassium) signals of the injured human brain tissue, it is possible to detect spreading depolarisations, which have been shown to be associated with poor TBI patient outcome. This paper describes the testing of a new 7.5 mm 2 ASIC fabricated in the commercially available AMS 0.35 μm CMOS technology. The ASIC has been designed to meet the demands of processing the injured brain tissue's ECoG signals, recorded by means of depth or brain surface electrodes, and neurochemical signals, recorded using microdialysis coupled to microfluidics-based electrochemical biosensors. The potentiostats use switchedcapacitor charge integration to record currents with 100 fA resolution, and allow automatic gain changing to track the falling sensitivity of a biosensor. This work supports the idea of a "behind the ear" wireless microplatform modality, which could enable the monitoring of currently non-monitored mobile TBI patients for the onset of secondary brain injury. ©2018 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

  12. Facial Resemblance Exaggerates Sex-Specific Jealousy-Based Decisions1

    Directory of Open Access Journals (Sweden)

    Steven M. Platek

    2007-01-01

    Full Text Available Sex differences in reaction to a romantic partner's infidelity are well documented and are hypothesized to be attributable to sex-specific jealousy mechanisms which are utilized to solve adaptive problems associated with risk of extra-pair copulation. Males, because of the risk of cuckoldry become more upset by sexual infidelity, while females, because of loss of resources and biparental investment tend to become more distressed by emotional infidelity. However, the degree to which these sex-specific reactions to jealousy interact with cues to kin are completely unknown. Here we investigated the interaction of facial resemblance with decisions about sex-specific jealousy scenarios. Fifty nine volunteers were asked to imagine that two different people (represented by facial composites informed them about their romantic partner's sexual or emotional infidelity. Consistent with previous research, males ranked sexual infidelity scenarios as most upsetting and females ranked emotional infidelity scenarios most upsetting. However, when information about the infidelity was provided by a face that resembled the subject, sex-specific reactions to jealousy were exaggerated. This finding highlights the use of facial resemblance as a putative self-referent phenotypic matching cue that impacts trusting behavior in sexual contexts.

  13. Individual differences in the effects of chronic stress on memory: behavioral and neurochemical correlates of resiliency.

    Science.gov (United States)

    Sweis, B M; Veverka, K K; Dhillon, E S; Urban, J H; Lucas, L R

    2013-08-29

    Chronic stress has been shown to impair memory, however, the extent to which memory can be impaired is often variable across individuals. Predisposed differences in particular traits, such as anxiety, may reveal underlying neurobiological mechanisms that could be driving individual differences in sensitivity to stress and, thus, stress resiliency. Such pre-morbid characteristics may serve as early indicators of susceptibility to stress. Neuropeptide Y (NPY) and enkephalin (ENK) are neurochemical messengers of interest implicated in modulating anxiety and motivation circuitry; however, little is known about how these neuropeptides interact with stress resiliency and memory. In this experiment, adult male rats were appetitively trained to locate sugar rewards in a motivation-based spatial memory task before undergoing repeated immobilization stress and then being tested for memory retention. Anxiety-related behaviors, among other characteristics, were monitored longitudinally. Results indicated that stressed animals which showed little to no impairments in memory post-stress (i.e., the more stress-resilient individuals) exhibited lower anxiety levels prior to stress when compared to stressed animals that showed large deficits in memory (i.e., the more stress-susceptible individuals). Interestingly, all stressed animals, regardless of memory change, showed reduced body weight gain as well as thymic involution, suggesting that the effects of stress on metabolism and the immune system were dissociated from the effects of stress on higher cognition, and that stress resiliency seems to be domain-specific rather than a global characteristic within an individual. Neurochemical analyses revealed that NPY in the hypothalamus and amygdala and ENK in the nucleus accumbens were modulated differentially between stress-resilient and stress-susceptible individuals, with elevated expression of these neuropeptides fostering anxiolytic and pro-motivation function, thus driving

  14. Binge Toluene Exposure Alters Glutamate, Glutamine and GABA in the Adolescent Rat Brain as Measured by Proton Magnetic Resonance Spectroscopy*

    Science.gov (United States)

    Perrine, Shane A.; O'Leary-Moore, Shonagh K.; Galloway, Matthew P.; Hannigan, John H.; Bowen, Scott E.

    2010-01-01

    Despite the high incidence of toluene abuse in adolescents, little is known regarding the effect of binge exposure on neurochemical profiles during this developmental stage. In the current study, the effects of binge toluene exposure during adolescence on neurotransmitter levels were determined using high-resolution proton magnetic resonance spectroscopy ex vivo at 11.7 T. Adolescent male Sprague-Dawley rats were exposed to toluene (0, 8,000 , or 12,000 ppm) for 15 min twice daily from postnatal day 28 (P28) through P34 and then euthanized either one or seven days later (on P35 or P42) to assess glutamate, glutamine, and GABA levels in intact tissue punches from the medial prefrontal cortex (mPFC), anterior striatum and hippocampus. In the mPFC, toluene reduced glutamate one day after exposure, with no effect on GABA, while after seven days, glutamate was no longer affected but there was an increase in GABA levels. In the hippocampus, neither GABA nor glutamate was altered one day after exposure, whereas seven days after exposure, increases were observed in GABA and glutamate. Striatal glutamate and GABA levels measured after either one or seven days were not altered after toluene exposure. These findings show that one week of binge toluene inhalation selectively alters these neurotransmitters in the mPFC and hippocampus in adolescent rats, and that some of these effects endure at least one week after the exposure. The results suggest that age-dependent, differential neurochemical responses to toluene may contribute to the unique behavioral patterns associated with drug abuse among older children and young teens. PMID:21126832

  15. In vivo and in vitro changes in neurochemical parameters related to mercury concentrations from specific brain regions of polar bears (Ursus maritimus).

    Science.gov (United States)

    Krey, Anke; Kwan, Michael; Chan, Hing Man

    2014-11-01

    Mercury (Hg) has been detected in polar bear brain tissue, but its biological effects are not well known. Relationships between Hg concentrations and neurochemical enzyme activities and receptor binding were assessed in the cerebellum, frontal lobes, and occipital lobes of 24 polar bears collected from Nunavik (Northern Quebec), Canada. The concentration-response relationship was further studied with in vitro experiments using pooled brain homogenate of 12 randomly chosen bears. In environmentally exposed brain samples, there was no correlative relationship between Hg concentration and cholinesterase (ChE) activity or muscarinic acetylcholine receptor (mAChR) binding in any of the 3 brain regions. Monoamine oxidase (MAO) activity in the occipital lobe showed a negative correlative relationship with total Hg concentration. In vitro experiments, however, demonstrated that Hg (mercuric chloride and methylmercury chloride) can inhibit ChE and MAO activities and muscarinic mAChR binding. These results show that Hg can alter neurobiochemical parameters but the current environmental Hg exposure level does have an effect on the neurochemistry of polar bears from northern Canada. © 2014 SETAC.

  16. Traumatic bone cyst resembling apical periodontitis.

    Science.gov (United States)

    Rosen, D J; Ardekian, L; Machtei, E E; Peled, M; Manor, R; Laufer, D

    1997-10-01

    Among the pseudocysts of the jaws, the traumatic bone cyst is known as an asymptomatic lesion often noted unintentionally during routine radiographic examinations. The lesion neither devitalizes the teeth within its borders, nor does it cause resorption of their roots. The well-demarcated traumatic bone cyst often projects into the intraradicular septa and hence has been described as having scalloped borders. The following presentation is of a traumatic bone cyst that resembled periodontal pathology in its appearance.

  17. Caffeine tolerance: behavioral, electrophysiological and neurochemical evidence

    International Nuclear Information System (INIS)

    Chou, D.T.; Khan, S.; Forde, J.; Hirsh, K.R.

    1985-01-01

    The development of tolerance to the stimulatory action of caffeine upon mesencephalic reticular neurons and upon spontaneous locomotor activity was evaluated in rats after two weeks of chronic exposure to low doses of caffeine (5-10 mg/kg/day via their drinking water). These doses are achievable through dietary intake of caffeine-containing beverages in man. Concomitant measurement of [ 3 H]-CHA binding in the mesencephalic reticular formation was also carried out in order to explore the neurochemical basis of the development of tolerance. Caffeine, 2.5 mg/kg i.v., markedly increased the firing rate of reticular neurons in caffeine naive rats but failed to modify the neuronal activity in a group exposed chronically to low doses of caffeine. In addition, in spontaneous locomotor activity studies, the data show a distinct shift to the right of the caffeine dose-response curve in caffeine pretreated rats. These results clearly indicate that tolerance develops to the stimulatory action of caffeine upon the reticular formation at the single neuronal activity level as well as upon spontaneous locomotor activity. Furthermore, in chronically caffeine exposed rats, an increase in the number of binding sites for [ 3 H]-CHA was observed in reticular formation membranes without any change in receptor affinity. 28 references, 4 figures

  18. Pareidolia in Neuroendocrinology: A Pituitary Macroadenoma Resembling "Big Bird".

    Science.gov (United States)

    de Herder, Wouter W

    2016-04-01

    The MRI picture of a pituitary macroadenoma with supra- and perisellar expansion resembled a famous character from a children's television series demonstrating that pareidolia is also observed in neuro-endocrinology and -radiology.

  19. Development of the Wireless Instantaneous Neurotransmitter Concentration System for intraoperative neurochemical monitoring using fast-scan cyclic voltammetry.

    Science.gov (United States)

    Bledsoe, Jonathan M; Kimble, Christopher J; Covey, Daniel P; Blaha, Charles D; Agnesi, Filippo; Mohseni, Pedram; Whitlock, Sidney; Johnson, David M; Horne, April; Bennet, Kevin E; Lee, Kendall H; Garris, Paul A

    2009-10-01

    Emerging evidence supports the hypothesis that modulation of specific central neuronal systems contributes to the clinical efficacy of deep brain stimulation (DBS) and motor cortex stimulation (MCS). Real-time monitoring of the neurochemical output of targeted regions may therefore advance functional neurosurgery by, among other goals, providing a strategy for investigation of mechanisms, identification of new candidate neurotransmitters, and chemically guided placement of the stimulating electrode. The authors report the development of a device called the Wireless Instantaneous Neurotransmitter Concentration System (WINCS) for intraoperative neurochemical monitoring during functional neurosurgery. This device supports fast-scan cyclic voltammetry (FSCV) at a carbon-fiber microelectrode (CFM) for real-time, spatially and chemically resolved neurotransmitter measurements in the brain. The FSCV study consisted of a triangle wave scanned between -0.4 and 1 V at a rate of 300 V/second and applied at 10 Hz. All voltages were compared with an Ag/AgCl reference electrode. The CFM was constructed by aspirating a single carbon fiber (r = 2.5 mum) into a glass capillary and pulling the capillary to a microscopic tip by using a pipette puller. The exposed carbon fiber (that is, the sensing region) extended beyond the glass insulation by approximately 100 microm. The neurotransmitter dopamine was selected as the analyte for most trials. Proof-of-principle tests included in vitro flow injection and noise analysis, and in vivo measurements in urethane-anesthetized rats by monitoring dopamine release in the striatum following high-frequency electrical stimulation of the medial forebrain bundle. Direct comparisons were made to a conventional hardwired system. The WINCS, designed in compliance with FDA-recognized consensus standards for medical electrical device safety, consisted of 4 modules: 1) front-end analog circuit for FSCV (that is, current-to-voltage transducer); 2

  20. Fathers see stronger family resemblances than non-fathers in unrelated children's faces.

    Science.gov (United States)

    Bressan, Paola; Dal Pos, Stefania

    2012-12-01

    Even after they have taken all reasonable measures to decrease the probability that their spouses cheat on them, men still face paternal uncertainty. Such uncertainty can lead to paternal disinvestment, which reduces the children's probability to survive and reproduce, and thus the reproductive success of the fathers themselves. A theoretical model shows that, other things being equal, men who feel confident that they have fathered their spouses' offspring tend to enjoy greater fitness (i.e., leave a larger number of surviving progeny) than men who do not. This implies that fathers should benefit from exaggerating paternal resemblance. We argue that the self-deceiving component of this bias could be concealed by generalizing this resemblance estimation boost to (1) family pairs other than father-child and (2) strangers. Here, we tested the prediction that fathers may see, in unrelated children's faces, stronger family resemblances than non-fathers. In Study 1, 70 men and 70 women estimated facial resemblances between children paired, at three different ages (as infants, children, and adolescents), either to themselves or to their parents. In Study 2, 70 men and 70 women guessed the true parents of the same children among a set of adults. Men who were fathers reported stronger similarities between faces than non-fathers, mothers, and non-mothers did, but were no better at identifying childrens' real parents. We suggest that, in fathers, processing of facial resemblances is biased in a manner that reflects their (adaptive) wishful thinking that fathers and children are related.

  1. Specific genetic deficiencies of the A and B isoenzymes of monoamine oxidase are characterized by distinct neurochemical and clinical phenotypes

    NARCIS (Netherlands)

    Lenders, J. W.; Eisenhofer, G.; Abeling, N. G.; Berger, W.; Murphy, D. L.; Konings, C. H.; Wagemakers, L. M.; Kopin, I. J.; Karoum, F.; van Gennip, A. H.; Brunner, H. G.

    1996-01-01

    Monoamine oxidase (MAO) exists as two isoenzymes and plays a central role in the metabolism of monoamine neurotransmitters. In this study we compared the neurochemical phenotypes of previously described subjects with genetically determined selective lack of MAO-A or a lack of both MAO-A and MAO-B

  2. Effects of Gladiolus dalenii on the Stress-Induced Behavioral, Neurochemical, and Reproductive Changes in Rats

    Directory of Open Access Journals (Sweden)

    David Fotsing

    2017-09-01

    Full Text Available Gladiolus dalenii is a plant commonly used in many regions of Cameroon as a cure for various diseases like headaches, epilepsy, schizophrenia, and mood disorders. Recent studies have revealed that the aqueous extract of G. dalenii (AEGD exhibited antidepressant-like properties in rats. Therefore, we hypothesized that the AEGD could protect from the stress-induced behavioral, neurochemical, and reproductive changes in rats. The objective of the present study was to elucidate the effect of the AEGD on behavioral, neurochemical, and reproductive characteristics, using female rats subjected to chronic immobilization stress. The chronic immobilization stress (3 h per day for 28 days was applied to induce female reproductive and behavioral impairments in rats. The immobilization stress was provoked in rats by putting them separately inside cylindrical restrainers with ventilated doors at ambient temperature. The plant extract was given to rats orally everyday during 28 days, 5 min before induction of stress. On a daily basis, a vaginal smear was made to assess the duration of the different phases of the estrous cycle and at the end of the 28 days of chronic immobilization stress, the rat’s behavior was assessed in the elevated plus maze. They were sacrificed by cervical disruption. The organs were weighed, the ovary histology done, and the biochemical parameters assessed. The findings of this research revealed that G. dalenii increased the entries and the time of open arm exploration in the elevated plus maze. Evaluation of the biochemical parameters levels indicated that there was a significant reduction in the corticosterone, progesterone, and prolactin levels in the G. dalenii aqueous extract treated rats compared to stressed rats whereas the levels of serotonin, triglycerides, adrenaline, cholesterol, glucose estradiol, follicle stimulating hormone and luteinizing hormone were significantly increased in the stressed rats treated with, G. dalenii

  3. Altered social behaviours in neurexin 1α knockout mice resemble core symptoms in neurodevelopmental disorders.

    Directory of Open Access Journals (Sweden)

    Hannah Mary Grayton

    Full Text Available BACKGROUND: Copy number variants have emerged as an important genomic cause of common, complex neurodevelopmental disorders. These usually change copy number of multiple genes, but deletions at 2p16.3, which have been associated with autism, schizophrenia and mental retardation, affect only the neurexin 1 gene, usually the alpha isoform. Previous analyses of neurexin 1α (Nrxn1α knockout (KO mouse as a model of these disorders have revealed impairments in synaptic transmission but failed to reveal defects in social behaviour, one of the core symptoms of autism. METHODS: We performed a detailed investigation of the behavioural effects of Nrxn1α deletion in mice bred onto a pure genetic background (C57BL/6J to gain a better understanding of its role in neurodevelopmental disorders. Wildtype, heterozygote and homozygote Nrxn1α KO male and female mice were tested in a battery of behavioural tests (n = 9-16 per genotype, per sex. RESULTS: In homozygous Nrxn1α KO mice, we observed altered social approach, reduced social investigation, and reduced locomotor activity in novel environments. In addition, male Nrxn1α KO mice demonstrated an increase in aggressive behaviours. CONCLUSIONS: These are the first experimental data that associate a deletion of Nrxn1α with alterations of social behaviour in mice. Since this represents one of the core symptom domains affected in autism spectrum disorders and schizophrenia in humans, our findings suggest that deletions within NRXN1 found in patients may be responsible for the impairments seen in social behaviours, and that the Nrxn1α KO mice are a useful model of human neurodevelopmental disorder.

  4. Altered Social Behaviours in Neurexin 1α Knockout Mice Resemble Core Symptoms in Neurodevelopmental Disorders

    Science.gov (United States)

    Grayton, Hannah Mary; Missler, Markus

    2013-01-01

    Background Copy number variants have emerged as an important genomic cause of common, complex neurodevelopmental disorders. These usually change copy number of multiple genes, but deletions at 2p16.3, which have been associated with autism, schizophrenia and mental retardation, affect only the neurexin 1 gene, usually the alpha isoform. Previous analyses of neurexin 1α (Nrxn1α) knockout (KO) mouse as a model of these disorders have revealed impairments in synaptic transmission but failed to reveal defects in social behaviour, one of the core symptoms of autism. Methods We performed a detailed investigation of the behavioural effects of Nrxn1α deletion in mice bred onto a pure genetic background (C57BL/6J) to gain a better understanding of its role in neurodevelopmental disorders. Wildtype, heterozygote and homozygote Nrxn1α KO male and female mice were tested in a battery of behavioural tests (n = 9–16 per genotype, per sex). Results In homozygous Nrxn1α KO mice, we observed altered social approach, reduced social investigation, and reduced locomotor activity in novel environments. In addition, male Nrxn1α KO mice demonstrated an increase in aggressive behaviours. Conclusions These are the first experimental data that associate a deletion of Nrxn1α with alterations of social behaviour in mice. Since this represents one of the core symptom domains affected in autism spectrum disorders and schizophrenia in humans, our findings suggest that deletions within NRXN1 found in patients may be responsible for the impairments seen in social behaviours, and that the Nrxn1α KO mice are a useful model of human neurodevelopmental disorder. PMID:23840597

  5. Neurochemical imaging of Alzheimer's disease and other degenerative dementias

    International Nuclear Information System (INIS)

    Frey, K.A.; Minoshima, S.; Kuhl, D.E.

    1998-01-01

    A wide variety of neurochemical and functional imaging approaches have been applied to the study of progressive dementias, particularly Alzheimer's disease (Ad) and related disorders. Despite considerable progress in the past decade, the cause((s) of most cases of Ad remain undetermined and preventive or protective therapies are lacking. Specifically-designed imaging procedures have permitted the testing of pathophysiological hypotheses of the etiology and progression of Ad, and have yielded important insights in several areas including the potential roles of cerebral cortical cholinergic lesions, cellular inflammation, and losses of cortical synapses. From the perspective of clinical diagnosis, PET glucose metabolism imaging with use of ( 18 F)2-fluorodeoxyglucose (FDG) is the most sensitive and specific imaging modality yet identified. The overall performance of PET FDG is favorable for routine clinical evaluation of suspected Ad, and will likely gain increasing utilization in the near future. Assessments of glucose metabolism and other, specific aspects of neurochemistry in Ad will provide direct measures of therapeutic drug actions and may permit distinction of symptomatic versus disease-modifying therapies as they are developed and introduced in clinical trials

  6. Wireless Amperometric Neurochemical Monitoring Using an Integrated Telemetry Circuit

    Science.gov (United States)

    Roham, Masoud; Halpern, Jeffrey M.; Martin, Heidi B.; Chiel, Hillel J.

    2015-01-01

    An integrated circuit for wireless real-time monitoring of neurochemical activity in the nervous system is described. The chip is capable of conducting high-resolution amperometric measurements in four settings of the input current. The chip architecture includes a first-order ΔΣ modulator (ΔΣM) and a frequency-shift-keyed (FSK) voltage-controlled oscillator (VCO) operating near 433 MHz. It is fabricated using the AMI 0.5 μm double-poly triple-metal n-well CMOS process, and requires only one off-chip component for operation. Measured dc current resolutions of ~250 fA, ~1.5 pA, ~4.5 pA, and ~17 pA were achieved for input currents in the range of ±5, ±37, ±150, and ±600 nA, respectively. The chip has been interfaced with a diamond-coated, quartz-insulated, microneedle, tungsten electrode, and successfully recorded dopamine concentration levels as low as 0.5 μM wirelessly over a transmission distance of ~0.5 m in flow injection analysis experiments. PMID:18990633

  7. Wireless amperometric neurochemical monitoring using an integrated telemetry circuit.

    Science.gov (United States)

    Roham, Masoud; Halpern, Jeffrey M; Martin, Heidi B; Chiel, Hillel J; Mohseni, Pedram

    2008-11-01

    An integrated circuit for wireless real-time monitoring of neurochemical activity in the nervous system is described. The chip is capable of conducting high-resolution amperometric measurements in four settings of the input current. The chip architecture includes a first-order Delta Sigma modulator (Delta Sigma M) and a frequency-shift-keyed (FSK) voltage-controlled oscillator (VCO) operating near 433 MHz. It is fabricated using the AMI 0.5 microm double-poly triple-metal n-well CMOS process, and requires only one off-chip component for operation. Measured dc current resolutions of approximately 250 fA, approximately 1.5 pA, approximately 4.5 pA, and approximately 17 pA were achieved for input currents in the range of +/-5, +/-37, +/-150, and +/-600 nA, respectively. The chip has been interfaced with a diamond-coated, quartz-insulated, microneedle, tungsten electrode, and successfully recorded dopamine concentration levels as low as 0.5 microM wirelessly over a transmission distance of approximately 0.5 m in flow injection analysis experiments.

  8. [The neurochemistry and neuropharmacology of frontotemporal dementia].

    Science.gov (United States)

    Alonso-Navarro, H; Jabbour-Wadih, T; Ayuso-Peralta, L; Jiménez-Jiménez, F J

    To review the neurochemical features and therapeutic options for frontotemporal dementia (FTD). The main neurochemical alterations in FTD are the serotoninergic and dopamine depletion. In contrast with Alzheimer's and diffuse Lewy bodies disease, there are not significant alterations of the cholinergic system. Cerebral perfusion and glucose metabolism studies usually show hypoperfusion or hypometabolism, with predominant involvement of temporal and frontal cortices. There have been described some alterations related with oxidative stress and apoptosis, although its pathogenetic role in FTD is not well known. Treatment of FTD is not well established, because there are only a few studies with some drugs. The most studied drugs are serotonin reuptake inhibitors, however, despite the well-known serotoninergic deficiency described in FTD, the results are not conclusive. The main neurochemical alterations of FTD are serotoninergic and dopaminergic deficiencies. The treatment is not well established, although it should be theoretically ideal to use drugs which modulate these neurotransmitter systems.

  9. Individual differences in the forced swimming test and neurochemical kinetics in the rat brain.

    Science.gov (United States)

    Sequeira-Cordero, Andrey; Mora-Gallegos, Andrea; Cuenca-Berger, Patricia; Fornaguera-Trías, Jaime

    2014-04-10

    Individual differences in the forced swimming test (FST) could be associated with differential temporal dynamics of gene expression and neurotransmitter activity. We tested juvenile male rats in the FST and classified the animals into those with low and high immobility according to the amount of immobility time recorded in FST. These groups and a control group which did not undergo the FST were sacrificed either 1, 6 or 24 h after the test. We analyzed the expression of the CRF, CRFR1, BDNF and TrkB in the prefrontal cortex, hippocampus and nucleus accumbens as well as norepinephrine, dopamine, serotonin, glutamate, GABA and glutamine in the hippocampus and nucleus accumbens. Animals with low immobility showed significant reductions of BDNF expression across time points in both the prefrontal cortex and the nucleus accumbens when compared with non-swim control. Moreover, rats with high immobility only showed a significant decrease of BDNF expression in the prefrontal cortex 6h after the FST. Regarding neurotransmitters, only accumbal dopamine turnover and hippocampal glutamate content showed an effect of individual differences (i.e. animals with low and high immobility), whereas nearly all parameters showed significant differences across time points. Correlational analyses suggest that immobility in the FST, probably reflecting despair, is related to prefrontal cortical BDNF and to the kinetics observed in several other neurochemical parameters. Taken together, our results suggest that individual differences observed in depression-like behavior can be associated not only with changes in the concentrations of key neurochemical factors but also with differential time courses of such factors. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Multiple ureterolithiasis resembling steinstrasse: An unusual presentation

    Directory of Open Access Journals (Sweden)

    Praveen Kumar Pandey

    2014-12-01

    Full Text Available Steinstrasse or “stone street” is an expected complication after extracorporeal shock wave lithotripsy in patients with high stone burden. However, there are published reports of multiple ureterolithiasis resembling steinstrasse in patients with distal renal tubular acidosis. Here we report an uncommon case of a 60-year-old woman who presented with right renal calculi. Her right ureter was studded with multiple calculi up to the vesicoureteric junction. The affected right kidney was nonfunctional and was managed by nephroureterectomy.

  11. Neurochemical properties of BDNF-containing neurons projecting to rostral ventromedial medulla in the ventrolateral periaqueductal gray

    Directory of Open Access Journals (Sweden)

    Jun-Bin eYin

    2014-11-01

    Full Text Available The periaqueductal gray (PAG modulates nociception via a descending pathway that relays in the rostral ventromedial medulla (RVM and terminates in the spinal cord. Previous behavioral pharmacology and electrophysiological evidence suggests that brain-derived neurotrophic factor (BDNF plays an important role in descending pain modulation, likely through the PAG-RVM pathway. However, there still lacks detailed information on the distribution of BDNF, activation of BDNF-containing neurons projecting to RVM in the condition of pain, and neurochemical properties of these neurons within the PAG. Through fluorescent in situ hybridization (FISH and immunofluorescent staining, the homogenous distributions of BDNF mRNA and protein were observed in the four subregions of PAG. Both neurons and astrocytes expressed BDNF, but not microglias. By combining retrograde tracing methods and formalin pain model, there were more BDNF-containing neurons projecting to RVM being activated in the ventrolateral PAG (vlPAG than other subregions of PAG. The neurochemical properties of BDNF-containing projection neurons in the vlPAG were investigated. BDNF-containing projection neurons expressed auto receptor Tropomyosin-related kinase B (TrkB in addition to serotonin (5-HT, neurotensin (NT, substance P (SP, calcitonin gene related peptide (CGRP, nitric oxide synthase (NOS, and parvalbumin (PV but not tyrosine decarboxylase (TH. It is speculated that BDNF released from projection neurons in the vlPAG might participate in the descending pain modulation through enhancing the presynaptic release of other neuroactive substances (NSs in the RVM.

  12. Allergic Contact Dermatitis to Benzoyl Peroxide Resembling Impetigo.

    Science.gov (United States)

    Kim, Changhyun; Craiglow, Brittany G; Watsky, Kalman L; Antaya, Richard J

    2015-01-01

    A 17-year-old boy presented with recurring severe dermatitis of the face of 5-months duration that resembled impetigo. He had been treated with several courses of antibiotics without improvement. Biopsy showed changes consistent with allergic contact dermatitis and patch testing later revealed sensitization to benzoyl peroxide, which the patient had been using for the treatment of acne vulgaris. © 2015 Wiley Periodicals, Inc.

  13. Effects of parenting quality on adolescents' personality resemblance to their parents. The TRAILS study.

    Science.gov (United States)

    Langenhof, M Rohaa; Komdeur, Jan; Oldehinkel, Albertine J

    2016-08-01

    This study considers the development of resemblance between 741 adolescents and their biological parents, across six NEO-PI-R personality traits known to be important in psychological problems: anger-hostility, impulsiveness, vulnerability, assertiveness, excitement-seeking, and self-discipline. We modelled the association between perceived parental warmth and rejection at age eleven and personality resemblance to parents at about age sixteen. Parenting experienced during early adolescence was related to the degree and direction in which adolescents resembled their parents five years later in life. Rejection, especially from fathers, significantly predicted a smaller resemblance to both the parents. Girls were more strongly affected by parental quality than boys, and there was some indication that adolescents responded in opposite ways to parenting from mothers and fathers. This study is a first step in uncovering the complex interplay between parenting, gender, and the current generation's ability to develop personality traits independent from the previous generation. Copyright © 2016 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

  14. Neuroanatomical and Neurochemical Basis of Impulsivity

    Directory of Open Access Journals (Sweden)

    Kemal Yazici

    2010-08-01

    tis paradigm, the tendency to prefer small immediate rewards over larger, more delayed reinforcers is measured. İmpulsive choice is defined by a greater tendency to value or choose smaller, more immediate reinforcers. Impulsivity is a multi-faceted behaviour. This behaviour may be studied by subdividing it into different processes neuroanatomically and neurochemically. Neuroanatomical data support the suggestion that behavioral disinhibition (impulsive action / motoric impulsivity and delay-discounting (impulsive choice / decision making differ in the degree to which various components of frontostriatal loops are implicated in their regulation. The dorsal prefrontal cortex does not appear to be involved in mediating impulsive choice, yet does have some role in regulating inhibitory processes. In contrast, there appears to be a pronounced role for the orbitofrontal cortex and basolateral amygdala in controlling impulsive choice. Other structures, however, such as the nucleus accumbens and subthalamic nucleus may be common to both circuits. From the neurochemical perspective, dopamine system and dopamine- 2 (D2 receptors in particular, seems to be closely involved in making impulsive choice. When the noradrenaline system does not function optimally, it might contribute to increased impulsivity. Serotonin might act upon prefrontal cortex to decrease impulsive choices. Interactions between the serotonin and the dopamine systems are important in the regulation of impulsive behaviour. It is possible that various receptor subtypes of the serotonin system may exert differing and even contrasting effects on impulsive behaviour. Although it is very informative to study neurotransmitter systems separately, it should be kept in mind that there are very intimate interactions between the neurotransmitter systems mentioned above. Based on the fact that impulsivity is regulated through multiple neurotransmitters and even more receptors, one may suggest that pharmacotherapy of

  15. Stereological brain volume changes in post-weaned socially isolated rats

    DEFF Research Database (Denmark)

    Fabricius, Katrine; Helboe, Lone; Steiniger-Brach, Björn

    2010-01-01

    Rearing rats in isolation after weaning is an environmental manipulation that leads to behavioural and neurochemical alterations that resemble what is seen in schizophrenia. The model is neurodevelopmental in origin and has been used as an animal model of schizophrenia. However, only a few studies...... Lister Hooded rats isolated from postnatal day 25 for 15 weeks. We observed the expected gender differences in total brain volume with males having larger brains than females. Further, we found that isolated males had significantly smaller brains than group-housed controls and larger lateral ventricles...... than controls. However, this was not seen in female rats. Isolated males had a significant smaller hippocampus, dentate gyrus and CA2/3 where isolated females had a significant smaller CA1 compared to controls. Thus, our results indicate that long-term isolation of male rats leads to neuroanatomical...

  16. In vivo neurochemical characterization of clothianidin induced striatal dopamine release.

    Science.gov (United States)

    Faro, L R F; Oliveira, I M; Durán, R; Alfonso, M

    2012-12-16

    Clothianidin (CLO) is a neonicotinoid insecticide with selective action on nicotinic acetylcholine receptors. The aim of this study was to determine the neurochemical basis for CLO-induced striatal dopamine release using the microdialysis technique in freely moving and conscious rats. Intrastriatal administration of CLO (3.5mM), produced an increase in both spontaneous (2462 ± 627% with respect to basal values) and KCl-evoked (4672 ± 706% with respect to basal values) dopamine release. This effect was attenuated in Ca(2+)-free medium, and was prevented in reserpine pre-treated animals or in presence of tetrodotoxin (TTX). To investigate the involvement of dopamine transporter (DAT), the effect of CLO was observed in presence of nomifensine. The coadministration of CLO and nomifensine produced an additive effect on striatal dopamine release. The results suggest that the effect of CLO on striatal dopamine release is predominantly mediated by an exocytotic mechanism, Ca(2+), vesicular and TTX-dependent and not by a mechanism mediated by dopamine transporter. Published by Elsevier Ireland Ltd.

  17. Familial Resemblance in Dietary Intakes of Children, Adolescents, and Parents

    DEFF Research Database (Denmark)

    Bogl, Leonie H.; Silventoinen, Karri; Hebestreit, Antje

    2017-01-01

    Information on familial resemblance is important for the design of effective family-based interventions. We aimed to quantify familial correlations and estimate the proportion of variation attributable to genetic and shared environmental effects (i.e., familiality) for dietary intake variables an...

  18. Neurochemical metabolomics reveals disruption to sphingolipid metabolism following chronic haloperidol administration

    Science.gov (United States)

    McClay, Joseph L.; Vunck, Sarah A.; Batman, Angela M.; Crowley, James J.; Vann, Robert E.; Beardsley, Patrick M.; van den Oord, Edwin J.

    2015-01-01

    Haloperidol is an effective antipsychotic drug for treatment of schizophrenia, but prolonged use can lead to debilitating side effects. To better understand the effects of long-term administration, we measured global metabolic changes in mouse brain following 3 mg/kg/day haloperidol for 28 days. These conditions lead to movement-related side effects in mice akin to those observed in patients after prolonged use. Brain tissue was collected following microwave tissue fixation to arrest metabolism and extracted metabolites were assessed using both liquid and gas chromatography mass spectrometry (MS). Over 300 unique compounds were identified across MS platforms. Haloperidol was found to be present in all test samples and not in controls, indicating experimental validity. Twenty-one compounds differed significantly between test and control groups at the p haloperidol-treated mice (p = 0.004), a marker previously associated with demyelination. This study further demonstrates the utility of murine neurochemical metabolomics as a method to advance understanding of CNS drug effects. PMID:25850894

  19. Impact of oral supplementation of Glutamate and GABA on memory performance and neurochemical profile in hippocampus of rats.

    Science.gov (United States)

    Tabassum, Saiqa; Ahmad, Saara; Madiha, Syeda; Khaliq, Saima; Shahzad, Sidrah; Batool, Zehra; Haider, Saida

    2017-05-01

    Glutamate (GLU) and gamma-amino butyric acid (GABA) are essential amino acids (AA) for brain function serving as excitatory and inhibitory neurotransmitter respectively. Their tablets are available in market for improving gut function and muscle performance. Despite of having a major role during memory formation and processing, effects of these tablets on brain functioning like learning and memory have not been investigated. Therefore, present study is aimed to investigate the effects of orally supplemented GLU and GABA on learning and memory performance and further to monitor related effects of these orally supplemented GLU and GABA on brain levels of these AA. Three groups of rats were supplemented orally with drinking water (control group) or suspension of tablets of GABA and Glutamate, respectively for four weeks. Cognitive performance was determined using behavioral tests (Novel object recognition test, Morris water maze, Passive avoidance test) measuring recognition, spatial reference and aversive memory. Levels of GLU, GABA and acetylcholine (ACh) were estimated in rat hippocampus. Results showed that chronic oral administration of GLU and GABA tablets has a significant impact on brain function and can alter GLU and GABA content in rat hippocampus. Compared to GABA, GLU supplementation specifically enhances memory performance via increasing ACh. Thus, GLU can be suggested as a useful supplement for improving learning and memory performance and neurochemical status of brain and in future could be effective in the treatment of neurological disorders affecting learning and memory performance.

  20. SU-F-I-68: Longitudinal Neurochemical Changes On Rat Prefrontal Cortex of Single Prolonged Stress Model by Using Proton Magnetic Resonance Spectroscopy at 9.4T

    International Nuclear Information System (INIS)

    Lim, S-I; Yoo, C-H; Song, K-H; Choe, B-Y; Woo, D-C

    2016-01-01

    Purpose: Single prolonged stress (SPS) is an animal model of posttraumatic stress disorder (PTSD). However, it has not been known how PTSD develops from the first exposure to traumatic events and neurochemical differences between acute/single stress and PTSD-triggering stress. Therefore, the object of this study is to determine time-dependent neurochemical changes in prefrontal cortex (PFC) of rats using in vivo proton magnetic resonance spectroscopy (1H-MRS). Methods: Male Sprague-Dawley rats (n=14; body weight=200–220g) were used. The SPS protocol was used in this study. Rats were restrained for 2h and then immediately forced to swim for 20min in water (20–24 Celsius). After a 15-min recuperation period, rats were exposed to ether (using a desiccator) until general anesthesia occurred (<5min). In vivo proton MRS was performed 30min before the SPS (Base), approximately 10min after the SPS (D+0), 3 (D+3) and 7 (D+7) days after SPS to investigate time-dependent changes on metabolites levels in the PFC. Acquisition of in vivo MRS spectra and MRI was conducted at the four time points using 9.4 T Agilent Scanner. Concentration of metabolites was quantified by LCModel. Results: Statistical significance was analyzed using one-way ANOVA with post hoc Tukey HSD tests to assess the metabolite changes in the PFC. The SPS resulted in significant stress-induced differences for 7 days in glutamine (F(3,52)=6.750, P=0.001), choline-containing compounds (F(3,52)=16.442, P=0.000), glutamine/glutamate concentrations (F(3,52)=7.352, P=0.000). Conclusion: PTSD in human is associated with decreased neuronal activity in the PFC. In this study, SPS altered total choline, glutamine levels but not NAA levels in the PFC of the rats. Therefore, for the three stressors and quiescent period of seven days, SPS attenuated excitatory tone and membrane turnover but did not affect neural integrity in the PFC.

  1. SU-F-I-68: Longitudinal Neurochemical Changes On Rat Prefrontal Cortex of Single Prolonged Stress Model by Using Proton Magnetic Resonance Spectroscopy at 9.4T

    Energy Technology Data Exchange (ETDEWEB)

    Lim, S-I; Yoo, C-H [Department of Biomedical Engineering, and Research Institute of Biomedical Engineering, The Catholic University of Korea College of Medicine, Seoul, Seoul (Korea, Republic of); Asan Institute for Life Sciences, Asan Medical Center, Seoul, Seoul (Korea, Republic of); Song, K-H; Choe, B-Y [Department of Biomedical Engineering, and Research Institute of Biomedical Engineering, The Catholic University of Korea College of Medicine, Seoul, Seoul (Korea, Republic of); Woo, D-C [Asan Institute for Life Sciences, Asan Medical Center, Seoul, Seoul (Korea, Republic of)

    2016-06-15

    Purpose: Single prolonged stress (SPS) is an animal model of posttraumatic stress disorder (PTSD). However, it has not been known how PTSD develops from the first exposure to traumatic events and neurochemical differences between acute/single stress and PTSD-triggering stress. Therefore, the object of this study is to determine time-dependent neurochemical changes in prefrontal cortex (PFC) of rats using in vivo proton magnetic resonance spectroscopy (1H-MRS). Methods: Male Sprague-Dawley rats (n=14; body weight=200–220g) were used. The SPS protocol was used in this study. Rats were restrained for 2h and then immediately forced to swim for 20min in water (20–24 Celsius). After a 15-min recuperation period, rats were exposed to ether (using a desiccator) until general anesthesia occurred (<5min). In vivo proton MRS was performed 30min before the SPS (Base), approximately 10min after the SPS (D+0), 3 (D+3) and 7 (D+7) days after SPS to investigate time-dependent changes on metabolites levels in the PFC. Acquisition of in vivo MRS spectra and MRI was conducted at the four time points using 9.4 T Agilent Scanner. Concentration of metabolites was quantified by LCModel. Results: Statistical significance was analyzed using one-way ANOVA with post hoc Tukey HSD tests to assess the metabolite changes in the PFC. The SPS resulted in significant stress-induced differences for 7 days in glutamine (F(3,52)=6.750, P=0.001), choline-containing compounds (F(3,52)=16.442, P=0.000), glutamine/glutamate concentrations (F(3,52)=7.352, P=0.000). Conclusion: PTSD in human is associated with decreased neuronal activity in the PFC. In this study, SPS altered total choline, glutamine levels but not NAA levels in the PFC of the rats. Therefore, for the three stressors and quiescent period of seven days, SPS attenuated excitatory tone and membrane turnover but did not affect neural integrity in the PFC.

  2. Archaic artifacts resembling celestial spheres

    Science.gov (United States)

    Dimitrakoudis, S.; Papaspyrou, P.; Petoussis, V.; Moussas, X.

    We present several bronze artifacts from the Archaic Age in Greece (750-480 BC) that resemble celestial spheres or forms of other astronomical significance. They are studied in the context of the Dark Age transition from Mycenaean Age astronomical themes to the philosophical and practical revival of astronomy in the Classical Age with its plethora of astronomical devices. These artifacts, mostly votive in nature are spherical in shape and appear in a variety of forms their most striking characteristic being the depiction of meridians and/or an equator. Most of those artifacts come from Thessaly, and more specifically from the temple of Itonia Athena at Philia, a religious center of pan-Hellenic significance. Celestial spheres, similar in form to the small artifacts presented in this study, could be used to measure latitudes, or estimate the time at a known place, and were thus very useful in navigation.

  3. Partners in health? Exploring resemblance in health between partners in married and cohabiting couples.

    Science.gov (United States)

    Monden, Christiaan

    2007-04-01

    Sociological theories on family formation and families and health suggest that married and cohabiting partners will resemble each other in health status, positively or negatively. The family is often seen as a health-enhancing agent for individuals. However, there are large health differences among families. This study aims to answer the question whether it is the case that the healthy live with the healthy and individuals with poor health have partners who are also in poor health. Moreover, it examines whether resemblance in health is a consequence of partner choice--educational homogamy in particular--behaviour or shared circumstances. Younger and older couples are compared to investigate whether health resemblance increases over the lifecourse. Analyses of a nationally representative sample of almost 12,000 Dutch couples show that partners are indeed significantly alike with regard to several health indicators. Respondents whose partner reports poor health are almost three times more likely to report poor health than respondents whose partner is in good health. There is a strong accumulation of health problems within households. Partner selection with regard to education causes part of the partner resemblance in health. Less support is found for the hypotheses that risk behaviour, mutual influence or the effects of shared circumstances cause similarity between partners' health status. Surprisingly, partners in older couples, who have been together for a longer time, do not resemble each other significantly more than partners in younger couples. The implications of these findings for sociological theory and social inequalities in health are discussed.

  4. The Texas Adoption Project: adopted children and their intellectual resemblance to biological and adoptive parents.

    Science.gov (United States)

    Horn, J M

    1983-04-01

    Intelligence test scores were obtained from parents and children in 300 adoptive families and compared with similar measures available for the biological mothers of the same adopted children. Results supported the hypothesis that genetic variability is an important influence in the development of individual differences for intelligence. The most salient finding was that adopted children resemble their biological mothers more than they resemble the adoptive parents who reared them from birth. A small subset of the oldest adopted children did not resemble their biological mothers. The suggestion that the influence of genes declines with age is treated with caution since other adoption studies report a trend in the opposite direction.

  5. Acute paretic syndrome in juvenile White Leghorn chickens resembles late stages of acute inflammatory demyelinating polyneuropathies in humans

    Directory of Open Access Journals (Sweden)

    Preisinger Rudolf

    2010-01-01

    Full Text Available Abstract Background Sudden limb paresis is a common problem in White Leghorn flocks, affecting about 1% of the chicken population before achievement of sexual maturity. Previously, a similar clinical syndrome has been reported as being caused by inflammatory demyelination of peripheral nerve fibres. Here, we investigated in detail the immunopathology of this paretic syndrome and its possible resemblance to human neuropathies. Methods Neurologically affected chickens and control animals from one single flock underwent clinical and neuropathological examination. Peripheral nervous system (PNS alterations were characterised using standard morphological techniques, including nerve fibre teasing and transmission electron microscopy. Infiltrating cells were phenotyped immunohistologically and quantified by flow cytometry. The cytokine expression pattern was assessed by quantitative real-time PCR (qRT-PCR. These investigations were accomplished by MHC genotyping and a PCR screen for Marek's disease virus (MDV. Results Spontaneous paresis of White Leghorns is caused by cell-mediated, inflammatory demyelination affecting multiple cranial and spinal nerves and nerve roots with a proximodistal tapering. Clinical manifestation coincides with the employment of humoral immune mechanisms, enrolling plasma cell recruitment, deposition of myelin-bound IgG and antibody-dependent macrophageal myelin-stripping. Disease development was significantly linked to a 539 bp microsatellite in MHC locus LEI0258. An aetiological role for MDV was excluded. Conclusions The paretic phase of avian inflammatory demyelinating polyradiculoneuritis immunobiologically resembles the late-acute disease stages of human acute inflammatory demyelinating polyneuropathy, and is characterised by a Th1-to-Th2 shift.

  6. The challenge of unravelling family resemblance related to illness behaviour.

    NARCIS (Netherlands)

    Cardol, M.; Groenewegen, P.P.; Spreeuwenberg, P.; Dijk, L. van; Bosch, W. van den; Bakker, D.H. de

    2005-01-01

    Background: Efforts to promote health or prevent disease may conflict with patients’ habits at home. Irrespective of the national setting, families are important social contexts in which illness occurs and resolves. Family members resemble each other in their illness behaviour, even across

  7. Chronic choline supplementation improves cognitive and motor performance via modulating oxidative and neurochemical status in rats.

    Science.gov (United States)

    Tabassum, Saiqa; Haider, Saida; Ahmad, Saara; Madiha, Syeda; Parveen, Tahira

    2017-08-01

    Choline, an essential nutrient, accounts for multiple functions in the body and brain. While its beneficial effects on healthy adults are not clear, choline supplementation is important during pregnancy for brain development, in elderly patients for support of cognitive performance and in patients with neurological disorders to reduce memory deficits. Thus, the aim of this study is to investigate whether choline administration in healthy adult rats beneficially impacts cognitive and locomotor performance, and associated oxidative and neurochemical outcomes. Two groups, control and choline, received tap water and choline bitartrate, respectively at the dose equivalent to adequate intake for five weeks. Food intake and body weight were monitored daily. Behavioral analysis comprising assessment of cognitive performance (by novel object recognition, passive avoidance and Morris Water Maze test) and locomotor performance (by Open field, Kondziela's inverted screen and beam walking test) were performed. Following testing, rats were decapitated and brain samples were collected for estimation of acetylcholine, redox profile and monoamine measurements. The results showed that chronic choline administration significantly improves cognitive and locomotor performance accompanied by a reduction in oxidative stress, enhanced cholinergic neurotransmission and monoamine levels in the brain of healthy adult rats. Hence, chronic choline intake was found to improve behavioral, oxidative and neurochemical outcomes in the normal population, so it can be suggested that choline tablets can be used as a safe and effective supplement for improving the neurological health of normal individuals and that they might also be beneficial in preventing cognitive and motor disorders later in life. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Paradoxical sleep deprivation: neurochemical, hormonal and behavioral alterations. Evidence from 30 years of research

    Directory of Open Access Journals (Sweden)

    Sergio Tufik

    2009-09-01

    Full Text Available Sleep comprises approximately one-third of a person's lifetime, but its impact on health and medical conditions remains partially unrecognized. The prevalence of sleep disorders is increasing in modern societies, with significant repercussions on people's well-being. This article reviews past and current literature on the paradoxical sleep deprivation method as well as data on its consequences to animals, ranging from behavioral changes to alterations in the gene expression. More specifically, we highlight relevant experimental studies and our group's contribution over the last three decades.O sono ocupa cerca de um terço de nossas vidas, entretanto seu impacto na saúde e sua influência nas condições patológicas ainda não foi completamente elucidado. A prevalência dos distúrbios de sono é cada vez maior, sobretudo nas regiões mais industrializadas, repercutindo diretamente no bem-estar da população. Este artigo tem como objetivo sintetizar e atualizar a literatura a respeito do método de privação de sono paradoxal e seu panorama de conseqüências desde comportamentais até genéticas em animais. Ainda, destacamos a contribuição e relevância dos estudos experimentais realizados por nosso grupo nas ultimas três décadas.

  9. Altered depression-related behavior and neurochemical changes in serotonergic neurons in mutant R406W human tau transgenic mice.

    Science.gov (United States)

    Egashira, Nobuaki; Iwasaki, Katsunori; Takashima, Akihiko; Watanabe, Takuya; Kawabe, Hideyuki; Matsuda, Tomomi; Mishima, Kenichi; Chidori, Shozo; Nishimura, Ryoji; Fujiwara, Michihiro

    2005-10-12

    Mutant R406W human tau was originally identified in frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) and causes a hereditary tauopathy that clinically resembles Alzheimer's disease (AD). In the current study, we examined the performance of R406W transgenic (Tg) mice in the forced swimming test, a test with high predictivity of antidepressant efficacy in human depression, and found an enhancement of the immobility time. In contrast, the motor function and anxiety-related emotional response of R406W Tg mice were normal. Furthermore, a selective serotonin reuptake inhibitor (SSRI), fluvoxamine (100 mg/kg, p.o.), significantly reduced this enhancement of the immobility time, whereas a noradrenaline reuptake inhibitor, desipramine, had no effect. In an in vivo microdialysis study, R406W Tg mice exhibited a significantly decreased extracellular 5-hydroxyindoleacetic acid (5-HIAA) level in the frontal cortex and also exhibited a tendency toward a decreased extracellular 5-hydroxytryptamine (5-HT) level. Moreover, fluvoxamine, which reduced the enhancement of the immobility time, significantly increased the extracellular 5-HT level in R406W Tg mice. These results suggest that R406W Tg mice exhibit changes in depression-related behavior involving serotonergic neurons and provide an animal model for investigating AD with depression.

  10. Traumatic funicular phlebitis of the thoracic wall resembling Mondor's disease: a case report

    Directory of Open Access Journals (Sweden)

    Kondo Takeshi

    2011-03-01

    Full Text Available Abstract Introduction Mondor's disease is a peculiar form of thrombophlebitis, involving a superficial vein in the subcutaneous fat of the breast or anterior chest wall. Case presentation The author presents a case of a 35-year-old male Japanese patient with cord-like induration in the right lateral thoracic wall. This lesion was diagnosed as traumatic funicular phlebitis, resembling Mondor's disease. Conclusion Traumatic funicular phlebitis, resembling Mondor's disease, is a clinical entity which may give suggestive insight to the etiology of Mondor's disease itself.

  11. Biochanin-A ameliorates behavioural and neurochemical derangements in cognitive-deficit mice for the betterment of Alzheimer's disease.

    Science.gov (United States)

    Biradar, S M; Joshi, H; Chheda, T K

    2014-04-01

    Biochanin-A (BCA), a potent phytoconstituent, has been previously used as an antitumour, a dopaminergic neuron protective agent, an antioxidant, an anticholinergic and on other pharmacological activities including neuroprotection. The present study was aimed to evaluate the behavioural and neurochemical evidence of BCA in cognitive-deficit mice in scopolamine challenged and natural aged-induced amnesia models in young and aged mice, respectively. BCA has exhibited decrease in the transfer latency and increase in step through latency significantly (p 0.05), BCA 10 mg kg(-1) (p betterment of Alzheimer's disease.

  12. RESEMBLANCE OF INDIRECTNESS IN POLITENESS OF EFL LEARNERS’ REQUEST REALIZATIONS

    Directory of Open Access Journals (Sweden)

    Indawan Syahri

    2013-07-01

    Full Text Available Abstract: Politeness principles are universally utilized by the speakers of any language when realizing various speech acts. However, the speakers of particular languages relatively apply politeness due to the cultural norms embedded. The present study attempts to delineate how the Indonesian learners of English (ILE apply the politeness principles in request realizations. Specifically it devotes to the types of politeness strategies applied and resemblance of the indirectness in politeness strategies in requesting acts. The FTAs and indirectness are the theoretical bases used to trace the typologies of both politeness and request strategies. The data werere collected by means of certain elicitation techniques, i.e. DCTs and Role-plays. The analyses werere done through three stages; determining request strategies, politeness strategies, and resemblance of indirectness in politeness. The results show that the indirectness generally is parallel to politeness. Besides, some pragmatic transfers are found in terms of applying native-culture norms in realizing target speech acts.

  13. Indication Of Hydrothermal Alteration Activities Based On Petrography Of Volcanic Rocks In Abang Komba Submarine Volcano, East Flores Sea

    OpenAIRE

    Sarmili, Lili; Hutabarat, Johanes

    2014-01-01

    The presence of mineral alteration or secondary processes to rocks on submarine volcano of Abang Komba was caused by an introduction of hydrothermal solutions. Those are indicated by the presence of a resembly of minerals alteration seen in their petrographic analyses. They are characterized by replacement partially surrounding of plagioclase phenocrysts, partially replacing plagioclase by sericite, carbonate and clay minerals. The replacement of pyroxene partly by chlorite, and the presence ...

  14. Rapid sensing of l-leucine by human and murine hypothalamic neurons: Neurochemical and mechanistic insights.

    Science.gov (United States)

    Heeley, Nicholas; Kirwan, Peter; Darwish, Tamana; Arnaud, Marion; Evans, Mark L; Merkle, Florian T; Reimann, Frank; Gribble, Fiona M; Blouet, Clemence

    2018-04-01

    Dietary proteins are sensed by hypothalamic neurons and strongly influence multiple aspects of metabolic health, including appetite, weight gain, and adiposity. However, little is known about the mechanisms by which hypothalamic neural circuits controlling behavior and metabolism sense protein availability. The aim of this study is to characterize how neurons from the mediobasal hypothalamus respond to a signal of protein availability: the amino acid l-leucine. We used primary cultures of post-weaning murine mediobasal hypothalamic neurons, hypothalamic neurons derived from human induced pluripotent stem cells, and calcium imaging to characterize rapid neuronal responses to physiological changes in extracellular l-Leucine concentration. A neurochemically diverse subset of both mouse and human hypothalamic neurons responded rapidly to l-leucine. Consistent with l-leucine's anorexigenic role, we found that 25% of mouse MBH POMC neurons were activated by l-leucine. 10% of MBH NPY neurons were inhibited by l-leucine, and leucine rapidly reduced AGRP secretion, providing a mechanism for the rapid leucine-induced inhibition of foraging behavior in rodents. Surprisingly, none of the candidate mechanisms previously implicated in hypothalamic leucine sensing (K ATP channels, mTORC1 signaling, amino-acid decarboxylation) were involved in the acute activity changes produced by l-leucine. Instead, our data indicate that leucine-induced neuronal activation involves a plasma membrane Ca 2+ channel, whereas leucine-induced neuronal inhibition is mediated by inhibition of a store-operated Ca 2+ current. A subset of neurons in the mediobasal hypothalamus rapidly respond to physiological changes in extracellular leucine concentration. Leucine can produce both increases and decreases in neuronal Ca 2+ concentrations in a neurochemically-diverse group of neurons, including some POMC and NPY/AGRP neurons. Our data reveal that leucine can signal through novel mechanisms to rapidly

  15. Voxel Scale Complex Networks of Functional Connectivity in the Rat Brain: Neurochemical State Dependence of Global and Local Topological Properties

    Directory of Open Access Journals (Sweden)

    Adam J. Schwarz

    2012-01-01

    Full Text Available Network analysis of functional imaging data reveals emergent features of the brain as a function of its topological properties. However, the brain is not a homogeneous network, and the dependence of functional connectivity parameters on neuroanatomical substrate and parcellation scale is a key issue. Moreover, the extent to which these topological properties depend on underlying neurochemical changes remains unclear. In the present study, we investigated both global statistical properties and the local, voxel-scale distribution of connectivity parameters of the rat brain. Different neurotransmitter systems were stimulated by pharmacological challenge (d-amphetamine, fluoxetine, and nicotine to discriminate between stimulus-specific functional connectivity and more general features of the rat brain architecture. Although global connectivity parameters were similar, mapping of local connectivity parameters at high spatial resolution revealed strong neuroanatomical dependence of functional connectivity in the rat brain, with clear differentiation between the neocortex and older brain regions. Localized foci of high functional connectivity independent of drug challenge were found in the sensorimotor cortices, consistent with the high neuronal connectivity in these regions. Conversely, the topological properties and node roles in subcortical regions varied with neurochemical state and were dependent on the specific dynamics of the different functional processes elicited.

  16. Ca-Fe and Alkali-Halide Alteration of an Allende Type B CAI: Aqueous Alteration in Nebular or Asteroidal Settings

    Science.gov (United States)

    Ross, D. K.; Simon, J. I.; Simon, S. B.; Grossman, L.

    2012-01-01

    Ca-Fe and alkali-halide alteration of CAIs is often attributed to aqueous alteration by fluids circulating on asteroidal parent bodies after the various chondritic components have been assembled, although debate continues about the roles of asteroidal vs. nebular modification processes [1-7]. Here we report de-tailed observations of alteration products in a large Type B2 CAI, TS4 from Allende, one of the oxidized subgroup of CV3s, and propose a speculative model for aqueous alteration of CAIs in a nebular setting. Ca-Fe alteration in this CAI consists predominantly of end-member hedenbergite, end-member andradite, and compositionally variable, magnesian high-Ca pyroxene. These phases are strongly concentrated in an unusual "nodule" enclosed within the interior of the CAI (Fig. 1). The Ca, Fe-rich nodule superficially resembles a clast that pre-dated and was engulfed by the CAI, but closer inspection shows that relic spinel grains are enclosed in the nodule, and corroded CAI primary phases interfinger with the Fe-rich phases at the nodule s margins. This CAI also contains abundant sodalite and nepheline (alkali-halide) alteration that occurs around the rims of the CAI, but also penetrates more deeply into the CAI. The two types of alteration (Ca-Fe and alkali-halide) are adjacent, and very fine-grained Fe-rich phases are associated with sodalite-rich regions. Both types of alteration appear to be replacive; if that is true, it would require substantial introduction of Fe, and transport of elements (Ti, Al and Mg) out of the nodule, and introduction of Na and Cl into alkali-halide rich zones. Parts of the CAI have been extensively metasomatized.

  17. Spontaneous de novo vaginal adenosis resembling Bartholin’s ...

    African Journals Online (AJOL)

    Adebayo Alade Adewole

    Spontaneous de novo vaginal adenosis resembling Bartholin's cyst: A case report ... 6 by 5 cm. The cervix, uterus, adnexa and Pouch of Douglas (POD) were normal. .... of vaginal cancer.2–4 Although, DES exposed daughters have an.

  18. Changes in neurochemicals within the ventrolateral medullary respiratory column in awake goats after carotid body denervation

    Science.gov (United States)

    Miller, Justin Robert; Neumueller, Suzanne; Muere, Clarissa; Olesiak, Samantha; Pan, Lawrence; Hodges, Matthew R.

    2013-01-01

    A current and major unanswered question is why the highly sensitive central CO2/H+ chemoreceptors do not prevent hypoventilation-induced hypercapnia following carotid body denervation (CBD). Because perturbations involving the carotid bodies affect central neuromodulator and/or neurotransmitter levels within the respiratory network, we tested the hypothesis that after CBD there is an increase in inhibitory and/or a decrease in excitatory neurochemicals within the ventrolateral medullary column (VMC) in awake goats. Microtubules for chronic use were implanted bilaterally in the VMC within or near the pre-Bötzinger Complex (preBötC) through which mock cerebrospinal fluid (mCSF) was dialyzed. Effluent mCSF was collected and analyzed for neurochemical content. The goats hypoventilated (peak +22.3 ± 3.4 mmHg PaCO2) and exhibited a reduced CO2 chemoreflex (nadir, 34.8 ± 7.4% of control ΔV̇E/ΔPaCO2) after CBD with significant but limited recovery over 30 days post-CBD. After CBD, GABA and glycine were above pre-CBD levels (266 ± 29% and 189 ± 25% of pre-CBD; P 0.05) different from control after CBD. Analyses of brainstem tissues collected 30 days after CBD exhibited 1) a midline raphe-specific reduction (P < 0.05) in the percentage of tryptophan hydroxylase–expressing neurons, and 2) a reduction (P < 0.05) in serotonin transporter density in five medullary respiratory nuclei. We conclude that after CBD, an increase in inhibitory neurotransmitters and a decrease in excitatory neuromodulation within the VMC/preBötC likely contribute to the hypoventilation and attenuated ventilatory CO2 chemoreflex. PMID:23869058

  19. Omega-3 Fatty Acid Deficient Male Rats Exhibit Abnormal Behavioral Activation in the Forced Swim Test Following Chronic Fluoxetine Treatment: Association with Altered 5-HT1A and Alpha2A Adrenergic Receptor Expression

    OpenAIRE

    Able, Jessica A.; Liu, Yanhong; Jandacek, Ronald; Rider, Therese; Tso, Patrick; McNamara, Robert K.

    2013-01-01

    Omega-3 fatty acid deficiency during development leads to enduing alterations in central monoamine neurotransmission in rat brain. Here we investigated the effects of omega-3 fatty acid deficiency on behavioral and neurochemical responses to chronic fluoxetine (FLX) treatment. Male rats were fed diets with (CON, n=34) or without (DEF, n=30) the omega-3 fatty acid precursor alpha-linolenic acid (ALA) during peri-adolescent development (P21-P90). A subset of CON (n=14) and DEF (n=12) rats were ...

  20. MRI findings of uterine tumor resembling ovarian sex-cord tumor: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Sung Hwan; Kim, Hee Jin; Han, Hyun Young; Hwang, In Taek; Kim, Ju Heon; Lee, Seung Yeon [Eulji University Hospital, Eulji University School of Medicine, Daejeon (Korea, Republic of)

    2017-04-15

    Uterine tumor resembling ovarian sex-cord tumor is a very rare uterine neoplasm that was first described by Clement and Scully in 1976. Since then, approximately 70 cases have been reported. However, these case reports have mainly described and discussed the pathologic and clinical features, and few radiologic findings have been presented. We experienced a case of a uterine tumor resembling ovarian sex-cord tumor, which was considered a uterine leiomyoma or leiomyosarcoma upon initial impression at preoperative evaluation including transvaginal ultrasonography and pelvic magnetic resonance imaging. Its diagnosis was pathologically confirmed after total abdominal hysterectomy.

  1. Anabolic steroids alter the physiological activity of aggression circuits in the lateral anterior hypothalamus.

    Science.gov (United States)

    Morrison, T R; Sikes, R W; Melloni, R H

    2016-02-19

    Syrian hamsters exposed to anabolic/androgenic steroids (AAS) during adolescence consistently show increased aggressive behavior across studies. Although the behavioral and anatomical profiles of AAS-induced alterations have been well characterized, there is a lack of data describing physiological changes that accompany these alterations. For instance, behavioral pharmacology and neuroanatomical studies show that AAS-induced changes in the vasopressin (AVP) neural system within the latero-anterior hypothalamus (LAH) interact with the serotonin (5HT) and dopamine (DA) systems to modulate aggression. To characterize the electrophysiological profile of the AAS aggression circuit, we recorded LAH neurons in adolescent male hamsters in vivo and microiontophoretically applied agonists and antagonists of aggressive behavior. The interspike interval (ISI) of neurons from AAS-treated animals correlated positively with aggressive behaviors, and adolescent AAS exposure altered parameters of activity in regular firing neurons while also changing the proportion of neuron types (i.e., bursting, regular, irregular). AAS-treated animals had more responsive neurons that were excited by AVP application, while cells from control animals showed the opposite effect and were predominantly inhibited by AVP. Both DA D2 antagonists and 5HT increased the firing frequency of AVP-responsive cells from AAS animals and dual application of AVP and D2 antagonists doubled the excitatory effect of AVP or D2 antagonist administration alone. These data suggest that multiple DA circuits in the LAH modulate AAS-induced aggressive responding. More broadly, these data show that multiple neurochemical interactions at the neurophysiological level are altered by adolescent AAS exposure. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  2. Resemblances of Parents and Twins in Sport Participation and Heart Rate

    NARCIS (Netherlands)

    Boomsma, D.I.; van den Bree, M.B.; Orlebeke, J.F.; Molenaar, P.C.M.

    1989-01-01

    A model to analyze resemblances of twins and parents using LISREL is outlined and applied to sports participation and heart-rate data. Sports participation and heart rate were measured in 44 monozygotic and 46 dizygotic adolescent twin pairs and in their parents. Genetic factors influence variation

  3. Brain Metabolism Alterations Induced by Pregnancy Swimming Decreases Neurological Impairments Following Neonatal Hypoxia-Ischemia in Very Immature Rats

    Directory of Open Access Journals (Sweden)

    Eduardo F. Sanches

    2018-06-01

    Full Text Available Introduction: Prematurity, through brain injury and altered development is a major cause of neurological impairments and can result in motor, cognitive and behavioral deficits later in life. Presently, there are no well-established effective therapies for preterm brain injury and the search for new strategies is needed. Intra-uterine environment plays a decisive role in brain maturation and interventions using the gestational window have been shown to influence long-term health in the offspring. In this study, we investigated whether pregnancy swimming can prevent the neurochemical metabolic alterations and damage that result from postnatal hypoxic-ischemic brain injury (HI in very immature rats.Methods: Female pregnant Wistar rats were divided into swimming (SW or sedentary (SE groups. Following a period of adaptation before mating, swimming was performed during the entire gestation. At postnatal day (PND3, rat pups from SW and SE dams had right common carotid artery occluded, followed by systemic hypoxia. At PND4 (24 h after HI, the early neurochemical profile was measured by 1H-magnetic resonance spectroscopy. Astrogliosis, apoptosis and neurotrophins protein expression were assessed in the cortex and hippocampus. From PND45, behavioral testing was performed. Diffusion tensor imaging and neurite orientation dispersion and density imaging were used to evaluate brain microstructure and the levels of proteins were quantified.Results: Pregnancy swimming was able to prevent early metabolic changes induced by HI preserving the energetic balance, decreasing apoptotic cell death and astrogliosis as well as maintaining the levels of neurotrophins. At adult age, swimming preserved brain microstructure and improved the performance in the behavioral tests.Conclusion: Our study points out that swimming during gestation in rats could prevent prematurity related brain damage in progeny with high translational potential and possibly interesting cost

  4. [Motivation and Emotional States: Structural Systemic, Neurochemical, Molecular and Cellular Mechanisms].

    Science.gov (United States)

    Bazyan, A S

    2016-01-01

    The structural, systemic, neurochemical, molecular and cellular mechanisms of organization and coding motivation and emotional states are describe. The GABA and glutamatergic synaptic systems of basal ganglia form a neural network and participate in the implementation of voluntary behavior. Neuropeptides, neurohormones and paracrine neuromodulators involved in the organization of motivation and emotional states, integrated with synaptic systems, controlled by neural networks and organizing goal-directed behavior. Structural centers for united and integrated of information in voluntary and goal-directed behavior are globus pallidus. Substantia nigra pars reticulata switches the information from corticobasal networks to thalamocortical networks, induces global dopaminergic (DA) signal and organize interaction of mesolimbic and nigostriatnoy DA systems controlled by prefrontal and motor cortex. Together with the motor cortex, substantia nigra displays information in the brainstem and spinal cord to implementation of behavior. Motivation states are formed in the interaction of neurohormonal and neuropeptide systems by monoaminergic systems of brain. Emotional states are formed by monoaminergic systems of the mid-brain, where the leading role belongs to the mesolimbic DA system. The emotional and motivation state of the encoded specific epigenetic molecular and chemical pattern of neuron.

  5. Family environment, not heredity, accounts for family resemblances in food preferences and attitudes: a twin study.

    Science.gov (United States)

    Rozin, P; Millman, L

    1987-04-01

    Monozygotic and same-sex dizygotic twin pairs reported on their food preferences, the variety of foods of the same general category (e.g. types of soup) in their diet, and their concern about contact of their food with disgusting or other unacceptable substances (contamination sensitivity). Although there was substantial resemblance between siblings for many of these items, there was no clear evidence for a heritable component on any item. The only case for which there was an interpretable and significantly greater resemblance among monozygotic than among dizygotic twins (out of 23 questions) was preferred degree of hotness resulting from chili pepper in foods. These results confirm the prediction that in omnivorous animals, such as humans, genetic predispositions will be minimal with respect to food. The modest sibling resemblances on a number of measures are primarily attributable to a shared environment.

  6. Mice deficient in transmembrane prostatic acid phosphatase display increased GABAergic transmission and neurological alterations.

    Directory of Open Access Journals (Sweden)

    Heidi O Nousiainen

    Full Text Available Prostatic acid phosphatase (PAP, the first diagnostic marker and present therapeutic target for prostate cancer, modulates nociception at the dorsal root ganglia (DRG, but its function in the central nervous system has remained unknown. We studied expression and function of TMPAP (the transmembrane isoform of PAP in the brain by utilizing mice deficient in TMPAP (PAP-/- mice. Here we report that TMPAP is expressed in a subpopulation of cerebral GABAergic neurons, and mice deficient in TMPAP show multiple behavioral and neurochemical features linked to hyperdopaminergic dysregulation and altered GABAergic transmission. In addition to increased anxiety, disturbed prepulse inhibition, increased synthesis of striatal dopamine, and augmented response to amphetamine, PAP-deficient mice have enlarged lateral ventricles, reduced diazepam-induced loss of righting reflex, and increased GABAergic tone in the hippocampus. TMPAP in the mouse brain is localized presynaptically, and colocalized with SNARE-associated protein snapin, a protein involved in synaptic vesicle docking and fusion, and PAP-deficient mice display altered subcellular distribution of snapin. We have previously shown TMPAP to reside in prostatic exosomes and we propose that TMPAP is involved in the control of GABAergic tone in the brain also through exocytosis, and that PAP deficiency produces a distinct neurological phenotype.

  7. Region-specific aging of the human brain as evidenced by neurochemical profiles measured noninvasively in the posterior cingulate cortex and the occipital lobe using 1H magnetic resonance spectroscopy at 7 T.

    Science.gov (United States)

    Marjańska, Małgorzata; McCarten, J Riley; Hodges, James; Hemmy, Laura S; Grant, Andrea; Deelchand, Dinesh K; Terpstra, Melissa

    2017-06-23

    The concentrations of fourteen neurochemicals associated with metabolism, neurotransmission, antioxidant capacity, and cellular structure were measured noninvasively from two distinct brain regions using 1 H magnetic resonance spectroscopy. Seventeen young adults (age 19-22years) and sixteen cognitively normal older adults (age 70-88years) were scanned. To increase sensitivity and specificity, 1 H magnetic resonance spectra were obtained at the ultra-high field of 7T and at ultra-short echo time. The concentrations of neurochemicals were determined using water as an internal reference and accounting for gray matter, white matter, and cerebrospinal fluid content of the volume of interest. In the posterior cingulate cortex (PCC), the concentrations of neurochemicals associated with energy (i.e., creatine plus phosphocreatine), membrane turnover (i.e., choline containing compounds), and gliosis (i.e., myo-inositol) were higher in the older adults while the concentrations of N-acetylaspartylglutamate (NAAG) and phosphorylethanolamine (PE) were lower. In the occipital cortex (OCC), the concentration of N-acetylaspartate (NAA), a marker of neuronal viability, concentrations of the neurotransmitters Glu and NAAG, antioxidant ascorbate (Asc), and PE were lower in the older adults while the concentration of choline containing compounds was higher. Altogether, these findings shed light on how the human brain ages differently depending on region. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  8. Chronic MDMA induces neurochemical changes in the hippocampus of adolescent and young adult rats: Down-regulation of apoptotic markers.

    Science.gov (United States)

    García-Cabrerizo, Rubén; García-Fuster, M Julia

    2015-07-01

    While hippocampus is a brain region particularly susceptible to the effects of MDMA, the cellular and molecular changes induced by MDMA are still to be fully elucidated, being the dosage regimen, the species and the developmental stage under study great variables. This study compared the effects of one and four days of MDMA administration following a binge paradigm (3×5 mg/kg, i.p., every 2 h) on inducing hippocampal neurochemical changes in adolescent (PND 37) and young adult (PND 58) rats. The results showed that chronic MDMA caused hippocampal protein deficits in adolescent and young adult rats at different levels: (1) impaired serotonergic (5-HT2A and 5-HT2C post-synaptic receptors) and GABAergic (GAD2 enzyme) signaling, and (2) decreased structural cytoskeletal neurofilament proteins (NF-H, NF-M and NF-L). Interestingly, these effects were not accompanied by an increase in apoptotic markers. In fact, chronic MDMA inhibited proteins of the apoptotic pathway (i.e., pro-apoptotic FADD, Bax and cytochrome c) leading to an inhibition of cell death markers (i.e., p-JNK1/2, cleavage of PARP-1) and suggesting regulatory mechanisms in response to the neurochemical changes caused by the drug. The data, together with the observed lack of GFAP activation, support the view that chronic MDMA effects, regardless of the rat developmental age, extends beyond neurotransmitter systems to impair other hippocampal structural cell markers. Interestingly, inhibitory changes in proteins from the apoptotic pathway might be taking place to overcome the protein deficits caused by MDMA. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Sunflower Oil but Not Fish Oil Resembles Positive Effects of Virgin Olive Oil on Aged Pancreas after Life-Long Coenzyme Q Addition

    Science.gov (United States)

    González-Alonso, Adrián; Ramírez-Tortosa, César L.; Varela-López, Alfonso; Roche, Enrique; Arribas, María I.; Ramírez-Tortosa, M. Carmen; Giampieri, Francesca; Ochoa, Julio J.; Quiles, José L.

    2015-01-01

    An adequate pancreatic structure is necessary for optimal organ function. Structural changes are critical in the development of age-related pancreatic disorders. In this context, it has been reported that different pancreatic compartments from rats were affected according to the fat composition consumed. Since there is a close relationship between mitochondria, oxidative stress and aging, an experimental approach has been developed to gain more insight into this process in the pancreas. A low dosage of coenzyme Q was administered life-long in rats in order to try to prevent pancreatic aging-related alterations associated to some dietary fat sources. According to that, three groups of rats were fed normocaloric diets containing Coenzyme Q (CoQ) for two years, where virgin olive, sunflower, or fish oil was included as unique fat source. Pancreatic samples for microscopy and blood samples were collected at the moment of euthanasia. The main finding is that CoQ supplementation gives different results according to fat used in diet. When sunflower oil was the main fat in the diet, CoQ supplementation seems to improve endocrine pancreas structure and in particular β-cell mass resembling positive effects of virgin olive oil. Conversely, CoQ intake does not seem to improve the structural alterations of exocrine compartment previously observed in fish oil fed rats. Therefore CoQ may improve pancreatic alterations associated to the chronic intake of some dietary fat sources. PMID:26426013

  10. Sunflower Oil but Not Fish Oil Resembles Positive Effects of Virgin Olive Oil on Aged Pancreas after Life-Long Coenzyme Q Addition

    Directory of Open Access Journals (Sweden)

    Adrián González-Alonso

    2015-09-01

    Full Text Available An adequate pancreatic structure is necessary for optimal organ function. Structural changes are critical in the development of age-related pancreatic disorders. In this context, it has been reported that different pancreatic compartments from rats were affected according to the fat composition consumed. Since there is a close relationship between mitochondria, oxidative stress and aging, an experimental approach has been developed to gain more insight into this process in the pancreas. A low dosage of coenzyme Q was administered life-long in rats in order to try to prevent pancreatic aging-related alterations associated to some dietary fat sources. According to that, three groups of rats were fed normocaloric diets containing Coenzyme Q (CoQ for two years, where virgin olive, sunflower, or fish oil was included as unique fat source. Pancreatic samples for microscopy and blood samples were collected at the moment of euthanasia. The main finding is that CoQ supplementation gives different results according to fat used in diet. When sunflower oil was the main fat in the diet, CoQ supplementation seems to improve endocrine pancreas structure and in particular β-cell mass resembling positive effects of virgin olive oil. Conversely, CoQ intake does not seem to improve the structural alterations of exocrine compartment previously observed in fish oil fed rats. Therefore CoQ may improve pancreatic alterations associated to the chronic intake of some dietary fat sources.

  11. Treatment of trigeminal ganglion neurons in vitro with NGF, GDNF or BDNF: effects on neuronal survival, neurochemical properties and TRPV1-mediated neuropeptide secretion

    Directory of Open Access Journals (Sweden)

    Patwardhan Amol M

    2005-01-01

    results illustrate that NGF, GDNF and BDNF differentially alter TG sensory neuron survival, neurochemical properties and TRPV1-mediated neuropeptide release in culture. In particular, our findings suggest that GDNF and NGF differentially modulate TRPV1-mediated neuropeptide secretion sensitivity, with NGF having a much greater effect on a per neuron basis than GDNF. These findings are discussed in relation to possible therapeutic roles for growth factors or their modulators in pathological pain states, especially as these relate to the trigeminal system.

  12. Neurobiology Underlying Fibromyalgia Symptoms

    Directory of Open Access Journals (Sweden)

    Marta Ceko

    2012-01-01

    Full Text Available Fibromyalgia is characterized by chronic widespread pain, clinical symptoms that include cognitive and sleep disturbances, and other abnormalities such as increased sensitivity to painful stimuli, increased sensitivity to multiple sensory modalities, and altered pain modulatory mechanisms. Here we relate experimental findings of fibromyalgia symptoms to anatomical and functional brain changes. Neuroimaging studies show augmented sensory processing in pain-related areas, which, together with gray matter decreases and neurochemical abnormalities in areas related to pain modulation, supports the psychophysical evidence of altered pain perception and inhibition. Gray matter decreases in areas related to emotional decision making and working memory suggest that cognitive disturbances could be related to brain alterations. Altered levels of neurotransmitters involved in sleep regulation link disordered sleep to neurochemical abnormalities. Thus, current evidence supports the view that at least some fibromyalgia symptoms are associated with brain dysfunctions or alterations, giving the long-held “it is all in your head” view of the disorder a new meaning.

  13. Neurochemical abnormalities in brains of renal failure patients treated by repeated hemodialysis.

    Science.gov (United States)

    Perry, T L; Yong, V W; Kish, S J; Ito, M; Foulks, J G; Godolphin, W J; Sweeney, V P

    1985-10-01

    We examined autopsied brain from 10 patients with end-stage renal failure who had undergone repeated hemodialysis. Eight had classic symptoms, and two had suggestive symptoms of dialysis encephalopathy. Findings were compared with those in autopsied brain from control adults who had never been hemodialyzed. Mean gamma-aminobutyric acid (GABA) contents were significantly reduced in frontal and occipital cortex, cerebellar cortex, dentate nucleus, caudate nucleus, and medial-dorsal thalamus of the hemodialyzed patients, the reduction being greater than 40% in cerebral cortex and thalamus. Choline acetyltransferase activity was reduced by 25-35% in three cortical regions in the hemodialyzed patients. These two abnormalities were observed in the brain of each hemodialyzed patient, regardless of whether or not the patient died with unequivocal dialysis encephalopathy. Pyridoxal phosphate contents were substantially reduced in brains of the hemodialyzed patients, but metabolites of noradrenaline, 3,4-dihydroxyphenylethylamine (dopamine), and 5-hydroxytryptamine (serotonin) were present in normal amounts. Aluminum levels were abnormally high in frontal cortical gray matter in the hemodialyzed patients. Although this study does not clarify the role played by aluminum toxicity in the pathogenesis of dialysis encephalopathy, the abnormalities we found suggest the need for further neurochemical investigations in this disorder.

  14. Effects of electroconvulsive seizures on depression-related behavior, memory and neurochemical changes in Wistar and Wistar-Kyoto rats.

    Science.gov (United States)

    Kyeremanteng, C; MacKay, J C; James, J S; Kent, P; Cayer, C; Anisman, H; Merali, Z

    2014-10-03

    Investigations in healthy outbred rat strains have shown a potential role for brain-derived neurotrophic factor (BDNF) and the hypothalamic-pituitary-adrenal (HPA) axis in the antidepressant and memory side effects of electroconvulsive therapy (ECT, or ECS in animals). The Wistar-Kyoto (WKY) rat strain is used as a genetic model of depression yet no studies to date have directly compared the impact of ECS on the WKY strain to its healthy outbred control (Wistar). The objective of this study is to examine behavioral (antidepressant and retrograde memory) and neurochemical (BDNF and HPA axis) changes immediately (1day) and at a longer delay (7days) after repeated ECS (5 daily administrations) in WKY and Wistar rats. Male Wistar and WKY rats received 5days of repeated ECS or sham treatment and were assessed 1 and 7days later for 1) depression-like behavior and mobility; 2) retrograde memory; and 3) brain BDNF protein, brain corticotropin-releasing factor (CRF) and plasma corticosterone levels. Both strains showed the expected antidepressant response and retrograde memory impairments at 1day following ECS, which were sustained at 7days. In addition, at 1day after ECS, Wistar and WKY rats showed similar elevations in brain BDNF and extra-hypothalamic CRF and no change in plasma corticosterone. At 7days after ECS, Wistar rats showed sustained elevations of brain BDNF and CRF, whereas WKY rats showed a normalization of brain BDNF, despite sustained elevations of brain CRF. The model of 5 daily ECS was effective at eliciting behavioral and neurochemical changes in both strains. A temporal association was observed between brain CRF levels, but not BDNF, and measures of antidepressant effectiveness of ECS and retrograde memory impairments suggesting that extra-hypothalamic CRF may be a potential important contributor to these behavioral effects after repeated ECS/ECT. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Learning and memory alterations are associated with hippocampal N-acetylaspartate in a rat model of depression as measured by 1H-MRS.

    Directory of Open Access Journals (Sweden)

    Guangjun Xi

    Full Text Available It is generally accepted that cognitive processes, such as learning and memory, are affected in depression. The present study used a rat model of depression, chronic unpredictable mild stress (CUMS, to determine whether hippocampal volume and neurochemical changes were involved in learning and memory alterations. A further aim was to determine whether these effects could be ameliorated by escitalopram treatment, as assessed with the non-invasive techniques of structural magnetic resonance imaging (MRI and magnetic resonance spectroscopy (MRS. Our results demonstrated that CUMS had a dramatic influence on spatial cognitive performance in the Morris water maze task, and CUMS reduced the concentration of neuronal marker N-acetylaspartate (NAA in the hippocampus. These effects could be significantly reversed by repeated administration of escitalopram. However, neither chronic stress nor escitalopram treatment influenced hippocampal volume. Of note, the learning and memory alterations of the rats were associated with right hippocampal NAA concentration. Our results indicate that in depression, NAA may be a more sensitive measure of cognitive function than hippocampal volume.

  16. In vivo and In vitro neurochemical-based assessments of wastewater effluents from the Maumee River area of concern

    International Nuclear Information System (INIS)

    Arini, Adeline; Cavallin, Jenna E.; Berninger, Jason P.; Marfil-Vega, Ruth; Mills, Marc; Villeneuve, Daniel L.; Basu, Niladri

    2016-01-01

    Wastewater treatment plant (WWTP) effluents contain potentially neuroactive chemicals though few methods are available to screen for the presence of such agents. Here, two parallel approaches (in vivo and in vitro) were used to assess WWTP exposure-related changes to neurochemistry. First, fathead minnows (FHM, Pimephales promelas) were caged for four days along a WWTP discharge zone into the Maumee River (Ohio, USA). Grab water samples were collected and extracts obtained for the detection of alkylphenols, bisphenol A (BPA) and steroid hormones. Second, the extracts were then used as a source of in vitro exposure to brain tissues from FHM and four additional species relevant to the Great Lakes ecosystem (rainbow trout (RT), river otter (RO), bald eagle (BE) and human (HU)). The ability of the wastewater (in vivo) or extracts (in vitro) to interact with enzymes (monoamine oxidase (MAO) and glutamine synthetase (GS)) and receptors (dopamine (D2) and N-methyl-D-aspartate receptor (NMDA)) involved in dopamine and glutamate-dependent neurotransmission were examined on brain homogenates. In vivo exposure of FHM led to significant decreases of NMDA receptor binding in females (24–42%), and increases of MAO activity in males (2.8- to 3.2-fold). In vitro, alkylphenol-targeted extracts significantly inhibited D2 (66% in FHM) and NMDA (24–54% in HU and RT) receptor binding, and induced MAO activity in RT, RO, and BE brains. Steroid hormone-targeted extracts inhibited GS activity in all species except FHM. BPA-targeted extracts caused a MAO inhibition in FHM, RT and BE brains. Using both in vivo and in vitro approaches, this study shows that WWTP effluents contain agents that can interact with neurochemicals important in reproduction and other neurological functions. Additional work is needed to better resolve in vitro to in vivo extrapolations (IVIVE) as well as cross-species differences. - Highlights: • We conducted in vivo and in vitro neurochemical

  17. Autosomal dominant syndrome resembling Coffin-Siris syndrome.

    Science.gov (United States)

    Flynn, Maureen A; Milunsky, Jeff M

    2006-06-15

    Coffin-Siris syndrome is a multiple congenital anomaly/mental retardation syndrome with phenotypic variability [OMIM 135900]. The diagnosis is based solely on clinical findings, as there is currently no molecular, biochemical, or cytogenetic analysis available to confirm a diagnosis. Although typically described as an autosomal recessive disorder, autosomal dominant inheritance has also been infrequently reported. We describe a mother and her two daughters who all have features that resemble Coffin-Siris syndrome. However, this is not a completely convincing diagnosis given that hypertelorism is not a feature of Coffin-Siris syndrome and the family is relatively mildly affected. Yet, this family provides further evidence of an autosomal dominant mode of inheritance for a likely variant of Coffin-Siris syndrome (at least in some families). In addition, Sibling 1 had premature thelarche. She is the second reported individual within the spectrum of Coffin-Siris syndrome to have premature thelarche, indicating that it may be a rare clinical feature. Copyright 2006 Wiley-Liss, Inc.

  18. A Low-Protein Diet Alters Rat Behavior and Neurotransmission in Normothermic and Hyperthermic Environments

    National Research Council Canada - National Science Library

    Lieberman, Harris R; Yeghiayan, Sylva K; Maher, Timothy J

    2005-01-01

    .... Therefore, the behavioral and neurochemical consequences of exposure to a brief (11 days), low-protein (4%) diet in animals exposed to normothermic and hyperthermic test conditions were examined...

  19. Children and Adolescents' Understandings of Family Resemblance: A Study of Naive Inheritance Concepts

    Science.gov (United States)

    Williams, Joanne M.

    2012-01-01

    This paper aims to provide developmental data on two connected naive inheritance concepts and to explore the coherence of children's naive biology knowledge. Two tasks examined children and adolescents' (4, 7, 10, and 14 years) conceptions of phenotypic resemblance across kin (in physical characteristics, disabilities, and personality traits). The…

  20. Effects of parenting quality on adolescents' personality resemblance to their parents. The TRAILS study

    NARCIS (Netherlands)

    Langenhof, M Rohaa; Komdeur, Jan; Oldehinkel, Albertine J.

    This study considers the development of resemblance between 741 adolescents and their biological parents, across six NEO-PI-R personality traits known to be important in psychological problems: anger-hostility, impulsiveness, vulnerability, assertiveness, excitement-seeking, and self-discipline. We

  1. Age and Gender Differences in Facial Attractiveness, but Not Emotion Resemblance, Contribute to Age and Gender Stereotypes

    Directory of Open Access Journals (Sweden)

    Rocco Palumbo

    2017-09-01

    Full Text Available Considerable research has shown effects of facial appearance on trait impressions and group stereotypes. We extended those findings in two studies that investigated the contribution of resemblance to emotion expressions and attractiveness to younger adults (YA and older adults (OA age and gender stereotypes on the dimensions of warmth and competence. Using connectionist modeling of facial metrics of 240 neutral younger and older faces, Study 1 found that, neutral expression older faces or female faces showed greater structural resemblance to happy expressions and less resemblance to angry expressions than did younger or male faces, respectively. In addition, neutral female faces showed greater resemblance to surprise expressions. In Study 2, YA and OA rated the faces of Study 1 for attractiveness and for 4 traits that we aggregated on the dimensions of competence (competent, healthy and warmth (trustworthy, not shrewd. We found that YA, but not OA, age stereotypes replicated previous research showing higher perceived warmth and lower perceived competence in older adults. In addition, previously documented gender stereotypes were moderated by face age for both YA and OA. The greater attractiveness of younger than older faces and female than male faces influenced age and gender stereotypes, including these deviations from prior research findings using category labels rather than faces. On the other hand, face age and face sex differences in emotion resemblance did not influence age or gender stereotypes, contrary to prediction. Our results provide a caveat to conclusions about age and gender stereotypes derived from responses to category labels, and they reveal the importance of assessing stereotypes with a methodology that is sensitive to influences of group differences in appearance that can exacerbate or mitigate stereotypes in more ecologically valid contexts. Although the gender differences in attractiveness in the present study may not have

  2. Age and Gender Differences in Facial Attractiveness, but Not Emotion Resemblance, Contribute to Age and Gender Stereotypes.

    Science.gov (United States)

    Palumbo, Rocco; Adams, Reginald B; Hess, Ursula; Kleck, Robert E; Zebrowitz, Leslie

    2017-01-01

    Considerable research has shown effects of facial appearance on trait impressions and group stereotypes. We extended those findings in two studies that investigated the contribution of resemblance to emotion expressions and attractiveness to younger adults (YA) and older adults (OA) age and gender stereotypes on the dimensions of warmth and competence. Using connectionist modeling of facial metrics of 240 neutral younger and older faces, Study 1 found that, neutral expression older faces or female faces showed greater structural resemblance to happy expressions and less resemblance to angry expressions than did younger or male faces, respectively. In addition, neutral female faces showed greater resemblance to surprise expressions. In Study 2, YA and OA rated the faces of Study 1 for attractiveness and for 4 traits that we aggregated on the dimensions of competence (competent, healthy) and warmth (trustworthy, not shrewd). We found that YA, but not OA, age stereotypes replicated previous research showing higher perceived warmth and lower perceived competence in older adults. In addition, previously documented gender stereotypes were moderated by face age for both YA and OA. The greater attractiveness of younger than older faces and female than male faces influenced age and gender stereotypes, including these deviations from prior research findings using category labels rather than faces. On the other hand, face age and face sex differences in emotion resemblance did not influence age or gender stereotypes, contrary to prediction. Our results provide a caveat to conclusions about age and gender stereotypes derived from responses to category labels, and they reveal the importance of assessing stereotypes with a methodology that is sensitive to influences of group differences in appearance that can exacerbate or mitigate stereotypes in more ecologically valid contexts. Although the gender differences in attractiveness in the present study may not have generalizability

  3. Neurochemical binding profiles of novel indole and benzofuran MDMA analogues.

    Science.gov (United States)

    Shimshoni, Jakob A; Winkler, Ilan; Golan, Ezekiel; Nutt, David

    2017-01-01

    3,4-Methylenedioxy-N-methylamphetamine (MDMA) has been shown to be effective in the treatment of post-traumatic stress disorder (PTSD) in numerous clinical trials. In the present study, we have characterized the neurochemical binding profiles of three MDMA-benzofuran analogues (1-(benzofuran-5-yl)-propan-2-amine, 5-APB; 1-(benzofuran-6-yl)-N-methylpropan-2-amine, 6-MAPB; 1-(benzofuran-5-yl)-N-methylpropan-2-amine, 5-MAPB) and one MDMA-indole analogue (1-(1H-indol-5-yl)-2-methylamino-propan-1-ol, 5-IT). These compounds were screened as potential second-generation anti-PTSD drugs, against a battery of human and non-human receptors, transporters, and enzymes, and their potencies as 5-HT 2 receptor agonist and monoamine uptake inhibitors determined. All MDMA analogues displayed high binding affinities for 5-HT 2a,b,c and NE α2 receptors, as well as significant 5-HT, DA, and NE uptake inhibition. 5-APB revealed significant agonist activity at the 5-HT 2a,b,c receptors, while 6-MAPB, 5-MAPB, and 5-IT exhibited significant agonist activity at the 5-HT 2c receptor. There was a lack of correlation between the results of functional uptake and the monoamine transporter binding assay. MDMA analogues emerged as potent and selective monoamine oxidase A inhibitors. Based on 6-MAPB favorable pharmacological profile, it was further subjected to IC 50 determination for monoamine transporters. Overall, all MDMA analogues displayed higher monoamine receptor/transporter binding affinities and agonist activity at the 5-HT 2a,c receptors as compared to MDMA.

  4. Wireless Instantaneous Neurotransmitter Concentration System-based amperometric detection of dopamine, adenosine, and glutamate for intraoperative neurochemical monitoring.

    Science.gov (United States)

    Agnesi, Filippo; Tye, Susannah J; Bledsoe, Jonathan M; Griessenauer, Christoph J; Kimble, Christopher J; Sieck, Gary C; Bennet, Kevin E; Garris, Paul A; Blaha, Charles D; Lee, Kendall H

    2009-10-01

    In a companion study, the authors describe the development of a new instrument named the Wireless Instantaneous Neurotransmitter Concentration System (WINCS), which couples digital telemetry with fast-scan cyclic voltammetry (FSCV) to measure extracellular concentrations of dopamine. In the present study, the authors describe the extended capability of the WINCS to use fixed potential amperometry (FPA) to measure extracellular concentrations of dopamine, as well as glutamate and adenosine. Compared with other electrochemical techniques such as FSCV or high-speed chronoamperometry, FPA offers superior temporal resolution and, in combination with enzyme-linked biosensors, the potential to monitor nonelectroactive analytes in real time. The WINCS design incorporated a transimpedance amplifier with associated analog circuitry for FPA; a microprocessor; a Bluetooth transceiver; and a single, battery-powered, multilayer, printed circuit board. The WINCS was tested with 3 distinct recording electrodes: 1) a carbon-fiber microelectrode (CFM) to measure dopamine; 2) a glutamate oxidase enzyme-linked electrode to measure glutamate; and 3) a multiple enzyme-linked electrode (adenosine deaminase, nucleoside phosphorylase, and xanthine oxidase) to measure adenosine. Proof-of-principle analyses included noise assessments and in vitro and in vivo measurements that were compared with similar analyses by using a commercial hardwired electrochemical system (EA161 Picostat, eDAQ; Pty Ltd). In urethane-anesthetized rats, dopamine release was monitored in the striatum following deep brain stimulation (DBS) of ascending dopaminergic fibers in the medial forebrain bundle (MFB). In separate rat experiments, DBS-evoked adenosine release was monitored in the ventrolateral thalamus. To test the WINCS in an operating room setting resembling human neurosurgery, cortical glutamate release in response to motor cortex stimulation (MCS) was monitored using a large-mammal animal model, the pig. The

  5. Wireless Instantaneous Neurotransmitter Concentration System–based amperometric detection of dopamine, adenosine, and glutamate for intraoperative neurochemical monitoring

    Science.gov (United States)

    Agnesi, Filippo; Tye, Susannah J.; Bledsoe, Jonathan M.; Griessenauer, Christoph J.; Kimble, Christopher J.; Sieck, Gary C.; Bennet, Kevin E.; Garris, Paul A.; Blaha, Charles D.; Lee, Kendall H.

    2009-01-01

    Object In a companion study, the authors describe the development of a new instrument named the Wireless Instantaneous Neurotransmitter Concentration System (WINCS), which couples digital telemetry with fast-scan cyclic voltammetry (FSCV) to measure extracellular concentrations of dopamine. In the present study, the authors describe the extended capability of the WINCS to use fixed potential amperometry (FPA) to measure extracellular concentrations of dopamine, as well as glutamate and adenosine. Compared with other electrochemical techniques such as FSCV or high-speed chronoamperometry, FPA offers superior temporal resolution and, in combination with enzyme-linked biosensors, the potential to monitor nonelectroactive analytes in real time. Methods The WINCS design incorporated a transimpedance amplifier with associated analog circuitry for FPA; a microprocessor; a Bluetooth transceiver; and a single, battery-powered, multilayer, printed circuit board. The WINCS was tested with 3 distinct recording electrodes: 1) a carbon-fiber microelectrode (CFM) to measure dopamine; 2) a glutamate oxidase enzyme-linked electrode to measure glutamate; and 3) a multiple enzyme-linked electrode (adenosine deaminase, nucleoside phosphorylase, and xanthine oxidase) to measure adenosine. Proof-of-principle analyses included noise assessments and in vitro and in vivo measurements that were compared with similar analyses by using a commercial hardwired electrochemical system (EA161 Picostat, eDAQ; Pty Ltd). In urethane-anesthetized rats, dopamine release was monitored in the striatum following deep brain stimulation (DBS) of ascending dopaminergic fibers in the medial forebrain bundle (MFB). In separate rat experiments, DBS-evoked adenosine release was monitored in the ventrolateral thalamus. To test the WINCS in an operating room setting resembling human neurosurgery, cortical glutamate release in response to motor cortex stimulation (MCS) was monitored using a large-mammal animal

  6. Familial resemblance of borderline personality disorder features: genetic or cultural transmission?

    Directory of Open Access Journals (Sweden)

    Marijn A Distel

    Full Text Available Borderline personality disorder is a severe personality disorder for which genetic research has been limited to family studies and classical twin studies. These studies indicate that genetic effects explain 35 to 45% of the variance in borderline personality disorder and borderline personality features. However, effects of non-additive (dominance genetic factors, non-random mating and cultural transmission have generally not been explored. In the present study an extended twin-family design was applied to self-report data of twins (N = 5,017 and their siblings (N = 1,266, parents (N = 3,064 and spouses (N = 939 from 4,015 families, to estimate the effects of additive and non-additive genetic and environmental factors, cultural transmission and non-random mating on individual differences in borderline personality features. Results showed that resemblance among biological relatives could completely be attributed to genetic effects. Variation in borderline personality features was explained by additive genetic (21%; 95% CI 17-26% and dominant genetic (24%; 95% CI 17-31% factors. Environmental influences (55%; 95% CI 51-60% explained the remaining variance. Significant resemblance between spouses was observed, which was best explained by phenotypic assortative mating, but it had only a small effect on the genetic variance (1% of the total variance. There was no effect of cultural transmission from parents to offspring.

  7. Crack cocaine inhalation induces schizophrenia-like symptoms and molecular alterations in mice prefrontal cortex.

    Science.gov (United States)

    Areal, Lorena Bianchine; Herlinger, Alice Laschuk; Pelição, Fabrício Souza; Martins-Silva, Cristina; Pires, Rita Gomes Wanderley

    2017-08-01

    Crack cocaine (crack) addiction represents a major social and health burden, especially seeing as users are more prone to engage in criminal and violent acts. Crack users show a higher prevalence of psychiatric comorbidities - particularly antisocial personality disorders - when compared to powder cocaine users. They also develop cognitive deficits related mainly to executive functions, including working memory. It is noteworthy that stimulant drugs can induce psychotic states, which appear to mimic some symptoms of schizophrenia among users. Social withdraw and executive function deficits are, respectively, negative and cognitive symptoms of schizophrenia mediated by reduced dopamine (DA) tone in the prefrontal cortex (PFC) of patients. That could be explained by an increased expression of D2R short isoform (D2S) in the PFC of such patients and/or by hypofunctioning NMDA receptors in this region. Reduced DA tone has already been described in the PFC of mice exposed to crack smoke. Therefore, it is possible that behavioral alterations presented by crack users result from molecular and biochemical neuronal alterations akin to schizophrenia. Accordingly, we found that upon crack inhalation mice have shown decreased social interaction and working memory deficits analogous to schizophrenia's symptoms, along with increased D2S/D2L expression ratio and decreased expression of NR1, NR2A and NR2B NMDA receptor subunits in the PFC. Herein we propose two possible mechanisms to explain the reduced DA tone in the PFC elicited by crack consumption in mice, bringing also the first direct evidence that crack use may result in schizophrenia-like neurochemical, molecular and behavioral alterations. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Household and familial resemblance in risk factors for type 2 diabetes and related cardiometabolic diseases in rural Uganda

    DEFF Research Database (Denmark)

    Nielsen, Jannie; Bahendeka, Silver K.; Whyte, Susan R.

    2017-01-01

    prevention and screening, we investigated the resemblance of T2D risk factors at household level and by type of familial dyadic relationship in a rural Ugandan community. Methods: This cross-sectional household-based study included 437 individuals ≥13 years of age from 90 rural households in south......-western Uganda. Resemblance in glycosylated haemoglobin (HbA1c), anthropometry, blood pressure, fitness status and sitting time were analysed using a general mixed model with random effects (by household or dyad) to calculate household intraclass correlation coefficients (ICCs) and dyadic regression coefficients...... (ICC=0.24), HbA1c (ICC=0.18) and systolic blood pressure (ICC=0.11). Regarding dyadic resemblance, the highest standardised regression coefficient was seen in fitness status for spouses (0.54, 95% CI 0.32 to 0.76), parent–offspring (0.41, 95% CI 0.28 0.54) and siblings (0.41, 95% CI 0.25 to 0...

  9. From FRA to RFN, or How the Family Resemblance Approach Can Be Transformed for Science Curriculum Analysis on Nature of Science

    Science.gov (United States)

    Kaya, Ebru; Erduran, Sibel

    2016-01-01

    The inclusion of Nature of Science (NOS) in the science curriculum has been advocated around the world for several decades. One way of defining NOS is related to the family resemblance approach (FRA). The family resemblance idea was originally described by Wittgenstein. Subsequently, philosophers and educators have applied Wittgenstein's idea to…

  10. How (and why) the immune system makes us sleep.

    Science.gov (United States)

    Imeri, Luca; Opp, Mark R

    2009-03-01

    Good sleep is necessary for physical and mental health. For example, sleep loss impairs immune function, and sleep is altered during infection. Immune signalling molecules are present in the healthy brain, where they interact with neurochemical systems to contribute to the regulation of normal sleep. Animal studies have shown that interactions between immune signalling molecules (such as the cytokine interleukin 1) and brain neurochemical systems (such as the serotonin system) are amplified during infection, indicating that these interactions might underlie the changes in sleep that occur during infection. Why should the immune system cause us to sleep differently when we are sick? We propose that the alterations in sleep architecture during infection are exquisitely tailored to support the generation of fever, which in turn imparts survival value.

  11. Morphological alterations of exogenous surfactant inhibited by meconium can be prevented by dextran

    Directory of Open Access Journals (Sweden)

    Stichtenoth Guido

    2006-06-01

    Full Text Available Abstract Background Surfactant dysfunction due to inhibition is involved in the pathophysiology of meconium aspiration syndrome. Dextran addition has been shown to reverse exogenous surfactant inactivation by meconium, but the precise mechanisms and the morphological correlate of this effect are yet unknown. Morphological surfactant analysis by transmission electron microscopy (TEM and stereology allows the differentiation of active (large aggregates = LA and inactive (small aggregates = SA subtypes. Methods To determine the in vitro effects of meconium and dextran addition on the morphology of a modified porcine natural surfactant (Curosurf, Curosurf samples were either incubated alone or together with meconium or with meconium and dextran, fixed and processed for TEM. Volume fractions of surfactant subtypes [lamellar body-like forms (LBL, multilamellar vesicles (MV, unilamellar vesicles (UV] were determined stereologically. Results All preparations contained LBL and MV (corresponding to LA as well as UV (corresponding to SA. The volume fraction of UV increased with addition of meconium and decreased with further addition of dextran. Correspondingly, the UV/(LBL+MV ratio (resembling the SA/LA ratio increased when meconium was added and decreased when dextran was added to the surfactant-meconium mixture. Conclusion Meconium causes alterations in the ultrastructural composition of Curosurf that can be visualized and analyzed by TEM and stereology. These alterations resemble an increase in the SA/LA ratio and are paralleled by an increase in minimum surface tension. Dextran prevents these effects and may therefore be a useful additive to exogenous surfactant preparations to preserve their structural and functional integrity, thereby improving their resistance to inactivation.

  12. Investigación neuroquímica cerebral y aplicación preventiva para la reducción de los índices de criminalidad/Neurochemical brain research and it’s preventive application to reduce the crime statistics

    Directory of Open Access Journals (Sweden)

    Osvaldo Tieghi (Argentina

    2014-01-01

    Full Text Available Investigación neuroquímica cerebral y aplicación preventiva para la reducción de los índices de criminalidad Neurochemical brain research and it’s preventive application to reduce the crime statistics

  13. Descriptive Understandings of the Nature of Science: Examining the Consensual and Family Resemblance Approaches

    Science.gov (United States)

    do Nascimento Rocha, Maristela; Gurgel, Ivã

    2017-01-01

    This paper performs a critical analysis of the consensual and family resemblance approaches to the nature of science. Despite the debate that surrounds them, between a pragmatic consensus and a more comprehensive understanding, both approaches have in common the goal of helping students to "internalize" knowledge about science in a…

  14. Intermittent Fasting Confers Protection in CNS Autoimmunity by Altering the Gut Microbiota.

    Science.gov (United States)

    Cignarella, Francesca; Cantoni, Claudia; Ghezzi, Laura; Salter, Amber; Dorsett, Yair; Chen, Lei; Phillips, Daniel; Weinstock, George M; Fontana, Luigi; Cross, Anne H; Zhou, Yanjiao; Piccio, Laura

    2018-06-05

    Multiple sclerosis (MS) is more common in western countries with diet being a potential contributing factor. Here we show that intermittent fasting (IF) ameliorated clinical course and pathology of the MS model, experimental autoimmune encephalomyelitis (EAE). IF led to increased gut bacteria richness, enrichment of the Lactobacillaceae, Bacteroidaceae, and Prevotellaceae families and enhanced antioxidative microbial metabolic pathways. IF altered T cells in the gut with a reduction of IL-17 producing T cells and an increase in regulatory T cells. Fecal microbiome transplantation from mice on IF ameliorated EAE in immunized recipient mice on a normal diet, suggesting that IF effects are at least partially mediated by the gut flora. In a pilot clinical trial in MS patients, intermittent energy restriction altered blood adipokines and the gut flora resembling protective changes observed in mice. In conclusion, IF has potent immunomodulatory effects that are at least partially mediated by the gut microbiome. Copyright © 2018 Elsevier Inc. All rights reserved.

  15. Novel mechanism for impaired nitrergic relaxation in achalasia

    NARCIS (Netherlands)

    Boeckxstaens, G. E.

    2006-01-01

    New insights into the pathogenesis of achalasia indicate that incubation with serum from patients with achalasia leads to altered neurochemical coding of the myenteric plexus and impairs the nitrergic response to nerve stimulation

  16. Resembling a viper: implications of mimicry for conservation of the endangered smooth snake.

    Science.gov (United States)

    Valkonen, Janne K; Mappes, Johanna

    2014-12-01

    The phenomenon of Batesian mimicry, where a palatable animal gains protection against predation by resembling an unpalatable model, has been a core interest of evolutionary biologists for 150 years. An extensive range of studies has focused on revealing mechanistic aspects of mimicry (shared education and generalization of predators) and the evolutionary dynamics of mimicry systems (co-operation vs. conflict) and revealed that protective mimicry is widespread and is important for individual fitness. However, according to our knowledge, there are no case studies where mimicry theories have been applied to conservation of mimetic species. Theoretically, mimicry affects, for example, frequency dependency of predator avoidance learning and human induced mortality. We examined the case of the protected, endangered, nonvenomous smooth snake (Coronella austriaca) that mimics the nonprotected venomous adder (Vipera berus), both of which occur in the Åland archipelago, Finland. To quantify the added predation risk on smooth snakes caused by the rarity of vipers, we calculated risk estimates from experimental data. Resemblance of vipers enhances survival of smooth snakes against bird predation because many predators avoid touching venomous vipers. Mimetic resemblance is however disadvantageous against human predators, who kill venomous vipers and accidentally kill endangered, protected smooth snakes. We found that the effective population size of the adders in Åland is very low relative to its smooth snake mimic (28.93 and 41.35, respectively).Because Batesian mimicry is advantageous for the mimic only if model species exist in sufficiently high numbers, it is likely that the conservation program for smooth snakes will fail if adders continue to be destroyed. Understanding the population consequences of mimetic species may be crucial to the success of endangered species conservation. We suggest that when a Batesian mimic requires protection, conservation planners should

  17. A wolf in sheep's clothing: The description of a fly resembling jumping spider of the genus Scoturius Simon, 1901 (Araneae: Salticidae: Huriini).

    Science.gov (United States)

    Perger, Robert; Rubio, Gonzalo D

    2018-01-01

    Fly resemblance in arthropods is much less common than e.g., resemblance to ants or wasps, and has been mainly observed in beetles. Putative fly mimicry in arachnids has been reported only from the jumping spider genus Saitis. However, recent literature has attributed the fly-resembling characteristics in Saitis to sexual signalling during courtship. The lack of observation of fly mimicry in spiders is not surprising as flies belong to the most important prey item group of spiders. In this study, a new fly-resembling species of the jumping spider tribe Huriini, Scoturius dipterioides sp. nov., from the pre-Andean Chiquitano forest at the Bolivian orocline is described and illustrated. The new species was tentatively placed into Scoturius because the epigynum has a single large elliptical opening. Scoturius dipterioides sp. nov. is distinguished from all other species of this tribe by a combination of following characteristics: epigynum with a large anterior elliptical atrium and initial portion of the copulation ducts dilated as a chamber (shared with Urupuyu); relatively joined copulation openings and short copulation ducts; kidney-shaped spermathecae, advanced at the atrium level. Several somatic features, two of them found exclusively in S. dipterioides sp. nov., increase the resemblance to flies. The Huriini are currently the only spider tribe that is suggested to feature fly mimics.

  18. Neutrophilic dermatosis resembling pyoderma gangrenosum in a dog with polyarthritis.

    Science.gov (United States)

    Bardagí, M; Lloret, A; Fondati, A; Ferrer, L

    2007-04-01

    This report describes a case of neutrophilic dermatosis in a dog, with a number of clinical and pathological similarities to human pyoderma gangrenosum. A seven-year-old, female German shepherd dog with a history of non-erosive idiopathic polyarthritis was presented with severe facial swelling, bilateral erosivoulcerative lesions on the muzzle and multiple, eroded, dermal-subcutaneous nodules on the cranial trunk. Histopathological examination of skin biopsies revealed a necrotising neutrophilic dermatitis. No infectious agents could be detected using specific stains, immunohistochemistry, serology and bacterial aerobic, anaerobic or fungal cultures. A sterile neutrophilic dermatosis resembling human pyoderma gangrenosum was presumptively diagnosed, and the patient showed an excellent response to treatment with prednisone and ciclosporin.

  19. Cocaine addiction: the hidden dimension.

    Science.gov (United States)

    Oswald, L M

    1989-06-01

    There is growing awareness within the nursing profession that nurses need to expand their knowledge about addiction and develop expertise in providing care for substance abusing clients. This report presents a discussion about cocaine abuse that is focused on evolving knowledge about the physiology of addiction. Researchers have recently described cocaine-induced neurochemical changes in the brain that may form the underpinnings for the behavioral manifestations and symptomatology that have been associated with cocaine addiction. These neurochemical alterations are described at the cellular level, and treatment implications for nurses are presented.

  20. A Para-Canalicular Abscess Resembling an Inflamed Chalazion

    Directory of Open Access Journals (Sweden)

    Diamantis Almaliotis

    2013-01-01

    Full Text Available Background. Lacrimal infections by Actinomyces are rare and commonly misdiagnosed for long periods of time. They account for 2% of all lacrimal diseases. Case Report. We report a case of a 70-year-old female patient suffering from a para-canalicular abscess in the medial canthus of the left eye, beside the lower punctum lacrimale, resembling a chalazion. Purulence exited from the punctum lacrimale due to inflammation of the inferior canaliculus (canaliculitis. When pressure was applied to the mass, a second exit of purulence was also observed under the palpebral conjunctiva below the lacrimal caruncle. A surgical excision was performed followed by administration of local antibiotic therapy. The histopathological examination of the extracted mass revealed the existence of actinomycosis. Conclusion. Persistent or recurrent infections and lumps of the eyelids should be thoroughly investigated. Actinomyces as a causative agent should be considered. Differential diagnosis is broad and should include canaliculitis, chalazion, and multiple types of neoplasias. For this reason, in nonconclusive cases, a histopathological examination should be performed.

  1. Muscular dystrophy in a dog resembling human becker muscular dystrophy.

    Science.gov (United States)

    Baroncelli, A B; Abellonio, F; Pagano, T B; Esposito, I; Peirone, B; Papparella, S; Paciello, O

    2014-05-01

    A 3-year-old, male Labrador retriever dog was presented with clinical signs of progressive exercise intolerance, bilateral elbow extension, rigidity of the forelimbs, hindlimb flexion and kyphosis. Microscopical examination of muscle tissue showed marked variability in myofibre size, replacement of muscle with mature adipose tissue and degeneration/regeneration of muscle fibres, consistent with muscular dystrophy. Immunohistochemical examination for dystrophin showed markedly reduced labelling with monoclonal antibodies specific for the rod domain and the carboxy-terminal of dystrophin, while expression of β-sarcoglycan, γ-sarcoglycan and β-dystroglycan was normal. Immunoblotting revealed a truncated dystrophin protein of approximately 135 kDa. These findings supported a diagnosis of congenital canine muscular dystrophy resembling Becker muscular dystrophy in man. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Menstrual blood closely resembles the uterine immune micro-environment and is clearly distinct from peripheral blood

    NARCIS (Netherlands)

    Molen, R.G. van der; Schutten, J.H.; Cranenbroek, B. van; Meer, M. ter; Donckers, J.; Scholten, R.R.; Heijden, O.W.H. van der; Spaanderman, M.E.A.; Joosten, I.

    2014-01-01

    STUDY QUESTION: Is menstrual blood a suitable source of endometrial derived lymphocytes? SUMMARY ANSWER: Mononuclear cells isolated from menstrual samples (menstrual blood mononuclear cells (MMC)) are clearly distinct from peripheral blood mononuclear cells (PBMC) and show a strong resemblance with

  3. Role of Neurochemicals in the Interaction between the Microbiota and the Immune and the Nervous System of the Host Organism.

    Science.gov (United States)

    Oleskin, Alexander V; Shenderov, Boris A; Rogovsky, Vladimir S

    2017-09-01

    This work is concerned with the role of evolutionary conserved substances, neurotransmitters, and neurohormones, within the complex framework of the microbial consortium-immune system-nervous system axis in the human or animal organism. Although the operation of each of these systems per se is relatively well understood, their combined effects on the host organism still await further research. Drawing on recent research on host-produced and microbial low-molecular-weight neurochemicals such as biogenic amines, amino acids, and short-chain fatty acids (SCFAs), we suggest that these mediators form a part of a universal neurochemical "language." It mediates the whole gamut of harmonious and disharmonious interactions between (a) the intestinal microbial consortium, (b) local and systemic immune cells, and (c) the central and peripheral nervous system. Importantly, the ongoing microbiota-host interactivity is bidirectional. We present evidence that a large number of microbially produced low-molecular-weight compounds are identical or homologous to mediators that are synthesized by immune or nervous cells and, therefore, can bind to the corresponding host receptors. In addition, microbial cells specifically respond to host-produced neuromediators/neurohormones because they have adapted to them during the course of many millions of years of microbiota-host coevolution. We emphasize that the terms "microbiota" and "microbial consortium" are to be used in the broadest sense, so as to include, apart from bacteria, also eukaryotic microorganisms. These are exemplified by the mycobiota whose role in the microbial consortium-immune system-nervous system axis researchers are only beginning to elucidate. In light of the above, it is imperative to reform the current strategies of using probiotic microorganisms and their metabolites for treating and preventing dysbiosis-related diseases. The review demonstrates, in the example of novel probiotics (psychobiotics), that many target

  4. Image and Global Resemblance in the Light of Hadith “Who So Imitates other People Becomes One of Them”

    Directory of Open Access Journals (Sweden)

    SERDAR DEMİREL

    2016-06-01

    Full Text Available In today’s world, people from different countries, cities and institutions unprecedentedly resemble each other in every aspect of life. Likewise, the deeds and imagery aspirations of Oriental and Occidental people also resemble. In such an atmosphere, the local cultures rooted in history become accessories and lose their historical significance and metaphysical aspects in the edifice of the society. This study aims to analyze Prophet Muhammad’s (s.a.w. warning, “Who so imitates other people becomes one of them”, its layers of meaning and its relationship with “image and global resemblence”.

  5. Consolation in the aftermath of robberies resembles post-aggression consolation in chimpanzees

    DEFF Research Database (Denmark)

    Lindegaard, Marie Rosenkrantz; Liebst, Lasse Suonperä; Bernasco, Wim

    2017-01-01

    Post-aggression consolation is assumed to occur in humans as well as in chimpanzees. While consolation following peer aggression has been observed in children, systematic evidence of consolation in human adults is rare. We used surveillance camera footage of the immediate aftermath of nonfatal...... to be consoled. Furthermore, we show that high levels of threat during the robbery increased the likelihood of receiving consolation afterwards. These patterns resemble post-aggression consolation in chimpanzees and suggest that emotions of empathic concern are involved in consolation across humans...... and chimpanzees....

  6. Mammographic texture resemblance generalizes as an independent risk factor for breast cancer

    DEFF Research Database (Denmark)

    Nielsen, Mads; Vachon, Celine M.; Scott, Christopher G.

    2014-01-01

    INTRODUCTION:Breast density has been established as a major risk factor for breast cancer. We have previously demonstrated that mammographic texture resemblance (MTR), recognizing the local texture patterns of the mammogram, is also a risk factor for breast cancer, independent of percent breast...... density. We examine if these findings generalize to another population.METHODS:Texture patterns were recorded in digitalized pre-diagnosis (3.7years) film mammograms of a nested case-control study within the Dutch screening program (S1) comprising of 245 breast cancers and 250 matched controls...

  7. Dermatitis and lymphadenitis resembling juvenile cellulitis in a four-year-old dog.

    Science.gov (United States)

    Neuber, A E; van den Broek, A H M; Brownstein, D; Thoday, K L; Hill, P B

    2004-05-01

    A four-year-old, entire male toy poodle was presented with a two-and-a-half-week history of ocular discharge progressing to periorbital alopecia, depigmentation, alopecia and ulceration around the muzzle. There was also a haemorrhagic discharge from the ears, pyrexia, lethargy and generalised lymphadenopathy. The clinical, cytological, bacteriological and histopathological findings were consistent with a diagnosis of dermatitis resembling juvenile cellulitis in an adult dog. Glucocorticoid therapy led to rapid resolution of the clinical signs and the dog has remained in remission for two years after cessation of treatment.

  8. Alteration of the platelet serotonin transporter in romantic love.

    Science.gov (United States)

    Marazziti, D; Akiskal, H S; Rossi, A; Cassano, G B

    1999-05-01

    The evolutionary consequences of love are so important that there must be some long-established biological process regulating it. Recent findings suggest that the serotonin (5-HT) transporter might be linked to both neuroticism and sexual behaviour as well as to obsessive-compulsive disorder (OCD). The similarities between an overvalued idea, such as that typical of subjects in the early phase of a love relationship, and obsession, prompted us to explore the possibility that the two conditions might share alterations at the level of the 5-HT transporter. Twenty subjects who had recently (within the previous 6 months) fallen in love, 20 unmedicated OCD patients and 20 normal controls, were included in the study. The 5-HT transporter was evaluated with the specific binding of 3H-paroxetine (3H-Par) to platelet membranes. The results showed that the density of 3H-Par binding sites was significantly lower in subjects who had recently fallen in love and in OCD patients than in controls. The main finding of the present study is that subjects who were in the early romantic phase of a love relationship were not different from OCD patients in terms of the density of the platelet 5-HT transporter, which proved to be significantly lower than in the normal controls. This would suggest common neurochemical changes involving the 5-HT system, linked to psychological dimensions shared by the two conditions, perhaps at an ideational level.

  9. Omega-3 Fatty Acid Deficiency Does Not Alter the Effects of Chronic Fluoxetine Treatment on Central Serotonin Turnover or Behavior in the Forced Swim Test in Female Rats

    OpenAIRE

    McNamara, Robert K.; Able, Jessica A.; Liu, Yanhong; Jandacek, Ronald; Rider, Therese; Tso, Patrick; Lipton, Jack W.

    2013-01-01

    While translational evidence suggests that long-chain omega-3 fatty acid status is positively associated with the efficacy of selective serotonin reuptake inhibitor drugs, the neurochemical mechanisms mediating this interaction are not known. Here we investigated the effects of dietary omega-3 (n-3) fatty acid insufficiency on the neurochemical and behavioral effects of chronic fluoxetine (FLX) treatment. Female rats were fed diets with (CON, n=56) or without (DEF, n=40) the n-3 fatty acids d...

  10. Body elimination attitude family resemblance in Kuwait.

    Science.gov (United States)

    Al-Fayez, Ghenaim; Awadalla, Abdelwahid; Arikawa, Hiroko; Templer, Donald I; Hutton, Shane

    2009-12-01

    The purpose of the present study was to determine the family resemblance of attitude toward body elimination in Kuwaiti participants. This study was conceptualized in the context of the theories of moral development, importance of cleanliness in the Muslim religion, cross-cultural differences in personal hygiene practices, previous research reporting an association between family attitudes and body elimination attitude, and health implications. The 24-item Likert-type format Body Elimination Attitude Scale-Revised was administered to 277 Kuwaiti high school students and 437 of their parents. Females scored higher, indicating greater disgust, than the males. Moreover, sons' body elimination attitude correlated more strongly with fathers' attitude (r = .85) than with that of the mothers (r = .64). Daughters' attitude was similarly associated with the fathers' (r = .89) and the mothers' attitude (r = .86). The high correlations were discussed within the context of Kuwait having a collectivistic culture with authoritarian parenting style. The higher adolescent correlations, and in particular the boys' correlation with fathers than with mothers, was explained in terms of the more dominant role of the Muslim father in the family. Public health and future research implications were suggested. A theoretical formulation was advanced in which "ideal" body elimination attitude is relative rather than absolute, and is a function of one's life circumstances, one's occupation, one's culture and subculture, and the society that one lives in.

  11. GENOMIC ANALYSIS OF PTU-INDUCED HYPOTHYROIDISM IN RAT HIPPOCAMPUS.

    Science.gov (United States)

    Propylthiouracil (PTU) exposure results in depletion of thyroid hormone by blocking its synthesis. It often is used to study the effects of hypothyroidism in the brain, where deficits during critical periods lead to neuroanatomical, molecular and neurochemical alterations. Decre...

  12. Altered activity of the sympathetic nervous system and changes in the balance of hypophyseal, pituitary and adrenal hormones in patients with cluster headache.

    Science.gov (United States)

    Strittmatter, M; Hamann, G F; Grauer, M; Fischer, C; Blaes, F; Hoffmann, K H; Schimrigk, K

    1996-05-17

    Twelve patients (age 43.4 +/- 6.3 years) with episodic cluster headache (CH) were examined during the cluster period. Plasma norepinephrine levels in patients suffering from CH were significantly decreased compared with the control group (p < 0.01). There were also statistically significant correlations between norepinephrine levels and clinical features of the pain attacks including duration (r = 0.75, p < 0.05), intensity (r = 0.64, p < 0.05) and frequency (r = 0.68, p < 0.06), thereby suggesting a pathophysiological involvement of the sympathetic nervous system in CH. Increased plasma levels of plasmacortisol and ACTH in patients with CH, especially in the morning and in the evening, suggest an alteration of the feedback circuit involving the hypothalamus, the pituitary and the adrenal gland, an imbalance in the hormones related to these structures, as well as an alteration of the circadian rhythm. In addition, CH patients demonstrated significantly decreased levels of norepinephrine (p < 0.05), HVA (p < 0.01) and 5-HIAA (p < 0.01) in the cerebrospinal fluid (CSF) consistent with a central genesis of CH. These significant relationships between neurochemical parameters and the clinical patterns suggest a complex interplay between the hypothalamus, neuroendocrinological parameters, activity of the autonomic nervous system and the pain of CH.

  13. Family resemblance in fat intake, nutrition attitudes and beliefs : a study among three generations of women

    NARCIS (Netherlands)

    Stafleu, A.

    1994-01-01

    In this thesis nutrition attitudes, beliefs, and fat intake in three generations of women are described. The aim of the study was twofold: the development of methods, and to study family resemblance in food habits. Based on literature study and qualitative pilot studies a questionnaire on

  14. The effect of chronic fluoxetine on social isolation-induced changes on sucrose consumption, immobility behavior, and on serotonin and dopamine function in hippocampus and ventral striatum.

    Science.gov (United States)

    Brenes, Juan C; Fornaguera, Jaime

    2009-03-02

    This study examined the effect of fluoxetine, a selective serotonin (5-HT) reuptake inhibitor, on isolation-induced changes on sucrose consumption and preference, spontaneous open-field activity, forced swimming behavior, and on tissue levels of 5-HT and dopamine (DA) in hippocampus and ventral striatum (VS). Male Sprague-Dawley rats were reared in social isolation or group housing from postnatal day 28. Thirty-two days later, half of the isolated animals were orally treated with fluoxetine (10mg/kg/day) during the following 34 days. At the end of this period, behavior was assessed and afterward ex-vivo tissue samples were obtained. It was found that fluoxetine restored isolation-increased sucrose consumption and immobility behavior, without affecting locomotor activity, which appeared slightly increased in isolated groups both treated and untreated. In the hippocampus, isolation rearing depleted 5-HT contents and increased 3,4-dihydroxyphenylacetic acid (DOPAC) levels, as well as 5-HT and DA turnover. These neurochemical alterations were reversed by fluoxetine. In VS, treated and untreated isolated rats showed higher 5-HT levels than grouped congeners. Although fluoxetine did not affect 5-HT and DA contents in this region, it slightly reversed the alterations in the 5-HT and DA turnover observed in isolated rats. Overall, social isolation impaired incentive and escape motivated behaviors. At the neurochemical level, isolation rearing affected 5-HT rather than DA activity, and this differential effect was more noticeable in hippocampus than in VS. The chronic treatment with fluoxetine during the last month of rearing somewhat prevented these behavioral and neurochemical alterations. Our data suggest that isolation rearing is an appropriate procedure to model some developmental-related alterations underlying depression disorders.

  15. Reducing prefrontal gamma-aminobutyric acid activity induces cognitive, behavioral, and dopaminergic abnormalities that resemble schizophrenia.

    Science.gov (United States)

    Enomoto, Takeshi; Tse, Maric T; Floresco, Stan B

    2011-03-01

    Perturbations in gamma-aminobutyric acid (GABA)-related markers have been reported in the prefrontal cortex of schizophrenic patients. However, a preclinical assessment of how suppression of prefrontal cortex GABA activity may reflect behavioral and cognitive pathologies observed in schizophrenia is forthcoming. We assessed the effects of pharmacologic blockade of prefrontal cortex GABA(A) receptors in rats on executive functions and other behaviors related to schizophrenia, as well as neural activity of midbrain dopamine neurons. Blockade of prefrontal cortex GABA(A) receptors with bicuculline (12.5-50 ng) did not affect working memory accuracy but did increase response latencies, resembling speed of processing deficits observed in schizophrenia. Prefrontal cortex GABA(A) blockade did not impede simple discrimination or reversal learning but did impair set-shifting in a manner dependent on when these treatments were given. Reducing GABA activity before the set-shift impaired the ability to acquire a novel strategy, whereas treatment before the initial discrimination increased perseveration during the shift. Latent inhibition was unaffected by bicuculline infusions before the preexposure/conditioning phases, suggesting that reduced prefrontal cortex GABA activity does not impair "learned irrelevance." GABA(A) blockade increased locomotor activity and showed synergic effects with a subthreshold dose of amphetamine. Furthermore, reducing medial prefrontal cortex GABA activity selectively increased phasic burst firing of ventral tegmental area dopamine neurons, without altering the their overall population activity. These results suggest that prefrontal cortex GABA hypofunction may be a key contributing factor to deficits in speed of processing, cognitive flexibility, and enhanced phasic dopamine activity observed in schizophrenia. Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  16. Altered metabolic signature in pre-diabetic NOD mice.

    Directory of Open Access Journals (Sweden)

    Rasmus Madsen

    Full Text Available Altered metabolism proceeding seroconversion in children progressing to Type 1 diabetes has previously been demonstrated. We tested the hypothesis that non-obese diabetic (NOD mice show a similarly altered metabolic profile compared to C57BL/6 mice. Blood samples from NOD and C57BL/6 female mice was collected at 0, 1, 2, 3, 4, 5, 6, 7, 9, 11, 13 and 15 weeks and the metabolite content was analyzed using GC-MS. Based on the data of 89 identified metabolites OPLS-DA analysis was employed to determine the most discriminative metabolites. In silico analysis of potential involved metabolic enzymes was performed using the dbSNP data base. Already at 0 weeks NOD mice displayed a unique metabolic signature compared to C57BL/6. A shift in the metabolism was observed for both strains the first weeks of life, a pattern that stabilized after 5 weeks of age. Multivariate analysis revealed the most discriminative metabolites, which included inosine and glutamic acid. In silico analysis of the genes in the involved metabolic pathways revealed several SNPs in either regulatory or coding regions, some in previously defined insulin dependent diabetes (Idd regions. Our result shows that NOD mice display an altered metabolic profile that is partly resembling the previously observation made in children progressing to Type 1 diabetes. The level of glutamic acid was one of the most discriminative metabolites in addition to several metabolites in the TCA cycle and nucleic acid components. The in silico analysis indicated that the genes responsible for this reside within previously defined Idd regions.

  17. Altering Height Data by Using Natural Logarithm as 3D Modelling Function for Reverse Engineering Application

    Science.gov (United States)

    Ilham Aminullah Abdulqawi, Nur; Salman Abu Mansor, Mohd

    2018-01-01

    The raw data extracted from reverse engineering based on vision mostly do not resemble the actual geometrical representation yet. Even though the higher object surface reflected the most visible light towards the camera and yield higher number of value based on Lambertian illumination model, this does not mean the curvature profile are always accurate. After all, there are many mathematical models to shape curvature profiles into the correct representation. However, one of the most appropriate models found is the natural logarithm function. The function itself has alteration properties towards the raw data generated from reverse engineering based on vision.

  18. Gastrointestinal symptoms resembling ulcerative proctitis caused by larvae of the drone fly Eristalis tenax.

    Science.gov (United States)

    Desoubeaux, Guillaume; Gaillard, Julien; Borée-Moreau, Diane; Bailly, Éric; Andres, Christian R; Chandenier, Jacques

    2014-04-01

    We report a case of facultative intestinal myiasis due to larvae of the drone fly Eristalis tenax, also named the rat-tailed maggots. The development of larvae in the lower bowel was responsible for non-specific gastrointestinal symptoms that resembled ulcerative proctitis. The diagnosis was established upon the observation of four spontaneously excreted mobile larvae. The definite identification of the E. tenax species was made possible by scanning electron microscopy. The clinical outcome was satisfactory.

  19. [Synchronous Double Cancer Involving Gastric Cancer Resembling a Submucosal Tumor with Stenosis in the Pylorus and Ascending Colon Cancer - A Case Report].

    Science.gov (United States)

    Miyauchi, Tatsuomi; Miyaki, Akira; Ida, Arika; Kishibe, Saki; Yamaguchi, Kentaro; Shiozawa, Shunichi; Usui, Takebumi; Kuhara, Kotaro; Kono, Teppei; Naritaka, Yoshihiko

    2016-11-01

    An 82-year-old woman presented to our hospital with a complaint of frequent vomiting. She was admitted for intensive examination and treatment. Abdominal computed tomography revealed that her stomach was severely expanded, and the wall of the ascending colon was thickened throughout its circumference. Upper gastrointestinal endoscopy uncovered severe stenosis in the pylorus and an elevated lesion resembling a submucosal tumor on the posterior wall of the pylorus. Biopsies of the lesion revealed that it was of Group 1. On colonoscopy, type 2 cancer was found in the ascending colon throughout the circumference, and the biopsies revealed that it was of Group 5. Upper gastrointestinal endoscopy was repeated, and the same result was obtained. The possibility of malignancy could not be excluded; therefore, distal gastrectomy and right colectomy were performed. In terms of histopathology, both resected specimens displayed poorly differentiated adenocarcinoma; however, immunohistochemical studies revealed differences in staining at the two sites. The case was diagnosed as synchronous double cancer involving gastric cancer resembling a submucosal tumor with stenosis in the pylorus and ascending colon cancer. Gastric cancer resembling a submucosal tumor is usually difficult to diagnose on biopsy. If the endoscopic findings reveal an elevated lesion resembling a submucosal tumor with stenosis, then the possibility of carcinoma should be considered, and the most suitable treatment should be selected.

  20. Combining different views of mammographic texture resemblance (MTR) marker of breast cancer risk

    DEFF Research Database (Denmark)

    Sun, S.; Karemore, Gopal; Chernoff, Konstantin

    the subsequent 4 years whereas 245 cases had a diagnosis 2-4 years post mammography. We employed the MTR supervised texture learning framework to perform risk evaluation from a single mammography view. In the framework 20,000 pixels were sampled and classified by a kNN pixel classifier. A feature selection step......PURPOSE Mammographic density is a well established breast cancer risk factor. Texture analysis in terms of the Mammographoc Texture Resemblance (MTR) marker has recently shown to add to risk segregation. Hitherto only single view MTR analysis has been performed. Standard mammography examinations...

  1. Inhalation exposure to white spirit causes region-dependent alterations in the levels of glial fibrillary acidic protein

    DEFF Research Database (Denmark)

    Lam, Henrik Rye; Ladefoged, Ole; østergaard, G.

    2000-01-01

    Enhanced expression of glial fibrillary acidic protein (GFAP) is known to be associated with toxicant-induced gliosis, a homotypic response of the central nervous system to neural injury. A variety of neurochemical and neurophysiological effects have been observed in experimental animals exposed ...

  2. Rapid generation of mitochondrial superoxide induces mitochondrion-dependent but caspase-independent cell death in hippocampal neuronal cells that morphologically resembles necroptosis

    International Nuclear Information System (INIS)

    Fukui, Masayuki; Choi, Hye Joung; Zhu, Bao Ting

    2012-01-01

    Studies in recent years have revealed that excess mitochondrial superoxide production is an important etiological factor in neurodegenerative diseases, resulting from oxidative modifications of cellular lipids, proteins, and nucleic acids. Hence, it is important to understand the mechanism by which mitochondrial oxidative stress causes neuronal death. In this study, the immortalized mouse hippocampal neuronal cells (HT22) in culture were used as a model and they were exposed to menadione (also known as vitamin K 3 ) to increase intracellular superoxide production. We found that menadione causes preferential accumulation of superoxide in the mitochondria of these cells, along with the rapid development of mitochondrial dysfunction and cellular ATP depletion. Neuronal death induced by menadione is independent of the activation of the MAPK signaling pathways and caspases. The lack of caspase activation is due to the rapid depletion of cellular ATP. It was observed that two ATP-independent mitochondrial nucleases, namely, AIF and Endo G, are released following menadione exposure. Silencing of their expression using specific siRNAs results in transient suppression (for ∼ 12 h) of mitochondrial superoxide-induced neuronal death. While suppression of the mitochondrial superoxide dismutase expression markedly sensitizes neuronal cells to mitochondrial superoxide-induced cytotoxicity, its over-expression confers strong protection. Collectively, these findings showed that many of the observed features associated with mitochondrial superoxide-induced cell death, including caspase independency, rapid depletion of ATP level, mitochondrial release of AIF and Endo G, and mitochondrial swelling, are distinctly different from those of apoptosis; instead they resemble some of the known features of necroptosis. -- Highlights: ► Menadione causes mitochondrial superoxide accumulation and injury. ► Menadione-induced cell death is caspase-independent, due to rapid depletion of ATP

  3. Rapid generation of mitochondrial superoxide induces mitochondrion-dependent but caspase-independent cell death in hippocampal neuronal cells that morphologically resembles necroptosis

    Energy Technology Data Exchange (ETDEWEB)

    Fukui, Masayuki; Choi, Hye Joung; Zhu, Bao Ting, E-mail: BTZhu@kumc.edu

    2012-07-15

    Studies in recent years have revealed that excess mitochondrial superoxide production is an important etiological factor in neurodegenerative diseases, resulting from oxidative modifications of cellular lipids, proteins, and nucleic acids. Hence, it is important to understand the mechanism by which mitochondrial oxidative stress causes neuronal death. In this study, the immortalized mouse hippocampal neuronal cells (HT22) in culture were used as a model and they were exposed to menadione (also known as vitamin K{sub 3}) to increase intracellular superoxide production. We found that menadione causes preferential accumulation of superoxide in the mitochondria of these cells, along with the rapid development of mitochondrial dysfunction and cellular ATP depletion. Neuronal death induced by menadione is independent of the activation of the MAPK signaling pathways and caspases. The lack of caspase activation is due to the rapid depletion of cellular ATP. It was observed that two ATP-independent mitochondrial nucleases, namely, AIF and Endo G, are released following menadione exposure. Silencing of their expression using specific siRNAs results in transient suppression (for ∼ 12 h) of mitochondrial superoxide-induced neuronal death. While suppression of the mitochondrial superoxide dismutase expression markedly sensitizes neuronal cells to mitochondrial superoxide-induced cytotoxicity, its over-expression confers strong protection. Collectively, these findings showed that many of the observed features associated with mitochondrial superoxide-induced cell death, including caspase independency, rapid depletion of ATP level, mitochondrial release of AIF and Endo G, and mitochondrial swelling, are distinctly different from those of apoptosis; instead they resemble some of the known features of necroptosis. -- Highlights: ► Menadione causes mitochondrial superoxide accumulation and injury. ► Menadione-induced cell death is caspase-independent, due to rapid depletion of

  4. SU-E-I-34: Intermittent Low- and High-Dose Ethanol Exposure Alters Neurochemical Responses in Adult Rat Brain: An Ex Vivo 1H NMR Spectroscopy at 11.7 T

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Do-Wan; Kim, Sang-Young; Song, Kyu-Ho; Choe, Bo-Young [Department of Biomedical Engineering, and Research Institute of Biomedical Engineering, The Catholic University of Korea College of Medicine, Seoul (Korea, Republic of)

    2014-06-01

    Purpose: The first goal of this study was to determine the influence of the dose-dependent effects of intermittent ethanol intoxication on cerebral neurochemical responses among sham controls and low- and high-dose-ethanol-exposed rats with ex vivo high-resolution spectra. The second goal of this study was to determine the correlations between the metabolite-metabolite levels (pairs-of-metabolite levels) from all of the individual data from the frontal cortex of the intermittent ethanol-intoxicated rats. Methods: Eight-week-old male Wistar rats were divided into 3 groups. Twenty rats in the LDE (n = 10) and the HDE (n = 10) groups received ethanol doses of 1.5 g/kg and 2.5 g/kg, respectively, through oral gavage every 8-h for 4 days. At the end of the 4-day intermittent ethanol exposure, one-dimensional ex vivo 500-MHz proton nuclear magnetic resonance spectra were acquired from 30 samples of the frontal cortex region (from the 3 groups). Results: Normalized total-N-acetylaspartate (tNAA: NAA + NAAG [N-acetylaspartyl-glutamate]), gamma-aminobutyric acid (GABA), and glutathione (GSH) levels were significantly lower in the frontal cortex of the HDE-exposed rats than that of the LDE-exposed rats. Moreover, compared to the CNTL group, the LDE rats exhibited significantly higher normalized GABA levels. The 6 pairs of normalized metabolite levels were positively (+) or negatively (−) correlated in the rat frontal cortex as follows: tNAA and GABA (+), tNAA and Aspartate (Asp) (−), myo-Inositol (mIns) and Asp (−), mIns and Alanine (+), mIns and Taurine (+), and mIns and tNAA (−). Conclusion: Our results suggested that repeated intermittent ethanol intoxication might result in neuronal degeneration and dysfunction, changes in the rate of GABA synthesis, and oxidative stress in the rat frontal cortex. Our ex vivo 1H high-resolution-magic angle spinning nuclear magnetic resonance spectroscopy results suggested some novel metabolic markers for the dose

  5. SU-E-I-34: Intermittent Low- and High-Dose Ethanol Exposure Alters Neurochemical Responses in Adult Rat Brain: An Ex Vivo 1H NMR Spectroscopy at 11.7 T

    International Nuclear Information System (INIS)

    Lee, Do-Wan; Kim, Sang-Young; Song, Kyu-Ho; Choe, Bo-Young

    2014-01-01

    Purpose: The first goal of this study was to determine the influence of the dose-dependent effects of intermittent ethanol intoxication on cerebral neurochemical responses among sham controls and low- and high-dose-ethanol-exposed rats with ex vivo high-resolution spectra. The second goal of this study was to determine the correlations between the metabolite-metabolite levels (pairs-of-metabolite levels) from all of the individual data from the frontal cortex of the intermittent ethanol-intoxicated rats. Methods: Eight-week-old male Wistar rats were divided into 3 groups. Twenty rats in the LDE (n = 10) and the HDE (n = 10) groups received ethanol doses of 1.5 g/kg and 2.5 g/kg, respectively, through oral gavage every 8-h for 4 days. At the end of the 4-day intermittent ethanol exposure, one-dimensional ex vivo 500-MHz proton nuclear magnetic resonance spectra were acquired from 30 samples of the frontal cortex region (from the 3 groups). Results: Normalized total-N-acetylaspartate (tNAA: NAA + NAAG [N-acetylaspartyl-glutamate]), gamma-aminobutyric acid (GABA), and glutathione (GSH) levels were significantly lower in the frontal cortex of the HDE-exposed rats than that of the LDE-exposed rats. Moreover, compared to the CNTL group, the LDE rats exhibited significantly higher normalized GABA levels. The 6 pairs of normalized metabolite levels were positively (+) or negatively (−) correlated in the rat frontal cortex as follows: tNAA and GABA (+), tNAA and Aspartate (Asp) (−), myo-Inositol (mIns) and Asp (−), mIns and Alanine (+), mIns and Taurine (+), and mIns and tNAA (−). Conclusion: Our results suggested that repeated intermittent ethanol intoxication might result in neuronal degeneration and dysfunction, changes in the rate of GABA synthesis, and oxidative stress in the rat frontal cortex. Our ex vivo 1H high-resolution-magic angle spinning nuclear magnetic resonance spectroscopy results suggested some novel metabolic markers for the dose

  6. Monocyte activation, brain-derived neurotrophic factor (BDNF), and S100B in bipolar offspring : a follow-up study from adolescence into adulthood

    NARCIS (Netherlands)

    Mesman, Esther; Hillegers, Manon H. J.; Ambree, Oliver; Arolt, Volker; Nolen, Willem A.; Drexhage, Hemmo A.

    ObjectivesThere is increasing evidence that both immune and neurochemical alterations are involved in the pathogenesis of bipolar disorder; however, their precise role remains unclear. In this study, we aimed to evaluate neuro-immune changes in a prospective study on children of patients with

  7. Monocyte activation, brain-derived neurotrophic factor (BDNF), and S100B in bipolar offspring : A follow-up study from adolescence into adulthood

    NARCIS (Netherlands)

    Mesman, Esther; Hillegers, Manon H J; Ambree, Oliver; Arolt, Volker; Nolen, Willem A.; Drexhage, Hemmo A.

    Objectives: There is increasing evidence that both immune and neurochemical alterations are involved in the pathogenesis of bipolar disorder; however, their precise role remains unclear. In this study, we aimed to evaluate neuro-immune changes in a prospective study on children of patients with

  8. Regional distribution of biogenic amines, amino acids and cholinergic markers in the CNS of the C57BL/6 strain

    NARCIS (Netherlands)

    Van Dam, D; Marescau, B; Cremers, T; Mulder, J; Engelborghs, S; De Deyn, PP

    A reliable extrapolation of neurochemical alterations from a mouse model to human metabolic brain disease requires knowledge of neurotransmitter levels and related compounds in control mouse brain. C57BL/6 is a widely used background strain for knockout and transgenic mouse models. A prerequisite

  9. A Drosophila gene encoding a protein resembling the human β-amyloid protein precursor

    International Nuclear Information System (INIS)

    Rosen, D.R.; Martin-Morris, L.; Luo, L.; White, K.

    1989-01-01

    The authors have isolated genomic and cDNA clones for a Drosophila gene resembling the human β-amyloid precursor protein (APP). This gene produces a nervous system-enriched 6.5-kilobase transcript. Sequencing of cDNAs derived from the 6.5-kilobase transcript predicts an 886-amino acid polypeptide. This polypeptide contains a putative transmembrane domain and exhibits strong sequence similarity to cytoplasmic and extracellular regions of the human β-amyloid precursor protein. There is a high probability that this Drosophila gene corresponds to the essential Drosophila locus vnd, a gene required for embryonic nervous system development

  10. Socioeconomic and Demographic Factors for Spousal Resemblance in Obesity Status and Habitual Physical Activity in the United States

    Directory of Open Access Journals (Sweden)

    Hsin-Jen Chen

    2014-01-01

    Full Text Available Studies suggested that the married population has an increased risk of obesity and assimilation between spouses’ body weight. We examined what factors may affect married spouses’ resemblance in weight status and habitual physical activity (HPA and the association of obesity/HPA with spouses’ sociodemoeconomic characteristics and lifestyles. Medical Expenditure Panel Survey data of 11,403 adult married couples in the US during years 2006–2008 were used. Absolute-scale difference and relative-scale resemblance indices (correlation and kappa coefficients in body mass index (BMI and HPA were estimated by couples’ socioeconomic and demographic characteristics. We found that spousal difference in BMI was smaller for couples with a lower household income, for who were both unemployed, and for older spouses. Correlation coefficient between spouses’ BMI was 0.24, differing by race/ethnicity and family size. Kappa coefficient for weight status (obesity: BMI ≥ 30, overweight: 30 > BMI ≥ 25 was 0.11 and 0.35 for HPA. Never-working women’s husbands had lower odds of obesity than employed women’s husbands (OR = 0.69 (95% CI = 0.53–0.89. Men’s unemployment status was associated with wives’ greater odds of obesity (OR = 1.31 (95% CI = 1.01–1.71. HPA was associated with men’s employment status and income level, but not with women’s. The population representative survey showed that spousal resemblance in weight status and HPA varied with socioeconomic and demographic factors.

  11. ¹H MRS characterization of neurochemical profiles in orthotopic mouse models of human brain tumors.

    Science.gov (United States)

    Hulsey, Keith M; Mashimo, Tomoyuki; Banerjee, Abhishek; Soesbe, Todd C; Spence, Jeffrey S; Vemireddy, Vamsidhara; Maher, Elizabeth A; Bachoo, Robert M; Choi, Changho

    2015-01-01

    Glioblastoma (GBM), the most common primary brain tumor, is resistant to currently available treatments. The development of mouse models of human GBM has provided a tool for studying mechanisms involved in tumor initiation and growth as well as a platform for preclinical investigation of new drugs. In this study we used (1) H MR spectroscopy to study the neurochemical profile of a human orthotopic tumor (HOT) mouse model of human GBM. The goal of this study was to evaluate differences in metabolite concentrations in the GBM HOT mice when compared with normal mouse brain in order to determine if MRS could reliably differentiate tumor from normal brain. A TE =19 ms PRESS sequence at 9.4 T was used for measuring metabolite levels in 12 GBM mice and 8 healthy mice. Levels for 12 metabolites and for lipids/macromolecules at 0.9 ppm and at 1.3 ppm were reliably detected in all mouse spectra. The tumors had significantly lower concentrations of total creatine, GABA, glutamate, total N-acetylaspartate, aspartate, lipids/macromolecules at 0.9 ppm, and lipids/macromolecules at 1.3 ppm than did the brains of normal mice. The concentrations of glycine and lactate, however, were significantly higher in tumors than in normal brain. Copyright © 2014 John Wiley & Sons, Ltd.

  12. Altered excitatory-inhibitory balance in the NMDA-hypofunction model of schizophrenia

    Directory of Open Access Journals (Sweden)

    Colin Kehrer

    2008-04-01

    Full Text Available Schizophrenia is a common psychiatric disorder of high incidence, affecting approximately 1% of the world population. The essential neurotransmitter pathology of schizophrenia remains poorly defined, despite huge advances over the past half-century in identifying neurochemical and pathological abnormalities in the disease. The dopamine/serotonin hypothesis has originally provided much of the momentum for neurochemical research in schizophrenia. In recent years, the attention has, however, shifted to the glutamate system, the major excitatory neurotransmitter in the CNS and towards a concept of functional imbalance between excitatory and inhibitory transmission at the network level in various brain regions in schizophrenia. The evidence indicating a central role for the NMDAreceptor subtype in the etiology of schizophrenia has led to the NMDA-hypofunction model of this disease and the use of phencyclidines as a means to induce the NMDA-hypofunction state in animal models. The purpose of this review is to discuss recent findings highlighting the importance of the NMDA-hypofunction model of schizophrenia, both from a clinical perspective, as well as in opening a line of research, which enables electrophysiological studies at the cellular and network level in vitro. In particular, changes in excitation-inhibition (E/I balance in the NMDA-hypofunction model of the disease and the resulting changes in network behaviours, particularly in gamma frequency oscillatory activity, will be discussed.

  13. Cerebrospinal fluid metabolomics reveals altered waste clearance and accelerated aging in HIV patients with neurocognitive impairment

    Science.gov (United States)

    Cassol, Edana; Misra, Vikas; Dutta, Anupriya; Morgello, Susan; Gabuzda, Dana

    2014-01-01

    Objective(s): HIV-associated neurocognitive disorders (HAND) remain prevalent in HIV-infected patients on antiretroviral therapy (ART), but the underlying mechanisms are unclear. Some features of HAND resemble those of age-associated cognitive decline in the absence of HIV, suggesting that overlapping mechanisms may contribute to neurocognitive impairment. Design: Cross-sectional analysis of cerebrospinal fluid (CSF) from 100 individuals (46 HIV-positive patients and 54 HIV-negative controls). Methods: Untargeted CSF metabolite profiling was performed using liquid/gas chromatography followed by mass spectrometry. Cytokine profiling was performed by Bioplex. Bioinformatic analyses were performed in Metaboanalyst and R. Results: Alterations in the CSF metabolome of HIV patients on ART mapped to pathways associated with neurotransmitter production, mitochondrial function, oxidative stress, and metabolic waste. Many CSF metabolites altered in HIV overlapped with those altered with advanced age in HIV-negative controls, suggesting a pattern indicative of accelerated aging. Machine learning models identified neurotransmitters (glutamate, N-acetylaspartate), markers of glial activation (myo-inositol), and ketone bodies (beta-hydroxybutyric acid, 1,2-propanediol) as top-ranked classifiers of HAND. These CSF metabolites correlated with worse neurocognitive test scores, plasma inflammatory biomarkers [interferon (IFN)-α, IFN-γ, interleukin (IL)-8, IL-1β, IL-6, IL-2Ra], and intrathecal IFN responses (IFN-γ and kynurenine : tryptophan ratio), suggesting inter-relationships between systemic and intrathecal inflammation and metabolic alterations in CSF. Conclusions: Alterations in the CSF metabolome of HIV patients on ART suggest that persistent inflammation, glial responses, glutamate neurotoxicity, and altered brain waste disposal systems contribute to mechanisms involved in HAND that may be augmented with aging. PMID:24752083

  14. Atypical mycobacterial infection resembles sporotrichosis in elderly patient

    Directory of Open Access Journals (Sweden)

    Siti Nurani Fauziah

    2018-04-01

    Full Text Available Atypical mycobacterial (AM infection is caused by Mycobacterium species other than M.tuberculosis. AM skin infection has clinical manifestations that resemble M. tuberculosis infection and deep fungal infection. Laboratory workup is necessary to confirm the diagnosis. An 83-year old female came with a painful lump and swelling on her right lower extremity since three months before admission. Physical examination revealed a plaque consisting, of multiple erythematous and hyperpigmented papules and nodules, diffuse erythematous lesion, and shallow ulcers partially covered with pus and crust. Histopathological features showed tuberculoid granuloma. Direct test and periodic acid-Schiff (PAS staining of the skin biopsy found no fungal element nor acid-fast bacilli (AFB. Culture and polymerase chain reaction (PCR of M. tuberculosis were negative. The working diagnosis was atypical mycobacterial infection and treatment with 450 mg rifampicin and 100 mg minocycline daily were administered accordingly. In two months observation following the treatment, the pain was no longer exist, the ulcers were completely healed, and some nodules were in the process of healing Among other Mycobacterium spp, M.marinum is the most common cause of AM infrections. Clinical manifestation of M. marinum infection may present as solitary or multiple nodules on the hands, feet, elbows and knees with sporotrichoid spreading patern. The diagnosis of AM was established based on clinical and laboratory examination. The diagnosis was also confirmed by good clinical response to minocycline and rifampicin.

  15. From FRA to RFN, or How the Family Resemblance Approach Can Be Transformed for Science Curriculum Analysis on Nature of Science

    Science.gov (United States)

    Kaya, Ebru; Erduran, Sibel

    2016-12-01

    The inclusion of Nature of Science (NOS) in the science curriculum has been advocated around the world for several decades. One way of defining NOS is related to the family resemblance approach (FRA). The family resemblance idea was originally described by Wittgenstein. Subsequently, philosophers and educators have applied Wittgenstein's idea to problems of their own disciplines. For example, Irzik and Nola adapted Wittgenstein's generic definition of the family resemblance idea to NOS, while Erduran and Dagher reconceptualized Irzik and Nola's FRA-to-NOS by synthesizing educational applications by drawing on perspectives from science education research. In this article, we use the terminology of "Reconceptualized FRA-to-NOS (RFN)" to refer to Erduran and Dagher's FRA version which offers an educational account inclusive of knowledge about pedagogical, instructional, curricular and assessment issues in science education. Our motivation for making this distinction is rooted in the need to clarify the various accounts of the family resemblance idea.The key components of the RFN include the aims and values of science, methods and methodological rules, scientific practices, scientific knowledge as well as the social-institutional dimensions of science including the social ethos, certification, and power relations. We investigate the potential of RFN in facilitating curriculum analysis and in determining the gaps related to NOS in the curriculum. We analyze two Turkish science curricula published 7 years apart and illustrate how RFN can contribute not only to the analysis of science curriculum itself but also to trends in science curriculum development. Furthermore, we present an analysis of documents from USA and Ireland and contrast them to the Turkish curricula thereby illustrating some trends in the coverage of RFN categories. The results indicate that while both Turkish curricula contain statements that identify science as a cognitive-epistemic system, they

  16. Spinal Cord Stimulation Alters Protein Levels in the Cerebrospinal Fluid of Neuropathic Pain Patients: A Proteomic Mass Spectrometric Analysis.

    Science.gov (United States)

    Lind, Anne-Li; Emami Khoonsari, Payam; Sjödin, Marcus; Katila, Lenka; Wetterhall, Magnus; Gordh, Torsten; Kultima, Kim

    2016-08-01

    Electrical neuromodulation by spinal cord stimulation (SCS) is a well-established method for treatment of neuropathic pain. However, the mechanism behind the pain relieving effect in patients remains largely unknown. In this study, we target the human cerebrospinal fluid (CSF) proteome, a little investigated aspect of SCS mechanism of action. Two different proteomic mass spectrometry protocols were used to analyze the CSF of 14 SCS responsive neuropathic pain patients. Each patient acted as his or her own control and protein content was compared when the stimulator was turned off for 48 hours, and after the stimulator had been used as normal for three weeks. Eighty-six proteins were statistically significantly altered in the CSF of neuropathic pain patients using SCS, when comparing the stimulator off condition to the stimulator on condition. The top 12 of the altered proteins are involved in neuroprotection (clusterin, gelsolin, mimecan, angiotensinogen, secretogranin-1, amyloid beta A4 protein), synaptic plasticity/learning/memory (gelsolin, apolipoprotein C1, apolipoprotein E, contactin-1, neural cell adhesion molecule L1-like protein), nociceptive signaling (neurosecretory protein VGF), and immune regulation (dickkopf-related protein 3). Previously unknown effects of SCS on levels of proteins involved in neuroprotection, nociceptive signaling, immune regulation, and synaptic plasticity are demonstrated. These findings, in the CSF of neuropathic pain patients, expand the picture of SCS effects on the neurochemical environment of the human spinal cord. An improved understanding of SCS mechanism may lead to new tracks of investigation and improved treatment strategies for neuropathic pain. © 2016 International Neuromodulation Society.

  17. Synthesis of hydroxylated sterols in transgenic Arabidopsis plants alters growth and steroid metabolism.

    Science.gov (United States)

    Beste, Lisa; Nahar, Nurun; Dalman, Kerstin; Fujioka, Shozo; Jonsson, Lisbeth; Dutta, Paresh C; Sitbon, Folke

    2011-09-01

    To explore mechanisms in plant sterol homeostasis, we have here increased the turnover of sterols in Arabidopsis (Arabidopsis thaliana) and potato (Solanum tuberosum) plants by overexpressing four mouse cDNA encoding cholesterol hydroxylases (CHs), hydroxylating cholesterol at the C-7, C-24, C-25, or C-27 positions. Compared to the wild type, the four types of Arabidopsis transformant showed varying degrees of phenotypic alteration, the strongest one being in CH25 lines, which were dark-green dwarfs resembling brassinosteroid-related mutants. Gas chromatography-mass spectrometry analysis of extracts from wild-type Arabidopsis plants revealed trace levels of α and β forms of 7-hydroxycholesterol, 7-hydroxycampesterol, and 7-hydroxysitosterol. The expected hydroxycholesterol metabolites in CH7-, CH24-, and CH25 transformants were identified and quantified using gas chromatography-mass spectrometry. Additional hydroxysterol forms were also observed, particularly in CH25 plants. In CH24 and CH25 lines, but not in CH7 ones, the presence of hydroxysterols was correlated with a considerable alteration of the sterol profile and an increased sterol methyltransferase activity in microsomes. Moreover, CH25 lines contained clearly reduced levels of brassinosteroids, and displayed an enhanced drought tolerance. Equivalent transformations of potato plants with the CH25 construct increased hydroxysterol levels, but without the concomitant alteration of growth and sterol profiles observed in Arabidopsis. The results suggest that an increased hydroxylation of cholesterol and/or other sterols in Arabidopsis triggers compensatory processes, acting to maintain sterols at adequate levels.

  18. Basic perceptual changes that alter meaning and neural correlates of recognition memory

    Directory of Open Access Journals (Sweden)

    Chuanji eGao

    2015-02-01

    Full Text Available It is difficult to pinpoint the border between perceptual and conceptual processing, despite their treatment as distinct entities in many studies of recognition memory. For instance, alteration of simple perceptual characteristics of a stimulus can radically change meaning, such as the color of bread changing from white to green. We sought to better understand the role of perceptual and conceptual processing in memory by identifying the effects of changing a basic perceptual feature (color on behavioral and neural correlates of memory in circumstances when this change would be expected to either change the meaning of a stimulus or to have no effect on meaning (i.e., to influence conceptual processing or not. Abstract visual shapes (squiggles were colorized during study and presented during test in either the same color or a different color. Those squiggles that subjects found to resemble meaningful objects supported behavioral measures of conceptual priming, whereas meaningless squiggles did not. Further, changing color from study to test had a selective effect on behavioral correlates of priming for meaningful squiggles, indicating that color change altered conceptual processing. During a recognition memory test, color change altered event-related brain potential correlates of memory for meaningful squiggles but not for meaningless squiggles. Specifically, color change reduced the amplitude of frontally distributed N400 potentials (FN400, indicating that these potentials indicated conceptual processing during recognition memory that was sensitive to color change. In contrast, color change had no effect on FN400 correlates of recognition for meaningless squiggles, which were overall smaller in amplitude than for meaningful squiggles (further indicating that these potentials signal conceptual processing during recognition. Thus, merely changing the color of abstract visual shapes can alter their meaning, changing behavioral and neural correlates

  19. The psychological and neurochemical mechanisms of drug memory reconsolidation: implications for the treatment of addiction.

    Science.gov (United States)

    Milton, Amy L; Everitt, Barry J

    2010-06-01

    Memory reconsolidation is the process by which memories, destabilised at retrieval, require restabilisation to persist in the brain. It has been demonstrated that even old, well-established memories require reconsolidation following retrieval; therefore, memory reconsolidation could potentially be exploited to disrupt, or even erase, aberrant memories that underlie psychiatric disorders, thereby providing a novel therapeutic target. Drug addiction is one such disorder; it is both chronic and relapsing, and one prominent risk factor for a relapse episode is the presentation of environmental cues that have previously been associated with drugs of abuse. This 'cue-induced relapse' can be accounted for in psychological terms by reinforcing memories of the pavlovian association between the cue and the drug, which can thus influence behaviour through at least three psychologically and neurobiologically dissociable mechanisms: conditioned reinforcement, conditioned approach and conditioned motivation. As each of these psychological processes could contribute to the resumption of drug-seeking following abstinence, it is important to develop treatments that can reduce drug-seeking re-established via influences on each or all of these pavlovian processes, in order to minimise the risk of a subsequent relapse. Investigation of the memory reconsolidation mechanisms of the memories underlying conditioned reinforcement, conditioned approach and conditioned motivation indicate that they depend upon different neurochemical systems, including the glutamatergic and adrenergic systems within limbic corticostriatal circuitry. We also discuss here the subsequent translation to the clinic of this preclinical work.

  20. Prion disease resembling frontotemporal dementia and parkinsonism linked to chromosome 17

    Directory of Open Access Journals (Sweden)

    Nitrini Ricardo

    2001-01-01

    Full Text Available OBJECTIVE: To compare the clinical features of a familial prion disease with those of frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17. BACKGROUND: Prion diseases are not usually considered in the differential diagnosis of FTDP-17, since familial Creutzfeldt-Jakob disease (CJD, the most common inherited prion disease, often manifests as a rapidly progressive dementia. Conversely, FTDP-17 usually has an insidious onset in the fifth decade, with abnormal behavior and parkinsonian features. METHOD: We present the clinical features of 12 patients from a family with CJD associated with a point mutation at codon 183 of the prion protein gene. RESULTS: The mean age at onset was 44.0 ± 3.7; the duration of the symptoms until death ranged from two to nine years. Behavioral disturbances were the predominant presenting symptoms. Nine patients were first seen by psychiatrists. Eight patients manifested parkinsonian signs. CONCLUSION: These clinical features bear a considerable resemblance to those described in FTDP-17.

  1. On Learning Natural-Science Categories That Violate the Family-Resemblance Principle.

    Science.gov (United States)

    Nosofsky, Robert M; Sanders, Craig A; Gerdom, Alex; Douglas, Bruce J; McDaniel, Mark A

    2017-01-01

    The general view in psychological science is that natural categories obey a coherent, family-resemblance principle. In this investigation, we documented an example of an important exception to this principle: Results of a multidimensional-scaling study of igneous, metamorphic, and sedimentary rocks (Experiment 1) suggested that the structure of these categories is disorganized and dispersed. This finding motivated us to explore what might be the optimal procedures for teaching dispersed categories, a goal that is likely critical to science education in general. Subjects in Experiment 2 learned to classify pictures of rocks into compact or dispersed high-level categories. One group learned the categories through focused high-level training, whereas a second group was required to simultaneously learn classifications at a subtype level. Although high-level training led to enhanced performance when the categories were compact, subtype training was better when the categories were dispersed. We provide an interpretation of the results in terms of an exemplar-memory model of category learning.

  2. Imaging manifestations of acquired elastopathy resembling pseudoxanthoma elasticum in patients with beta thalassaemia major and sickle cell disease

    International Nuclear Information System (INIS)

    Narayana, Harish; Cheng, Ken; Lau, Ken; Harish, Radhika; Bowden, Donald K.

    2016-01-01

    Development of an acquired systemic elastopathy resembling pseudoxanthoma elasticum in patients with chronic haemoglobinopathies such as beta thalassaemia major and sickle cell disease is well documented. There is paucity of any comprehensive literature on the radiological manifestations of this entity. This pictorial review aims to describe and illustrate the multi system and multi modality imaging findings of this condition.

  3. What's in a child's face? : effects of facial resemblance, love withdrawal, empathy and context on behavioral and neural responses

    NARCIS (Netherlands)

    Heckendorf, E.

    2018-01-01

    The aim of this thesis is to increase our knowledge of individual differences in the neural processing and appraisal of children’s faces that differ in their degree of resemblance with the participant’s face. Chapter 2 focuses on participants’ neural responses to child faces that differ in

  4. Mammographic Texture Resemblance generalizes as an independent risk factor of breast cancer

    DEFF Research Database (Denmark)

    Chernoff, Konstantin; Christopher, S G; Karemore, Gopal

    PURPOSE Breast density has been established as a risk factor of breast cancer in numerous studies. Mammographic Texture Resemblance (MTR) has shown to be a density independent risk factor, but only on a single study. We examine if the statistics of the texture recorded in one study generalize...... as an independent risk factor in an unrelated cohort. METHOD AND MATERIALS The statistics of texture were recorded in digitalized film-mammograms of one 4-year prospective study (S1, Dutch screening program) of 245 breast cancers and 250 matched controls. From an independent cohort study (S2, Mayo Mammography...... Health Study cohort) 226 incident breast cancer cases diagnosed through 2008 and 442 matched controls (on age) were used for scoring screening digitized mammograms that were ascertained years prior to diagnosis 1993-2006. Mammographic percent density (PD), using Cumulus, and other major risk factors were...

  5. Individual behavioral and neurochemical markers of unadapted decision-making processes in healthy inbred mice.

    Science.gov (United States)

    Pittaras, Elsa; Callebert, Jacques; Chennaoui, Mounir; Rabat, Arnaud; Granon, Sylvie

    2016-12-01

    One of the hallmarks of decision-making processes is the inter-individual variability between healthy subjects. These behavioral patterns could constitute risk factors for the development of psychiatric disorders. Therefore, finding predictive markers of safe or risky decision-making is an important challenge for psychiatry research. We set up a mouse gambling task (MGT)-adapted from the human Iowa gambling task with uncertain contingencies between response and outcome that furthermore enables the emergence of inter-individual differences. Mice (n = 54) were further individually characterized for locomotive, emotional and cognitive behavior. Individual basal rates of monoamines and brain activation after the MGT were assessed in brain regions related to reward, emotion or cognition. In a large healthy mice population, 44 % showed a balanced strategy with limited risk-taking and flexible choices, 29 % showed a safe but rigid strategy, while 27 % adopted risky behavior. Risky mice took also more risks in other apparatus behavioral devices and were less sensitive to reward. No difference existed between groups regarding anxiety, working memory, locomotion and impulsivity. Safe/rigid mice exhibited a hypoactivation of prefrontal subareas, a high level of serotonin in the orbitofrontal cortex combined with a low level of dopamine in the putamen that predicted the emergence of rigid behavior. By contrast, high levels of dopamine, serotonin and noradrenalin in the hippocampus predicted the emergence of more exploratory and risky behaviors. The coping of C57bl/6J mice in MGT enables the determination of extreme patterns of choices either safe/rigid or risky/flexible, related to specific neurochemical and behavioral markers.

  6. Vaginal Microbiota of Adolescent Girls Prior to the Onset of Menarche Resemble Those of Reproductive-Age Women

    Science.gov (United States)

    Hickey, Roxana J.; Zhou, Xia; Settles, Matthew L.; Erb, Julie; Malone, Kristin; Hansmann, Melanie A.; Shew, Marcia L.; Van Der Pol, Barbara

    2015-01-01

    ABSTRACT Puberty is an important developmental stage wherein hormonal shifts mediate the physical and physiological changes that lead to menarche, but until now, the bacterial composition of vaginal microbiota during this period has been poorly characterized. We performed a prospective longitudinal study of perimenarcheal girls to gain insight into the timing and sequence of changes that occur in the vaginal and vulvar microbiota during puberty. The study enrolled 31 healthy, premenarcheal girls between the ages of 10 and 12 years and collected vaginal and vulvar swabs quarterly for up to 3 years. Bacterial composition was characterized by Roche 454 pyrosequencing and classification of regions V1 to V3 of 16S rRNA genes. Contrary to expectations, lactic acid bacteria, primarily Lactobacillus spp., were dominant in the microbiota of most girls well before the onset of menarche in the early to middle stages of puberty. Gardnerella vaginalis was detected at appreciable levels in approximately one-third of subjects, a notable finding considering that this organism is commonly associated with bacterial vaginosis in adults. Vulvar microbiota closely resembled vaginal microbiota but often exhibited additional taxa typically associated with skin microbiota. Our findings suggest that the vaginal microbiota of girls begin to resemble those of adults well before the onset of menarche. PMID:25805726

  7. Enrichment of MCI and early Alzheimer's disease treatment trials using neurochemical and imaging candidate biomarkers.

    LENUS (Irish Health Repository)

    Hampel, H

    2012-02-01

    In the earliest clinical stages of Alzheimer\\'s Disease (AD), when symptoms are mild, clinical diagnosis will still be difficult. AD related molecular mechanisms precede symptoms. Biological markers can serve as early diagnostic indicators, as markers of preclinical pathological change, e.g. underlying mechanisms of action (MoA). Hypothesis based candidates are derived from structural and functional neuroimaging as well as from cerebrospinal fluid (CSF) and plasma. Unbiased exploratory approaches e.g. proteome analysis or rater independent fully automated imaging post-processing methods yield novel candidates. Recent progress in the validation of core feasible imaging and neurochemical biomarkers for functions such as early detection, classification, progression and prediction of AD is summarized. Single core feasible biomarkers can already be used to enrich populations at risk for AD and may be further enhanced using distinct combinations. Some biomarkers are currently in the process of implementation as primary or secondary outcome variables into regulatory guideline documents, e.g. regarding phase II in drug development programs as outcome measures in proof of concept or dose finding studies. There are specific biomarkers available depending on the hypothesized mechanism of action of a medicinal product, e.g. impact on the amyloidogenic cascade or on tauhyperphosphorylation. Ongoing large-scale international controlled multi-center trials will provide further validation of selected core feasible imaging and CSF biomarker candidates as outcome measures in early AD for use in phase III clinical efficacy trials. There is a need of rigorous co-development of biological trait- and statemarker candidates facilitated through planned synergistic collaboration between academic, industrial and regulatory partners.

  8. Resemblance in dietary intakes between urban low-income African American adolescents and their mothers: The HEALTH-KIDS Study

    Science.gov (United States)

    Wang, Youfa; Li, Ji; Caballero, Benjamin

    2009-01-01

    Objectives To examine the association and predictors of dietary intake resemblance between urban low-income African American adolescents and their mothers. Methods Detailed dietary data collected from 121 child-parent pairs in Chicago in Fall 2003 were used. The association was assessed using correlation coefficients, kappa, and percentage of agreement, and logistic regression models. Results Overall, the association was weak as indicated by correlations and other measures. None of the mother-son correlations for nutrients and food groups were greater than 0.20. Mother-daughter pairs had stronger correlations (0.26 for energy and 0.30 for fat). The association was stronger in normal weight- than overweight or obese mothers. Logistic models showed that mother being a current smoker, giving child more pocket money, and allowing child to eat or purchase snacks without parental permission or presence predicted a higher probability of resemblance in undesirable eating patterns, such as high-energy, high-fat, and high-snack intakes (p<0.05). Conclusions Mother-child diet association was generally weak, and varied considerably across groups and intake variables in this homogenous population. Some maternal characteristics seem to affect the association. PMID:19103323

  9. Subchronic steroid administration induces long lasting changes in neurochemical and behavioral response to cocaine in rats.

    Science.gov (United States)

    Kailanto, Sanna; Kankaanpää, Aino; Seppälä, Timo

    2011-11-01

    The abuse of anabolic androgenic steroids (AASs), such as nandrolone, is not only a problem in the world of sports but is associated with the polydrug use of non-athletes. Among other adverse effects, AAS abuse has been associated with long term or even persistent psychiatric problems. We have previously found that nandrolone decanoate treatment could produce prolonged changes in rats' brain reward circuits associated to drug dependence. The aim in this study was to evaluate whether AAS-induced neurochemical and behavioral changes are reversible. The increases in extracellular dopamine (DA) and serotonin (5-HT) concentration, as well as stereotyped behavior and locomotor activity (LMA) evoked by cocaine were attenuated by pretreatment with nandrolone. The recovery period, which was needed for the DA system to return back to the basic level, was fairly long compared to the dosing period of the steroid. In the 5-HT system, the time that system needed to return back to the basal level, was even longer than in the DA system. The attenuation was still seen though there were no detectable traces of nandrolone in the blood samples. Given that accumbal outflow of DA and 5-HT, as well as LMA and stereotyped behavior are all related to reward of stimulant drugs, this study suggests that nandrolone decanoate has significant, long-lasting but reversible effects on the rewarding properties of cocaine. Copyright © 2011 Elsevier Ltd. All rights reserved.

  10. Discrimination of artificial categories structured by family resemblances: a comparative study in people (Homo sapiens) and pigeons (Columba livia).

    Science.gov (United States)

    Makino, Hiroshi; Jitsumori, Masako

    2007-02-01

    Adult humans (Homo sapiens) and pigeons (Columba livia) were trained to discriminate artificial categories that the authors created by mimicking 2 properties of natural categories. One was a family resemblance relationship: The highly variable exemplars, including those that did not have features in common, were structured by a similarity network with the features correlating to one another in each category. The other was a polymorphous rule: No single feature was essential for distinguishing the categories, and all the features overlapped between the categories. Pigeons learned the categories with ease and then showed a prototype effect in accord with the degrees of family resemblance for novel stimuli. Some evidence was also observed for interactive effects of learning of individual exemplars and feature frequencies. Humans had difficulty in learning the categories. The participants who learned the categories generally responded to novel stimuli in an all-or-none fashion on the basis of their acquired classification decision rules. The processes that underlie the classification performances of the 2 species are discussed.

  11. The Gastric Ganglion of Octopus vulgaris: Preliminary Characterization of Gene- and Putative Neurochemical-Complexity, and the Effect of Aggregata octopiana Digestive Tract Infection on Gene Expression

    Directory of Open Access Journals (Sweden)

    Elena Baldascino

    2017-12-01

    Full Text Available The gastric ganglion is the largest visceral ganglion in cephalopods. It is connected to the brain and is implicated in regulation of digestive tract functions. Here we have investigated the neurochemical complexity (through in silico gene expression analysis and immunohistochemistry of the gastric ganglion in Octopus vulgaris and tested whether the expression of a selected number of genes was influenced by the magnitude of digestive tract parasitic infection by Aggregata octopiana. Novel evidence was obtained for putative peptide and non-peptide neurotransmitters in the gastric ganglion: cephalotocin, corticotrophin releasing factor, FMRFamide, gamma amino butyric acid, 5-hydroxytryptamine, molluscan insulin-related peptide 3, peptide PRQFV-amide, and tachykinin–related peptide. Receptors for cholecystokininA and cholecystokininB, and orexin2 were also identified in this context for the first time. We report evidence for acetylcholine, dopamine, noradrenaline, octopamine, small cardioactive peptide related peptide, and receptors for cephalotocin and octopressin, confirming previous publications. The effects of Aggregata observed here extend those previously described by showing effects on the gastric ganglion; in animals with a higher level of infection, genes implicated in inflammation (NFκB, fascin, serpinB10 and the toll-like 3 receptor increased their relative expression, but TNF-α gene expression was lower as was expression of other genes implicated in oxidative stress (i.e., superoxide dismutase, peroxiredoxin 6, and glutathione peroxidase. Elevated Aggregata levels in the octopuses corresponded to an increase in the expression of the cholecystokininA receptor and the small cardioactive peptide-related peptide. In contrast, we observed decreased relative expression of cephalotocin, dopamine β-hydroxylase, peptide PRQFV-amide, and tachykinin-related peptide genes. A discussion is provided on (i potential roles of the various molecules

  12. The Gastric Ganglion of Octopus vulgaris: Preliminary Characterization of Gene- and Putative Neurochemical-Complexity, and the Effect of Aggregata octopiana Digestive Tract Infection on Gene Expression

    Science.gov (United States)

    Baldascino, Elena; Di Cristina, Giulia; Tedesco, Perla; Hobbs, Carl; Shaw, Tanya J.; Ponte, Giovanna; Andrews, Paul L. R.

    2017-01-01

    The gastric ganglion is the largest visceral ganglion in cephalopods. It is connected to the brain and is implicated in regulation of digestive tract functions. Here we have investigated the neurochemical complexity (through in silico gene expression analysis and immunohistochemistry) of the gastric ganglion in Octopus vulgaris and tested whether the expression of a selected number of genes was influenced by the magnitude of digestive tract parasitic infection by Aggregata octopiana. Novel evidence was obtained for putative peptide and non-peptide neurotransmitters in the gastric ganglion: cephalotocin, corticotrophin releasing factor, FMRFamide, gamma amino butyric acid, 5-hydroxytryptamine, molluscan insulin-related peptide 3, peptide PRQFV-amide, and tachykinin–related peptide. Receptors for cholecystokininA and cholecystokininB, and orexin2 were also identified in this context for the first time. We report evidence for acetylcholine, dopamine, noradrenaline, octopamine, small cardioactive peptide related peptide, and receptors for cephalotocin and octopressin, confirming previous publications. The effects of Aggregata observed here extend those previously described by showing effects on the gastric ganglion; in animals with a higher level of infection, genes implicated in inflammation (NFκB, fascin, serpinB10 and the toll-like 3 receptor) increased their relative expression, but TNF-α gene expression was lower as was expression of other genes implicated in oxidative stress (i.e., superoxide dismutase, peroxiredoxin 6, and glutathione peroxidase). Elevated Aggregata levels in the octopuses corresponded to an increase in the expression of the cholecystokininA receptor and the small cardioactive peptide-related peptide. In contrast, we observed decreased relative expression of cephalotocin, dopamine β-hydroxylase, peptide PRQFV-amide, and tachykinin-related peptide genes. A discussion is provided on (i) potential roles of the various molecules in food intake

  13. Growth hormone receptor-deficient pigs resemble the pathophysiology of human Laron syndrome and reveal altered activation of signaling cascades in the liver.

    Science.gov (United States)

    Hinrichs, Arne; Kessler, Barbara; Kurome, Mayuko; Blutke, Andreas; Kemter, Elisabeth; Bernau, Maren; Scholz, Armin M; Rathkolb, Birgit; Renner, Simone; Bultmann, Sebastian; Leonhardt, Heinrich; de Angelis, Martin Hrabĕ; Nagashima, Hiroshi; Hoeflich, Andreas; Blum, Werner F; Bidlingmaier, Martin; Wanke, Rüdiger; Dahlhoff, Maik; Wolf, Eckhard

    2018-05-01

    of JAK2 was significantly increased, possibly due to the increased serum leptin levels and increased hepatic leptin receptor expression and activation in GHR-KO pigs. In addition, increased mTOR phosphorylation was observed in GHR-KO liver samples, and phosphorylation studies of downstream substrates suggested the activation of mainly mTOR complex 2. GHR-KO pigs resemble the pathophysiology of LS and are an interesting model for mechanistic studies and treatment trials. Copyright © 2018 The Authors. Published by Elsevier GmbH.. All rights reserved.

  14. Growth hormone receptor-deficient pigs resemble the pathophysiology of human Laron syndrome and reveal altered activation of signaling cascades in the liver

    Directory of Open Access Journals (Sweden)

    Arne Hinrichs

    2018-05-01

    significantly reduced. In contrast, phosphorylation of JAK2 was significantly increased, possibly due to the increased serum leptin levels and increased hepatic leptin receptor expression and activation in GHR-KO pigs. In addition, increased mTOR phosphorylation was observed in GHR-KO liver samples, and phosphorylation studies of downstream substrates suggested the activation of mainly mTOR complex 2. Conclusion: GHR-KO pigs resemble the pathophysiology of LS and are an interesting model for mechanistic studies and treatment trials. Keywords: Growth hormone receptor, Laron syndrome, Pig model, Dwarfism, Hypoglycemia, Insulin-like growth factor 1, Signaling

  15. Membrane alterations induced by nonstructural proteins of human norovirus.

    Directory of Open Access Journals (Sweden)

    Sylvie Y Doerflinger

    2017-10-01

    Full Text Available Human noroviruses (huNoV are the most frequent cause of non-bacterial acute gastroenteritis worldwide, particularly genogroup II genotype 4 (GII.4 variants. The viral nonstructural (NS proteins encoded by the ORF1 polyprotein induce vesical clusters harboring the viral replication sites. Little is known so far about the ultrastructure of these replication organelles or the contribution of individual NS proteins to their biogenesis. We compared the ultrastructural changes induced by expression of norovirus ORF1 polyproteins with those induced upon infection with murine norovirus (MNV. Characteristic membrane alterations induced by ORF1 expression resembled those found in MNV infected cells, consisting of vesicle accumulations likely built from the endoplasmic reticulum (ER which included single membrane vesicles (SMVs, double membrane vesicles (DMVs and multi membrane vesicles (MMVs. In-depth analysis using electron tomography suggested that MMVs originate through the enwrapping of SMVs with tubular structures similar to mechanisms reported for picornaviruses. Expression of GII.4 NS1-2, NS3 and NS4 fused to GFP revealed distinct membrane alterations when analyzed by correlative light and electron microscopy. Expression of NS1-2 induced proliferation of smooth ER membranes forming long tubular structures that were affected by mutations in the active center of the putative NS1-2 hydrolase domain. NS3 was associated with ER membranes around lipid droplets (LDs and induced the formation of convoluted membranes, which were even more pronounced in case of NS4. Interestingly, NS4 was the only GII.4 protein capable of inducing SMV and DMV formation when expressed individually. Our work provides the first ultrastructural analysis of norovirus GII.4 induced vesicle clusters and suggests that their morphology and biogenesis is most similar to picornaviruses. We further identified NS4 as a key factor in the formation of membrane alterations of huNoV and

  16. Guinea-pig interpubic joint (symphysis pubica relaxation at parturition: Underlying cellular processes that resemble an inflammatory response

    Directory of Open Access Journals (Sweden)

    Muñoz-de-Toro Mónica

    2003-11-01

    Full Text Available Abstract Background At term, cervical ripening in coordination with uterine contractions becomes a prerequisite for a normal vaginal delivery. Currently, cervical ripening is considered to occur independently from uterine contractions. Many evidences suggest that cervical ripening resembles an inflammatory process. Comparatively little attention has been paid to the increased flexibility of the pelvic symphysis that occurs in many species to enable safe delivery. The aim of this study was to investigate whether the guinea-pig interpubic joint relaxation process observed during late pregnancy and parturition resembles an inflammatory process. Methods Samples of pubic symphysis were taken from pregnant guinea-pigs sacrificed along gestation, parturition and postpartum. Serial sections of paraffin-embedded tissues were used to measure the interpubic distance on digitalized images, stained with Giemsa to quantify leukocyte infiltration and to describe the vascular area changes, or studied by the picrosirius-polarization method to evaluate collagen remodeling. P4 and E2 serum levels were measured by a sequential immunometric assay. Results Data showed that the pubic relaxation is associated with an increase in collagen remodeling. In addition, a positive correlation between E2 serum levels and the increase in the interpubic distance was found. On the other hand, a leukocyte infiltration in the interpubic tissue around parturition was described, with the presence of almost all inflammatory cells types. At the same time, histological images show an increase in vascular area (angiogenesis. Eosinophils reached their highest level immediately before parturition; whereas for the neutrophilic and mononuclear infiltration higher values were recorded one day after parturition. Correlation analysis showed that eosinophils and mononuclear cells were positively correlated with E2 levels, but only eosinophilic infiltration was associated with collagen remodeling

  17. Extended retroperitoneal necrotizing fasciitis with genital involvement, resembling fournier gangrene.

    Science.gov (United States)

    Sugimoto, Motokazu; Matsuura, Kenji; Takayama, Hiroshi; Kayo, Munefumi; Ie, Tomotsugu

    2010-10-01

    Necrotizing fasciitis is a serious infection that originates in the subcutaneous tissues. Although many reports have been published about necrotizing infections of other anatomical sites, retroperitoneal necrotizing soft tissue infection is a rare entity that has been described in only a few case reports. The etiology and clinical course of retroperitoneal necrotizing fasciitis can be variable and it is often difficult to identify the etiology of the infective process. We report a 58-year-old man with rapidly progressive, gas-producing, necrotizing inflammation in the retroperitoneum, complicated with genital involvement resembling Fournier gangrene. The patient was managed successfully by aggressive drainage, debridement, and sequential laparotomies to track and control the extensive necrosis of the retroperitoneum and perineum, in addition to systemic care to control sepsis. After his general condition stabilized, early rectosigmoid adenocarcinoma was identified and resected curatively. He remained well at follow up, six months after discharge. In retrospect, the trigger of the disease process was unclear. Although it was believed possibly to be due to the colon lesion, adenocarcinoma of the rectosigmoid colon was identified and the patient was managed successfully. Similar to necrotizing infections at other anatomical sites, early diagnosis and timely surgical intervention and systemic antimicrobial therapy are mandatory for treating patients with retroperitoneal necrotizing fasciitis.

  18. Nicotine and endogenous opioids: neurochemical and pharmacological evidence.

    Science.gov (United States)

    Hadjiconstantinou, Maria; Neff, Norton H

    2011-06-01

    Although the mesolimbic dopamine hypothesis is the most influential theory of nicotine reward and reinforcement, there has been a consensus that other neurotransmitter systems contribute to the addictive properties of nicotine as well. In this regard, the brain opioidergic system is of interest. Striatum is rich in opioid peptides and opioid receptors, and striatal opioidergic neurons are engaged in a bidirectional communication with midbrain dopaminergic neurons, closely regulating each other's activity. Enkephalins and dynorphins exert opposing actions on dopaminergic neurons, increasing and decreasing dopamine release respectively, and are components of circuits promoting positive or negative motivational and affective states. Moreover, dopamine controls the synthesis of striatal enkephalins and dynorphins. Evidence suggests that opioidergic function is altered after nicotine and endogenous opioids are involved in nicotine's behavioral effects. 1) The synthesis and release of β-endorphin, met-enkephalin and dynorphin in brain, especially nucleus accumbens (NAc), are altered after acute or chronic nicotine treatment and during nicotine withdrawal. 2) Although opioid receptor binding and mRNA do not appear to change in the striatum during nicotine withdrawal, the activity of κ-opioid (KOPr) and δ-opioid (DOPr) receptors is attenuated in NAc. 3) The nicotine withdrawal syndrome reminisces that of opiates, and naloxone precipitates some of its somatic, motivational, and affective signs. 4) Genetic and pharmacological studies indicate that μ-opioid (MOPr) receptors are mainly involved in nicotine reward, while DOPrs contribute to the emotional and KOPrs to the aversive responses of nicotine. 5) Finally, MOPrs and enkephalin, but not β-endorphin or dynorphin, are necessary for the physical manifestations of nicotine withdrawal. This article is part of a Special Issue entitled 'Trends in neuropharmacology: in memory of Erminio Costa'. Copyright © 2010 Elsevier

  19. Basic perceptual changes that alter meaning and neural correlates of recognition memory.

    Science.gov (United States)

    Gao, Chuanji; Hermiller, Molly S; Voss, Joel L; Guo, Chunyan

    2015-01-01

    It is difficult to pinpoint the border between perceptual and conceptual processing, despite their treatment as distinct entities in many studies of recognition memory. For instance, alteration of simple perceptual characteristics of a stimulus can radically change meaning, such as the color of bread changing from white to green. We sought to better understand the role of perceptual and conceptual processing in memory by identifying the effects of changing a basic perceptual feature (color) on behavioral and neural correlates of memory in circumstances when this change would be expected to either change the meaning of a stimulus or to have no effect on meaning (i.e., to influence conceptual processing or not). Abstract visual shapes ("squiggles") were colorized during study and presented during test in either the same color or a different color. Those squiggles that subjects found to resemble meaningful objects supported behavioral measures of conceptual priming, whereas meaningless squiggles did not. Further, changing color from study to test had a selective effect on behavioral correlates of priming for meaningful squiggles, indicating that color change altered conceptual processing. During a recognition memory test, color change altered event-related brain potential (ERP) correlates of memory for meaningful squiggles but not for meaningless squiggles. Specifically, color change reduced the amplitude of frontally distributed N400 potentials (FN400), implying that these potentials indicated conceptual processing during recognition memory that was sensitive to color change. In contrast, color change had no effect on FN400 correlates of recognition for meaningless squiggles, which were overall smaller in amplitude than for meaningful squiggles (further indicating that these potentials signal conceptual processing during recognition). Thus, merely changing the color of abstract visual shapes can alter their meaning, changing behavioral and neural correlates of memory

  20. Alterations in neuropeptides in aging and disease. Pathophysiology and potential for clinical intervention.

    Science.gov (United States)

    Leake, A; Ferrier, I N

    1993-01-01

    Marked specific and selective changes in the levels of some neuropeptides in age-related diseases, such as senile dementia of the Alzheimer (SDAT) or Lewy body (SDLT) types, Parkinson's disease, Huntington's disease and major depressive disorder, versus normal aging have been noted. However, the levels of most neuropeptides are normal. The only 2 peptides consistently altered in SDAT are somatostatin and corticotrophin-releasing hormone both of which are reduced. In Huntington's disease, the level of substance P in the basal ganglia is reduced suggesting a preferential vulnerability of spiny neurones in this disease. In Parkinson's disease, substance P is attenuated in the basal ganglia while somatostatin is reduced in the neocortex. These and other results suggest that substance P deficits are related to movement disorders while somatostatin deficits are related to cognitive impairment. SDLT is a type of dementia with features common to both SDAT and Parkinson's disease, although the changes in neuropeptides suggest that neurochemically the disease is more closely related to SDAT. In major depressive disorder, the level of corticotrophin-releasing hormone is reduced while there is a reciprocal increase in corticotrophin-releasing hormone receptors suggesting that the neurones remain functional. Potential clinical intervention has been limited by problems such as poor penetration of agents into the brain and the short half-lives of neuropeptide agonists and antagonists. However, some currently available agents may act, at least in part, through modulation of neuropeptide pathways, e.g. carbamazepine and alprazolam both modulate the corticotrophin-releasing hormone system in animals, and both have clinically proven antidepressant activity.

  1. [Neurobiological foundations underlying normal and disturbed sexuality].

    Science.gov (United States)

    Krüger, T H C; Kneer, J

    2017-05-01

    Sexual functions are regulated by hormonal and neurochemical factors as well as neuronal networks. An understanding of these basic principles is necessary for the diagnostics, counselling and treatment of sexual problems. Description of essential mechanisms of sexual function on a neurochemical and neuronal level. Literature search, selection and discussion of relevant studies. Analogous to the dual control model there are primary inhibitory (e. g. serotonin) and excitatory neurotransmitter systems (e.g. sex steroids and dopamine). Moreover, neuronal structures have been identified that are responsible for processing sexual stimuli. These networks are altered in subjects with sexual disorders or by pharmacological treatment, e. g. antiandrogens and selective serotonin reuptake inhibitors (SSRI) CONCLUSION: Knowledge of the neurobiology of sexuality forms the foundations for the treatment of sexual dysfunctions in psychiatry and other disciplines.

  2. How Electroconvulsive Therapy Works?: Understanding the Neurobiological Mechanisms

    Science.gov (United States)

    Singh, Amit; Kar, Sujita Kumar

    2017-01-01

    Electroconvulsive therapy (ECT) is a time tested treatment modality for the management of various psychiatric disorders. There have been a lot of modifications in the techniques of delivering ECT over decades. Despite lots of criticisms encountered, ECT has still been used commonly in clinical practice due to its safety and efficacy. Research evidences found multiple neuro-biological mechanisms for the therapeutic effect of ECT. ECT brings about various neuro-physiological as well as neuro-chemical changes in the macro- and micro-environment of the brain. Diverse changes involving expression of genes, functional connectivity, neurochemicals, permeability of blood-brain-barrier, alteration in immune system has been suggested to be responsible for the therapeutic effects of ECT. This article reviews different neurobiological mechanisms responsible for the therapeutic efficacy of ECT. PMID:28783929

  3. Do general radiographic examinations resemble a person-centred environment?

    International Nuclear Information System (INIS)

    Hayre, C.M.; Blackman, S.; Eyden, A.

    2016-01-01

    Aim and objective: It is argued whether general radiographic examinations adhere to a person-centred approach within the direct digital radiography (DDR) environment. General radiographic examinations continue to increase and constitute approximately 90% of all examinations undertaken in the clinical environment. This study explored the potential impact patients experience whilst undergoing general imaging examinations. Method: An ethnographic methodology provided insight of two general radiography environments in the United Kingdom (UK) using participant observation and semi-structured interviews. Findings: The findings highlighted an ‘in and out’ culture whereby patients are ‘hurried’ and ‘rushed’ out of X-ray rooms in response to increasing time pressures experienced by diagnostic radiographers. In addition, this study challenged that patients may begin to rank ‘speed’ and ‘waiting times’ above other elements of radiographic care thus presenting new challenges for radiographers within the clinical environment. Conclusion: It is asserted that radiographers should remain holistic healthcare professionals and not begin to resemble operators on the production line. Further, it challenges whether patients are beginning to rank aspects of radiographic care within contemporary practices. Advances in knowledge: Few studies have explored the radiographer–patient relationship within the DDR environment, yet this study provides insight of person-centred practices within contemporary practices. - Highlights: • Challenges whether the use of DDR conforms to a person-centred approach. • Challenges whether radiographers are ‘treating patients as persons’ using DDR. • Patients may begin to rank ‘speed’ and ‘waiting times’ above other aspects of radiographic care.

  4. Corticotropin releasing hormone and imaging, rethinking the stress axis

    International Nuclear Information System (INIS)

    Contoreggi, Carlo

    2015-01-01

    The stress system provides integration of both neurochemical and somatic physiologic functions within organisms as an adaptive mechanism to changing environmental conditions throughout evolution. In mammals and primates the complexity and sophistication of these systems have surpassed other species in triaging neurochemical and physiologic signaling to maximize chances of survival. Corticotropin releasing hormone (CRH) and its related peptides and receptors have been identified over the last three decades and are fundamental molecular initiators of the stress response. They are crucial in the top down regulatory cascade over a myriad of neurochemical, neuroendocrine and sympathetic nervous system events. From neuroscience, we've seen that stress activation impacts behavior, endocrine and somatic physiology and influences neurochemical events that one can capture in real time with current imaging technologies. To delineate these effects one can demonstrate how the CRH neuronal networks infiltrate critical cognitive, emotive and autonomic regions of the central nervous system (CNS) with somatic effects. Abundant preclinical and clinical studies show inter-regulatory actions of CRH with multiple neurotransmitters/peptides. Stress, both acute and chronic has epigenetic effects which magnify genetic susceptibilities to alter neurochemistry; stress system activation can add critical variables in design and interpretation of basic and clinical neuroscience and related research. This review will attempt to provide an overview of the spectrum of known functions and speculative actions of CRH and stress responses in light of imaging technology and its interpretation. Metabolic and neuroreceptor positron emission/single photon tomography (PET/SPECT), functional magnetic resonance imaging (fMRI), anatomic MRI, diffusion tensor imaging (DTI), and proton magnetic resonance spectroscopy (pMRS) are technologies that can delineate basic mechanisms of neurophysiology and

  5. Meningiomas with conventional MRI findings resembling intraaxial tumors: can perfusion-weighted MRI be helpful in differentiation?

    International Nuclear Information System (INIS)

    Hakyemez, Bahattin; Yildirim, Nalan; Erdogan, Cueneyt; Parlak, Mufit; Kocaeli, Hasan; Korfali, Ender

    2006-01-01

    To investigate the contribution of perfusion-weighted MRI to the differentiation of meningiomas with atypical conventional MRI findings from intraaxial tumors. We retrospectively analyzed 54 meningiomas, 12 glioblastomas and 13 solitary metastases. We detected 6 meningiomas with atypical features on conventional MRI resembling intraaxial tumors. The regional cerebral blood flow (rCBV) ratios of all tumors were calculated via perfusion-weighted MRI. The signal intensity-time curves were plotted and three different curve patterns were observed. The type 1 curve resembled normal brain parenchyma or the postenhancement part was minimally below the baseline, the type 2 curve was similar to the type 1 curve but with the postenhancement part above the baseline, and the type 3 curve had the postenhancement part below the baseline accompanied by widening of the curve. Student's t-test was used for statistical analysis. On CBV images meningiomas were hypervascular and the mean rCBV ratio was 10.58±2.00. For glioblastomas and metastatic lesions, the rCBV ratios were 5.02±1.40 and 4.68±1.54, respectively. There was a statistically significant difference in rCBV ratios between meningiomas and glioblastomas and metastases (P<0.001). Only one of the meningiomas displayed a type 2 curve while five showed a type 3 curve. Glioblastomas and metastases displayed either a type 1 or a type 2 curve. None of the meningiomas showed a type 1 curve and none of the glioblastomas or metastases showed a type 3 curve. (orig.)

  6. Meningiomas with conventional MRI findings resembling intraaxial tumors: can perfusion-weighted MRI be helpful in differentiation?

    Energy Technology Data Exchange (ETDEWEB)

    Hakyemez, Bahattin [Uludag University Medical School, Department of Radiology, Bursa (Turkey); Bursa State Hospital, Department of Radiology, Bursa (Turkey); Yildirim, Nalan; Erdogan, Cueneyt; Parlak, Mufit [Uludag University Medical School, Department of Radiology, Bursa (Turkey); Kocaeli, Hasan; Korfali, Ender [Uludag University Medical School, Department of Neurosurgery, Bursa (Turkey)

    2006-10-15

    To investigate the contribution of perfusion-weighted MRI to the differentiation of meningiomas with atypical conventional MRI findings from intraaxial tumors. We retrospectively analyzed 54 meningiomas, 12 glioblastomas and 13 solitary metastases. We detected 6 meningiomas with atypical features on conventional MRI resembling intraaxial tumors. The regional cerebral blood flow (rCBV) ratios of all tumors were calculated via perfusion-weighted MRI. The signal intensity-time curves were plotted and three different curve patterns were observed. The type 1 curve resembled normal brain parenchyma or the postenhancement part was minimally below the baseline, the type 2 curve was similar to the type 1 curve but with the postenhancement part above the baseline, and the type 3 curve had the postenhancement part below the baseline accompanied by widening of the curve. Student's t-test was used for statistical analysis. On CBV images meningiomas were hypervascular and the mean rCBV ratio was 10.58{+-}2.00. For glioblastomas and metastatic lesions, the rCBV ratios were 5.02{+-}1.40 and 4.68{+-}1.54, respectively. There was a statistically significant difference in rCBV ratios between meningiomas and glioblastomas and metastases (P<0.001). Only one of the meningiomas displayed a type 2 curve while five showed a type 3 curve. Glioblastomas and metastases displayed either a type 1 or a type 2 curve. None of the meningiomas showed a type 1 curve and none of the glioblastomas or metastases showed a type 3 curve. (orig.)

  7. Alteration of striatal dopamine levels under various partial pressure of oxygen in pre-convulsive and convulsive phases in freely-moving rats.

    Science.gov (United States)

    Lavoute, Cécile; Weiss, Michel; Risso, Jean-Jacques; Rostain, Jean-Claude

    2014-02-01

    The purpose of this study was to investigate the change in the striatal dopamine (DA) level in freely-moving rat exposed to different partial pressure of oxygen (from 1 to 5 ATA). Some works have suggested that DA release by the substantia nigra pars compacta (SNc) neurons in the striatum could be disturbed by hyperbaric oxygen (HBO) exposure, altering therefore the basal ganglia activity. Such changes could result in a change in glutamatergic and GABAergic control of the dopaminergic neurons into the SNc. Such alterations could provide more information about the oxygen-induced seizures observed at 5 ATA in rat. DA-sensitive electrodes were implanted into the striatum under general anesthesia. After 1 week rest, awaked rats were exposed to oxygen-nitrogen mixture at a partial pressure of oxygen of 1, 2, 3, 4 and 5 ATA. DA level was monitored continuously (every 3 min) by in vivo voltammetry before and during HBO exposure. HBO induced a decrease in DA level in relationship to the increase in partial pressure of oxygen from 1 ATA to 4 ATA (-15 % at 1 ATA, -30 % at 2 ATA, -40 % at 3 ATA, -45 % at 4 ATA), without signs of oxygen toxicity. At 5 ATA, DA level strongly decreases (-75 %) before seizure which occurred after 27 min ± 7 HBO exposure. After the epileptic seizure the decrease in DA level disappeared. These changes and the biphasic effect of HBO were discussed in function of HBO action on neurochemical regulations of the nigro striatal pathway.

  8. Leprae reaction resembling rheumatologic disease as presenting feature of leprosy.

    Science.gov (United States)

    Baharuddin, Hazlyna; Taib, Tarita; Zain, Mollyza Mohd; Ch'ng, Shereen

    2016-10-01

    Leprosy is a chronic granulomatous infection caused by Mycobacterium leprae with predominant involvement of skin and nerves. We present a 70-year-old man with leprosy whose initial presentation resembled rheumatologic disease, due to leprae reaction. He presented with an 8-week history of worsening neuropathic pain in the right forearm, associated with necrotic skin lesions on his fingers that had ulcerated. Physical examination revealed two tender necrotic ulcers at the tip of the right middle finger and the dorsal aspect of the left middle finger. The patient had right wrist tenosynovitis and right elbow bursitis. Apart from raised inflammatory markers, the investigations for infection, connective tissue disease, vasculitis, thromboembolic disease and malignancy were negative. During the fourth week of hospitalization, we noticed a 2-cm hypoesthetic indurated plaque on the right inner arm. Further examination revealed thickened bilateral ulnar, radial and popliteal nerves. A slit skin smear was negative. Two skin biopsies and a biopsy of the olecranon bursa revealed granulomatous inflammation. He was diagnosed with paucibacillary leprosy with neuritis. He responded well to multidrug therapy and prednisolone; his symptoms resolved over a few weeks. This case illustrates the challenges in diagnosing a case of leprosy with atypical presentation in a non-endemic country. © 2016 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.

  9. Neurogenesis in Aplysia californica resembles nervous system formation in vertebrates

    International Nuclear Information System (INIS)

    Jacob, M.H.

    1984-01-01

    The pattern of neurogenesis of the central nervous system of Aplysia californica was investigated by [ 3 H]thymidine autoradiography. Large numbers of animals at a series of early developmental stages were labeled with [ 3 H]thymidine for 24 or 48 hr and were subsequently sampled at specific intervals throughout the life cycle. I found that proliferative zones, consisting of columnar and placodal ectodermal cells, are established in regions of the body wall adjacent to underlying mesodermal cells. Mitosis in the proliferative zones generates a population of cells which leave the surface and migrate inward to join the nearby forming ganglia. Tracing specific [ 3 H]thymidine-labeled cells from the body wall to a particular ganglion and within the ganglion over time suggests that the final genomic replication of the neuronal precursors occurs before the cells join the ganglion while glial cell precursors and differentiating glial cells continue to divide within the ganglion for some time. Ultrastructural examination of the morphological features of the few mitosing cells observed within the Aplysia central nervous system supports this interpretation. The pattern of neurogenesis in the Aplysia central nervous system resembles the proliferation of cells in the neural tube and the migration of neural crest and ectodermal placode cells in the vertebrate nervous system but differs from the pattern described for other invertebrates

  10. White spot syndrome virus induces metabolic changes resembling the warburg effect in shrimp hemocytes in the early stage of infection.

    Science.gov (United States)

    Chen, I-Tung; Aoki, Takashi; Huang, Yun-Tzu; Hirono, Ikuo; Chen, Tsan-Chi; Huang, Jiun-Yan; Chang, Geen-Dong; Lo, Chu-Fang; Wang, Han-Ching

    2011-12-01

    The Warburg effect is an abnormal glycolysis response that is associated with cancer cells. Here we present evidence that metabolic changes resembling the Warburg effect are induced by a nonmammalian virus. When shrimp were infected with white spot syndrome virus (WSSV), changes were induced in several metabolic pathways related to the mitochondria. At the viral genome replication stage (12 h postinfection [hpi]), glucose consumption and plasma lactate concentration were both increased in WSSV-infected shrimp, and the key enzyme of the pentose phosphate pathway, glucose-6-phosphate dehydrogenase (G6PDH), showed increased activity. We also found that at 12 hpi there was no alteration in the ADP/ATP ratio and that oxidative stress was lower than that in uninfected controls. All of these results are characteristic of the Warburg effect as it is present in mammals. There was also a significant decrease in triglyceride concentration starting at 12 hpi. At the late stage of the infection cycle (24 hpi), hemocytes of WSSV-infected shrimp showed several changes associated with cell death. These included the induction of mitochondrial membrane permeabilization (MMP), increased oxidative stress, decreased glucose consumption, and disrupted energy production. A previous study showed that WSSV infection led to upregulation of the voltage-dependent anion channel (VDAC), which is known to be involved in both the Warburg effect and MMP. Here we show that double-stranded RNA (dsRNA) silencing of the VDAC reduces WSSV-induced mortality and virion copy number. For these results, we hypothesize a model depicting the metabolic changes in host cells at the early and late stages of WSSV infection.

  11. Rhythmicity in mice selected for extremes in stress reactivity: behavioural, endocrine and sleep changes resembling endophenotypes of major depression.

    Directory of Open Access Journals (Sweden)

    Chadi Touma

    Full Text Available Dysregulation of the hypothalamic-pituitary-adrenal (HPA axis, including hyper- or hypo-activity of the stress hormone system, plays a critical role in the pathophysiology of mood disorders such as major depression (MD. Further biological hallmarks of MD are disturbances in circadian rhythms and sleep architecture. Applying a translational approach, an animal model has recently been developed, focusing on the deviation in sensitivity to stressful encounters. This so-called 'stress reactivity' (SR mouse model consists of three separate breeding lines selected for either high (HR, intermediate (IR, or low (LR corticosterone increase in response to stressors.In order to contribute to the validation of the SR mouse model, our study combined the analysis of behavioural and HPA axis rhythmicity with sleep-EEG recordings in the HR/IR/LR mouse lines. We found that hyper-responsiveness to stressors was associated with psychomotor alterations (increased locomotor activity and exploration towards the end of the resting period, resembling symptoms like restlessness, sleep continuity disturbances and early awakenings that are commonly observed in melancholic depression. Additionally, HR mice also showed neuroendocrine abnormalities similar to symptoms of MD patients such as reduced amplitude of the circadian glucocorticoid rhythm and elevated trough levels. The sleep-EEG analyses, furthermore, revealed changes in rapid eye movement (REM and non-REM sleep as well as slow wave activity, indicative of reduced sleep efficacy and REM sleep disinhibition in HR mice.Thus, we could show that by selectively breeding mice for extremes in stress reactivity, clinically relevant endophenotypes of MD can be modelled. Given the importance of rhythmicity and sleep disturbances as biomarkers of MD, both animal and clinical studies on the interaction of behavioural, neuroendocrine and sleep parameters may reveal molecular pathways that ultimately lead to the discovery of new

  12. Transient alterations in neurotransmitter activity in the caudate nucleus of rat brain after a high dose of ionizing radiation

    International Nuclear Information System (INIS)

    Hunt, W.A.; Dalton, T.K.; Darden, J.H.

    1979-01-01

    A single 10,000-rad dose of high-energy electrons induced an increase in dopaminergic and cholinergic activity in the caudate nucleus of the rat brain as assessed by K + -stimulated dopamine release in vitro and high-affinity choline uptake. These alterations occur during early transient incapacitation (ETI) and dissipate as the animal recovers behaviorally, in about 30 min after irradiation. Although the responses observed resemble those that result from blockade of dopamine receptors, no radiation-induced changes were found in dopamine-sensitive adenylate cyclase activity and [ 3 H]haloperidol binding, two indices of dopaminergic receptor function. The data suggest that changes in dopaminergic and cholinergic activity are associated with the development of ETI and may play a role in the behavioral decrement observed under this condition

  13. Nuclear security culture in comparison with nuclear safety culture. Resemblances and differences

    International Nuclear Information System (INIS)

    Kawata, Norio

    2015-01-01

    Since the terrorist attacks on the U.S. on September 11th, 2001, Nuclear Security has been focused on and treated as a global issue in the international community and it has also been discussed as a real and serious threat to nuclear power plants in the world since 'The Great East Japan Earthquake' in March, 2011. The International Atomic Energy Agency (IAEA) issued a document including Nuclear Security Recommendations (INFCIRC/225/Rev.5) (NSS 13) in the Nuclear Security Series and emphasized the necessity of fostering Nuclear Security Culture. Nuclear Security Culture has been frequently discussed at various kinds of seminars and events. Since the officials in charge of Nuclear Security are familiar with the area of Nuclear Safety, the relationships between Nuclear Safety Culture and Nuclear Security Culture have been the point in controversy. This paper clarifies relevance between Nuclear Safety and Security, considers resemblances and differences of their concepts and lessons learned for each culture from nuclear power plant accidents, and promotes deeper understanding of Nuclear Safety and Nuclear Security Culture. (author)

  14. Synthesis of Hydroxylated Sterols in Transgenic Arabidopsis Plants Alters Growth and Steroid Metabolism1[C][W][OA

    Science.gov (United States)

    Beste, Lisa; Nahar, Nurun; Dalman, Kerstin; Fujioka, Shozo; Jonsson, Lisbeth; Dutta, Paresh C.; Sitbon, Folke

    2011-01-01

    To explore mechanisms in plant sterol homeostasis, we have here increased the turnover of sterols in Arabidopsis (Arabidopsis thaliana) and potato (Solanum tuberosum) plants by overexpressing four mouse cDNA encoding cholesterol hydroxylases (CHs), hydroxylating cholesterol at the C-7, C-24, C-25, or C-27 positions. Compared to the wild type, the four types of Arabidopsis transformant showed varying degrees of phenotypic alteration, the strongest one being in CH25 lines, which were dark-green dwarfs resembling brassinosteroid-related mutants. Gas chromatography-mass spectrometry analysis of extracts from wild-type Arabidopsis plants revealed trace levels of α and β forms of 7-hydroxycholesterol, 7-hydroxycampesterol, and 7-hydroxysitosterol. The expected hydroxycholesterol metabolites in CH7-, CH24-, and CH25 transformants were identified and quantified using gas chromatography-mass spectrometry. Additional hydroxysterol forms were also observed, particularly in CH25 plants. In CH24 and CH25 lines, but not in CH7 ones, the presence of hydroxysterols was correlated with a considerable alteration of the sterol profile and an increased sterol methyltransferase activity in microsomes. Moreover, CH25 lines contained clearly reduced levels of brassinosteroids, and displayed an enhanced drought tolerance. Equivalent transformations of potato plants with the CH25 construct increased hydroxysterol levels, but without the concomitant alteration of growth and sterol profiles observed in Arabidopsis. The results suggest that an increased hydroxylation of cholesterol and/or other sterols in Arabidopsis triggers compensatory processes, acting to maintain sterols at adequate levels. PMID:21746809

  15. Polycystic ovary syndrome resembling histopathological alterations in ovaries from prenatal androgenized female rats

    Directory of Open Access Journals (Sweden)

    Wang Fang

    2012-05-01

    Full Text Available Abstract Background The polycystic ovary syndrome (PCOS affects approximately 6-10% of women of reproductive age and is characterized by chronic anovulation and hyperandrogenism. However, a comprehensive understanding of the mechanisms that dictate androgen overproduction is lacking, which may account for inconsistencies between measures of androgen excess and clinical presentation in individual cases. Methods A rat model of PCOS was established by injecting dehydroepiandrosterone sulfoconjugate (DHEAS into pregnant females. Rats were administered with DHEAS (60 mg/kg/d subcutaneously (s.c. for all 20 days of pregnancy (Group A, or for the first 10 days (Group B, or from day 11 to day 20 (Group C. Controls were administered with injection oil (0.2 ml/day s.c. throughout pregnancy (Group D. The litter rate, abortion rate, and offspring survival rate in each group were recorded. Serum androgen and estrogen were measured and the morphological features of the ovaries were examined by light and electron microscopy in the offspring of each group. Results We found that rats injected with DHEAS throughout pregnancy (group A lost fertility. Rats injected with DHEAS during early pregnancy (group B exhibited more serious aberrations in fertility than both Group C, in which rats were injected with DHEAS during late pregnancy (P  Conclusions Our results indicate that androgen excess during pregnancy can decrease rat fertility. Excess androgen at the early stage of pregnancy causes high reproductive toxicity, leading to abnormality of ovarian morphology and functions in female offspring.

  16. ENPP1 Mutation Causes Recessive Cole Disease by Altering Melanogenesis.

    Science.gov (United States)

    Chourabi, Marwa; Liew, Mei Shan; Lim, Shawn; H'mida-Ben Brahim, Dorra; Boussofara, Lobna; Dai, Liang; Wong, Pui Mun; Foo, Jia Nee; Sriha, Badreddine; Robinson, Kim Samirah; Denil, Simon; Common, John Ea; Mamaï, Ons; Ben Khalifa, Youcef; Bollen, Mathieu; Liu, Jianjun; Denguezli, Mohamed; Bonnard, Carine; Saad, Ali; Reversade, Bruno

    2018-02-01

    Cole disease is a genodermatosis of pigmentation following a strict dominant mode of inheritance. In this study, we investigated eight patients affected with an overlapping genodermatosis after recessive inheritance. The patients presented with hypo- and hyperpigmented macules over the body, resembling dyschromatosis universalis hereditaria in addition to punctuate palmoplantar keratosis. By homozygosity mapping and whole-exome sequencing, a biallelic p.Cys120Arg mutation in ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) was identified in all patients. We found that this mutation, like those causing dominant Cole disease, impairs homodimerization of the ENPP1 enzyme that is mediated by its two somatomedin-B-like domains. Histological analysis revealed structural and molecular changes in affected skin that were likely to originate from defective melanocytes because keratinocytes do not express ENPP1. Consistently, RNA-sequencing analysis of patient-derived primary melanocytes revealed alterations in melanocyte development and in pigmentation signaling pathways. We therefore conclude that germline ENPP1 cysteine-specific mutations, primarily affecting the melanocyte lineage, cause a clinical spectrum of dyschromatosis, in which the p.Cys120Arg allele represents a recessive and more severe form of Cole disease. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  17. Acral peeling skin syndrome resembling epidermolysis bullosa simplex in a 10-month-old boy.

    Science.gov (United States)

    Kavaklieva, S; Yordanova, I; Bruckner-Tuderman, L; Has, C

    2013-01-01

    The acral peeling skin syndrome (APSS) is a rare autosomal recessive disorder clinically characterized by asymptomatic desquamation of the skin limited to the hands and feet and histologically by cleavage at the stratum granulosum and stratum corneum level [Kiritsi et al.: J Invest Dermatol 2010;130:1741-1746]. We report on a 10-month-old boy with a history of skin peeling limited to the hands and feet since 2 months of age. Clinical examination revealed erythematous erosions with peripheral desquamation and flaccid blisters. DNA mutation analysis detected two heterozygous TGM5 mutations: c.2T>C, p.M1T in exon 1 and c.337G>T, p.G113C in exon 3 in keeping with the diagnosis of APSS. The clinical presentation of APSS alone might be confusing and strongly resemble epidermolysis bullosa simplex making the differential diagnosis difficult.

  18. A zinc complex of heparan sulfate destabilises lysozyme and alters its conformation

    International Nuclear Information System (INIS)

    Hughes, Ashley J.; Hussain, Rohanah; Cosentino, Cesare; Guerrini, Marco; Siligardi, Giuliano; Yates, Edwin A.; Rudd, Timothy R.

    2012-01-01

    Highlights: ► Zinc–heparan sulfate complex destabilises lysozyme, a model amyloid protein. ► Addition of zinc, without heparan sulfate, stabilises lysozyme. ► Heparan sulfate cation complexes provide alternative protein folding routes. -- Abstract: The naturally occurring anionic cell surface polysaccharide heparan sulfate is involved in key biological activities and is implicated in amyloid formation. Following addition of Zn–heparan sulfate, hen lysozyme, a model amyloid forming protein, resembled β-rich amyloid by far UV circular dichroism (increased β-sheet: +25%), with a significantly reduced melting temperature (from 68 to 58 °C) by fluorescence shift assay. Secondary structure stability of the Zn–heparan sulfate complex with lysozyme was also distinct from that with heparan sulfate, under stronger denaturation conditions using synchrotron radiation circular dichroism. Changing the cation associated with heparan sulfate is sufficient to alter the conformation and stability of complexes formed between heparan sulfate and lysozyme, substantially reducing the stability of the protein. Complexes of heparan sulfate and cations, such as Zn, which are abundant in the brain, may provide alternative folding routes for proteins.

  19. Altered social cognition in male BDNF heterozygous mice and following chronic methamphetamine exposure.

    Science.gov (United States)

    Manning, Elizabeth E; van den Buuse, Maarten

    2016-05-15

    Growing clinical evidence suggests that persistent psychosis which occurs in methamphetamine users is closely related to schizophrenia. However, preclinical studies in animal models have focussed on psychosis-related behaviours following methamphetamine, and less work has been done to assess endophenotypes relevant to other deficits observed in schizophrenia. Altered social behaviour is a feature of both the negative symptoms and cognitive deficits in schizophrenia, and significantly impacts patient functioning. We recently found that brain-derived neurotrophic factor (BDNF) heterozygous mice show disrupted sensitization to methamphetamine, supporting other work suggesting an important role of this neurotrophin in the pathophysiology of psychosis and the neuronal response to stimulant drugs. In the current study, we assessed social and cognitive behaviours in methamphetamine-treated BDNF heterozygous mice and wildtype littermate controls. Following chronic methamphetamine exposure male wildtype mice showed a 50% reduction in social novelty preference. Vehicle-treated male BDNF heterozygous mice showed a similar impairment in social novelty preference, with a trend for no further disruption by methamphetamine exposure. Female mice were unaffected in this task, and no groups showed any changes in sociability or short-term spatial memory. These findings suggest that chronic methamphetamine alters behaviour relevant to disruption of social cognition in schizophrenia, supporting other studies which demonstrate a close resemblance between persistent methamphetamine psychosis and schizophrenia. Together these findings suggest that dynamic regulation of BDNF signalling is necessary to mediate the effects of methamphetamine on behaviours relevant to schizophrenia. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. A high fat diet alters metabolic and bioenergetic function in the brain: A magnetic resonance spectroscopy study

    OpenAIRE

    Raider, Kayla; Ma, Delin; Harris, Janna L.; Fuentes, Isabella; Rogers, Robert S.; Wheatley, Joshua L.; Geiger, Paige C.; Yeh, Hung-Wen; Choi, In-Young; Brooks, William M.; Stanford, John A.

    2016-01-01

    Diet-induced obesity and associated metabolic effects can lead to neurological dysfunction and increase the risk of developing Alzheimer's disease (AD) and Parkinson's disease (PD). Despite these risks, the effects of a high-fat diet on the central nervous system are not well understood. To better understand the mechanisms underlying the effects of high fat consumption on brain regions affected by AD and PD, we used proton magnetic resonance spectroscopy (1H-MRS) to measure neurochemicals in ...

  1. Molecular and neurochemical substrates of the audiogenic seizure strains: The GASH:Sal model.

    Science.gov (United States)

    Prieto-Martín, Ana I; Aroca-Aguilar, J Daniel; Sánchez-Sánchez, Francisco; Muñoz, Luis J; López, Dolores E; Escribano, Julio; de Cabo, Carlos

    2017-06-01

    Animal models of audiogenic epilepsy are useful tools to understand the mechanisms underlying human reflex epilepsies. There is accumulating evidence regarding behavioral, anatomical, electrophysiological, and genetic substrates of audiogenic seizure strains, but there are still aspects concerning their neurochemical basis that remain to be elucidated. Previous studies have shown the involved of γ-amino butyric acid (GABA) in audiogenic seizures. The aim of our research was to clarify the role of the GABAergic system in the generation of epileptic seizures in the genetic audiogenic seizure-prone hamster (GASH:Sal) strain. We studied the K + /Cl - cotransporter KCC2 and β2-GABAA-type receptor (GABAAR) and β3-GABAAR subunit expressions in the GASH:Sal both at rest and after repeated sound-induced seizures in different brain regions using the Western blot technique. We also sequenced the coding region for the KCC2 gene both in wild- type and GASH:Sal hamsters. Lower expression of KCC2 protein was found in GASH:Sal when compared with controls at rest in several brain areas: hippocampus, cortex, cerebellum, hypothalamus, pons-medulla, and mesencephalon. Repeated induction of seizures caused a decrease in KCC2 protein content in the inferior colliculus and hippocampus and an increase in the pons-medulla. When compared to controls, the basal β 2 -GABA A R subunit in the GASH:Sal was overexpressed in the inferior colliculus, rest of the mesencephalon, and cerebellum, whereas basal β 3 subunit levels were lower in the inferior colliculus and rest of the mesencephalon. Repeated seizures increased β2 both in the inferior colliculus and in the hypothalamus and β 3 in the hypothalamus. No differences in the KCC2 gene-coding region were found between GASH:Sal and wild-type hamsters. These data indicate that GABAergic system functioning is impaired in the GASH:Sal strain, and repeated seizures seem to aggravate this dysfunction. These results have potential clinical

  2. Brief daily postpartum separations from the litter alter dam response to psychostimulants and to stress

    Directory of Open Access Journals (Sweden)

    P.P. Silveira

    2013-05-01

    Full Text Available Neonatal handling induces several behavioral and neurochemical alterations in pups, including decreased responses to stress and reduced fear in new environments. However, there are few reports in the literature concerning the behavioral effects of this neonatal intervention on the dams during the postpartum period. Therefore, the aim of the current study was to determine if brief postpartum separation from pups has a persistent impact on the dam's stress response and behavior. Litters were divided into two neonatal groups: 1 non-handled and 2 handled [10 min/day, from postnatal day (PND 1 to 10]. Weaning occurred at PND 21 when behavioral tasks started to be applied to the dams, including sweet food ingestion (PND 21, forced swimming test (PND 28, and locomotor response to a psychostimulant (PND 28. On postpartum day 40, plasma was collected at baseline for leptin assays and after 1 h of restraint for corticosterone assay. Regarding sweet food consumption, behavior during the forced swimming test or plasma leptin levels did not differ between dams briefly separated and non-separated from their pups during the postpartum period. On the other hand, both increased locomotion in response to diethylpropion and increased corticosterone secretion in response to acute stress were detected in dams briefly separated from their pups during the first 10 postnatal days. Taken together, these findings suggest that brief, repeated separations from the pups during the neonatal period persistently impact the behavior and induce signs of dopaminergic sensitization in the dam.

  3. Does My Baby Really Look Like Me? Using Tests for Resemblance between Parent and Child to Teach Topics in Categorical Data Analysis

    Science.gov (United States)

    Froelich, Amy G.; Nettleton, Dan

    2013-01-01

    In this article, we present a study to test whether neutral observers perceive a resemblance between a parent and a child. We demonstrate the general approach for two separate parent/ child pairs using survey data collected from introductory statistics students serving as neutral observers. We then present ideas for incorporating the study design…

  4. Social isolation stress and chronic glutathione deficiency have a common effect on the glutamine-to-glutamate ratio and myo-inositol concentration in the mouse frontal cortex.

    Science.gov (United States)

    Corcoba, Alberto; Gruetter, Rolf; Do, Kim Q; Duarte, João M N

    2017-09-01

    Environmental stress can interact with genetic predisposition to increase the risk of developing psychopathology. In this work, we tested the hypothesis that social isolation stress interacts with impaired glutathione synthesis and have cumulative effects on the neurochemical profile of the frontal cortex. A mouse model with chronic glutathione deficit induced by knockout (-/-) of the glutamate-cysteine ligase modulatory subunit (Gclm) was exposed to social isolation stress from weaning to post-natal day 65. Using magnetic resonance methods at high-field (14.1 T), we analysed the neurochemical profile in the frontal cortex, brain size and ventricular volume of adult animals. Glutathione deficit was accompanied by elevated concentrations of N-acetylaspartate, alanine, and glutamine, as well as the ratio of glutamine-to-glutamate (Gln/Glu), and by a reduction in levels of myo-inositol and choline-containing compounds in the frontal cortex of -/- animals with respect to wild-type littermates. Although there was no significant interaction between social isolation stress and glutathione deficiency, mice reared in isolation displayed lower myo-inositol concentration (-8.4%, p social isolation had no effect on these parameters. We conclude that social isolation caused neurochemical alterations that may add to those associated to impaired glutathione synthesis. © 2017 International Society for Neurochemistry.

  5. Acral Peeling Skin Syndrome Resembling Epidermolysis Bullosa Simplex in a 10-Month-Old Boy

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    S. Kavaklieva

    2013-08-01

    Full Text Available The acral peeling skin syndrome (APSS is a rare autosomal recessive disorder clinically characterized by asymptomatic desquamation of the skin limited to the hands and feet and histologically by cleavage at the stratum granulosum and stratum corneum level [Kiritsi et al.: J Invest Dermatol 2010;130:1741-1746]. We report on a 10-month-old boy with a history of skin peeling limited to the hands and feet since 2 months of age. Clinical examination revealed erythematous erosions with peripheral desquamation and flaccid blisters. DNA mutation analysis detected two heterozygous TGM5 mutations: c.2T>C, p.M1T in exon 1 and c.337G>T, p.G113C in exon 3 in keeping with the diagnosis of APSS. The clinical presentation of APSS alone might be confusing and strongly resemble epidermolysis bullosa simplex making the differential diagnosis difficult.

  6. Sleep Deprivation Alters Choice Strategy Without Altering Uncertainty or Loss Aversion Preferences

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    O'Dhaniel A Mullette-Gillman

    2015-10-01

    Full Text Available Sleep deprivation alters decision making; however, it is unclear what specific cognitive processes are modified to drive altered choices. In this manuscript, we examined how one night of total sleep deprivation (TSD alters economic decision making. We specifically examined changes in uncertainty preferences dissociably from changes in the strategy with which participants engage with presented choice information. With high test-retest reliability, we show that TSD does not alter uncertainty preferences or loss aversion. Rather, TSD alters the information the participants rely upon to make their choices. Utilizing a choice strategy metric which contrasts the influence of maximizing and satisficing information on choice behavior, we find that TSD alters the relative reliance on maximizing information and satisficing information, in the gains domain. This alteration is the result of participants both decreasing their reliance on cognitively-complex maximizing information and a concomitant increase in the use of readily-available satisficing information. TSD did not result in a decrease in overall information use in either domain. These results show that sleep deprivation alters decision making by altering the informational strategies that participants employ, without altering their preferences.

  7. Sleep deprivation alters choice strategy without altering uncertainty or loss aversion preferences.

    Science.gov (United States)

    Mullette-Gillman, O'Dhaniel A; Kurnianingsih, Yoanna A; Liu, Jean C J

    2015-01-01

    Sleep deprivation alters decision making; however, it is unclear what specific cognitive processes are modified to drive altered choices. In this manuscript, we examined how one night of total sleep deprivation (TSD) alters economic decision making. We specifically examined changes in uncertainty preferences dissociably from changes in the strategy with which participants engage with presented choice information. With high test-retest reliability, we show that TSD does not alter uncertainty preferences or loss aversion. Rather, TSD alters the information the participants rely upon to make their choices. Utilizing a choice strategy metric which contrasts the influence of maximizing and satisficing information on choice behavior, we find that TSD alters the relative reliance on maximizing information and satisficing information, in the gains domain. This alteration is the result of participants both decreasing their reliance on cognitively-complex maximizing information and a concomitant increase in the use of readily-available satisficing information. TSD did not result in a decrease in overall information use in either domain. These results show that sleep deprivation alters decision making by altering the informational strategies that participants employ, without altering their preferences.

  8. Studies of petrography, metasomatic alteration, and genesis of Kamtal iron-copper skarn, northeast of Kharvana, East-Azarbaijan

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    Rasool Ferdowsi

    2012-04-01

    Full Text Available Kamtal skarn is located 15 km northeast of Kharvana, East-Azarbaijan. A quartz-monzonitic stock of Oligocene age intruded the upper Cretaceous sedimentary sequence (claystone, limestone, marl, and siltstone developing noticeable metamorphic (marble, hornfels and metasomatic (skarn alteration zones along the contact. Kamtal skarn is of calcic type and consists of both endoskarn and exoskarn zones. Exoskarn includes two zones of garnet skarn and epidote skarn. Skarnification processes are divided mainly in two major stages (1 prograde and (2 retrograde. During prograde stage, the emplacement of intrusive body caused isochemical metamorphism of the wall rocks and developed marble and hornfels units in enclosing rocks. Crystallization of intrusive body led to evolvement of hydrothermal fluid phase which infiltrated into enclosing rocks. Reaction of these fluids with the early-formed metamorphosed wall rocks brought about extensive progressive metasomatic alteration characterized by the formation of anhydrous calc-silicate minerals such as garnets and pyroxenes at a temperature range of 420-550°C and ¦O2=10-22-10-25. Retrograde stage was accompanied by some physicochemical changes (decrease in temperature to <420°C and increase in ¦S2 which caused the alteration of pre-existing anhydrous calc-silicates to hydrous calc-silicates (epidote, and tremolite-actinolite, silicates (quartz, chlorites, and other clay minerals, oxides (magnetite and hematite, sulfides (pyrite, chalcopyrite, and tetrahedrite, and carbonate (calcite. Comparison of Kamtal skarn with some other ones of corresponding type from Iran and other countries shows that Kamtal skarn well resembles to Anjerd and Pahnavar skarns in East-Azarbaijan.

  9. Behavioral and neurochemical effects of alpha lipoic acid associated with omega-3 in tardive dyskinesia induced by chronic haloperidol in rats.

    Science.gov (United States)

    de Araújo, Dayane Pessoa; Camboim, Thaisa Gracielle Martins; Silva, Ana Patrícia Magalhães; Silva, Caio da Fonseca; de Sousa, Rebeca Canuto; Barbosa, Mabson Delâno Alves; Oliveira, Lucidio Clebeson; Cavalcanti, José Rodolfo Lopes de Paiva; Lucena, Eudes Euler de Souza; Guzen, Fausto Pierdoná

    2017-07-01

    Tardive dyskinesia (TD) is characterized by involuntary movements of the lower portion of the face being related to typical antipsychotic therapy. TD is associated with the oxidative imbalance in the basal ganglia. Lipoic acid (LA) and omega-3 (ω-3) are antioxidants acting as enzyme cofactors, regenerating antioxidant enzymes. This study aimed to investigate behavioral and neurochemical effects of supplementation with LA (100 mg/kg) and ω-3 (1 g/kg) in the treatment of TD induced by chronic use of haloperidol (HAL) (1 mg/kg) in rats. Wistar male rats were used, weighing between 180-200 g. The animals were treated chronically (31 days) with LA alone or associated with HAL or ω-3. Motor behavior was assessed by open-field test, the catalepsy test, and evaluation of orofacial dyskinesia. Oxidative stress was accessed by determination of lipid peroxidation and concentration of nitrite. LA and ω-3 alone or associated caused an improvement in motor performance by increasing locomotor activity in the open-field test and decreased the permanence time on the bar in the catalepsy test and decreased the orofacial dyskinesia. LA and ω-3 showed antioxidant effects, decreasing lipid peroxidation and nitrite levels. Thus, the use of LA associated with ω-3 reduced the extrapyramidal effects produced by chronic use of HAL.

  10. Doença dos tiques: aspectos genéticos e neuroquímicos atuais Genetic and neurochemical factors in tic disorders

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    JAMES PITÁGORAS DE MATTOS

    1999-06-01

    Full Text Available Após breve revisão dos dados históricos, do conceito, do quadro clínico e dos critérios para o diagnóstico, analisamos os principais aspectos genéticos e neuroquímicos atuais dos tiques e da síndrome de Gilles de La Tourette. Dados epidemiológicos sugerem que todo tique seja de natureza orgânica, a maioria de origem genética, e que obedecem a transmissão autossômica dominante com penetrância aproximada de 100%. Ressaltamos, ainda, os recentes estudos imuno-histoquímicos, particularmente os que se referem aos sistemas dopaminérgico, noradrenérgico e serotoninérgico, que modulam a atividade dos circuitos córtico-estriato-talâmico-cortical, envolvidos na gênese dos tiques e dos transtornos obsessivos-compulsivos.We review historical, conceptual, clinical and diagnostic criteria as well as present genetic and neurochemical factors of tic disorders. Epidemiologic data sugest that tic is an organic disease with autosomal dominant transmission. We emphasize imunohistochemical studies particularly related to the dopaminergic, noradrenergic and serotonergic systems. These modulate the activity of the cortico-striato-thalamocortical circuits implicated in both Tourette's syndrome and obsessive-compulsive disorder.

  11. Sex differences in abuse-related neurochemical and behavioral effects of 3,4-methylenedioxymethamphetamine (MDMA) in rats.

    Science.gov (United States)

    Lazenka, M F; Suyama, J A; Bauer, C T; Banks, M L; Negus, S S

    2017-01-01

    3,4-Methylenedioxymethamphetamine (MDMA) is a substrate for dopamine (DA), norepinephrine and serotonin (5HT) transporters that produces greater pharmacological effects on certain endpoints in females than males in both clinical and rodent preclinical studies. To evaluate potential for sex differences in abuse-related MDMA effects, the present study compared MDMA effects on intracranial self-stimulation (ICSS) and on in vivo microdialysis measurements of DA or 5HT in the nucleus accumbens (NAc) in female and male Sprague-Dawley rats. For ICSS studies, electrodes were implanted in the medial forebrain bundle and rats trained to press for electrical stimulation over a range of frequencies (56-158Hz, 0.05 log increments) under a fixed-ratio 1 schedule, and the potency (0.32-3.2mg/kg, 10min pretreatment) and time course (3.2. mg/kg, 10-180min pretreatment) of MDMA effects were determined. For in vivo microdialysis, rats were implanted with bilateral guide cannulae targeting the NAc, and the time course of MDMA effects (1.0-3.2mg/kg, 0-180min) on DA and 5HT was determined. MDMA produced qualitatively similar effects in both sexes on ICSS (both increases in low ICSS rates maintained by low brain-stimulation frequencies and decreases in high ICSS rates maintained by high brain-stimulation frequencies) and microdialysis (increases in both DA and 5HT). The duration and peak levels of both abuse-related ICSS facilitation and increases in NAc DA were longer in females. MDMA was also more potent to increase 5HT in females. These results provide evidence for heightened sensitivity of females to abuse-related behavioral and neurochemical effects of MDMA in rats. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Aqueous alteration of Japanese simulated waste glass P0798: Effects of alteration-phase formation on alteration rate and cesium retention

    International Nuclear Information System (INIS)

    Inagaki, Y.; Shinkai, A.; Idemistu, K.; Arima, T.; Yoshikawa, H.; Yui, M.

    2006-01-01

    Aqueous alteration tests were performed with a Japanese simulated waste glass P0798 in alkaline solutions as a function of pH or species/concentration of alkaline metals in the solution in order to evaluate the alteration conditions determining whether smectite (2:1 clay mineral) or analcime (zeolite) forms as the major alteration-phase. XRD analysis of the alteration-phases showed that smectite forms at any pH between 9.5 and 12, and analcime forms at pH above 11, though the formation also depends on species and concentrations of alkaline metals in the solution. These results cannot agree with the thermodynamically predicted phase stability, e.g., smectite is more stable than the thermodynamic prediction shows. On the basis of the results of alteration conditions, the alteration tests were performed under smectite forming conditions, where only smectite forms or no crystalline phases form, in order to evaluate the alteration rate and the mechanism of cesium release/retention. The results showed that the glass alteration proceeds slowly in proportion to square root of time under smectite forming conditions, which indicates that the alteration rate can be controlled by a diffusion process. It was suggested that the alteration rate under smectite forming conditions is independent of the pH, alkaline metal species/concentration in the solution and whether smectite actually forms or not. The results also indicated that most of cesium dissolved from the glass can be retained in the alteration-phases by reversible sorption onto smectite or irreversible incorporation into analcime, pollucite or solid solutions of them

  13. Neurochemical and Neuroanatomical Plasticity Following Memory Training and Yoga Interventions in Older Adults with Mild Cognitive Impairment

    Directory of Open Access Journals (Sweden)

    Hongyu Yang

    2016-11-01

    Full Text Available Behavioral interventions are becoming increasingly popular approaches to ameliorate age-related cognitive decline, but their underlying neurobiological mechanisms and clinical efficiency have not been fully elucidated. The present study explored brain plasticity associated with two behavioral interventions, memory enhancement training (MET and a mind-body practice (yogic meditation, in healthy seniors with mild cognitive impairment (MCI using structural magnetic resonance imaging (MRI and proton magnetic resonance spectroscopy (1H-MRS. Senior participants (age ≥ 55 years with MCI were randomized to the MET or yogic meditation interventions. For both interventions, participants completed either MET training or Kundalini yoga for 60-min sessions over 12 weeks, with 12-min daily homework assignments. Gray matter volume and metabolite concentrations in the dorsal anterior cingulate cortex (dACC and bilateral hippocampus were measured by structural MRI and 1H-MRS at baseline and after 12 weeks of training. Metabolites measured included glutamate-glutamine (Glx, choline-containing compounds (Cho, including glycerophosphocholine and phosphocholine, gamma-aminobutyric acid (GABA, and N-acetyl aspartate and N-acetylaspartyl-glutamate (NAA-NAAG. In total, 11 participants completed MET and 14 completed yogic meditation for this study. Structural MRI analysis showed an interaction between time and group in dACC, indicating a trend towards increased gray matter volume after the MET intervention. 1H-MRS analysis showed an interaction between time and group in choline-containing compounds in bilateral hippocampus, induced by significant decreases after the MET intervention. Though preliminary, our results suggest that memory training induces structural and neurochemical plasticity in seniors with mild cognitive impairment. Further research is needed to determine whether mind-body interventions like yoga yield similar neuroplastic changes.

  14. Neurochemical and Neuroanatomical Plasticity Following Memory Training and Yoga Interventions in Older Adults with Mild Cognitive Impairment.

    Science.gov (United States)

    Yang, Hongyu; Leaver, Amber M; Siddarth, Prabha; Paholpak, Pattharee; Ercoli, Linda; St Cyr, Natalie M; Eyre, Harris A; Narr, Katherine L; Khalsa, Dharma S; Lavretsky, Helen

    2016-01-01

    Behavioral interventions are becoming increasingly popular approaches to ameliorate age-related cognitive decline, but their underlying neurobiological mechanisms and clinical efficiency have not been fully elucidated. The present study explored brain plasticity associated with two behavioral interventions, memory enhancement training (MET) and a mind-body practice (yogic meditation), in healthy seniors with mild cognitive impairment (MCI) using structural magnetic resonance imaging (s-MRI) and proton magnetic resonance spectroscopy ( 1 H-MRS). Senior participants (age ≥55 years) with MCI were randomized to the MET or yogic meditation interventions. For both interventions, participants completed either MET training or Kundalini Yoga (KY) for 60-min sessions over 12 weeks, with 12-min daily homework assignments. Gray matter volume and metabolite concentrations in the dorsal anterior cingulate cortex (dACC) and bilateral hippocampus were measured by structural MRI and 1 H-MRS at baseline and after 12 weeks of training. Metabolites measured included glutamate-glutamine (Glx), choline-containing compounds (Cho, including glycerophosphocholine and phosphocholine), gamma-aminobutyric acid (GABA), and N-acetyl aspartate and N-acetylaspartyl-glutamate (NAA-NAAG). In total, 11 participants completed MET and 14 completed yogic meditation for this study. Structural MRI analysis showed an interaction between time and group in dACC, indicating a trend towards increased gray matter volume after the MET intervention. 1 H-MRS analysis showed an interaction between time and group in choline-containing compounds in bilateral hippocampus, induced by significant decreases after the MET intervention. Though preliminary, our results suggest that memory training induces structural and neurochemical plasticity in seniors with MCI. Further research is needed to determine whether mind-body interventions like yoga yield similar neuroplastic changes.

  15. Omega-3 fatty acid deficient male rats exhibit abnormal behavioral activation in the forced swim test following chronic fluoxetine treatment: association with altered 5-HT1A and alpha2A adrenergic receptor expression.

    Science.gov (United States)

    Able, Jessica A; Liu, Yanhong; Jandacek, Ronald; Rider, Therese; Tso, Patrick; McNamara, Robert K

    2014-03-01

    Omega-3 fatty acid deficiency during development leads to enduing alterations in central monoamine neurotransmission in rat brain. Here we investigated the effects of omega-3 fatty acid deficiency on behavioral and neurochemical responses to chronic fluoxetine (FLX) treatment. Male rats were fed diets with (CON, n = 34) or without (DEF, n = 30) the omega-3 fatty acid precursor alpha-linolenic acid (ALA) during peri-adolescent development (P21-P90). A subset of CON (n = 14) and DEF (n = 12) rats were administered FLX (10 mg/kg/d) through their drinking water for 30 d beginning on P60. The forced swimming test (FST) was initiated on P90, and regional brain mRNA markers of serotonin and noradrenaline neurotransmission were determined. Dietary ALA depletion led to significant reductions in frontal cortex docosahexaenoic acid (DHA, 22:6n-3) composition in DEF (-26%, p = 0.0001) and DEF + FLX (-32%, p = 0.0001) rats. Plasma FLX and norfluoxetine concentrations did not different between FLX-treated DEF and CON rats. During the 15-min FST pretest, DEF + FLX rats exhibited significantly greater climbing behavior compared with CON + FLX rats. During the 5-min test trial, FLX treatment reduced immobility and increased swimming in CON and DEF rats, and only DEF + FLX rats exhibited significant elevations in climbing behavior. DEF + FLX rats exhibited greater midbrain, and lower frontal cortex, 5-HT1A mRNA expression compared with all groups including CON + FLX rats. DEF + FLX rats also exhibited greater midbrain alpha2A adrenergic receptor mRNA expression which was positively correlated with climbing behavior in the FST. These preclinical data demonstrate that low omega-3 fatty acid status leads to abnormal behavioral and neurochemical responses to chronic FLX treatment in male rats. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. Effects Of Hydrothermal Alteration On Magnetic Properties And Magnetic Signatures - Implications For Predictive Magnetic Exploration Models

    Science.gov (United States)

    Clark, D.

    2012-12-01

    Magnetics is the most widely used geophysical method in hard rock exploration and magnetic surveys are an integral part of exploration programs for many types of mineral deposit, including porphyry Cu, intrusive-related gold, volcanic-hosted epithermal Au, IOCG, VMS, and Ni sulfide deposits. However, the magnetic signatures of ore deposits and their associated mineralized systems are extremely variable and exploration that is based simply on searching for signatures that resemble those of known deposits and systems is rarely successful. Predictive magnetic exploration models are based upon well-established geological models, combined with magnetic property measurements and geological information from well-studied deposits, and guided by magnetic petrological understanding of the processes that create, destroy and modify magnetic minerals in rocks. These models are designed to guide exploration by predicting magnetic signatures that are appropriate to specific geological settings, taking into account factors such as tectonic province; protolith composition; post-formation tilting/faulting/ burial/ exhumation and partial erosion; and metamorphism. Patterns of zoned hydrothermal alteration are important indicators of potentially mineralized systems and, if properly interpreted, can provided vectors to ore. Magnetic signatures associated with these patterns at a range of scales can provide valuable information on prospectivity and can guide drilling, provided they are correctly interpreted in geological terms. This presentation reviews effects of the important types of hydrothermal alteration on magnetic properties within mineralized systems, with particular reference to porphyry copper and IOCG deposits. For example, an unmodified gold-rich porphyry copper system, emplaced into mafic-intermediate volcanic host rocks (such as Bajo de la Alumbrera, Argentina) exhibits an inner potassic zone that is strongly mineralized and magnetite-rich, which is surrounded by an outer

  17. Congenital biliary tract malformation resembling biliary cystadenoma in a captive juvenile African lion (Panthera leo).

    Science.gov (United States)

    Caliendo, Valentina; Bull, Andrew C J; Stidworthy, Mark F

    2012-12-01

    A captive 3-mo-old white African lion (Panthera leo) presented with clinical signs of acute pain and a distended abdomen. Despite emergency treatment, the lion died a few hours after presentation. Postmortem examination revealed gross changes in the liver, spleen, and lungs and an anomalous cystic structure in the bile duct. Histologic examination identified severe generalized multifocal to coalescent necrotizing and neutrophilic hepatitis, neutrophilic splenitis, and mild interstitial pneumonia, consistent with bacterial septicemia. The abnormal biliary structures resembled biliary cystadenoma. However, due to the age of the animal, they were presumed to be congenital in origin. Biliary tract anomalies and cystadenomas have been reported previously in adult lions, and this case suggests that at least some of these examples may have a congenital basis. It is unclear whether the lesion was an underlying factor in the development of hepatitis.

  18. Lynch Syndrome Associated Colon Adenocarcinoma Resembling Lymphoma on Fluoro-Deoxyglucose-Positron Emission Tomography/Computed Tomography

    International Nuclear Information System (INIS)

    Aparici, Carina Mari; Win, Aung Zaw

    2015-01-01

    The patient was a 46-year-old Asian male diagnosed with lynch syndrome associated colon adenocarcinoma in the right ascending colon. A presurgical staging 18-fluoro-deoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) found increased metabolic activity in the cervical, axillary, mediastinal, supraclavicular, para-aortic and mesenteric lymph nodes. This pattern of metastasis was very unusual for lynch syndrome associated colon adenocarcinoma and the involvement of those lymph nodes resembles the pattern of spread of lymphoma. He underwent right hemicolectomy and he was subsequently treated with 12 cycles of folinic acid (leucovorin), fluorouracil (5-FU), irinotecan. A restaging FDG-PET/CT at the end of the chemotherapy showed interval decrease in size and metabolic activity in the affected lymph nodes. FDG-PET/CT is a useful imaging modality in following-up the treatment response in colon adenocarcinoma

  19. Food, mood and health: a neurobiologic outlook

    Directory of Open Access Journals (Sweden)

    C. Prasad

    1998-12-01

    Full Text Available Hippocrates was the first to suggest the healing power of food; however, it was not until the medieval ages that food was considered a tool to modify temperament and mood, although scientific methods as we know them today were not in use at the time. Modern scientific methods in neuroscience began to emerge much later, leading investigators to examine the role of diet in health, including mental well-being, with greater precision. This review shows how short- and long-term forced dietary interventions bring about changes in brain structure, chemistry, and physiology, leading to altered animal behavior. Examples will be presented to show how diets alter brain chemistry, behavior, and the action of neuroactive drugs. Most humans and most animal species examined in a controlled setting exhibit a fairly reproducible pattern of what and how they eat. Recent data suggest that these patterns may be under the neurochemical and hormonal control of the organisms themselves. Other data show that in many instances food may be used unconsciously to regulate mood by seemingly normal subjects as well as those undergoing drug withdrawal or experiencing seasonal affective disorders and obesity-related social withdrawal. We will discuss specific examples that illustrate that manipulation of dietary preference is actually an attempt to correct neurochemical make-up.

  20. Protective effect of minocycline, a semi-synthetic second-generation tetracycline against 3-nitropropionic acid (3-NP)-induced neurotoxicity

    International Nuclear Information System (INIS)

    Ahuja, Manuj; Bishnoi, Mahendra; Chopra, Kanwaljit

    2008-01-01

    3-Nitropropionic acid (3-NP) is an irreversible inhibitor of the electron transport enzyme succinate dehydrogenase, a mitochondrial Complex II enzyme. Minocycline is a semi-synthetic second-generation tetracycline with neuroprotective activity and has the capability to effectively cross the blood-brain barrier. We investigated the effects of minocycline on behavioral, biochemical, inflammation related and neurochemical alterations induced by the sub-chronic administration of 3-nitropropionic acid to rats. Chronic pre-administration of minocycline (50 and 100 mg/kg) dose dependently prevented 3-NP-induced dysfunction behavioral (hypoactivity, memory retention, locomotor and rota-rod activity). In addition, 3-NP produced a marked increase in lipid peroxidation levels whereas decreased the activities of catalase and succinate dehydrogenase. In contrast, pretreatment of 3-NP injected rats with minocycline resulted in the attenuation of all these alterations. A marked increase in an inflammatory cytokine TNF-α by 3-NP was also decreased by minocycline treatment. Neurochemically, the administration of 3-NP significantly decreased the levels of catecholamines in the brain homogenates (dopamine, norepinephrine and serotonin) which were reversed by pretreatment of minocycline. The present finding explains the neuroprotective effect of minocycline against 3-NP toxicity by virtue of its antioxidant and anti-inflammatory activity

  1. Extended phenotype: nematodes turn ants into bird-dispersed fruits

    DEFF Research Database (Denmark)

    Hughes, D P; Kronauer, D J C; Boomsma, J J

    2008-01-01

    A recent study has discovered a novel extended phenotype of a nematode which alters its ant host to resemble ripe fruit. The infected ants are in turn eaten by frugivorous birds that disperse the nematode's eggs.......A recent study has discovered a novel extended phenotype of a nematode which alters its ant host to resemble ripe fruit. The infected ants are in turn eaten by frugivorous birds that disperse the nematode's eggs....

  2. Behavioral and neurochemical effects of chronic administration of reserpine and SKF-38393 in rats

    International Nuclear Information System (INIS)

    Neisewander, J.L.; Lucki, I.; McGonigle, P.

    1991-01-01

    Alterations in the density of dopamine receptor subtypes and behaviors mediated by the D1-selective agonist SKF-38393 were examined in rats treated chronically with reserpine, SKF-38393 or the combination of these drugs. Animals received either vehicle or reserpine (1 mg/kg s.c.) on days 1 to 28 and, in addition, half of each of these groups were treated with vehicle and half were treated with SKF-38393 (5-10 mg/kg s.c.) on days 15 to 29. Quantitative autoradiographic measurement of D1 receptors labeled with [ 3 H]SCH-23390 and D2 receptors labeled with [ 3 H]spiroperidol revealed that chronic administration of reserpine increased the density of both receptor subtypes in the nucleus accumbens and caudate-putamen, but not in the substantia nigra. Chronic administration of SKF-38393 alone did not alter D1 receptor density in any of these regions. However, chronic administration of the agonist in reserpinized animals decreased D1 receptor density in the nucleus accumbens, but not in the caudate-putamen or substantia nigra, demonstrating that this partial agonist can selectively down-regulate D1 receptors when endogenous dopaminergic tone is removed. The chronic drug treatments also altered behavioral responses. Chronic administration of SKF-38393 alone produced sensitization of the oral dyskinesia response elicited by a challenge injection of the agonist, but no significant change in the grooming response. Acute administration of SKF-38393 in rats treated with reserpine for 14 days produced stereotypy which was not altered after chronic administration of the agonist. Surprisingly, chronic administration of reserpine alone produced a spontaneous oral dyskinesia, which was blocked dose-dependently by the D2-selective antagonist spiroperidol. These findings are discussed in terms of their relevance to Parkinson's disease and tardive dyskinesia

  3. Altered dopaminergic regulation of the dorsal striatum is able to induce tic-like movements in juvenile rats

    Science.gov (United States)

    Rizzo, Francesca; Boeckers, Tobias; Schulze, Ulrike

    2018-01-01

    Motor tics are sudden, repetitive, involuntary movements representing the hallmark behaviors of the neurodevelopmental disease Tourette’s syndrome (TS). The primary cause of TS remains unclear. The initial observation that dopaminergic antagonists alleviate tics led to the development of a dopaminergic theory of TS etiology which is supported by post mortem and in vivo studies indicating that non-physiological activation of the striatum could generate tics. The striatum controls movement execution through the balanced activity of dopamine receptor D1 and D2-expressing medium spiny neurons of the direct and indirect pathway, respectively. Different neurotransmitters can activate or repress striatal activity and among them, dopamine plays a major role. In this study we introduced a chronic dopaminergic alteration in juvenile rats, in order to modify the delicate balance between direct and indirect pathway. This manipulation was done in the dorsal striatum, that had been associated with tic-like movements generation in animal models. The results were movements resembling tics, which were categorized and scored according to a newly developed rating scale and were reduced by clonidine and riluzole treatment. Finally, post mortem analyses revealed altered RNA expression of dopaminergic receptors D1 and D2, suggesting an imbalanced dopaminergic regulation of medium spiny neuron activity as being causally related to the observed phenotype. PMID:29698507

  4. Neurochemical pathways that converge on thalamic trigeminovascular neurons: potential substrate for modulation of migraine by sleep, food intake, stress and anxiety.

    Directory of Open Access Journals (Sweden)

    Rodrigo Noseda

    Full Text Available Dynamic thalamic regulation of sensory signals allows the cortex to adjust better to rapidly changing behavioral, physiological and environmental demands. To fulfill this role, thalamic neurons must themselves be subjected to constantly changing modulatory inputs that originate in multiple neurochemical pathways involved in autonomic, affective and cognitive functions. Our overall goal is to define an anatomical framework for conceptualizing how a 'decision' is made on whether a trigeminovascular thalamic neuron fires, for how long, and at what frequency. To begin answering this question, we determine which neuropeptides/neurotransmitters are in a position to modulate thalamic trigeminovascular neurons. Using a combination of in-vivo single-unit recording, juxtacellular labeling with tetramethylrhodamine dextran (TMR and in-vitro immunohistochemistry, we found that thalamic trigeminovascular neurons were surrounded by high density of axons containing biomarkers of glutamate, GABA, dopamine and serotonin; moderate density of axons containing noradrenaline and histamine; low density of axons containing orexin and melanin concentrating hormone (MCH; but not axons containing CGRP, serotonin 1D receptor, oxytocin or vasopressin. In the context of migraine, the findings suggest that the transmission of headache-related nociceptive signals from the thalamus to the cortex may be modulated by opposing forces (i.e., facilitatory, inhibitory that are governed by continuous adjustments needed to keep physiological, behavioral, cognitive and emotional homeostasis.

  5. Redox Dysregulation in the Pathophysiology of Schizophrenia and Bipolar Disorder

    DEFF Research Database (Denmark)

    Kulak, Anita; Steullet, Pascal; Cabungcal, Jan-Harry

    2013-01-01

    Abstract Significance: Schizophrenia (SZ) and bipolar disorder (BD) are classified as two distinct diseases. However, accumulating evidence shows that both disorders share genetic, pathological, and epidemiological characteristics. Based on genetic and functional findings, redox dysregulation due...... abnormal prefrontal levels of glutathione (GSH), the major cellular redox regulator and antioxidant. Here we review experimental data from rodent models demonstrating that permanent as well as transient GSH deficit results in behavioral, morphological, electrophysiological, and neurochemical alterations...... hypofunction, elevated glutamate levels, impairment of parvalbumin GABA interneurons, abnormal neuronal synchronization, altered dopamine neurotransmission, and deficient myelination. Critical Issues: Treatment with the GSH precursor and antioxidant N-acetylcysteine normalizes some of those deficits in mice...

  6. Sodium Butyrate, a Histone Deacetylase Inhibitor, Reverses Behavioral and Mitochondrial Alterations in Animal Models of Depression Induced by Early- or Late-life Stress.

    Science.gov (United States)

    Valvassori, Samira S; Resende, Wilson R; Budni, Josiane; Dal-Pont, Gustavo C; Bavaresco, Daniela V; Réus, Gislaine Z; Carvalho, André F; Gonçalves, Cinara L; Furlanetto, Camila B; Streck, Emilio L; Quevedo, João

    2015-01-01

    The aim of the present study was to evaluate the effects of sodium butyrate on depressive-like behavior and mitochondrial alteration parameters in animal models of depression induced by maternal deprivation or chronic mild stress in Wistar rats. maternal deprivation was established by separating pups from their mothers for 3 h daily from postnatal day 1 to day 10. Chronic mild stress was established by water deprivation, food deprivation, restraint stress, isolation and flashing lights. Sodium butyrate or saline was administered twice a day for 7 days before the behavioral tests. Depressive behavior was evaluated using the forced swim test. The activity of tricarboxylic acid cycle enzymes (succinate dehydrogenase and malate dehydrogenase) and of mitochondrial chain complexes (I, II, II-III and IV) was measured in the striatum of rats. From these analyses it can be observed that sodium butyrate reversed the depressive-like behavior observed in both animal models of depression. Additionally, maternal deprivation and chronic mild stress inhibited mitochondrial respiratory chain complexes and increased the activity of tricarboxylic acid cycle enzymes. Sodium butyrate treatment reversed -maternal deprivation and chronic mild stress- induced dysfunction in the striatum of rats. In conclusion, sodium butyrate showed antidepressant effects in maternal deprivation and chronic mild stress-treated rats, and this effect can be attributed to its action on the neurochemical pathways related to depression.

  7. Reinforcing and neurochemical effects of cannabinoid CB1 receptor agonists, but not cocaine, are altered by an adenosine A2A receptor antagonist.

    Science.gov (United States)

    Justinová, Zuzana; Ferré, Sergi; Redhi, Godfrey H; Mascia, Paola; Stroik, Jessica; Quarta, Davide; Yasar, Sevil; Müller, Christa E; Franco, Rafael; Goldberg, Steven R

    2011-07-01

    Several recent studies suggest functional and molecular interactions between striatal adenosine A(2A) and cannabinoid CB(1) receptors. Here, we demonstrate that A(2A) receptors selectively modulate reinforcing effects of cannabinoids. We studied effects of A(2A) receptor blockade on the reinforcing effects of delta-9-tetrahydrocannabinol (THC) and the endogenous CB(1) receptor ligand anandamide under a fixed-ratio schedule of intravenous drug injection in squirrel monkeys. A low dose of the selective adenosine A(2A) receptor antagonist MSX-3 (1 mg/kg) caused downward shifts of THC and anandamide dose-response curves. In contrast, a higher dose of MSX-3 (3 mg/kg) shifted THC and anandamide dose-response curves to the left. MSX-3 did not modify cocaine or food pellet self-administration. Also, MSX-3 neither promoted reinstatement of extinguished drug-seeking behavior nor altered reinstatement of drug-seeking behavior by non-contingent priming injections of THC. Finally, using in vivo microdialysis in freely-moving rats, a behaviorally active dose of MSX-3 significantly counteracted THC-induced, but not cocaine-induced, increases in extracellular dopamine levels in the nucleus accumbens shell. The significant and selective results obtained with the lower dose of MSX-3 suggest that adenosine A(2A) antagonists acting preferentially at presynaptic A(2A) receptors might selectively reduce reinforcing effects of cannabinoids that lead to their abuse. However, the appearance of potentiating rather than suppressing effects on cannabinoid reinforcement at the higher dose of MSX-3 would likely preclude the use of such a compound as a medication for cannabis abuse. Adenosine A(2A) antagonists with more selectivity for presynaptic versus postsynaptic receptors could be potential medications for treatment of cannabis abuse. Addiction Biology © 2010 Society for the Study of Addiction. No claim to original US government works.

  8. Oxycodone Self-Administration Induces Alterations in Expression of Integrin, Semaphorin and Ephrin Genes in the Mouse Striatum

    Directory of Open Access Journals (Sweden)

    Vadim Yuferov

    2018-06-01

    Full Text Available Oxycodone is one a commonly used medication for pain, and is also a widely abused prescription opioid, like other short-acting MOPr agonists. Neurochemical and structural adaptations in brain following chronic MOPr-agonist administration are thought to underlie pathogenesis and persistence of opiate addiction. Many axon guidance molecules, such as integrins, semaphorins, and ephrins may contribute to oxycodone-induced neuroadaptations through alterations in axon-target connections and synaptogenesis, that may be implicated in the behaviors associated with opiate addiction. However, little is known about this important area. The aim of this study is to investigate alterations in expression of selected integrin, semaphorin, ephrins, netrin, and slit genes in the nucleus accumbens (NAc and caudate putamen (CPu of mice following extended 14-day oxycodone self-administration (SA, using RNAseq.Methods: Total RNA from the NAc and CPu were isolated from adult male C57BL/6J mice within 1 h after the last session of oxycodone in a 14-day self-administration paradigm (4h/day, 0.25 mg/kg/infusion, FR1 or from yoked saline controls. Gene expressions were examined using RNA sequencing (RNA-Seq technology. RNA-Seq libraries were prepared using Illumina's TruSeq® Stranded Total RNA LT kit. The reads were aligned to the mouse reference genome (version mm10 using STAR. DESeq2 was applied to the counts of protein coding genes to estimate the fold change between the treatment groups. False Discovery Rate (FDR q < 0.1 were used to select genes that have a significant expression change. For selection of a subset of genes related to axon guidance pathway, REACTOME was used.Results: Among 38 known genes of the integrin, semaphorin, and ephrin gene families, RNA-seq data revealed up-regulation of six genes in the NAc: heterodimer receptor, integrins Itgal, Itgb2, and Itgam, and its ligand semaphorin Sema7a, two semaphorin receptors, plexins Plxnd1 and Plxdc1. There was

  9. Diet and Age Interactions with Regards to Cholesterol Regulation and Brain Pathogenesis

    Directory of Open Access Journals (Sweden)

    Romina M. Uranga

    2010-01-01

    Full Text Available Cholesterol is an essential molecule for brain homeostasis; yet, hypercholesterolemia and its numerous complications are believed to play a role in promoting multiple aspects of brain pathogenesis. An ever increasing number of individuals in modern Western Society are regularly consuming diets high in fat which promote the development of hypercholesterolemia. Additionally, modern societies are becoming increasingly aged, causing a collision between increased hypercholesterolemia and increased aging, which will likely lead to the development of increased pathological conditions due to hypercholesterolemia, thereby promoting deleterious neurochemical and behavioral changes in the brain. Lastly, while beneficial in controlling cholesterol levels, the long-term use of statins itself may potentially promote adverse effects on brain homeostasis, although specifics on this remain largely unknown. This review will focus on linking the current understanding of diet-induced hypercholesterolemia (as well as statin use to the development of oxidative stress, neurochemical alterations, and cognitive disturbances in the aging brain.

  10. Prefrontal cortex executive processes affected by stress in health and disease.

    Science.gov (United States)

    Girotti, Milena; Adler, Samantha M; Bulin, Sarah E; Fucich, Elizabeth A; Paredes, Denisse; Morilak, David A

    2017-07-06

    Prefrontal cortical executive functions comprise a number of cognitive capabilities necessary for goal directed behavior and adaptation to a changing environment. Executive dysfunction that leads to maladaptive behavior and is a symptom of psychiatric pathology can be instigated or exacerbated by stress. In this review we survey research addressing the impact of stress on executive function, with specific focus on working memory, attention, response inhibition, and cognitive flexibility. We then consider the neurochemical pathways underlying these cognitive capabilities and, where known, how stress alters them. Finally, we review work exploring potential pharmacological and non-pharmacological approaches that can ameliorate deficits in executive function. Both preclinical and clinical literature indicates that chronic stress negatively affects executive function. Although some of the circuitry and neurochemical processes underlying executive function have been characterized, a great deal is still unknown regarding how stress affects these processes. Additional work focusing on this question is needed in order to make progress on developing interventions that ameliorate executive dysfunction. Published by Elsevier Inc.

  11. Resemblance profiles as clustering decision criteria: Estimating statistical power, error, and correspondence for a hypothesis test for multivariate structure.

    Science.gov (United States)

    Kilborn, Joshua P; Jones, David L; Peebles, Ernst B; Naar, David F

    2017-04-01

    Clustering data continues to be a highly active area of data analysis, and resemblance profiles are being incorporated into ecological methodologies as a hypothesis testing-based approach to clustering multivariate data. However, these new clustering techniques have not been rigorously tested to determine the performance variability based on the algorithm's assumptions or any underlying data structures. Here, we use simulation studies to estimate the statistical error rates for the hypothesis test for multivariate structure based on dissimilarity profiles (DISPROF). We concurrently tested a widely used algorithm that employs the unweighted pair group method with arithmetic mean (UPGMA) to estimate the proficiency of clustering with DISPROF as a decision criterion. We simulated unstructured multivariate data from different probability distributions with increasing numbers of objects and descriptors, and grouped data with increasing overlap, overdispersion for ecological data, and correlation among descriptors within groups. Using simulated data, we measured the resolution and correspondence of clustering solutions achieved by DISPROF with UPGMA against the reference grouping partitions used to simulate the structured test datasets. Our results highlight the dynamic interactions between dataset dimensionality, group overlap, and the properties of the descriptors within a group (i.e., overdispersion or correlation structure) that are relevant to resemblance profiles as a clustering criterion for multivariate data. These methods are particularly useful for multivariate ecological datasets that benefit from distance-based statistical analyses. We propose guidelines for using DISPROF as a clustering decision tool that will help future users avoid potential pitfalls during the application of methods and the interpretation of results.

  12. Parent–offspring resemblance in colony-specific adult survival of cliff swallows

    Science.gov (United States)

    Brown, Charles R.; Roche, Erin A.; Brown, Mary Bomberger

    2015-01-01

    Survival is a key component of fitness. Species that occupy discrete breeding colonies with different characteristics are often exposed to varying costs and benefits associated with group size or environmental conditions, and survival is an integrative net measure of these effects. We investigated the extent to which survival probability of adult (≥1-year old) cliff swallows (Petrochelidon pyrrhonota) occupying different colonies resembled that of their parental cohort and thus whether the natal colony had long-term effects on individuals. Individuals were cross-fostered between colonies soon after hatching and their presence as breeders monitored at colonies in the western Nebraska study area for the subsequent decade. Colony-specific adult survival probabilities of offspring born and reared in the same colony, and those cross-fostered away from their natal colony soon after birth, were positively and significantly related to subsequent adult survival of the parental cohort from the natal colony. This result held when controlling for the effect of natal colony size and the age composition of the parental cohort. In contrast, colony-specific adult survival of offspring cross-fostered to a site was unrelated to that of their foster parent cohort or to the cohort of non-fostered offspring with whom they were reared. Adult survival at a colony varied inversely with fecundity, as measured by mean brood size, providing evidence for a survival–fecundity trade-off in this species. The results suggest some heritable variation in adult survival, likely maintained by negative correlations between fitness components. The study provides additional evidence that colonies represent non-random collections of individuals.

  13. Pulmonary Extramedullary Hematopoiesis in a Patient with Chronic Asthma Resembling Lung Cancer: A Case Report

    Directory of Open Access Journals (Sweden)

    Massood Hosseinzadeh

    2012-01-01

    Full Text Available Background. Extramedullary hematopoiesis is most often seen in reticuloendothelial organs specially spleen, liver, or lymph nodes, and it is rarely seen in lung parenchyma. Almost all reported cases of pulmonary extramedullary hematopoiesis occurred following myeloproliferative disorders specially myelofibrosis. Other less common underlying causes are thalassemia syndromes and other hemoglobinopathies. There was not any reported case of pulmonary extramedullary hematopoiesis in asthmatic patients in the medical literature. Case. Here we reported a 65-year-old lady who was a known case of bronchial asthma with recent developed right lower lobe lung mass. Chest X-ray and CT studies showed an infiltrating mass resembling malignancy. Fine needle aspiration cytology of mass revealed pulmonary extramedullary hematopoiesis. The patient followed for 10 months with serial physical examination and laboratory evaluations which were unremarkable. Conclusion. Extramedullary hematopoiesis of lung parenchyma can be mistaken for lung cancer radiologically. Although previous reported cases occurred with myelofibrosis or hemoglobinopathies, we are reporting the first case of asthma-associated extramedullary hematopoiesis.

  14. A high fat diet alters metabolic and bioenergetic function in the brain: A magnetic resonance spectroscopy study.

    Science.gov (United States)

    Raider, Kayla; Ma, Delin; Harris, Janna L; Fuentes, Isabella; Rogers, Robert S; Wheatley, Joshua L; Geiger, Paige C; Yeh, Hung-Wen; Choi, In-Young; Brooks, William M; Stanford, John A

    2016-07-01

    Diet-induced obesity and associated metabolic effects can lead to neurological dysfunction and increase the risk of developing Alzheimer's disease (AD) and Parkinson's disease (PD). Despite these risks, the effects of a high-fat diet on the central nervous system are not well understood. To better understand the mechanisms underlying the effects of high fat consumption on brain regions affected by AD and PD, we used proton magnetic resonance spectroscopy ((1)H-MRS) to measure neurochemicals in the hippocampus and striatum of rats fed a high fat diet vs. normal low fat chow. We detected lower concentrations of total creatine (tCr) and a lower glutamate-to-glutamine ratio in the hippocampus of high fat rats. Additional effects observed in the hippocampus of high fat rats included higher N-acetylaspartylglutamic acid (NAAG), and lower myo-inositol (mIns) and serine (Ser) concentrations. Post-mortem tissue analyses revealed lower phosphorylated AMP-activated protein kinase (pAMPK) in the striatum but not in the hippocampus of high fat rats. Hippocampal pAMPK levels correlated significantly with tCr, aspartate (Asp), phosphoethanolamine (PE), and taurine (Tau), indicating beneficial effects of AMPK activation on brain metabolic and energetic function, membrane turnover, and edema. A negative correlation between pAMPK and glucose (Glc) indicates a detrimental effect of brain Glc on cellular energy response. Overall, these changes indicate alterations in neurotransmission and in metabolic and bioenergetic function in the hippocampus and in the striatum of rats fed a high fat diet. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. A novel and automatic mammographic texture resemblance marker is an independent risk factor for breast cancer

    DEFF Research Database (Denmark)

    Nielsen, Mads; Karemore, Gopal; Loog, Marco

    2011-01-01

    Objective: We investigated whether breast cancer is predicted by a breast cancer risk mammographic texture resemblance (MTR) marker. Methods: A previously published case-control study included 495 women of which 245 were diagnosed with breast cancer. In baseline mammograms, 2-4 years prior...... to diagnosis, the following mammographic parameters were analysed for relation to breast cancer risk: (C) categorical parenchymal pattern scores; (R) radiologist's percentage density, (P) computer-based percentage density; (H) computer-based breast cancer risk MTR marker; (E) computer-based hormone replacement...... treatment MTR marker; and (A) an aggregate of P and H. Results: Density scores, C, R, and P correlated (tau=0.3-0.6); no other pair of scores showed large (tau>0.2) correlation. For the parameters, the odds ratios of future incidence of breast cancer comparing highest to lowest categories (146 and 106...

  16. The Pattern of Sexual Interest of Female-to-Male Transsexual Persons With Gender Identity Disorder Does Not Resemble That of Biological Men: An Eye-Tracking Study

    Directory of Open Access Journals (Sweden)

    Akira Tsujimura

    2017-09-01

    Tsujimura A, Kiuchi H, Soda T, et al. The Pattern of Sexual Interest of Female-to-Male Transsexual Persons With Gender Identity Disorder Does Not Resemble That of Biological Men: An Eye-Tracking Study. Sex Med 2017;5:e169–e174.

  17. Adult family members and their resemblance of coronary heart disease risk factors: The Cardiovascular Disease Study in Finnmark

    International Nuclear Information System (INIS)

    Brenn, Tormod

    1997-01-01

    Coronary heart disease tends to run in families, and the familial resemblance of major risk factors for the disease was examined among various types of adult family members. Family units were assembled from a total of 4,738 men and women who took part in a cross sectional health survey in four Norwegian municipalities where all inhabitants between 20 and 52 years of age were invited. After adjusting for age and other confounders, correlation coefficients were derived as a measure of the degree of resemblance. Viewed across all types of investigated familial relationships, similarity was found to be stronger for total cholesterol than for high-density lipoprotein cholesterol and triglycerides, and also stronger for systolic than for diastolic blood pressure. Between husbands and wives (3,060 subjects), correlations were small (between 0.02 and 0.06), except for 0.11 for total cholesterol. Lipid and blood pressure correlations ranged from 0.13 to 0.27 for parents and their offspring (471 subjects, p < 0.05) and from 0.11 to 0.22 among siblings (2,166 subjects, p < 0.01). Sibling correlations were consistent across age groups. Furthermore, reports from each individual on daily smoking (yes or no) revealed that husbands and wives had similar habits in 63.5% of all marriages as compared with the expected 49.4% had no smoking similarity at all been present. Smoking concordance was also demonstrated among siblings (p < 0.01). The persistent pattern of lipid and blood pressure aggregation among genetically related individuals from 20 to 52 years of age and the much weaker such similarity between husbands and wives, point towards genes or commonly shared environment at early ages as a major reason why coronary heart disease runs in families

  18. Modelling glass alteration in an altered argillaceous environment

    International Nuclear Information System (INIS)

    Bildstein, O.; Trotignon, L.; Pozo, C.; Jullien, M.

    2007-01-01

    The long term behaviour of materials such as glass, steel and clay has been investigated in the context of deep geological disposal of radioactive wastes. The interactions between vitrified wastes, canister corrosion products (CPs) and clay are studied using a modified version of the reaction-transport code Crunch, especially looking at pH changes and possible cementation at the interface with the clayey materials. These perturbations may indeed affect the lifetime of glass matrix in deep repositories, e.g., high pH enhances the rate of glass alteration. This work focuses on the argillite of Bure. The calculations were performed at 323 K with a glass alteration rate switching from a high initial rate to a residual rate according to the sorption capacity of CPs. The time at which this sorption capacity is saturated is crucial to the system in terms of wastes package lifetime. The results show that the glass alteration imposes a high pH value at the interface with CPs and clay: up to a value of 9.2, compared to 7.3 which is the initial pH value in the argillite. Experimental data show that the rate of glass alteration is much higher in such pH conditions. For a R7T7-type glass, the rate is about five times higher at pH 9 than at pH 7. This pH perturbation migrates through the clayey domain as a result of the migration of mobile elements such as boron and sodium, and despite the existence of strong pH buffers in the argillite. The cementation of porosity at the interface between glass and clay is predicted by the model due to the massive precipitation of iron corrosion products and glass alteration products. At this point of the evolution of the system, the pH starts to decrease and the alteration rate of the glass could be significantly reduced. This porosity clogging effect is difficult to confirm by experiments especially since existing data on short term experiments tend to show a pervasive precipitation of silica in the domain instead of a localized precipitation

  19. Behavioral and Neurochemical Effects of Alpha-Lipoic Acid in the Model of Parkinson’s Disease Induced by Unilateral Stereotaxic Injection of 6-Ohda in Rat

    Directory of Open Access Journals (Sweden)

    Dayane Pessoa de Araújo

    2013-01-01

    Full Text Available This study aimed to investigate behavioral and neurochemical effects of α-lipoic acid (100 mg/kg or 200 mg/kg alone or associated with L-DOPA using an animal model of Parkinson’s disease induced by stereotaxic injection of 6-hydroxydopamine (6-OHDA in rat striatum. Motor behavior was assessed by monitoring body rotations induced by apomorphine, open field test and cylinder test. Oxidative stress was accessed by determination of lipid peroxidation using the TBARS method, concentration of nitrite and evaluation of catalase activity. α-Lipoic acid decreased body rotations induced by apomorphine, as well as caused an improvement in motor performance by increasing locomotor activity in the open field test and use of contralateral paw (in the opposite side of the lesion produced by 6-OHDA at cylinder test. α-lipoic acid showed antioxidant effects, decreasing lipid peroxidation and nitrite levels and interacting with antioxidant system by decreasing of endogenous catalase activity. Therefore, α-lipoic acid prevented the damage induced by 6-OHDA or by chronic use of L-DOPA in dopaminergic neurons, suggesting that α-lipoic could be a new therapeutic target for Parkinson's disease prevention and treatment.

  20. Pharmacological, neurochemical, and behavioral profile of JB-788, a new 5-HT1A agonist.

    Science.gov (United States)

    Picard, M; Morisset, S; Cloix, J F; Bizot, J C; Guerin, M; Beneteau, V; Guillaumet, G; Hevor, T K

    2010-09-01

    A novel pyridine derivative, 8-{4-[(6-methoxy-2,3-dihydro-[1,4]dioxino[2,3-b]pyridine-3-ylmethyl)-amino]-butyl}-8-aza-spiro[4.5]decane-7,9-dione hydrochloride, termed JB-788, was designed to selectively target 5-HT(1A) receptors. In the present study, the pharmacological profile of JB-788 was characterized in vitro using radioligands binding tests and in vivo using neurochemical and behavioural experiments. JB-788 bound tightly to human 5-HT(1A) receptor expressed in human embryonic kidney 293 (HEK-293) cells with a K(i) value of 0.8 nM. Its binding affinity is in the same range as that observed for the (+/-)8-OH-DPAT, a reference 5HT(1A) agonist compound. Notably, JB-788 only bound weakly to 5-HT(1B) or 5-HT(2A) receptors and moreover the drug displayed only weak or indetectable binding to muscarinic, alpha(2), beta(1) and beta(2) adrenergic receptors, or dopaminergic D(1) receptors. JB-788 was found to display substantial binding affinity for dopaminergic D(2) receptors and, to a lesser extend to alpha(1) adrenoreceptors. JB-788 dose-dependently decreased forskolin-induced cAMP accumulation in HEK cells expressing human 5-HT(1A), thus acting as a potent 5-HT(1A) receptor agonist (E(max.) 75%, EC(50) 3.5 nM). JB-788 did not exhibit any D(2) receptor agonism but progressively inhibited the effects of quinpirole, a D(2) receptor agonist, in the cAMP accumulation test with a K(i) value of 250 nM. JB-788 induced a weak change in cAMP levels in mouse brain but, like some antipsychotics, transiently increased glycogen contents in various brain regions. Behavioral effects were investigated in mice using the elevated plus-maze. JB-788 was found to increase the time duration spent by animals in anxiogenic situations. Locomotor hyperactivity induced by methamphetamine in mouse, a model of antipsychotic activity, was dose-dependently inhibited by JB-788. Altogether, these results suggest that JB-788 displays pharmacological properties, which could be of interest in the area

  1. Connectomics and neuroticism: an altered functional network organization.

    Science.gov (United States)

    Servaas, Michelle N; Geerligs, Linda; Renken, Remco J; Marsman, Jan-Bernard C; Ormel, Johan; Riese, Harriëtte; Aleman, André

    2015-01-01

    The personality trait neuroticism is a potent risk marker for psychopathology. Although the neurobiological basis remains unclear, studies have suggested that alterations in connectivity may underlie it. Therefore, the aim of the current study was to shed more light on the functional network organization in neuroticism. To this end, we applied graph theory on resting-state functional magnetic resonance imaging (fMRI) data in 120 women selected based on their neuroticism score. Binary and weighted brain-wide graphs were constructed to examine changes in the functional network structure and functional connectivity strength. Furthermore, graphs were partitioned into modules to specifically investigate connectivity within and between functional subnetworks related to emotion processing and cognitive control. Subsequently, complex network measures (ie, efficiency and modularity) were calculated on the brain-wide graphs and modules, and correlated with neuroticism scores. Compared with low neurotic individuals, high neurotic individuals exhibited a whole-brain network structure resembling more that of a random network and had overall weaker functional connections. Furthermore, in these high neurotic individuals, functional subnetworks could be delineated less clearly and the majority of these subnetworks showed lower efficiency, while the affective subnetwork showed higher efficiency. In addition, the cingulo-operculum subnetwork demonstrated more ties with other functional subnetworks in association with neuroticism. In conclusion, the 'neurotic brain' has a less than optimal functional network organization and shows signs of functional disconnectivity. Moreover, in high compared with low neurotic individuals, emotion and salience subnetworks have a more prominent role in the information exchange, while sensory(-motor) and cognitive control subnetworks have a less prominent role.

  2. Differential response to gepirone but not to chlordiazepoxide in malnourished rats subjected to learned helplessness.

    Science.gov (United States)

    Camargo, L M M; Nascimento, A B; Almeida, S S

    2008-01-01

    The learned helplessness (LH) paradigm is characterized by learning deficits resulting from inescapable events. The aims of the present study were to determine if protein-calorie malnutrition (PCM) alters learning deficits induced by LH and if the neurochemical changes induced by malnutrition alter the reactivity to treatment with GABA-ergic and serotonergic drugs during LH. Well-nourished (W) and PCM Wistar rats (61 days old) were exposed or not to inescapable shocks (IS) and treated with gepirone (GEP, 0.0-7.5 mg/kg, intraperitoneally, N = 128) or chlordiazepoxide (0.0-7.5 mg/kg, intraperitoneally, N = 128) 72 h later, 30 min before the test session (30 trials of escape learning). The results showed that rats exposed to IS had higher escape latency than non-exposed rats (12.6 +/- 2.2 vs 4.4 +/- 0.8 s) and that malnutrition increased learning impairment produced by LH. GEP increased the escape latency of W animals exposed or non-exposed to IS, but did not affect the response of PCM animals, while chlordiazepoxide reduced the escape deficit of both W and PCM rats. The data suggest that PCM animals were more sensitive to the impairment produced by LH and that PCM led to neurochemical changes in the serotonergic system, resulting in hyporeactivity to the anxiogenic effects of GEP in the LH paradigm.

  3. Differential response to gepirone but not to chlordiazepoxide in malnourished rats subjected to learned helplessness

    Directory of Open Access Journals (Sweden)

    L.M.M Camargo

    2008-01-01

    Full Text Available The learned helplessness (LH paradigm is characterized by learning deficits resulting from inescapable events. The aims of the present study were to determine if protein-calorie malnutrition (PCM alters learning deficits induced by LH and if the neurochemical changes induced by malnutrition alter the reactivity to treatment with GABA-ergic and serotonergic drugs during LH. Well-nourished (W and PCM Wistar rats (61 days old were exposed or not to inescapable shocks (IS and treated with gepirone (GEP, 0.0-7.5 mg/kg, intraperitoneally, N = 128 or chlordiazepoxide (0.0-7.5 mg/kg, intraperitoneally, N = 128 72 h later, 30 min before the test session (30 trials of escape learning. The results showed that rats exposed to IS had higher escape latency than non-exposed rats (12.6 ± 2.2 vs 4.4 ± 0.8 s and that malnutrition increased learning impairment produced by LH. GEP increased the escape latency of W animals exposed or non-exposed to IS, but did not affect the response of PCM animals, while chlordiazepoxide reduced the escape deficit of both W and PCM rats. The data suggest that PCM animals were more sensitive to the impairment produced by LH and that PCM led to neurochemical changes in the serotonergic system, resulting in hyporeactivity to the anxiogenic effects of GEP in the LH paradigm.

  4. GABAA receptor positive allosteric modulators modify the abuse-related behavioral and neurochemical effects of methamphetamine in rhesus monkeys.

    Science.gov (United States)

    Berro, Laís F; Andersen, Monica L; Tufik, Sergio; Howell, Leonard L

    2017-09-01

    GABA A receptor positive allosteric modulators (GABA A receptor modulators) are commonly used for the treatment of insomnia. Nevertheless, the effects of these compounds on psychostimulant-induced sleep impairment are poorly understood. Because GABA A receptor modulators have been shown to decrease the abuse-related effects of psychostimulants, the aim of the present study was to evaluate the effects of temazepam (0.3, 1.0 or 3.0 mg/kg) and eszopiclone (0.3, 1.0 or 3.0 mg/kg), two GABA A receptor modulators, on the behavioral neuropharmacology of methamphetamine in adult rhesus macaques (n = 5). Sleep-like measures and general daytime activity were evaluated with Actiwatch monitors. Methamphetamine self-administration (0.03 mg/kg/inf) was evaluated during morning sessions. Methamphetamine-induced dopamine overflow was assessed through in vivo microdialysis targeting the nucleus accumbens. Nighttime treatment with either temazepam or eszopiclone was ineffective in improving sleep-like measures disrupted by methamphetamine self-administration. Acute pretreatment with a low dose of temazepam before self-administration sessions increased methamphetamine self-administration without affecting normal daytime home-cage activity. At a high dose, acute temazepam pretreatment decreased methamphetamine self-administration and attenuated methamphetamine-induced increases in dopamine in the nucleus accumbens, without decreasing general daytime activity. Acute eszopiclone treatment exerted no effects on methamphetamine intake or drug-induced increases in dopamine. Our study suggests that treatments based on GABA A receptor modulators are not effective for the treatment of sleep disruption in the context of psychostimulant use. In addition, distinct GABA A receptor modulators differentially modulated the abuse-related effects of methamphetamine, with acute treatment with the high efficacy GABA A receptor modulator temazepam decreasing the behavioral and neurochemical effects

  5. A detailed analysis of open-field habituation and behavioral and neurochemical antidepressant-like effects in postweaning enriched rats.

    Science.gov (United States)

    Brenes, Juan C; Padilla, Michael; Fornaguera, Jaime

    2009-01-30

    Our previous work has shown that male Sprague-Dawley rats reared in social isolation, standard housing and environmental enrichment differ in their spontaneous open-field activity and in some neurobehavioral depressive-like parameters. Here, we extended this evidence by using a shorter postweaning rearing period (1 month) and including additional evaluations. First, in order to obtain a better characterization of the exploratory strategies among rearing conditions we analyzed in detail the spontaneous activity at the first minute and during the 10-min session. Second, we asked whether the changes in open-field activity were related with basal anxiety levels in the elevated plus-maze. Third, behavior in the forced-swimming test was analyzed and afterward, the tissue levels of hippocampal norepinephrine and serotonin were assessed. The possible relationship between neurotransmitters and forced-swimming behavior were explored through correlation analyses. We found that rearing conditions (i) differed on locomotor habituation and on sensory-motor exploration at the first minute and during the 10-min session without modifying the plus-maze behavior; (ii) affected differentially the grooming time, its sequential components, and the relationship between grooming and locomotor parameters; (iii) modified forced-swimming behavior and the hippocampal concentration of norepinephrine, serotonin, and its turnover; and (iv) produced different correlation patterns between both neurotransmitters and forced-swimming behaviors. Overall, environmental enrichment accelerated open-field habituation and led to behavioral and neurochemical antidepressant-like effects. In contract, isolation rearing strongly impaired habituation and simple information processing, but showed marginal effects on depressive-like behavior and on hippocampal neurochemistry. The current results suggest that differential rearing is not only a useful procedure to study behavioral plasticity or rigidity in response

  6. Cultural immersion alters emotion perception: Neurophysiological evidence from Chinese immigrants to Canada.

    Science.gov (United States)

    Liu, Pan; Rigoulot, Simon; Pell, Marc D

    2017-12-01

    To explore how cultural immersion modulates emotion processing, this study examined how Chinese immigrants to Canada process multisensory emotional expressions, which were compared to existing data from two groups, Chinese and North Americans. Stroop and Oddball paradigms were employed to examine different stages of emotion processing. The Stroop task presented face-voice pairs expressing congruent/incongruent emotions and participants actively judged the emotion of one modality while ignoring the other. A significant effect of cultural immersion was observed in the immigrants' behavioral performance, which showed greater interference from to-be-ignored faces, comparable with what was observed in North Americans. However, this effect was absent in their N400 data, which retained the same pattern as the Chinese. In the Oddball task, where immigrants passively viewed facial expressions with/without simultaneous vocal emotions, they exhibited a larger visual MMN for faces accompanied by voices, again mirroring patterns observed in Chinese. Correlation analyses indicated that the immigrants' living duration in Canada was associated with neural patterns (N400 and visual mismatch negativity) more closely resembling North Americans. Our data suggest that in multisensory emotion processing, adopting to a new culture first leads to behavioral accommodation followed by alterations in brain activities, providing new evidence on human's neurocognitive plasticity in communication.

  7. Curcumin reverses neurochemical, histological and immuno-histochemical alterations in the model of global brain ischemia

    Directory of Open Access Journals (Sweden)

    Glaura Fernandes Teixeira de Alcântara

    2017-01-01

    Full Text Available Curcumin, a curcuminoid from Curcuma longa, presents antioxidant and anti-inflammatory actions and, among pathological changes of cerebral ischemic injury, inflammation is an important one. The objectives were to study the neuroprotective action of curcumin, in a model of global ischemia. Male Wistar rats (sham-operated, ischemic untreated and ischemic treated with curcumin, 25 or 50 mg/kg, p.o. were anesthesized and their carotid arteries occluded, for 30 min. The SO group had the same procedure, except for carotid occlusion. In the 1st protocol, animals were treated 1 h before ischemia and 24 h later; and in the 2nd protocol, treatments began 1 h before ischemia, continuing for 7 days. Twenty four hours after the last administration, animals were euthanized and measurements for striatal monoamines were performed, at the 1st and 7th days after ischemia, as well as histological and immunohistochemical assays in hippocampi. We showed in both protocols, depletions of DA and its metabolites (DOPAC and HVA, in the ischemic group, but these effects were reversed by curcumin. Additionally, a decrease seen in 5-HT contents, 1 day after ischemia, was also reversed by curcumin. This reversion was not seen 7 days later. On the other hand, a decrease observed in NE levels, at the 7th day, was totally reversed by curcumin. Furthermore, curcumin treatments increased neuronal viability and attenuated the immunoreactivity for COX-2 and TNF-alpha, in the hippocampus in both protocols. We showed that curcumin exerts neuroprotective actions, in a model of brain ischemia that are probably related to its anti-inflammatory activity.

  8. Nitriles at Silica Interfaces Resemble Supported Lipid Bilayers.

    Science.gov (United States)

    Berne, Bruce J; Fourkas, John T; Walker, Robert A; Weeks, John D

    2016-09-20

    Nitriles are important solvents not just for bulk reactions but also for interfacial processes such as separations, heterogeneous catalysis, and electrochemistry. Although nitriles have a polar end and a lipophilic end, the cyano group is not hydrophilic enough for these substances to be thought of as prototypical amphiphiles. This picture is now changing, as research is revealing that at a silica surface nitriles can organize into structures that, in many ways, resemble lipid bilayers. This unexpected organization may be a key component of unique interfacial behavior of nitriles that make them the solvents of choice for so many applications. The first hints of this lipid-bilayer-like (LBL) organization of nitriles at silica interfaces came from optical Kerr effect (OKE) experiments on liquid acetonitrile confined in the pores of sol-gel glasses. The orientational dynamics revealed by OKE spectroscopy suggested that the confined liquid is composed of a relatively immobile sublayer of molecules that accept hydrogen bonds from the surface silanol groups and an interdigitated, antiparallel layer that is capable of exchanging into the centers of the pores. This picture of acetonitrile has been borne out by molecular dynamics simulations and vibrational sum-frequency generation (VSFG) experiments. Remarkably, these simulations further indicate that the LBL organization is repeated with increasing disorder at least 20 Å into the liquid from a flat silica surface. Simulations and VSFG and OKE experiments indicate that extending the alkyl chain to an ethyl group leads to the formation of even more tightly packed LBL organization featuring entangled alkyl tails. When the alkyl portion of the molecule is a bulky t-butyl group, packing constraints prevent well-ordered LBL organization of the liquid. In each case, the surface-induced organization of the liquid is reflected in its interfacial dynamics. Acetonitrile/water mixtures are favored solvent systems for separations

  9. 'Hair-on-end' skull changes resembling thalassemia caused by marrow expansion in uncorrected complex cyanotic heart disease

    International Nuclear Information System (INIS)

    Walor, David M.; Berdon, Walter E.; Westra, Sjirk J.

    2005-01-01

    ''Hair-on-end'' skull changes resembling thalassemia were rarely described in the 1950s and 1960s in children with cyanotic congenital heart diseases; these changes were described almost entirely in patients with tetralogy of Fallot or D-transposition of the great arteries. As these lesions have become correctable, the osseous changes, never common, seem now only to exist in a small number of patients with uncorrectable complex cyanotic congenital heart disease who survive in a chronic hypoxic state. We present two cases: a case of marked marrow expansion in the skull of a 5-year-old boy with uncorrectable cyanotic heart disease studied by CT, and a second case of an 8-year-old with tetralogy of Fallot and pulmonary atresia studied by plain skull radiographs. The true incidence of these findings is unknown. (orig.)

  10. Does the calcification of adamantinomatous craniopharyngioma resemble the calcium deposition of osteogenesis/odontogenesis?

    Science.gov (United States)

    Song-Tao, Qi; Xiao-Rong, Yan; Jun, Pan; Yong-Jian, Deng; Jin, Liang; Guang-Long, Huang; Yun-Tao, Lu; Jian, Ruan; Xiang-Zhao, Li; Jia-Ming, Xu

    2014-02-01

    Calcification in adamantinomatous craniopharyngioma (ACP) is troublesome for surgical intervention. The aim of this study was to examine the osteogenic proteins that play important roles in the calcium deposition of the odontogenic/osteogenic tissues in craniopharyngioma. Craniopharyngiomas (n = 89) were investigated for the presence and expression pattern of the osteoinductive/odontoinductive factor bone morphogenetic protein-2 (Bmp2) and two osteoblastic differentiation makers, Runt-related transcription factor-2 (Runx2) and Osterix, using immunohistochemistry and Western blotting. Our results showed that Bmp2, Runx2 and Osterix levels increased in cases with high calcification and correlated positively with the degree of calcification in ACP, whereas they showed little or no expression in squamous papillary craniopharyngioma. In ACP, Bmp2 was expressed primarily in the stellate reticulum and whorl-like array cells; Runx2 and Osterix tended to be expressed in calcification-related epithelia, including whorl-like array cells and epithelia in/around wet keratin and calcification lesions. Our study indicated, for the first time, that osteogenic factor Bmp2 may play an important role in the calcification of ACP via autocrine or paracrine mechanisms. Given the presence of osteogenic markers (Runx2 and Osterix), craniopharyngioma cells could differentiate into an osteoblast-like lineage, and the process of craniopharyngioma calcification resembles that which occurs in osteogenesis/odontogenesis. © 2014 John Wiley & Sons Ltd.

  11. Alterations to prepulse inhibition magnitude and latency in adult rats following neonatal treatment with domoic acid and social isolation rearing.

    Science.gov (United States)

    Marriott, Amber L; Tasker, R Andrew; Ryan, Catherine L; Doucette, Tracy A

    2016-02-01

    Deficits in perceptual, informational, and attentional processing are consistently identified as a core feature in schizophrenia and related neuropsychiatric disorders. Neonatal injections of low doses of the AMPA/kainate agonist domoic acid (DOM) have previously been shown to alter various aspects of perceptual and attentional processing in adult rats. The current study investigated the effects of combined neonatal DOM treatment with isolation rearing on prepulse inhibition behaviour and relevant neurochemical measures, to assess the usefulness of these paradigms in modeling neurodevelopmental disorders. Daily subcutaneous injections of DOM (20 μg/kg) or saline were administered to male and female rat pups from postnatal days (PND) 8-14. After weaning, rats were either housed alone or in groups of 4. Both the magnitude and latency of prepulse inhibition were determined in adulthood (approximately 4.5 months of age) and post-mortem brain tissue was assayed using Western blot. Social isolation alone significantly lowered PPI magnitude in male (but not female) rats while DOM treatment appeared to make animals refractory to this effect. Combining social isolation and DOM treatment caused an additive decrease in PPI startle latency. No statistically significant differences were found in the expression of D1, D2, TH, GAD65 or GAD67 protein in either the prefrontal cortex or hippocampus, although some tendencies toward differences were noted. We conclude that both neonatal low-dose DOM and social isolation affect prepulse inhibition in rats but that each paradigm exerts these effects through different neuronal signalling systems. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Effects of Short-Term Thermal Alteration on Organic Matter in Experimentally-Heated Tagish Lake Observed by Raman Spectroscopy

    Science.gov (United States)

    Chan, Q. H. S.; Nakato, A.; Zolensky, M. E.; Nakamura, T.; Kebukawa, Y.; Maisano, J.; Colbert, M.; Martinez, J. E.

    2017-01-01

    Carbonaceous chondrites exhibit a wide range of aqueous and thermal alteration characteristics, while some are known to demonstrate mineralogical and petrologic evidence of having been thermally metamorphosed after aqueous alteration. This group of meteorites are commonly referred as thermally met-amorphosed carbonaceous chondrites (TMCCs), and their reflectance spectra show resemblances to that of C-type asteroids which typically have low albedos. This suggests that the surfaces of the C-type asteroids are also composed of both hydrous and dehydrated minerals, and thus TMCCs are among the best samples that can be studied in laboratory to reveal the true nature of the C-type asteroids. Although TMCCs are usually meteorites that were previously categorized as CI and CM chondrites, they are not strictly CI/CM because they exhibit isotopic and petrographic characteristics that significantly deviate from typical CI/CM. More appropriately, they are called CI-like and/or CM-like chondrites. Typical examples of TMCCs include the C2-ung/CM2TIV Belgica (B)-7904 and Yamato (Y) 86720. Thermal alteration is virtually complete in these meteorites and thus they are considered typical end-members of TMCCs exhibiting complete dehydration of matrix phyllosilicates. The estimated heating conditions are 10 to 103 days at 700 C to 1 to 100 hours at 890 C, i.e. short-term heating induced by impact and/or solar radiation. While the petrology and chemistry of TMCCs have only recently been extensively characterized, we have just begun to study in detail their organic contents. In order to understand how short-term heating affects the maturity of insoluble organic matter (IOM) in hydrous chondrites, we investigated experimentally-heated Tagish Lake meteorite using Raman spectroscopy, as the chemical and bulk oxygen isotopic compositions of the matrix of the carbonate (CO3)-poor lithology of the Tagish Lake (hereafter Tag) meteorite bears similarities to the TMCCs.

  13. Alteration of consciousness in focal epilepsy: the global workspace alteration theory.

    Science.gov (United States)

    Bartolomei, Fabrice; McGonigal, Aileen; Naccache, Lionel

    2014-01-01

    Alteration of consciousness (AOC) is an important clinical manifestation of partial seizures that greatly impacts the quality of life of patients with epilepsy. Several theories have been proposed in the last fifty years. An emerging concept in neurology is the global workspace (GW) theory that postulates that access to consciousness (from several sensorial modalities) requires transient coordinated activity from associative cortices, in particular the prefrontal cortex and the posterior parietal associative cortex. Several lines of evidence support the view that partial seizures alter consciousness through disturbance of the GW. In particular, a nonlinear relation has been shown between excess of synchronization in the GW regions and the degree of AOC. Changes in thalamocortical synchrony occurring during the spreading of the ictal activity seem particularly involved in the mechanism of altered consciousness. This link between abnormal synchrony and AOC offers new perspectives in the treatment of the AOC since means of decreasing consciousness alteration in seizures could improve patients' quality of life. © 2013.

  14. Network analysis of genomic alteration profiles reveals co-altered functional modules and driver genes for glioblastoma.

    Science.gov (United States)

    Gu, Yunyan; Wang, Hongwei; Qin, Yao; Zhang, Yujing; Zhao, Wenyuan; Qi, Lishuang; Zhang, Yuannv; Wang, Chenguang; Guo, Zheng

    2013-03-01

    The heterogeneity of genetic alterations in human cancer genomes presents a major challenge to advancing our understanding of cancer mechanisms and identifying cancer driver genes. To tackle this heterogeneity problem, many approaches have been proposed to investigate genetic alterations and predict driver genes at the individual pathway level. However, most of these approaches ignore the correlation of alteration events between pathways and miss many genes with rare alterations collectively contributing to carcinogenesis. Here, we devise a network-based approach to capture the cooperative functional modules hidden in genome-wide somatic mutation and copy number alteration profiles of glioblastoma (GBM) from The Cancer Genome Atlas (TCGA), where a module is a set of altered genes with dense interactions in the protein interaction network. We identify 7 pairs of significantly co-altered modules that involve the main pathways known to be altered in GBM (TP53, RB and RTK signaling pathways) and highlight the striking co-occurring alterations among these GBM pathways. By taking into account the non-random correlation of gene alterations, the property of co-alteration could distinguish oncogenic modules that contain driver genes involved in the progression of GBM. The collaboration among cancer pathways suggests that the redundant models and aggravating models could shed new light on the potential mechanisms during carcinogenesis and provide new indications for the design of cancer therapeutic strategies.

  15. On the pathologically altered pulmonary pattern

    International Nuclear Information System (INIS)

    Ginzburg, M.A.; Kinoshenko, Yu.T.

    1982-01-01

    The notions ''normal'' and ''pathologically altered pulmonary pattern'' are specified. A grouping of lung pattern alterations based on morphopathogenetic features is provided: blood and lymphatic vascular alterations, changes in the bronchi, lung stroma, and combined alterations. Radiologic appearance of the altered pulmonary pattern is classified in keeping with the basic principles of an X-ray shade examination. The terms, such as ''enriching'', ''strengthening'', ''deformation'', etc., used for describing the pathologically altered pulmonary pattern are defined

  16. Dopamine Release and Uptake Impairments and Behavioral Alterations Observed in Mice that Model Fragile X Mental Retardation Syndrome.

    Science.gov (United States)

    Fulks, Jenny L; O'Bryhim, Bliss E; Wenzel, Sara K; Fowler, Stephen C; Vorontsova, Elena; Pinkston, Jonathan W; Ortiz, Andrea N; Johnson, Michael A

    2010-10-20

    In this study we evaluated the relationship between amphetamine-induced behavioral alterations and dopamine release and uptake characteristics in Fmr1 knockout (Fmr1 KO) mice, which model fragile X syndrome. The behavioral analyses, obtained at millisecond temporal resolution and 2 mm spatial resolution using a force-plate actometer, revealed that Fmr1 KO mice express a lower degree of focused stereotypy compared to wild type (WT) control mice after injection with 10 mg/kg (ip) amphetamine. To identify potentially related neurochemical mechanisms underlying this phenomenon, we measured electrically-evoked dopamine release and uptake using fast-scan cyclic voltammetry at carbon-fiber microelectrodes in striatal brain slices. At 10 weeks of age, dopamine release per pulse, which is dopamine release corrected for differences in uptake, was unchanged. However, at 15 (the age of behavioral testing) and 20 weeks of age, dopamine per pulse and the maximum rate of dopamine uptake was diminished in Fmr1 KO mice compared to WT mice. Dopamine uptake measurements, obtained at different amphetamine concentrations, indicated that dopamine transporters in both genotypes have equal affinities for amphetamine. Moreover, dopamine release measurements from slices treated with quinpirole, a D2-family receptor agonist, rule out enhanced D2 autoreceptor sensitivity as a mechanism of release inhibition. However, dopamine release, uncorrected for uptake and normalized against the corresponding pre-drug release peaks, increased in Fmr1 KO mice, but not in WT mice. Collectively, these data are consistent with a scenario in which a decrease in extracellular dopamine levels in the striatum result in diminished expression of focused stereotypy in Fmr1 KO mice.

  17. Wfs1-deficient mice display altered function of serotonergic system and increased behavioural response to antidepressants

    Directory of Open Access Journals (Sweden)

    Tanel eVisnapuu

    2013-07-01

    Full Text Available It has been shown that mutations in the WFS1 gene make humans more susceptible to mood disorders. Besides that, mood disorders are associated with alterations in the activity of serotonergic and noradrenergic systems. Therefore, in this study, the effects of imipramine, an inhibitor of serotonin (5-HT and noradrenaline (NA reuptake, and paroxetine, a selective inhibitor of 5-HT reuptake, were studied in tests of behavioural despair. The tail suspension test (TST and forced swimming test (FST were performed in Wfs1-deficient mice. Simultaneously, gene expression and monoamine metabolism studies were conducted to evaluate changes in 5-HT- and NA-ergic systems of Wfs1-deficient mice. The basal immobility time of Wfs1-deficient mice in TST and FST did not differ from that of their wild-type littermates. However, a significant reduction of immobility time in response to lower doses of imipramine and paroxetine was observed in homozygous Wfs1-deficient mice, but not in their wild-type littermates. In gene expression studies, the levels of 5-HT transporter (SERT were significantly reduced in the pons of homozygous animals. Monoamine metabolism was assayed separately in the dorsal and ventral striatum of naive mice and mice exposed for 30 minutes tobrightly lit motility boxes. We found that this aversive challenge caused a significant increase in the levels of 5-HT and 5-hydroxyindoleacetic acid (5-HIAA, a metabolite of 5-HT, in the ventral and dorsal striatum of wild-type mice, but not in their homozygous littermates. Taken together, the blunted 5-HT metabolism and reduced levels of SERT are a likely reason for the elevated sensitivity of these mice to the action of imipramine and paroxetine. These changes in the pharmacological and neurochemical phenotype of Wfs1-deficient mice may help to explain the increased susceptibility of Wolfram syndrome patients to depressive states.

  18. Pathogenesis of Candida albicans infections in the alternative chorio-allantoic membrane chicken embryo model resembles systemic murine infections.

    Directory of Open Access Journals (Sweden)

    Ilse D Jacobsen

    Full Text Available Alternative models of microbial infections are increasingly used to screen virulence determinants of pathogens. In this study, we investigated the pathogenesis of Candida albicans and C. glabrata infections in chicken embryos infected via the chorio-allantoic membrane (CAM and analyzed the virulence of deletion mutants. The developing immune system of the host significantly influenced susceptibility: With increasing age, embryos became more resistant and mounted a more balanced immune response, characterized by lower induction of proinflammatory cytokines and increased transcription of regulatory cytokines, suggesting that immunopathology contributes to pathogenesis. While many aspects of the chicken embryo response resembled murine infections, we also observed significant differences: In contrast to systemic infections in mice, IL-10 had a beneficial effect in chicken embryos. IL-22 and IL-17A were only upregulated after the peak mortality in the chicken embryo model occurred; thus, the role of the Th17 response in this model remains unclear. Abscess formation occurs frequently in murine models, whereas the avian response was dominated by granuloma formation. Pathogenicity of the majority of 15 tested C. albicans deletion strains was comparable to the virulence in mouse models and reduced virulence was associated with significantly lower transcription of proinflammatory cytokines. However, fungal burden did not correlate with virulence and for few mutants like bcr1Δ and tec1Δ different outcomes in survival compared to murine infections were observed. C. albicans strains locked in the yeast stage disseminated significantly more often from the CAM into the embryo, supporting the hypothesis that the yeast morphology is responsible for dissemination in systemic infections. These data suggest that the pathogenesis of C. albicans infections in the chicken embryo model resembles systemic murine infections but also differs in some aspects. Despite

  19. Cigarette smoking substantially alters plasma microRNA profiles in healthy subjects

    Energy Technology Data Exchange (ETDEWEB)

    Takahashi, Kei; Yokota, Shin-ichi; Tatsumi, Naoyuki; Fukami, Tatsuki; Yokoi, Tsuyoshi; Nakajima, Miki, E-mail: nmiki@p.kanazawa-u.ac.jp

    2013-10-01

    Circulating microRNAs (miRNAs) are receiving attention as potential biomarkers of various diseases, including cancers, chronic obstructive pulmonary disease, and cardiovascular disease. However, it is unknown whether the levels of circulating miRNAs in a healthy subject might vary with external factors in daily life. In this study, we investigated whether cigarette smoking, a habit that has spread throughout the world and is a risk factor for various diseases, affects plasma miRNA profiles. We determined the profiles of 11 smokers and 7 non-smokers by TaqMan MicroRNA array analysis. A larger number of miRNAs were detected in smokers than in non-smokers, and the plasma levels of two-thirds of the detected miRNAs (43 miRNAs) were significantly higher in smokers than in non-smokers. A principal component analysis of the plasma miRNA profiles clearly separated smokers and non-smokers. Twenty-four of the miRNAs were previously reported to be potential biomarkers of disease, suggesting the possibility that smoking status might interfere with the diagnosis of disease. Interestingly, we found that quitting smoking altered the plasma miRNA profiles to resemble those of non-smokers. These results suggested that the differences in the plasma miRNA profiles between smokers and non-smokers could be attributed to cigarette smoking. In addition, we found that an acute exposure of ex-smokers to cigarette smoke (smoking one cigarette) did not cause a dramatic change in the plasma miRNA profile. In conclusion, we found that repeated cigarette smoking substantially alters the plasma miRNA profile, interfering with the diagnosis of disease or signaling potential smoking-related diseases. - Highlights: • Plasma miRNA profiles were unambiguously different between smokers and non-smokers. • Smoking status might interfere with the diagnosis of disease using plasma miRNAs. • Changes of plasma miRNA profiles may be a signal of smoking-related diseases.

  20. Cigarette smoking substantially alters plasma microRNA profiles in healthy subjects

    International Nuclear Information System (INIS)

    Takahashi, Kei; Yokota, Shin-ichi; Tatsumi, Naoyuki; Fukami, Tatsuki; Yokoi, Tsuyoshi; Nakajima, Miki

    2013-01-01

    Circulating microRNAs (miRNAs) are receiving attention as potential biomarkers of various diseases, including cancers, chronic obstructive pulmonary disease, and cardiovascular disease. However, it is unknown whether the levels of circulating miRNAs in a healthy subject might vary with external factors in daily life. In this study, we investigated whether cigarette smoking, a habit that has spread throughout the world and is a risk factor for various diseases, affects plasma miRNA profiles. We determined the profiles of 11 smokers and 7 non-smokers by TaqMan MicroRNA array analysis. A larger number of miRNAs were detected in smokers than in non-smokers, and the plasma levels of two-thirds of the detected miRNAs (43 miRNAs) were significantly higher in smokers than in non-smokers. A principal component analysis of the plasma miRNA profiles clearly separated smokers and non-smokers. Twenty-four of the miRNAs were previously reported to be potential biomarkers of disease, suggesting the possibility that smoking status might interfere with the diagnosis of disease. Interestingly, we found that quitting smoking altered the plasma miRNA profiles to resemble those of non-smokers. These results suggested that the differences in the plasma miRNA profiles between smokers and non-smokers could be attributed to cigarette smoking. In addition, we found that an acute exposure of ex-smokers to cigarette smoke (smoking one cigarette) did not cause a dramatic change in the plasma miRNA profile. In conclusion, we found that repeated cigarette smoking substantially alters the plasma miRNA profile, interfering with the diagnosis of disease or signaling potential smoking-related diseases. - Highlights: • Plasma miRNA profiles were unambiguously different between smokers and non-smokers. • Smoking status might interfere with the diagnosis of disease using plasma miRNAs. • Changes of plasma miRNA profiles may be a signal of smoking-related diseases

  1. Nonparenchymal cells cultivated from explants of fibrotic liver resemble endothelial and smooth muscle cells from blood vessel walls

    International Nuclear Information System (INIS)

    Voss, B.; Rauterberg, J.; Pott, G.; Brehmer, U.; Allam, S.; Lehmann, R.; von Bassewitz, D.B.

    1982-01-01

    Tissue specimens from human fibrotic liver obtained by needle biopsy were cultured. Two cell types emerged from the tissue explants. From their morphology and biosynthetic products they resembled smooth muscle cells and endothelial cells from blood vessel walls. In the endothelial cells, factor VIII-associated protein was demonstrated by indirect immunofluorescence. Synthesis of collagen types I and III, basement membrane collagen types IV and V, and fibronectin by both cell types was observed by immunofluorescence microscopy. Homogeneous cultures of smooth muscle cells were observed in subcultures. After incubation with [ 14 C]glycine, collagen was isolated and characterized by CM cellulose chromatography, and consisted mainly of types I and III. These data suggest involvement of mesenchymal cells in hepatic fibrosis; they presumably originate from blood vessel or sinusoidal walls

  2. Vaginal microbiota of adolescent girls prior to the onset of menarche resemble those of reproductive-age women.

    Science.gov (United States)

    Hickey, Roxana J; Zhou, Xia; Settles, Matthew L; Erb, Julie; Malone, Kristin; Hansmann, Melanie A; Shew, Marcia L; Van Der Pol, Barbara; Fortenberry, J Dennis; Forney, Larry J

    2015-03-24

    Puberty is an important developmental stage wherein hormonal shifts mediate the physical and physiological changes that lead to menarche, but until now, the bacterial composition of vaginal microbiota during this period has been poorly characterized. We performed a prospective longitudinal study of perimenarcheal girls to gain insight into the timing and sequence of changes that occur in the vaginal and vulvar microbiota during puberty. The study enrolled 31 healthy, premenarcheal girls between the ages of 10 and 12 years and collected vaginal and vulvar swabs quarterly for up to 3 years. Bacterial composition was characterized by Roche 454 pyrosequencing and classification of regions V1 to V3 of 16S rRNA genes. Contrary to expectations, lactic acid bacteria, primarily Lactobacillus spp., were dominant in the microbiota of most girls well before the onset of menarche in the early to middle stages of puberty. Gardnerella vaginalis was detected at appreciable levels in approximately one-third of subjects, a notable finding considering that this organism is commonly associated with bacterial vaginosis in adults. Vulvar microbiota closely resembled vaginal microbiota but often exhibited additional taxa typically associated with skin microbiota. Our findings suggest that the vaginal microbiota of girls begin to resemble those of adults well before the onset of menarche. This study addresses longitudinal changes in vaginal and vulvar microbial communities prior to and immediately following menarche. The research is significant because microbial ecology of the vagina is an integral aspect of health, including resistance to infections. The physiologic changes of puberty and initiation of cyclic menstruation are likely to have profound effects on vaginal microbiota, but almost nothing is known about changes that normally occur during this time. Our understanding has been especially hampered by the lack of thorough characterization of microbial communities using techniques

  3. Muscle-type nicotinic receptor modulation by 2,6-dimethylaniline, a molecule resembling the hydrophobic moiety of lidocaine

    Directory of Open Access Journals (Sweden)

    Armando Alberola-Die

    2016-11-01

    Full Text Available To identify the molecular determinants responsible for lidocaine blockade of muscle-type nAChRs, we have studied the effects on this receptor of 2,6-dimethylaniline (DMA, which resembles lidocaine’s hydrophobic moiety. Torpedo marmorata nAChRs were microtransplanted to Xenopus oocytes and currents elicited by ACh (IACh, either alone or co-applied with DMA, were recorded. DMA reversibly blocked IACh and, similarly to lidocaine, exerted a closed-channel blockade, as evidenced by the enhancement of IACh blockade when DMA was pre-applied before its co-application with ACh, and hastened IACh decay. However, there were marked differences among its mechanisms of nAChR inhibition and those mediated by either the entire lidocaine molecule or diethylamine (DEA, a small amine resembling lidocaine’s hydrophilic moiety. Thereby, the IC50 for DMA, estimated from the dose-inhibition curve, was in the millimolar range, which is one order of magnitude higher than that for either DEA or lidocaine. Besides, nAChR blockade by DMA was voltage-independent in contrast to the increase of IACh inhibition at negative potentials caused by the more polar lidocaine or DEA molecules. Accordingly, virtual docking assays of DMA on nAChRs showed that this molecule binds predominantly at intersubunit crevices of the transmembrane-spanning domain, but also at the extracellular domain. Furthermore, DMA interacted with residues inside the channel pore, although only in the open-channel conformation. Interestingly, co-application of ACh with DEA and DMA, at their IC50s, had additive inhibitory effects on IACh and the extent of blockade was similar to that predicted by the allotopic model of interaction, suggesting that DEA and DMA bind to nAChRs at different loci. These results indicate that DMA mainly mimics the low potency and non-competitive actions of lidocaine on nAChRs, as opposed to the high potency and voltage-dependent block by lidocaine, which is emulated by the

  4. An Investigation into the Mechanics of Windblown Dust Entrainment from Nickel Slag Surfaces Resembling Armoured Desert Pavements

    Science.gov (United States)

    Sanderson, Robert Steven

    The purpose of this thesis is to investigate the dynamics of PM 10 emission from a nickel slag stockpile that closely resembles a desert pavement in physical characteristics. In the field, it was observed that slag surfaces develop by natural processes into a well-armoured surface over some period of time. The surface then consists of two distinct layers; a surficial armour layer containing only non-erodible gravel and cobble-sized clasts, and an underlying dust-laden layer, which contains a wide size range of slag particles, from clay-sized to cobble-sized. This surficial armour layer protects the underlying fines from wind entrainment, at least under typical wind conditions; however, particle emissions still do occur under high wind speeds. The dynamics of particle entrainment from within these surfaces are investigated herein. It is shown that the dynamics of the boundary layer flow over these lag surfaces are influenced by the inherent roughness and permeability of the surficial armour layer, such that the flow resembles those observed over and within vegetation canopies, and those associated with permeable gravel-bed river channels. Restriction of air flow within the permeable surface produces a high-pressure zone within the pore spaces, resulting in a Kelvin-Helmholtz shear instability, which triggers coherent motions in the form of repeating burst-sweep cycles. Using Laser Doppler Anemometry (LDA), it is demonstrated that the lower boundary layer is characterized by both Q4 sweeping motions and Q2 bursting motions, while the upper boundary layer is dominated by Q2 bursts. Pore air motions within the slag material were measured using buried pressure ports. It is shown that the mean pressure gradient which forms within the slag material results in net upward displacement of air, or wind pumping. However, this net upward motion is a result of rapid oscillatory motions which are directly driven by coherent boundary layer motions. It is also demonstrated that

  5. Effect of prenatal methadone and ethanol on opioid receptor development in rats

    Energy Technology Data Exchange (ETDEWEB)

    Peters, M.A.; Braun, R.L. (Loma Linda Univ., CA (United States))

    1991-03-11

    The current literature shows that the offspring of female rats exposed to methadone or ethanol display similar neurochemical and neurobehavioral alterations, and suggests that these drugs may be operating through a common mechanism. If this hypothesis is true, their effect on the endogenous opioid systems should be qualitatively similar. In this study virgin females were treated with methadone or 10% ethanol oral solution starting prior to conception and continued throughout gestation. When the offspring had reached 15 or 30 days of age they were sacrificed, the brain was removed and prepared for opioid receptor binding studies. ({sup 3}H)DAGO and ({sup 3}H)DADLE were used as ligands for the mu and delta receptors, respectively. These studies show significant treatment-related differences in both the number of mu and delta binding sites as well as in apparent receptor affinity. Significant sex- and age-related differences between treatments were also observed. These data show that methadone and ethanol, while manifesting some similar neurochemical and behavioral effects, have unique effects on opioid receptor binding, suggesting that they may be acting by different mechanisms.

  6. Distinct Neurochemical Adaptations Within the Nucleus Accumbens Produced by a History of Self-Administered vs Non-Contingently Administered Intravenous Methamphetamine

    Science.gov (United States)

    Lominac, Kevin D; Sacramento, Arianne D; Szumlinski, Karen K; Kippin, Tod E

    2012-01-01

    Methamphetamine is a highly addictive psychomotor stimulant yet the neurobiological consequences of methamphetamine self-administration remain under-characterized. Thus, we employed microdialysis in rats trained to self-administer intravenous (IV) infusions of methamphetamine (METH-SA) or saline (SAL) and a group of rats receiving non-contingent IV infusions of methamphetamine (METH-NC) at 1 or 21 days withdrawal to determine the dopamine and glutamate responses in the nucleus accumbens (NAC) to a 2 mg/kg methamphetamine intraperitoneal challenge. Furthermore, basal NAC extracellular glutamate content was assessed employing no net-flux procedures in these three groups at both time points. At both 1- and 21-day withdrawal points, methamphetamine elicited a rise in extracellular dopamine in SAL animals and this effect was sensitized in METH-NC rats. However, METH-SA animals showed a much greater sensitized dopamine response to the drug challenge compared with the other groups. Additionally, acute methamphetamine decreased extracellular glutamate in both SAL and METH-NC animals at both time-points. In contrast, METH-SA rats exhibited a modest and delayed rise in glutamate at 1-day withdrawal and this rise was sensitized at 21 days withdrawal. Finally, no net-flux microdialysis revealed elevated basal glutamate and increased extraction fraction at both withdrawal time-points in METH-SA rats. Although METH-NC rats exhibited no change in the glutamate extraction fraction, they exhibited a time-dependent elevation in basal glutamate levels. These data illustrate for the first time that a history of methamphetamine self-administration produces enduring changes in NAC neurotransmission and that non-pharmacological factors have a critical role in the expression of these methamphetamine-induced neurochemical adaptations. PMID:22030712

  7. Calpain 1 inhibitor BDA-410 ameliorates α-klotho-deficiency phenotypes resembling human aging-related syndromes.

    Science.gov (United States)

    Nabeshima, Yoko; Washida, Miwa; Tamura, Masaru; Maeno, Akiteru; Ohnishi, Mutsuko; Shiroishi, Toshihiko; Imura, Akihiro; Razzaque, M Shawkat; Nabeshima, Yo-ichi

    2014-08-01

    Taking good care of elderly is a major challenge of our society, and thus identification of potential drug targets to reduce age-associated disease burden is desirable. α-klotho(-/-) (α-kl) is a short-lived mouse model that displays multiple phenotypes resembling human aging-related syndromes. Such ageing phenotype of α-kl(-/-) mice is associated with activation of a proteolytic enzyme, Calpain-1. We hypothesized that uncontrolled activation of calpain-1 might be causing age-related phenotypes in α-kl-deficient mice. We found that daily administration of BDA-410, a calpain-1 inhibitor, strikingly ameliorated multiple aging-related phenotypes. Treated mice showed recovery of reproductive ability, increased body weight, reduced organ atrophy, and suppression of ectopic calcifications, bone mineral density reduction, pulmonary emphysema and senile atrophy of skin. We also observed ectopic expression of FGF23 in calcified arteries of α-kl(-/-) mice, which might account for the clinically observed association of increased FGF23 level with increased risk of cardiovascular mortality. These findings allow us to propose that modulation of calpain-1 activity is a potential therapeutic option for delaying age-associated organ pathology, particularly caused by the dysregulation of mineral ion homeostasis.

  8. Behavioural, neurochemical and neuroendocrine effects of the endogenous β-carboline harmane in fear-conditioned rats.

    Science.gov (United States)

    Smith, Karen L; Ford, Gemma K; Jessop, David S; Finn, David P

    2013-02-01

    The putative endogenous imidazoline binding site ligand harmane enhances neuronal activation in response to psychological stress and alters behaviour in animal models of anxiety and antidepressant efficacy. However, the neurobiological mechanisms underlying harmane's psychotropic effects are poorly understood. We investigated the effects of intraperitoneal injection of harmane (2.5 and 10 mg/kg) on fear-conditioned behaviour, hypothalamo-pituitary-adrenal axis activity, and monoaminergic activity within specific fear-associated areas of the rat brain. Harmane had no significant effect on the duration of contextually induced freezing or 22 kHz ultrasonic vocalisations and did not alter the contextually induced suppression of motor activity, including rearing. Harmane reduced the duration of rearing and tended to increase freezing in non-fear-conditioned controls, suggesting potential sedative effects. Harmane increased plasma ACTH and corticosterone concentrations, and serotonin (in hypothalamus, amygdaloid cortex, prefrontal cortex and hippocampus) and noradrenaline (prefrontal cortex) content, irrespective of fear-conditioning. Furthermore, harmane reduced dopamine and serotonin turnover in the PFC and hypothalamus, and serotonin turnover in the amygdaloid cortex in both fear-conditioned and non-fear-conditioned rats. In contrast, harmane increased dopamine and noradrenaline content and reduced dopamine turnover in the amygdala of fear-conditioned rats only, suggesting differential effects on catecholaminergic transmission in the presence and absence of fear. The precise mechanism(s) mediating these effects of harmane remain to be determined but may involve its inhibitory action on monoamine oxidases. These findings support a role for harmane as a neuromodulator, altering behaviour, brain neurochemistry and neuroendocrine function.

  9. Chemistry, mineralogy and alteration intensity of hydrothermal altered Mt Unzen conduit rocks (Shimabara/Japan)

    Science.gov (United States)

    Hess, Kai-Uwe; Yilmaz, Tim; Gilg, H. Albert; Janots, Emilie; Mayer, Klaus; Nakada, Setsuya; Dingwell, Donald

    2017-04-01

    Investigations were carried out on hydrothermally altered coherent dacitic dykes samples from (USDP-4) drill core at Mt Unzen stratovolcano (Shimabara/Japan). XRF, XRD, EMPA, C-O-isotope, hot-cathode CL and SEM analysis led to insights concerning chemistry, mineralogy, and intensity and type of alteration as well as the origin of carbonate-precipitating fluids. Additionally a textural characterization of the occurring replacement features in the volcanic conduit rocks was performed. The occurrence of the main secondary phases such as chlorite, pyrite, carbonates, and R1 (Reichweite parameter) illite-smectite and kaolinite group minerals indicate a weak to moderate propylitic to phyllic hydrothermal alteration. The dacitic samples of the dykes show different hydrothermal alteration features: (i) carbonate and chlorite pseudomorphs after hornblende as well as core and zonal textures due to replacement of plagioclase by R1 illite-smectite as well as kaolinite group minerals, (ii) colloform banded fracture fillings and fillings in dissolution vugs, and (iii) chlorite, R1 illite-smectite as well as kaolinite group minerals in the groundmass. Late chlorite veins crosscut precipitates of R1 illite-smectite as well as kaolinite group minerals. Carbonates in fractures and in pseudomorphs after hornblende comprise iron-rich dolomite solid solutions ("ankerite") and calcite. Isotopic values indicate a hydrothermal-magmatic origin for the carbonate formation. The chlorite-carbonate-pyrite index (CCPI) and the Ishikawa alteration index (AI), applied to the investigated samples show significant differences (CCPI=52.7-57.8; AI=36.1-40.6) indicating their different degree of alteration. According to Nakada et al., 2005, the C13 to C16 dykes represent the feeder dyke from the latest eruption (1991-1995) whereas C8 represents an earlier dyke feeder dyke from an older eruption. Weakest alteration, which was obtained in samples C16-1-5 and C13-2-5, correlates with the alteration

  10. Test of 134Cs, 85,89Sr leaching rate in a resemble vitrifiable cement waste form

    International Nuclear Information System (INIS)

    Lin Meiqiong; Wei Feng; Yin Qi; Fan Xianhua; Xu Shengli; Li Yongde

    2003-01-01

    A novel material--resemble vitrifiable cement for conditioning low and mediate level radioactive waste has been developed. Waste form has been characterized for their physical and chemical performance, phase composition. The cement formulation has been patented. In this experiment the cement is mixed with simulated wastes spiked with 134 Cs and 85,89 Sr by 5 min at least. The Ratio of the waste to the cement is 0.45-0.55. The mixture is packed into cylindrical molds which has the same dimension of diameter and height . The grouts are cured for a period of 28 d in a room temperature curing chamber at an atmospheric pressure. The cured waste form is then completely immersed into deionized water. According to standard GB7023-86, leaching rate of 134 Cs and 85,89 Sr are measured. The result shows that the leaching rate of the species 134 Cs and 85,89 Sr is to be on the order 10 -4 and 10 -5 on the 42 d immersion, respectively and is better than that of commercial cement

  11. An analysis on equal width quantization and linearly separable subcode encoding-based discretization and its performance resemblances

    Directory of Open Access Journals (Sweden)

    Lim Meng-Hui

    2011-01-01

    Full Text Available Abstract Biometric discretization extracts a binary string from a set of real-valued features per user. This representative string can be used as a cryptographic key in many security applications upon error correction. Discretization performance should not degrade from the actual continuous features-based classification performance significantly. However, numerous discretization approaches based on ineffective encoding schemes have been put forward. Therefore, the correlation between such discretization and classification has never been made clear. In this article, we aim to bridge the gap between continuous and Hamming domains, and provide a revelation upon how discretization based on equal-width quantization and linearly separable subcode encoding could affect the classification performance in the Hamming domain. We further illustrate how such discretization can be applied in order to obtain a highly resembled classification performance under the general Lp distance and the inner product metrics. Finally, empirical studies conducted on two benchmark face datasets vindicate our analysis results.

  12. Paraquat and psychological stressor interactions as pertains to Parkinsonian co-morbidity

    Directory of Open Access Journals (Sweden)

    Chris Rudyk

    2015-01-01

    Full Text Available A number of epidemiological and experimental studies have implicated the non-selective herbicide, paraquat, in the development of sporadic Parkinson's disease (PD. While preclinical research has focused mainly on elucidating the nigrostriatal effects of paraquat, relatively little data are available concerning non-motor brain systems and inflammatory immune processes (which have been implicated in PD. Hence, in the present study, we sought to take a multi-system approach to characterize the influence of paraquat upon extra-nigrostriatal brain regions, as well ascertain whether the impact of the pesticide might be enhanced in the context of chronic intermittent stressor exposure. Our findings support the contention that paraquat itself acted as a systemic stressor, with the pesticide increasing plasma corticosterone, as well as altering neurochemical activity in the locus coeruleus, paraventricular nucleus of the hypothalamus, nucleus accumbens, dorsal striatum, and central amygdala. However, with the important exception striatal dopamine turnover, the stressor treatment did not further augment these effects. Additionally, paraquat altered inter-cytokine correlations and, to a lesser extent, circulating cytokine levels, and concomitant stress exposure modulated some of these effects. Finally, paraquat provoked significant (albeit modest reductions of sucrose preference and weight gain, hinting at possible anhendonic-like or sickness responses. These data suggest that, in addition to being a well known oxidative stress generator, paraquat can act as a systemic stressor affecting hormonal and neurochemical activity, but largely not interacting with a concomitant stressor regimen.

  13. The identical-twin transfusion syndrome: a source of error in estimating IQ resemblance and heritability.

    Science.gov (United States)

    Munsinger, H

    1977-01-01

    Published studies show that among identical twins, lower birthweight is associated with lower adult intelligence. However, no such relation between birthweight and adult IQ exists among fraternal twins. A likely explanation for the association between birthweight and intelligence among identical twins is the identical twin transfusion syndrome which occurs only between some monochorionic identical twin pairs. The IQ scores from separated identical twins were reanalysed to explore the consequences of identical twin transfusion syndrome for IQ resemblance and heritability. Among 129 published cases of identical twin pairs reared apart, 76 pairs contained some birthweight information. The 76 pairs were separated into three classes: 23 pairs in which there was clear evidence of a substantial birthweight differences (indicating the probable existence of the identical twin transfusion syndrome), 27 pairs in which the information on birthweight was ambiguous (?), and 26 pairs in which there was clear evidence that the twins were similar in birthweight. The reanalyses showed: (1) birthweight differences are positively associated with IQ differences in the total sample of separated identical twins; (2) within the group of 23 twin pairs who showed large birthweight differences, there was a positive relation between birthweight differences and IQ differences; (3) when heritability of IQ is estimated for those twins who do not suffer large birthweight differences, the resemblance (and thus, h2/b) of the separated identical twins' IG is 0-95. Given that the average reliability of the individual IQ test is around 0-95, these data suggest that genetic factors and errors of measurement cause the individual differences in IQ among human beings. Because of the identical twin transfusion syndrome, previous studies of MZ twins have underestimated the effect of genetic factors on IQ. An analysis of the IQs for heavier and lighter birthweight twins suggests that the main effect of the

  14. Severely impaired bone material quality in Chihuahua zebrafish resembles classical dominant human osteogenesis imperfecta.

    Science.gov (United States)

    Fiedler, Imke A K; Schmidt, Felix N; Wölfel, Eva M; Plumeyer, Christine; Milovanovic, Petar; Gioia, Roberta; Tonelli, Francesca; Bale, Hrishikesh A; Jähn, Katharina; Besio, Roberta; Forlino, Antonella; Busse, Björn

    2018-04-17

    Excessive skeletal deformations and brittle fractures in the vast majority of patients suffering from osteogenesis imperfecta (OI) are a result of substantially reduced bone quality. Since the mechanical competence of bone is dependent on the tissue characteristics at small length scales, it is of crucial importance to assess how osteogenesis imperfecta manifests at the micro- and nanoscale of bone. In this context, the Chihuahua (Chi/ +) zebrafish, carrying a heterozygous glycine substitution in the α1 chain of collagen type I, has recently been proposed as suitable animal model of classical dominant OI, showing skeletal deformities, altered mineralization patterns and a smaller body size. This study assessed the bone quality properties of Chi/+ at multiple length scales using micro-computed tomography (micro-CT), histomorphometry, quantitative back-scattered electron imaging, Fourier transform infrared spectroscopy, nanoindentation and X-ray microscopy. At the skeletal level, Chi/+ display smaller body size, deformities and fracture calli in the ribs. Morphological changes at the whole bone level showed that the vertebrae in Chi/+ had a smaller size, smaller thickness and distorted shape. At the tissue level, Chi/+ displayed a higher degree of mineralization, lower collagen maturity, lower mineral maturity, altered osteoblast morphology, and lower osteocyte lacunar density compared to WT. The alterations in the cellular, compositional and structural properties of Chi/+ bones bear an explanation for the impaired local mechanical properties, which promote an increase in overall bone fragility in Chi/ +. The quantitative assessment of bone quality in Chi/+ thus further validates this mutant as an important model reflecting osseous characteristics associated with human classical dominant osteogenesis imperfecta. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  15. Prenatal Exposure to Unconventional Oil and Gas Operation Chemical Mixtures Altered Mammary Gland Development in Adult Female Mice.

    Science.gov (United States)

    Sapouckey, Sarah A; Kassotis, Christopher D; Nagel, Susan C; Vandenberg, Laura N

    2018-03-01

    Unconventional oil and gas (UOG) operations, which combine hydraulic fracturing (fracking) and directional drilling, involve the use of hundreds of chemicals, including many with endocrine-disrupting properties. Two previous studies examined mice exposed during early development to a 23-chemical mixture of UOG compounds (UOG-MIX) commonly used or produced in the process. Both male and female offspring exposed prenatally to one or more doses of UOG-MIX displayed alterations to endocrine organ function and serum hormone concentrations. We hypothesized that prenatal UOG-MIX exposure would similarly disrupt development of the mouse mammary gland. Female C57Bl/6 mice were exposed to ~3, ~30, ~ 300, or ~3000 μg/kg/d UOG-MIX from gestational day 11 to birth. Although no effects were observed on the mammary glands of these females before puberty, in early adulthood, females exposed to 300 or 3000 μg/kg/d UOG-MIX developed more dense mammary epithelial ducts; females exposed to 3 μg/kg/d UOG-MIX had an altered ratio of apoptosis to proliferation in the mammary epithelium. Furthermore, adult females from all UOG-MIX-treated groups developed intraductal hyperplasia that resembled terminal end buds (i.e., highly proliferative structures typically seen at puberty). These results suggest that the mammary gland is sensitive to mixtures of chemicals used in UOG production at exposure levels that are environmentally relevant. The effect of these findings on the long-term health of the mammary gland, including its lactational capacity and its risk of cancer, should be evaluated in future studies. Copyright © 2018 Endocrine Society.

  16. Na+ Influx Induced by New Antimalarials Causes Rapid Alterations in the Cholesterol Content and Morphology of Plasmodium falciparum.

    Directory of Open Access Journals (Sweden)

    Sudipta Das

    2016-05-01

    Full Text Available Among the several new antimalarials discovered over the past decade are at least three clinical candidate drugs, each with a distinct chemical structure, that disrupt Na+ homeostasis resulting in a rapid increase in intracellular Na+ concentration ([Na+]i within the erythrocytic stages of Plasmodium falciparum. At present, events triggered by Na+ influx that result in parasite demise are not well-understood. Here we report effects of two such drugs, a pyrazoleamide and a spiroindolone, on intraerythrocytic P. falciparum. Within minutes following the exposure to these drugs, the trophozoite stage parasite, which normally contains little cholesterol, was made permeant by cholesterol-dependent detergents, suggesting it acquired a substantial amount of the lipid. Consistently, the merozoite surface protein 1 and 2 (MSP1 and MSP2, glycosylphosphotidylinositol (GPI-anchored proteins normally uniformly distributed in the parasite plasma membrane, coalesced into clusters. These alterations were not observed following drug treatment of P. falciparum parasites adapted to grow in a low [Na+] growth medium. Both cholesterol acquisition and MSP1 coalescence were reversible upon the removal of the drugs, implicating an active process of cholesterol exclusion from trophozoites that we hypothesize is inhibited by high [Na+]i. Electron microscopy of drug-treated trophozoites revealed substantial morphological changes normally seen at the later schizont stage including the appearance of partial inner membrane complexes, dense organelles that resemble "rhoptries" and apparent nuclear division. Together these results suggest that [Na+]i disruptor drugs by altering levels of cholesterol in the parasite, dysregulate trophozoite to schizont development and cause parasite demise.

  17. Socially isolated rats exhibit changes in dopamine homeostasis pertinent to schizophrenia

    DEFF Research Database (Denmark)

    Fabricius, Katrine; Steiniger-Brach, Björn; Helboe, Lone

    2011-01-01

    Post-weaning social isolation of rats produces an array of behavioral and neurochemical changes indicative of altered dopamine function. It has therefore been suggested that post-weaning social isolation mimics some aspects of schizophrenia. Here we replicate and extent these findings to include...... dopamine levels in the nucleus accumbens, it did cause a significant reduction of basal dopamine release in the prefrontal cortex. In addition, social isolation lead to a significantly larger dopamine response to an amphetamine challenge, in both the nucleus accumbens and the prefrontal cortex compared...

  18. Anxiety-like behaviour and associated neurochemical and endocrinological alterations in male pups exposed to prenatal stress.

    Science.gov (United States)

    Laloux, Charlotte; Mairesse, Jérôme; Van Camp, Gilles; Giovine, Angela; Branchi, Igor; Bouret, Sebastien; Morley-Fletcher, Sara; Bergonzelli, Gabriela; Malagodi, Marithé; Gradini, Roberto; Nicoletti, Ferdinando; Darnaudéry, Muriel; Maccari, Stefania

    2012-10-01

    Epidemiological studies suggest that emotional liability in infancy could be a predictor of anxiety-related disorders in the adulthood. Rats exposed to prenatal restraint stress ("PRS rats") represent a valuable model for the study of the interplay between environmental triggers and neurodevelopment in the pathogenesis of anxious/depressive like behaviours. Repeated episodes of restraint stress were delivered to female Sprague-Dawley rats during pregnancy and male offspring were studied. Ultrasonic vocalization (USV) was assessed in pups under different behavioural paradigms. After weaning, anxiety was measured by conventional tests. Expression of GABA(A) receptor subunits and metabotropic glutamate (mGlu) receptors was assessed by immunoblotting. Plasma leptin levels were measured using a LINCOplex bead assay kit. The offspring of stressed dams emitted more USVs in response to isolation from their mothers and showed a later suppression of USV production when exposed to an unfamiliar male odour, indicating a pronounced anxiety-like profile. Anxiety like behaviour in PRS pups persisted one day after weaning. PRS pups did not show the plasma peak in leptin levels that is otherwise seen at PND14. In addition, PRS pups showed a reduced expression of the γ2 subunit of GABA(A) receptors in the amygdala at PND14 and PND22, an increased expression of mGlu5 receptors in the amygdala at PND22, a reduced expression of mGlu5 receptors in the hippocampus at PND14 and PND22, and a reduced expression of mGlu2/3 receptors in the hippocampus at PND22. These data offer a clear-cut demonstration that the early programming triggered by PRS could be already translated into anxiety-like behaviour during early postnatal life. Copyright © 2012 Elsevier Ltd. All rights reserved.

  19. Family Resemblances: Human Reproductive Cloning as an Example for Reconsidering the Mutual Relationships between Bioethics and Science Fiction.

    Science.gov (United States)

    Hansen, Solveig L

    2018-03-08

    In the traditions of narrative ethics and casuistry, stories have a well-established role. Specifically, illness narratives provide insight into patients' perspectives and histories. However, because they tend to see fiction as an aesthetic endeavour, practitioners in these traditions often do not realize that fictional stories are valuable moral sources of their own. In this paper I employ two arguments to show the mutual relationship between bioethics and fiction, specifically, science fiction. First, both discourses use imagination to set a scene and determine a perspective. Second, bioethics and science fiction share the family resemblance of expressing moral beliefs. I then consider how understanding bioethics and science fiction as interrelated discourses can be the basis of a methodology for inquiry into relational autonomy in the context of biotechnologies and medicine. As an example of this methodology, I analyse Fay Weldon's novel The Cloning of Joanna May (1989).

  20. From Hills to Holes: How Climate Change and Mining are Altering Runoff Processes in Canada

    Science.gov (United States)

    Carey, S. K.

    2015-12-01

    Canadian environments are under considerable pressure from both climate and land-use change. While warming temperatures are widespread and amplified in the north, surface mining has resulted in large-scale landscape disturbance. How these changes affect catchment response is profound, fundamentally altering the cycling and delivery of water and geochemicals to the drainage network. In permafrost-underlain environments, coupled mass and energy processes control runoff response, and as ground thaw increases, new subsurface pathways become accessible while changing overall catchment storage. With surface mining, watersheds are altered such that they bare little resemblance to what existed prior to mining. In this presentation, data will be presented from long-term experiments exploring the impact of climate and mining on runoff processes in cold catchments using stable isotopes of water and associated hydrometric measurements. In southern Yukon, results from the Wolf Creek Research Basin highlights the influence of surface energy balances on controlling the timing and magnitude of flow response, with inter-annual variability largely driven by how atmospheric forcing interacts with permafrost-underlain areas of the catchment. In mountainous areas of southern British Columbia, surface mining reconfigures landscapes as valleys are filled with waste-rock. Mine-influenced catchments exhibit attenuated flows with delays in spring freshet and a more muted to precipitation. Stable isotopes in stream water suggests that both waste-rock and reference catchments are well mixed, however reference catchments are more responsive to enrichment and depletion events and that mine-influenced catchments had a heavier isotope signature than reference watersheds, suggesting enhanced influence of rainfall on recharge. In both cases, snow storage and release exerts considerable control on streamflow responses, and future changes in streamflow regimes will reflect both a changes in the snow

  1. Experimentally-induced maternal hypothyroidism alters crucial enzyme activities in the frontal cortex and hippocampus of the offspring rat.

    Science.gov (United States)

    Koromilas, Christos; Tsakiris, Stylianos; Kalafatakis, Konstantinos; Zarros, Apostolos; Stolakis, Vasileios; Kimpizi, Despoina; Bimpis, Alexios; Tsagianni, Anastasia; Liapi, Charis

    2015-02-01

    Thyroid hormone insufficiency during neurodevelopment can result into significant structural and functional changes within the developing central nervous system (CNS), and is associated with the establishment of serious cognitive impairment and neuropsychiatric symptomatology. The aim of the present study was to shed more light on the effects of gestational and/or lactational maternal exposure to propylthiouracil (PTU)-induced hypothyroidism as a multilevel experimental approach to the study of hypothyroidism-induced changes on crucial brain enzyme activities of 21-day-old Wistar rat offspring in a brain region-specific manner. This experimental approach has been recently developed and characterized by the authors based on neurochemical analyses performed on newborn and 21-day-old rat offspring whole brain homogenates; as a continuum to this effort, the current study focused on two CNS regions of major significance for cognitive development: the frontal cortex and the hippocampus. Maternal exposure to PTU in the drinking water during gestation and/or lactation resulted into changes in the activities of acetylcholinesterase and two important adenosinetriphosphatases (Na(+),K(+)- and Mg(2+)-ATPase), that seemed to take place in a CNS-region-specific manner and that were dependent upon the PTU-exposure timeframe followed. As these findings are analyzed and compared to the available literature, they: (i) highlight the variability involved in the changes of the aforementioned enzymatic parameters in the studied CNS regions (attributed to both the different neuroanatomical composition and the thyroid-hormone-dependent neurodevelopmental growth/differentiation patterns of the latter), (ii) reveal important information with regards to the neurochemical mechanisms that could be involved in the way clinical hypothyroidism could affect optimal neurodevelopment and, ultimately, cognitive function, as well as (iii) underline the need for the adoption of more consistent

  2. Chlorite alteration in aqueous solutions and uranium removal by altered chlorite

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Eungyeong; Ahn, Hyangsig [Department of Earth and Environmental Sciences, Korea University, Anam-dong, Seongbuk-gu, Seoul 02841 (Korea, Republic of); Jo, Ho Young, E-mail: hyjo@korea.ac.kr [Department of Earth and Environmental Sciences, Korea University, Anam-dong, Seongbuk-gu, Seoul 02841 (Korea, Republic of); Ryu, Ji-Hun; Koh, Yong-Kwon [Korea Atomic Energy Research Institute, 1045 Daedeokdaero, Yuseong-gu, Daejeon 34057 (Korea, Republic of)

    2017-04-05

    Highlights: • Chlorite alteration and the U removal capacity of altered chlorite were investigated. • Initial pH affected more chlorite dissolution than ionic strength. • Chlorite dissolution at pH{sub o} = 3–8 was inversely proportional to the U removal capacity. • Chlorite dissolution at pH{sub o} = 10 was proportional to the U removal capacity. • The formation of Fe-containing secondary minerals affected the U removal capacity. - Abstract: Chlorite alteration and the U removal capacity of altered chlorite were investigated. Batch kinetic dissolution tests using clinochlore CCa-2 were conducted for 60 days in aqueous solutions of various pHs and ionic strengths. Batch sorption tests using these altered chlorite samples were conducted for 48 h with natural groundwater containing 3.06 × 10{sup −6} M U. Chlorite dissolution was influenced more by pH{sub o} than by the ionic strength of the solution. TEM analysis revealed Fe(oxy)hydroxide aggregates in the solid residue from the batch dissolution test with 0.1 M NaClO{sub 4} solution at pH{sub o} = 10. The U removal capacity of the reacted chlorite samples at pH{sub o} = 6–10 was higher than that of the reacted chlorite samples at pH{sub o} = 3. The degree of dissolution of chlorite samples reacted at pH{sub o} = 3–8 was inversely proportional to the U removal capacity, but that of chlorite samples reacted at pH{sub o} = 10 was proportional to the U removal capacity. The positive correlation between the U removal capacity and degree of chlorite dissolution at pH{sub o} = 10 might be due to the formation of Fe-containing secondary minerals and changes in the reactive sites.

  3. Resemblance in dietary intakes between urban low-income African-American adolescents and their mothers: the healthy eating and active lifestyles from school to home for kids study.

    Science.gov (United States)

    Wang, Youfa; Li, Ji; Caballero, Benjamin

    2009-01-01

    To examine the association and predictors of dietary intake resemblance between urban low-income African-American adolescents and their mothers. Detailed dietary data collected from 121 child-parent pairs in Chicago during fall 2003 were used. The association was assessed using correlation coefficients, kappa, and percentage of agreement, as well as logistic regression models. Overall, the association was weak as indicated by correlations and other measures. None of the mother-son correlations for nutrients and food groups were greater than 0.20. Mother-daughter pairs had stronger correlations (0.26 for energy and 0.30 for fat). The association was stronger in normal-weight mothers than in mothers with overweight or obesity. Logistic models showed that mother being a current smoker, giving child more pocket money, and allowing child to eat or purchase snacks without parental permission or presence predicted a higher probability of resemblance in undesirable eating patterns, such as high-energy, high-fat, and high-snack intakes (P<0.05). Mother-child diet association was generally weak, and varied considerably across groups and intake variables in this homogenous population. Some maternal characteristics seem to affect the association.

  4. Altered Sensory Feedbacks in Pianist's Dystonia: the altered auditory feedback paradigm and the glove effect

    Directory of Open Access Journals (Sweden)

    Felicia Pei-Hsin Cheng

    2013-12-01

    Full Text Available Background: This study investigates the effect of altered auditory feedback (AAF in musician's dystonia (MD and discusses whether altered auditory feedback can be considered as a sensory trick in MD. Furthermore, the effect of AAF is compared with altered tactile feedback, which can serve as a sensory trick in several other forms of focal dystonia. Methods: The method is based on scale analysis (Jabusch et al. 2004. Experiment 1 employs synchronization paradigm: 12 MD patients and 25 healthy pianists had to repeatedly play C-major scales in synchrony with a metronome on a MIDI-piano with 3 auditory feedback conditions: 1. normal feedback; 2. no feedback; 3. constant delayed feedback. Experiment 2 employs synchronization-continuation paradigm: 12 MD patients and 12 healthy pianists had to repeatedly play C-major scales in two phases: first in synchrony with a metronome, secondly continue the established tempo without the metronome. There are 4 experimental conditions, among them 3 are the same altered auditory feedback as in Experiment 1 and 1 is related to altered tactile sensory input. The coefficient of variation of inter-onset intervals of the key depressions was calculated to evaluate fine motor control. Results: In both experiments, the healthy controls and the patients behaved very similarly. There is no difference in the regularity of playing between the two groups under any condition, and neither did AAF nor did altered tactile feedback have a beneficial effect on patients’ fine motor control. Conclusions: The results of the two experiments suggest that in the context of our experimental designs, AAF and altered tactile feedback play a minor role in motor coordination in patients with musicians' dystonia. We propose that altered auditory and tactile feedback do not serve as effective sensory tricks and may not temporarily reduce the symptoms of patients suffering from MD in this experimental context.

  5. Neurobiological circuits regulating attention, cognitive control, motivation, and emotion: disruptions in neurodevelopmental psychiatric disorders.

    Science.gov (United States)

    Arnsten, Amy F T; Rubia, Katya

    2012-04-01

    This article aims to review basic and clinical studies outlining the roles of prefrontal cortical (PFC) networks in the behavior and cognitive functions that are compromised in childhood neurodevelopmental disorders and how these map into the neuroimaging evidence of circuit abnormalities in these disorders. Studies of animals, normally developing children, and patients with neurodevelopmental disorders were reviewed, with focus on neuroimaging studies. The PFC provides "top-down" regulation of attention, inhibition/cognitive control, motivation, and emotion through connections with posterior cortical and subcortical structures. Dorsolateral and inferior PFC regulate attention and cognitive/inhibitory control, whereas orbital and ventromedial structures regulate motivation and affect. PFC circuitries are very sensitive to their neurochemical environment, and small changes in the underlying neurotransmitter systems, e.g. by medications, can produce large effects on mediated function. Neuroimaging studies of children with neurodevelopmental disorders show altered brain structure and function in distinctive circuits respecting this organization. Children with attention-deficit/hyperactivity disorder show prominent abnormalities in the inferior PFC and its connections to striatal, cerebellar, and parietal regions, whereas children with conduct disorder show alterations in the paralimbic system, comprising ventromedial, lateral orbitofrontal, and superior temporal cortices together with specific underlying limbic regions, regulating motivation and emotion control. Children with major depressive disorder show alterations in ventral orbital and limbic activity, particularly in the left hemisphere, mediating emotions. Finally, children with obsessive-compulsive disorder appear to have a dysregulation in orbito-fronto-striatal inhibitory control pathways, but also deficits in dorsolateral fronto-parietal systems of attention. Altogether, there is a good correspondence

  6. 'Hair-on-end' skull changes resembling thalassemia caused by marrow expansion in uncorrected complex cyanotic heart disease

    Energy Technology Data Exchange (ETDEWEB)

    Walor, David M.; Berdon, Walter E. [Columbia University Medical Center, Department of Radiology Children' s Hospital of New York, New York, NY (United States); Westra, Sjirk J. [Massachusetts General Hospital, Department of Radiology, Boston, MA (United States)

    2005-07-01

    ''Hair-on-end'' skull changes resembling thalassemia were rarely described in the 1950s and 1960s in children with cyanotic congenital heart diseases; these changes were described almost entirely in patients with tetralogy of Fallot or D-transposition of the great arteries. As these lesions have become correctable, the osseous changes, never common, seem now only to exist in a small number of patients with uncorrectable complex cyanotic congenital heart disease who survive in a chronic hypoxic state. We present two cases: a case of marked marrow expansion in the skull of a 5-year-old boy with uncorrectable cyanotic heart disease studied by CT, and a second case of an 8-year-old with tetralogy of Fallot and pulmonary atresia studied by plain skull radiographs. The true incidence of these findings is unknown. (orig.)

  7. Romantic Love vs. Drug Addiction May Inspire a New Treatment for Addiction.

    Science.gov (United States)

    Zou, Zhiling; Song, Hongwen; Zhang, Yuting; Zhang, Xiaochu

    2016-01-01

    Drug addiction is a complex neurological dysfunction induced by recurring drug intoxication. Strategies to prevent and treat drug addiction constitute a topic of research interest. Early-stage romantic love is characterized by some characteristics of addiction, which gradually disappear as the love relationship progresses. Therefore, comparison of the concordance and discordance between romantic love and drug addiction may elucidate potential treatments for addiction. This focused review uses the evidences from our recent studies to compare the neural alterations between romantic love and drug addiction, moreover we also compare the behavioral and neurochemical alterations between romantic love and drug addiction. From the behavioral comparisons we find that there are many similarities between the early stage of romantic love and drug addiction, and this stage romantic love is considered as a behavioral addiction, while significant differences exist between the later stage of romantic love and drug addiction, and this stage of romantic love eventually developed into a prosocial behavior. The neuroimaging comparisons suggest that romantic love and drug addiction both display the functional enhancement in reward and emotion regulation network. Except the similar neural changes, romantic love display special function enhancement in social cognition network, while drug addiction display special dysfunction in cognitive control network. The neurochemical comparisons show that there are many similarities in the dopamine (DA) system, while significant differences in oxytocin (OT) system for romantic love and drug addiction. These findings indicate that the functional alterations in reward and emotion regulation network and the DA system may be the neurophysiological basis of romantic love as a behavioral addiction, and the functional alterations in social cognition network and the OT system may be the neurophysiological basis of romantic love as a prosocial behavior. It

  8. Epithelial proliferation in small ducts of salivary cystadenoma resembling atypical ductal hyperplasia of breast.

    Science.gov (United States)

    Fahim, Lisa; Weinreb, Ilan; Alexander, Cherupushpam; Perez Ordoñez, Bayardo

    2008-09-01

    Salivary gland cystadenomas are cystic neoplasms with diverse architecture and cytology. Cystadenomas may have a considerable intracystic epithelial component, but an epithelial proliferation in small ducts and cysts resembling atypical ductal hyperplasia of breast has not been documented. The patient was a 68-year-old man with a slow growing right submandibular mass. He has no recurrence 13 months after resection. The tumor was polycystic and measured 3.0 x 2.5 x 2.5 cm. The epithelium of the larger cysts was composed of flat, cuboidal, columnar, and apocrine-like cells. Many of the larger cysts showed "Roman bridges", epithelial tufting, and papillae. The smaller cysts and ducts had apocrine-like cells forming secondary glandular lumens. The ductal cells were surrounded by clear myoepithelial cells. Nuclear pleomorphism and hyperchromasia was seen in the apocrine-like cells. Adjacent to the larger cysts, there was an adenomatoid proliferation of small ducts surrounded by myoepithelial cells. No mitotic activity, necrosis, or stromal invasion was identified. The ductal cells were diffusely positive for keratin 7 and androgen receptors with focal expression of keratin 19 and high-molecular weight keratin. S-100, estrogen and progesterone receptors, and BRST-2 were negative in the ductal cells. Recognition of a prominent intraductal epithelial component in cystadenomas is important to avoid a misdiagnosis of cystadenocarcinoma or low-grade salivary duct carcinoma. Cystadenomas join the list of salivary gland lesions with microscopic similarities to primary lesions of the breast.

  9. The Group 2 Metabotropic Glutamate Receptor Agonist LY379268 Rescues Neuronal, Neurochemical and Motor Abnormalities in R6/2 Huntington’s Disease Mice

    Science.gov (United States)

    Reiner, A.; Lafferty, D.C.; Wang, H.B.; Del Mar, N.; Deng, Y.P.

    2012-01-01

    Excitotoxic injury to striatum by dysfunctional cortical input or aberrant glutamate uptake may contribute to Huntington’s Disease (HD) pathogenesis. Since corticostriatal terminals possess mGluR2/3 autoreceptors, whose activation dampens glutamate release, we tested the ability of the mGluR2/3 agonist LY379268 to improve the phenotype in R6/2 HD mice with 120–125 CAG repeats. Daily subcutaneous injection of a maximum tolerated dose (MTD) of LY379268 (20mg/kg) had no evident adverse effects in WT mice, and diverse benefits in R6/2 mice, both in a cohort of mice tested behaviorally until the end of R6/2 lifespan and in a cohort sacrificed at 10 weeks of age for blinded histological analysis. MTD LY379268 yielded a significant 11% increase in R6/2 survival, an improvement on rotarod, normalization and/or improvement in locomotor parameters measured in open field (activity, speed, acceleration, endurance, and gait), a rescue of a 15–20% cortical and striatal neuron loss, normalization of SP striatal neuron neurochemistry, and to a lesser extent enkephalinergic striatal neuron neurochemistry. Deficits were greater in male than female R6/2 mice, and drug benefit tended to be greater in males. The improvements in SP striatal neurons, which facilitate movement, are consistent with the improved movement in LY379268-treated R6/2 mice. Our data indicate that mGluR2/3 agonists may be particularly useful for ameliorating the morphological, neurochemical and motor defects observed in HD. PMID:22472187

  10. [Epigenetic alterations in acute lymphoblastic leukemia].

    Science.gov (United States)

    Navarrete-Meneses, María Del Pilar; Pérez-Vera, Patricia

    Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. It is well-known that genetic alterations constitute the basis for the etiology of ALL. However, genetic abnormalities are not enough for the complete development of the disease, and additional alterations such as epigenetic modifications are required. Such alterations, like DNA methylation, histone modifications, and noncoding RNA regulation have been identified in ALL. DNA hypermethylation in promoter regions is one of the most frequent epigenetic modifications observed in ALL. This modification frequently leads to gene silencing in tumor suppressor genes, and in consequence, contributes to leukemogenesis. Alterations in histone remodeling proteins have also been detected in ALL, such as the overexpression of histone deacetylases enzymes, and alteration of acetyltransferases and methyltransferases. ALL also shows alteration in the expression of miRNAs, and in consequence, the modification in the expression of their target genes. All of these epigenetic modifications are key events in the malignant transformation since they lead to the deregulation of oncogenes as BLK, WNT5B and WISP1, and tumor suppressors such as FHIT, CDKN2A, CDKN2B, and TP53, which alter fundamental cellular processes and potentially lead to the development of ALL. Both genetic and epigenetic alterations contribute to the development and evolution of ALL. Copyright © 2017 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

  11. The expression of Toll-like receptor 4, 7 and co-receptors in neurochemical sub-populations of rat trigeminal ganglion sensory neurons.

    Science.gov (United States)

    Helley, M P; Abate, W; Jackson, S K; Bennett, J H; Thompson, S W N

    2015-12-03

    The recent discovery that mammalian nociceptors express Toll-like receptors (TLRs) has raised the possibility that these cells directly detect and respond to pathogens with implications for either direct nociceptor activation or sensitization. A range of neuronal TLRs have been identified, however a detailed description regarding the distribution of expression of these receptors within sub-populations of sensory neurons is lacking. There is also some debate as to the composition of the TLR4 receptor complex on sensory neurons. Here we use a range of techniques to quantify the expression of TLR4, TLR7 and some associated molecules within neurochemically-identified sub-populations of trigeminal (TG) and dorsal root (DRG) ganglion sensory neurons. We also detail the pattern of expression and co-expression of two isoforms of lysophosphatidylcholine acyltransferase (LPCAT), a phospholipid remodeling enzyme previously shown to be involved in the lipopolysaccharide-dependent TLR4 response in monocytes, within sensory ganglia. Immunohistochemistry shows that both TLR4 and TLR7 preferentially co-localize with transient receptor potential vallinoid 1 (TRPV1) and purinergic receptor P2X ligand-gated ion channel 3 (P2X3), markers of nociceptor populations, within both TG and DRG. A gene expression profile shows that TG sensory neurons express a range of TLR-associated molecules. LPCAT1 is expressed by a proportion of both nociceptors and non-nociceptive neurons. LPCAT2 immunostaining is absent from neuronal profiles within both TG and DRG and is confined to non-neuronal cell types under naïve conditions. Together, our results show that nociceptors express the molecular machinery required to directly respond to pathogenic challenge independently from the innate immune system. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  12. Fetuin-A/albumin-mineral complexes resembling serum calcium granules and putative nanobacteria: demonstration of a dual inhibition-seeding concept.

    Directory of Open Access Journals (Sweden)

    Cheng-Yeu Wu

    2009-11-01

    Full Text Available Serum-derived granulations and purported nanobacteria (NB are pleomorphic apatite structures shown to resemble calcium granules widely distributed in nature. They appear to be assembled through a dual inhibitory-seeding mechanism involving proteinaceous factors, as determined by protease (trypsin and chymotrypsin and heat inactivation studies. When inoculated into cell culture medium, the purified proteins fetuin-A and albumin fail to induce mineralization, but they will readily combine with exogenously added calcium and phosphate, even in submillimolar amounts, to form complexes that will undergo morphological transitions from nanoparticles to spindles, films, and aggregates. As a mineralization inhibitor, fetuin-A is much more potent than albumin, and it will only seed particles at higher mineral-to-protein concentrations. Both proteins display a bell-shaped, dose-dependent relationship, indicative of the same dual inhibitory-seeding mechanism seen with whole serum. As ascertained by both seeding experiments and gel electrophoresis, fetuin-A is not only more dominant but it appears to compete avidly for nanoparticle binding at the expense of albumin. The nanoparticles formed in the presence of fetuin-A are smaller than their albumin counterparts, and they have a greater tendency to display a multi-layered ring morphology. In comparison, the particles seeded by albumin appear mostly incomplete, with single walls. Chemically, spectroscopically, and morphologically, the protein-mineral particles resemble closely serum granules and NB. These particles are thus seen to undergo an amorphous to crystalline transformation, the kinetics and completeness of which depend on the protein-to-mineral ratios, with low ratios favoring faster conversion to crystals. Our results point to a dual inhibitory-seeding, de-repression model for the assembly of particles in supersaturated solutions like serum. The presence of proteins and other inhibitory factors tend

  13. Recent developments in altering the fatty acid composition of ruminant-derived foods.

    Science.gov (United States)

    Shingfield, K J; Bonnet, M; Scollan, N D

    2013-03-01

    There is increasing evidence to indicate that nutrition is an important factor involved in the onset and development of several chronic human diseases including cancer, cardiovascular disease (CVD), type II diabetes and obesity. Clinical studies implicate excessive consumption of medium-chain saturated fatty acids (SFA) and trans-fatty acids (TFA) as risk factors for CVD, and in the aetiology of other chronic conditions. Ruminant-derived foods are significant sources of medium-chain SFA and TFA in the human diet, but also provide high-quality protein, essential micronutrients and several bioactive lipids. Altering the fatty acid composition of ruminant-derived foods offers the opportunity to align the consumption of fatty acids in human populations with public health policies without the need for substantial changes in eating habits. Replacing conserved forages with fresh grass or dietary plant oil and oilseed supplements can be used to lower medium-chain and total SFA content and increase cis-9 18:1, total conjugated linoleic acid (CLA), n-3 and n-6 polyunsaturated fatty acids (PUFA) to a variable extent in ruminant milk. However, inclusion of fish oil or marine algae in the ruminant diet results in marginal enrichment of 20- or 22-carbon PUFA in milk. Studies in growing ruminants have confirmed that the same nutritional strategies improve the balance of n-6/n-3 PUFA, and increase CLA and long-chain n-3 PUFA in ruminant meat, but the potential to lower medium-chain and total SFA is limited. Attempts to alter meat and milk fatty acid composition through changes in the diet fed to ruminants are often accompanied by several-fold increases in TFA concentrations. In extreme cases, the distribution of trans 18:1 and 18:2 isomers in ruminant foods may resemble that of partially hydrogenated plant oils. Changes in milk fat or muscle lipid composition in response to diet are now known to be accompanied by tissue-specific alterations in the expression of one or more

  14. Motor impulsivity in APP-SWE mice: a model of Alzheimer's disease.

    Science.gov (United States)

    Adriani, Walter; Ognibene, Elisa; Heuland, Emilie; Ghirardi, Orlando; Caprioli, Antonio; Laviola, Giovanni

    2006-09-01

    Among transgenic mouse models of Alzheimer's disease, APP-SWE mice have been shown to develop beta-amyloid plaques and to exhibit progressive impairment of cognitive function. Human Alzheimer's disease, however, also includes secondary clinical manifestations, spanning from hyperactivity to agitation. The aim of this study was a better characterization of motor impulsivity in APP-SWE mice, observed at 12 months of age, when levels of soluble beta-amyloid are elevated and beta-amyloid neuritic plaques start to appear. Mice were tested for spatial learning abilities in the Morris water maze (seven daily sessions, four trials per day). The distance traveled to reach the hidden platform showed a learning curve in both groups. This profile, however, was somewhat delayed in APP-SWE mice, thus confirming slightly impaired spatial capacities. To evaluate motor impulsivity, animals were trained to nose-poke for a food reward, which was delivered after a waiting interval that increased over days (15-60 s). Further nose-poking during this signaled waiting interval resulted in food-reward loss and electric-shock punishment. APP-SWE mice received an increased quantity of punishment and were able to earn fewer food rewards, suggesting inability to wait already at the lowest delay. After the animals were killed, prefrontal cortex samples were assessed for neurochemical parameters. Serotonin turnover was elevated in the prefrontal cortex of APP-SWE mice compared with controls. The results clearly confirm cognitive deficits, and are consistent with the hypothesis of reduced behavioral-inhibition abilities. Together with recent findings, APP-SWE mice emerge as a suitable animal model, characterized by a number of specific behavioral alterations, resembling primary and secondary symptoms of human Alzheimer's disease.

  15. A Longitudinal Study of Cognition, Proton MR Spectroscopy and Synaptic and Neuronal Pathology in Aging Wild-type and AβPPswe-PS1dE9 Mice

    Science.gov (United States)

    Jansen, Diane; Zerbi, Valerio; Janssen, Carola I. F.; Dederen, Pieter J. W. C.; Mutsaers, Martina P. C.; Hafkemeijer, Anne; Janssen, Anna-Lena; Nobelen, Cindy L. M.; Veltien, Andor; Asten, Jack J.; Heerschap, Arend; Kiliaan, Amanda J.

    2013-01-01

    Proton magnetic resonance spectroscopy (1H MRS) is a valuable tool in Alzheimer’s disease research, investigating the functional integrity of the brain. The present longitudinal study set out to characterize the neurochemical profile of the hippocampus, measured by single voxel 1H MRS at 7 Tesla, in the brains of AβPPSswe-PS1dE9 and wild-type mice at 8 and 12 months of age. Furthermore, we wanted to determine whether alterations in hippocampal metabolite levels coincided with behavioral changes, cognitive decline and neuropathological features, to gain a better understanding of the underlying neurodegenerative processes. Moreover, correlation analyses were performed in the 12-month-old AβPP-PS1 animals with the hippocampal amyloid-β deposition, TBS-T soluble Aβ levels and high-molecular weight Aβ aggregate levels to gain a better understanding of the possible involvement of Aβ in neurochemical and behavioral changes, cognitive decline and neuropathological features in AβPP-PS1 transgenic mice. Our results show that at 8 months of age AβPPswe-PS1dE9 mice display behavioral and cognitive changes compared to age-matched wild-type mice, as determined in the open field and the (reverse) Morris water maze. However, there were no variations in hippocampal metabolite levels at this age. AβPP-PS1 mice at 12 months of age display more severe behavioral and cognitive impairment, which coincided with alterations in hippocampal metabolite levels that suggest reduced neuronal integrity. Furthermore, correlation analyses suggest a possible role of Aβ in inflammatory processes, synaptic dysfunction and impaired neurogenesis. PMID:23717459

  16. Sertraline and venlafaxine improves motor performance and neurobehavioral deficit in quinolinic acid induced Huntington's like symptoms in rats: Possible neurotransmitters modulation.

    Science.gov (United States)

    Gill, Jaskamal Singh; Jamwal, Sumit; Kumar, Puneet; Deshmukh, Rahul

    2017-04-01

    Huntington Disease is autosomal, fatal and progressive neurodegenerative disorder for which clinically available drugs offer only symptomatic relief. Emerging strides have indicated that antidepressants improve motor performance, restore neurotransmitters level, ameliorates striatal atrophy, increases BDNF level and may enhance neurogenesis. Therefore, we investigated sertraline and venlafaxine, clinically available drugs for depression with numerous neuroprotective properties, for their beneficial effects, if any, in quinolinic acid induced Huntington's like symptoms in rats. Rats were administered quinolinic acid (QA) (200 nmol/2μl saline) intrastriatal bilaterally on 0day. Sertraline and venlafaxine (10 and 20mg/kg, po) each were administered for 21days once a day. Motor performance was assessed using rotarod test, grip strength test, narrow beam walk test on weekly basis. On day 22, animals were sacrificed and rat striatum was isolated for biochemical (LPO, GSH and Nitrite), neuroinflammation (TNF-α, IL-1β and IL-6) and neurochemical analysis (GABA, glutamate, norepinephrine, dopamine, serotonin, DOPAC, HVA and 5-HIAA). QA treatment significantly altered body weight, motor performance, oxidative defense (increased LPO, nitrite and decreased GSH), pro-inflammatory cytokines levels (TNF-α, IL-6 and IL-1β), neurochemical level (GABA, glutamate, nor-epinephrine, dopamine, serotonin, HVA, DOPAC, 5-HIAA). Sertraline and venlafaxine at selected doses significantly attenuated QA induced alterations in striatum. The present study suggests that modulation of monoamines level, normalization of GABA and glutamatergic signaling, anti-oxidant and anti-inflammatory properties could underlie the neuroprotective effect of sertraline and venlafaxine in QA induced Huntington's like symptoms. Copyright © 2016. Published by Elsevier Urban & Partner Sp. z o.o.

  17. Estrous cycle affects the neurochemical and neurobehavioral profile of carvacrol-treated female rats

    International Nuclear Information System (INIS)

    Trabace, L.; Zotti, M.; Morgese, M.G.; Tucci, P.; Colaianna, M.; Schiavone, S.; Avato, P.; Cuomo, V.

    2011-01-01

    Carvacrol is the major constituent of essential oils from aromatic plants. It showed antimicrobial, anticancer and antioxidant properties. Although it was approved for food use and included in the chemical flavorings list, no indication on its safety has been estimated. Since the use of plant extracts is relatively high among women, aim of this study was to evaluate carvacrol effects on female physiology and endocrine profiles by using female rats in proestrus and diestrus phases. Serotonin and metabolite tissue content in prefrontal cortex and nucleus accumbens, after carvacrol administration (0.15 and 0.45 g/kg p.o.), was measured. Drug effects in behavioral tests for alterations in motor activity, depression, anxiety-related behaviors and endocrine alterations were also investigated. While in proestrus carvacrol reduced serotonin and metabolite levels in both brain areas, no effects were observed in diestrus phase. Only in proestrus phase, carvacrol induced a depressive-like behavior in forced swimming test, without accompanying changes in ambulation. The improvement of performance in FST after subchronic treatment with fluoxetine (20 mg/kg) suggested a specific involvement of serotonergic system. No differences were found across the groups with regard to self-grooming behavior. Moreover, in proestrus phase, carvacrol reduced only estradiol levels without binding hypothalamic estradiol receptors. Our study showed an estrous-stage specific effect of carvacrol on depressive behaviors and endocrine parameters, involving serotonergic system. Given the wide carvacrol use not only as feed additive, but also as cosmetic essence and herbal remedy, our results suggest that an accurate investigation on the effects of its chronic exposure is warranted. - Highlights: → Carvacrol induced a depressive-like phenotype in rats, depending on ovarian cyclicity. → Carvacrol selectively reduced serotonin content in female rats in proestrus phase. → Carvacrol reduced serotonin

  18. An alter-centric perspective on employee innovation: The importance of alters' creative self-efficacy and network structure.

    Science.gov (United States)

    Grosser, Travis J; Venkataramani, Vijaya; Labianca, Giuseppe Joe

    2017-09-01

    While most social network studies of employee innovation behavior examine the focal employees' ("egos'") network structure, we employ an alter-centric perspective to study the personal characteristics of employees' network contacts-their "alters"-to better understand employee innovation. Specifically, we examine how the creative self-efficacy (CSE) and innovation behavior of employees' social network contacts affects their ability to generate and implement novel ideas. Hypotheses were tested using a sample of 144 employees in a U.S.-based product development organization. We find that the average CSE of alters in an employee's problem solving network is positively related to that employee's innovation behavior, with this relationship being mediated by these alters' average innovation behavior. The relationship between the alters' average innovation behavior and the employee's own innovation behavior is strengthened when these alters have less dense social networks. Post hoc results suggest that having network contacts with high levels of CSE also leads to an increase in ego's personal CSE 1 year later in cases where the employee's initial level of CSE was relatively low. Implications for theory and practice are discussed. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  19. Gestational flu exposure induces changes in neurochemicals, affiliative hormones and brainstem inflammation, in addition to autism-like behaviors in mice.

    Science.gov (United States)

    Miller, V M; Zhu, Y; Bucher, C; McGinnis, W; Ryan, L K; Siegel, A; Zalcman, S

    2013-10-01

    The prevalence of neurodevelopmental disorders such as autism is increasing, however the etiology of these disorders is unclear and thought to involve a combination of genetic, environmental and immune factors. A recent epidemiological study found that gestational viral exposure during the first trimester increases risk of autism in offspring by twofold. In mice gestational viral exposures alter behavior of offspring, but the biological mechanisms which underpin these behavioral changes are unclear. We hypothesized that gestational viral exposure induces changes in affiliative hormones, brainstem autonomic nuclei and neurotransmitters which are associated with behavioral alterations in offspring. To address this hypothesis, we exposed pregnant mice to influenza A virus (H3N2) on gestational day 9 and determined behavioral, hormonal and brainstem changes in male and female offspring. We found that gestational flu exposure induced dose-dependent alterations in social and aggressive behaviors (p≤0.05) in male and female offspring and increases in locomotor behaviors particularly in male offspring (p≤0.05). We found that flu exposure was also associated with reductions in oxytocin and serotonin (p≤0.05) levels in male and female offspring and sex-specific changes in dopamine metabolism. In addition we found changes in catecholaminergic and microglia density in brainstem tissues of male flu exposed offspring only (p≤0.05). This study demonstrates that gestational viral exposure induces behavioral changes in mice, which are associated with alterations in affiliative hormones. In addition we found sex-specific changes in locomotor behavior, which may be associated with sex-specific alterations in dopamine metabolism and brainstem inflammation. Further investigations into maternal immune responses are necessary to unravel the molecular mechanisms which underpin abnormal hormonal, immune and behavioral responses in offspring after gestational viral exposure

  20. Heterozygosity for the Mood Disorder-Associated Variant Gln460Arg Alters P2X7 Receptor Function and Sleep Quality.

    Science.gov (United States)

    Metzger, Michael W; Walser, Sandra M; Dedic, Nina; Aprile-Garcia, Fernando; Jakubcakova, Vladimira; Adamczyk, Marek; Webb, Katharine J; Uhr, Manfred; Refojo, Damian; Schmidt, Mathias V; Friess, Elisabeth; Steiger, Axel; Kimura, Mayumi; Chen, Alon; Holsboer, Florian; Arzt, Eduardo; Wurst, Wolfgang; Deussing, Jan M

    2017-11-29

    A single nucleotide polymorphism substitution from glutamine (Gln, Q) to arginine (Arg, R) at codon 460 of the purinergic P2X7 receptor (P2X7R) has repeatedly been associated with mood disorders. The P2X7R-Gln460Arg variant per se is not compromised in its function. However, heterologous expression of P2X7R-Gln460Arg together with wild-type P2X7R has recently been demonstrated to impair receptor function. Here we show that this also applies to humanized mice coexpressing both human P2X7R variants. Primary hippocampal cells derived from heterozygous mice showed an attenuated calcium uptake upon agonist stimulation. While humanized mice were unaffected in their behavioral repertoire under basal housing conditions, mice that harbor both P2X7R variants showed alterations in their sleep quality resembling signs of a prodromal disease stage. Also healthy heterozygous human subjects showed mild changes in sleep parameters. These results indicate that heterozygosity for the wild-type P2X7R and its mood disorder-associated variant P2X7R-Gln460Arg represents a genetic risk factor, which is potentially able to convey susceptibility to mood disorders. SIGNIFICANCE STATEMENT Depression and bipolar disorder are the most common mood disorders. The P2X7 receptor (P2X7R) regulates many cellular functions. Its polymorphic variant Gln460Arg has repeatedly been associated with mood disorders. Genetically engineered mice, with human P2X7R, revealed that heterozygous mice (i.e., they coexpress the disease-associated Gln460Arg variant together with its normal version) have impaired receptor function and showed sleep disturbances. Human participants with the heterozygote genotype also had subtle alterations in their sleep profile. Our findings suggest that altered P2X7R function in heterozygote individuals disturbs sleep and might increase the risk for developing mood disorders. Copyright © 2017 the authors 0270-6474/17/3711688-13$15.00/0.

  1. Longitudinal Diffusion Tensor Imaging Resembles Patterns of Pathology Progression in Behavioral Variant Frontotemporal Dementia (bvFTD

    Directory of Open Access Journals (Sweden)

    Jan Kassubek

    2018-03-01

    Full Text Available Objective: Recently, the characteristic longitudinal distribution pattern of the underlying phosphorylated TDP-43 (pTDP-43 pathology in the behavioral variant of frontotemporal dementia (bvFTD excluding Pick's disease (PiD across specific brain regions was described. The aim of the present study was to investigate whether in vivo investigations of bvFTD patients by use of diffusion tensor imaging (DTI were consistent with these proposed patterns of progression.Methods: Sixty-two bvFTD patients and 47 controls underwent DTI in a multicenter study design. Of these, 49 bvFTD patients and 34 controls had a follow-up scan after ~12 months. Cross-sectional and longitudinal alterations were assessed by a two-fold analysis, i.e., voxelwise comparison of fractional anisotropy (FA maps and a tract of interest-based (TOI approach, which identifies tract structures that could be assigned to brain regions associated with disease progression.Results: Whole brain-based spatial statistics showed white matter alterations predominantly in the frontal lobes cross-sectionally and longitudinally. The TOIs of bvFTD neuroimaging stages 1 and 2 (uncinate fascicle—bvFTD pattern I; corticostriatal pathway—bvFTD pattern II showed highly significant differences between bvFTD patients and controls. The corticospinal tract-associated TOI (bvFTD pattern III did not differ between groups, whereas the differences in the optic radiation (bvFTD pattern IV reached significance. The findings in the corticospinal tract were due to a “dichotomous” behavior of FA changes there.Conclusion: Longitudinal TOI analysis demonstrated a pattern of white matter pathways alterations consistent with patterns of pTDP-43 pathology.

  2. CADDIS Volume 2. Sources, Stressors and Responses: Flow Alteration

    Science.gov (United States)

    Introduction to the flow alteration module, when to list flow alteration as a candidate cause, ways to measure flow alteration, simple and detailed conceptual model diagrams for flow alteration, flow alteration module references and literature reviews.

  3. Functional and neurochemical characterization of angiotensin type 1A receptor-expressing neurons in the nucleus of the solitary tract of the mouse.

    Science.gov (United States)

    Carter, D A; Choong, Y-T; Connelly, A A; Bassi, J K; Hunter, N O; Thongsepee, N; Llewellyn-Smith, I J; Fong, A Y; McDougall, S J; Allen, A M

    2017-10-01

    Angiotensin II acts via two main receptors within the central nervous system, with the type 1A receptor (AT 1A R) most widely expressed in adult neurons. Activation of the AT 1 R in the nucleus of the solitary tract (NTS), the principal nucleus receiving central synapses of viscerosensory afferents, modulates cardiovascular reflexes. Expression of the AT 1 R occurs in high density within the NTS of most mammals, including humans, but the fundamental electrophysiological and neurochemical characteristics of the AT 1A R-expressing NTS neurons are not known. To address this, we have used a transgenic mouse, in which the AT 1A R promoter drives expression of green fluorescent protein (GFP). Approximately one-third of AT 1A R-expressing neurons express the catecholamine-synthetic enzyme tyrosine hydroxylase (TH), and a subpopulation of these stained for the transcription factor paired-like homeobox 2b (Phox2b). A third group, comprising approximately two-thirds of the AT 1A R-expressing NTS neurons, showed Phox2b immunoreactivity alone. A fourth group in the ventral subnucleus expressed neither TH nor Phox2b. In whole cell recordings from slices in vitro, AT 1A R-GFP neurons exhibited voltage-activated potassium currents, including the transient outward current and the M-type potassium current. In two different mouse strains, both AT 1A R-GFP neurons and TH-GFP neurons showed similar AT 1A R-mediated depolarizing responses to superfusion with angiotensin II. These data provide a comprehensive description of AT 1A R-expressing neurons in the NTS and increase our understanding of the complex actions of this neuropeptide in the modulation of viscerosensory processing. Copyright © 2017 the American Physiological Society.

  4. A kernel version of multivariate alteration detection

    DEFF Research Database (Denmark)

    Nielsen, Allan Aasbjerg; Vestergaard, Jacob Schack

    2013-01-01

    Based on the established methods kernel canonical correlation analysis and multivariate alteration detection we introduce a kernel version of multivariate alteration detection. A case study with SPOT HRV data shows that the kMAD variates focus on extreme change observations.......Based on the established methods kernel canonical correlation analysis and multivariate alteration detection we introduce a kernel version of multivariate alteration detection. A case study with SPOT HRV data shows that the kMAD variates focus on extreme change observations....

  5. Investigation of alteration zones in Garandake and Kurokawa

    Energy Technology Data Exchange (ETDEWEB)

    Kinbara, K [Geological Survey of Japan, Kawasaki; Sudo, S

    1977-01-01

    The eastern part of the Garan area contains both the Myoban and Tsukahara hot springs. The springs are associated with the Sanin Formation, and an alteration zone is present which strikes easterly. Throughout the altered area, a clear zonation of the alteration is present. The zonation runs: silicified - alunitized - kaolin/argillized - montmorillonite/zeolite. In the Kurokawa area, a total of 0.96 km/sup 2/ of altered zones were observed near Suzumejigoku and throughout Yoshikawa and Tawara. The most heavily altered areas were at Kurokawa hot springs and Yoshikawa, where alunite and kaolinite are abundant. The time of alteration is believed to be prior to the deposition of the Hisazumi pumice. Around the Kurokawa hot springs, where the water temperature is 98/sup 0/C, the alteration extends as far as the pumice.

  6. Altered elementary calcium release events and enhanced calcium release by thymol in rat skeletal muscle.

    Science.gov (United States)

    Szentesi, Péter; Szappanos, Henrietta; Szegedi, Csaba; Gönczi, Monika; Jona, István; Cseri, Julianna; Kovács, László; Csernoch, László

    2004-03-01

    The effects of thymol on steps of excitation-contraction coupling were studied on fast-twitch muscles of rodents. Thymol was found to increase the depolarization-induced release of calcium from the sarcoplasmic reticulum, which could not be attributed to a decreased calcium-dependent inactivation of calcium release channels/ryanodine receptors or altered intramembrane charge movement, but rather to a more efficient coupling of depolarization to channel opening. Thymol increased ryanodine binding to heavy sarcoplasmic reticulum vesicles, with a half-activating concentration of 144 micro M and a Hill coefficient of 1.89, and the open probability of the isolated and reconstituted ryanodine receptors, from 0.09 +/- 0.03 to 0.22 +/- 0.04 at 30 micro M. At higher concentrations the drug induced long-lasting open events on a full conducting state. Elementary calcium release events imaged using laser scanning confocal microscopy in the line-scan mode were reduced in size, 0.92 +/- 0.01 vs. 0.70 +/- 0.01, but increased in duration, 56 +/- 1 vs. 79 +/- 1 ms, by 30 micro M thymol, with an increase in the relative proportion of lone embers. Higher concentrations favored long events, resembling embers in control, with duration often exceeding 500 ms. These findings provide direct experimental evidence that the opening of a single release channel will generate an ember, rather than a spark, in mammalian skeletal muscle.

  7. 28 CFR 36.405 - Alterations: Historic preservation.

    Science.gov (United States)

    2010-07-01

    ... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Alterations: Historic preservation. 36... Alterations: Historic preservation. (a) Alterations to buildings or facilities that are eligible for listing in the National Register of Historic Places under the National Historic Preservation Act (16 U.S.C...

  8. Radiation protection philosophy alters

    International Nuclear Information System (INIS)

    Firmin, G.

    1977-01-01

    Two significant events that have taken place this year in the field of radiation protection are reported. New SI units have been proposed (and effectively adopted), and the ICRP has revised its recommendations. Changes of emphasis in the latest recommendations (ICRP Publication 26) imply an altered radiation protection philosophy, in particular the relation of dose limits to estimates of average risk, an altered view of the critical organ approach and a new attitude to genetic dose to the population. (author)

  9. 28 CFR 36.403 - Alterations: Path of travel.

    Science.gov (United States)

    2010-07-01

    ... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Alterations: Path of travel. 36.403... Alterations: Path of travel. (a) General. An alteration that affects or could affect the usability of or... the maximum extent feasible, the path of travel to the altered area and the restrooms, telephones, and...

  10. Music and Alterity Processes

    Directory of Open Access Journals (Sweden)

    Josep Martí

    2014-10-01

    Full Text Available The concept of alterity constitutes an important issue in anthropological research and, therefore, in the study of musical practices, as well. Without it, we could hardly understand other kinds of music situated in different spaces and time from the observer. In order to effectively approach these musical practices, we have to develop strategies to help us reduce as much as possible that which distorts the vision of the other. However, beyond the strictly epistemological and methodological issues, the study of music cannot ignore the ethical question related to the manner in which Western thought has understood and treated the other: through a hierarchical and stereotypical type of thinking based on the condition of otherness. Throughout the article, different alterity procedures are presented and discussed, such as synecdochization, exoticization, undervaluation, overvaluation, misunderstanding and exclusion. Taking these different alterity strategies into account may help us to better understand how the musical other is constructed, used and ultimately instrumentalized.

  11. Characterization of Mediators of Cardiac And Renal Development in Response to Increased Prenatal Testosterone

    National Research Council Canada - National Science Library

    Maresh, Ryan W

    2008-01-01

    .... Exposure to excess prenatal androgens has been previously shown to cause growth restriction, alter sexual development and function, and cause the onset of symptoms that closely resemble those seen...

  12. Oncogenic events associated with endometrial and ovarian cancers are rare in endometriosis

    DEFF Research Database (Denmark)

    Vestergaard, Anna Lindeløv; Thorup, Katrine; Knudsen, Ulla Breth

    2011-01-01

    Endometriosis displays some features that resemble malignant processes, including invasive growth, resistance to apoptosis, and distant implantation. The objective of this study was to investigate whether gene alterations that are frequent in endometrial and/or ovarian cancers contribute to the p......Endometriosis displays some features that resemble malignant processes, including invasive growth, resistance to apoptosis, and distant implantation. The objective of this study was to investigate whether gene alterations that are frequent in endometrial and/or ovarian cancers contribute...... to the pathogenesis of endometriosis. Biopsies were obtained from ectopic endometriosis lesions from 23 patients with revised American Fertility Score (rAFS) stage 1 (N=1), 2 (N=10), 3 (N=11), or 4 (N=1) endometriosis. Six genes (APC, CDKN2A, PYCARD, RARB, RASSF1, and ESR1) were analyzed for promoter hypermethylation...... in a single lesion. No gene alterations were found in the remaining samples. Our data suggest that genetic and epigenetic events contributing to endometrial and ovarian cancers are rare in endometriosis. However, other proto-oncogenes and tumor suppressor genes should be tested for alterations in order...

  13. Microbial Endocrinology in the Pathogenesis of Infectious Disease.

    Science.gov (United States)

    Lyte, Mark

    2016-04-01

    Microbial endocrinology represents the intersection of two seemingly disparate fields, microbiology and neurobiology, and is based on the shared presence of neurochemicals that are exactly the same in host as well as in the microorganism. The ability of microorganisms to not only respond to, but also produce, many of the same neurochemicals that are produced by the host, such as during periods of stress, has led to the introduction of this evolutionary-based mechanism which has a role in the pathogenesis of infectious disease. The consideration of microbial endocrinology-based mechanisms has demonstrated, for example, that the prevalent use of catecholamine-based synthetic drugs in the clinical setting contributes to the formation of biofilms in indwelling medical devices. Production of neurochemicals by microorganisms most often employs the same biosynthetic pathways as those utilized by the host, indicating that acquisition of host neurochemical-based signaling system in the host may have been acquired due to lateral gene transfer from microorganisms. That both host and microorganism produce and respond to the very same neurochemicals means that there is bidirectionality contained with the theoretical underpinnings of microbial endocrinology. This can be seen in the role of microbial endocrinology in the microbiota-gut-brain axis and its relevance to infectious disease. Such shared pathways argue for a role of microorganism-neurochemical interactions in infectious disease.

  14. Early life adversities or high fat diet intake reduce cognitive function and alter BDNF signaling in adult rats: Interplay of these factors changes these effects.

    Science.gov (United States)

    Arcego, Danusa Mar; Krolow, Rachel; Lampert, Carine; Toniazzo, Ana Paula; Berlitz, Carolina; Lazzaretti, Camilla; Schmitz, Felipe; Rodrigues, André Felipe; Wyse, Angela T S; Dalmaz, Carla

    2016-05-01

    Environmental factors, like early exposure to stressors or high caloric diets, can alter the early programming of central nervous system, leading to long-term effects on cognitive function, increased vulnerability to cognitive decline and development of psychopathologies later in life. The interaction between these factors and their combined effects on brain structure and function are still not completely understood. In this study, we evaluated long-term effects of social isolation in the prepubertal period, with or without chronic high fat diet access, on memory and on neurochemical markers in the prefrontal cortex of rats. We observed that early social isolation led to impairment in short-term and working memory in adulthood, and to reductions of Na(+),K(+)-ATPase activity and the immunocontent of phospho-AKT, in prefrontal cortex. Chronic exposure to a high fat diet impaired short-term memory (object recognition), and decreased BDNF levels in that same brain area. Remarkably, the association of social isolation with chronic high fat diet rescued the memory impairment on the object recognition test, as well as the changes in BDNF levels, Na(+),K(+)-ATPase activity, MAPK, AKT and phospho-AKT to levels similar to the control-chow group. In summary, these findings showed that a brief social isolation period and access to a high fat diet during a sensitive developmental period might cause memory deficits in adulthood. On the other hand, the interplay between isolation and high fat diet access caused a different brain programming, preventing some of the effects observed when these factors are separately applied. Copyright © 2016 ISDN. Published by Elsevier Ltd. All rights reserved.

  15. Extending the honey bee venome with the antimicrobial peptide apidaecin and a protein resembling wasp antigen 5.

    Science.gov (United States)

    Van Vaerenbergh, M; Cardoen, D; Formesyn, E M; Brunain, M; Van Driessche, G; Blank, S; Spillner, E; Verleyen, P; Wenseleers, T; Schoofs, L; Devreese, B; de Graaf, D C

    2013-04-01

    Honey bee venom is a complex mixture of toxic proteins and peptides. In the present study we tried to extend our knowledge of the venom composition using two different approaches. First, worker venom was analysed by liquid chromatography-mass spectrometry and this revealed the antimicrobial peptide apidaecin for the first time in such samples. Its expression in the venom gland was confirmed by reverse transcription PCR and by a peptidomic analysis of the venom apparatus tissue. Second, genome mining revealed a list of proteins with resemblance to known insect allergens or venom toxins, one of which showed homology to proteins of the antigen 5 (Ag5)/Sol i 3 cluster. It was demonstrated that the honey bee Ag5-like gene is expressed by venom gland tissue of winter bees but not of summer bees. Besides this seasonal variation, it shows an interesting spatial expression pattern with additional production in the hypopharyngeal glands, the brains and the midgut. Finally, our immunoblot study revealed that both synthetic apidaecin and the Ag5-like recombinant from bacteria evoke no humoral activity in beekeepers. Also, no IgG4-based cross-reactivity was detected between the honey bee Ag5-like protein and its yellow jacket paralogue Ves v 5. © 2013 Royal Entomological Society.

  16. Cerebral (1)H MRS alterations in recreational 3, 4-methylenedioxymethamphetamine (MDMA, "ecstasy") users.

    Science.gov (United States)

    Chang, L; Ernst, T; Grob, C S; Poland, R E

    1999-10-01

    3,4-methylenedioxymethamphetamine (MDMA) is an illicit drug that has been associated with serotonergic axonal degeneration in animals. This study evaluates neurochemical abnormalities in recreational MDMA users. Twenty-two MDMA users and 37 normal subjects were evaluated with magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy ((1)H MRS) in the mid-frontal, mid-occipital, and parietal brain regions. (1)H MRS showed normal N-acetyl (NA) compounds in all brain regions. The myo-inositol (MI) concentration (+16.3%, P = 0.04) and the MI to creatine (CR) ratio (+14.1%, P = 0. 01) were increased in the parietal white matter of MDMA users. The cumulative lifetime MDMA dose showed significant effects on [MI] in the parietal white matter and the occipital cortex. The normal NA concentration suggests a lack of significant neuronal injury in recreational MDMA users. However, the usage-related increase in MI suggests that exposure to MDMA, even at recreational doses, may cause increased glial content. J. Magn. Reson. Imaging 1999;10:521-526. Copyright 1999 Wiley-Liss, Inc.

  17. A naturally derived gastric cancer cell line shows latency I Epstein-Barr virus infection closely resembling EBV-associated gastric cancer

    International Nuclear Information System (INIS)

    Oh, Sang Taek; Seo, Jung Seon; Moon, Uk Yeol; Kang, Kyeong Hee; Shin, Dong-Jik; Yoon, Sungjoo Kim; Kim, Woo Ho; Park, Jae-Gahb; Lee, Suk Kyeong

    2004-01-01

    In a process seeking out a good model cell line for Epstein-Barr virus (EBV)-associated gastric cancer, we found that one previously established gastric adenocarcinoma cell line is infected with type 1 EBV. This SNU-719 cell line from a Korean patient expressed cytokeratin without CD19 or CD21 expression. In SNU-719, EBNA1 and LMP2A were expressed, while LMP1 and EBNA2 were not. None of the tested lytic EBV proteins were detected in this cell line unless stimulated with phorbol ester. EBV infection was also shown in the original carcinoma tissue of SNU-719 cell line. Our results support the possibility of a CD21-independent EBV infection of gastric epithelial cells in vivo. As the latent EBV gene expression pattern of SNU-719 closely resembles that of the EBV-associated gastric cancer, this naturally derived cell line may serve as a valuable model system to clarify the precise role of EBV in gastric carcinogenesis

  18. Plasma fatty acid profile in depressive disorder resembles insulin resistance state.

    Science.gov (United States)

    Vareka, Tomas; Vecka, Marek; Jirak, Roman; Tvrzicka, Eva; Macasek, Jaroslav; Zak, Ales; Zeman, Miroslav

    2012-01-01

    Depressive disorder is related to an increased risk of type 2 diabetes mellitus (DM2) and cardiovascular disease (CVD). Insulin resistance (IR), connected with altered fatty acid (FA) composition, namely with decreased proportion of polyunsaturated FA could participate in these associations. The aim of the study was to investigate the composition of FA in plasma cholesterol esters (CE) and phosphatidylcholine (PC) as well as indices of insulin resistance and oxidative stress in the patients with depressive disorder. Parameters of lipid and glucose homeostasis, concentrations of FA in plasma cholesteryl esters (CE) and phosphatidylcholine (PC) and conjugated dienes in LDL were investigated in a group of 47 patients (9M/38F) with depression and compared with 47 control persons (16M/31F). Delta-9 desaturase (D9D) and D6D desaturase were estimated as product to precursor fatty acid ratios. In depressive patients increased concentrations of palmitoleic acid and total monounsaturated FA with decreased proportion of total polyunsaturated FA n-6 (PUFA n-6) (all pinsulin resistance. Dysregulation of FA could participate in the pathogenesis of depression and be associated with an increased risk of CVD and DM2.

  19. Immunization alters body odor.

    Science.gov (United States)

    Kimball, Bruce A; Opiekun, Maryanne; Yamazaki, Kunio; Beauchamp, Gary K

    2014-04-10

    Infections have been shown to alter body odor. Because immune activation accompanies both infection and immunization, we tested the hypothesis that classical immunization might similarly result in the alteration of body odors detectable by trained biosensor mice. Using a Y-maze, we trained biosensor mice to distinguish between urine odors from rabies-vaccinated (RV) and unvaccinated control mice. RV-trained mice generalized this training to mice immunized with the equine West Nile virus (WNV) vaccine compared with urine of corresponding controls. These results suggest that there are similarities between body odors of mice immunized with these two vaccines. This conclusion was reinforced when mice could not be trained to directly discriminate between urine odors of RV- versus WNV-treated mice. Next, we trained biosensor mice to discriminate the urine odors of mice treated with lipopolysaccharide (LPS; a general elicitor of innate immunological responses) from the urine of control mice. These LPS-trained biosensors could distinguish between the odors of LPS-treated mouse urine and RV-treated mouse urine. Finally, biosensor mice trained to distinguish between the odors of RV-treated mouse urine and control mouse urine did not generalize this training to discriminate between the odors of LPS-treated mouse urine and control mouse urine. From these experiments, we conclude that: (1) immunization alters urine odor in similar ways for RV and WNV immunizations; and (2) immune activation with LPS also alters urine odor but in ways different from those of RV and WNV. Published by Elsevier Inc.

  20. Evaluation of bentonite alteration due to interactions with iron. Sensitivity analyses to identify the important factors for the bentonite alteration

    International Nuclear Information System (INIS)

    Sasamoto, Hiroshi; Wilson, James; Sato, Tsutomu

    2013-01-01

    Performance assessment of geological disposal systems for high-level radioactive waste requires a consideration of long-term systems behaviour. It is possible that the alteration of swelling clay present in bentonite buffers might have an impact on buffer functions. In the present study, iron (as a candidate overpack material)-bentonite (I-B) interactions were evaluated as the main buffer alteration scenario. Existing knowledge on alteration of bentonite during I-B interactions was first reviewed, then the evaluation methodology was developed considering modeling techniques previously used overseas. A conceptual model for smectite alteration during I-B interactions was produced. The following reactions and processes were selected: 1) release of Fe 2+ due to overpack corrosion; 2) diffusion of Fe 2+ in compacted bentonite; 3) sorption of Fe 2+ on smectite edge and ion exchange in interlayers; 4) dissolution of primary phases and formation of alteration products. Sensitivity analyses were performed to identify the most important factors for the alteration of bentonite by I-B interactions. (author)

  1. HIV, Vascular and Aging Injuries in the Brain of Clinically Stable HIV-Infected Adults: A 1H MRS Study

    Science.gov (United States)

    Cysique, Lucette A.; Moffat, Kirsten; Moore, Danielle M.; Lane, Tammy A.; Davies, Nicholas W. S.; Carr, Andrew; Brew, Bruce J.; Rae, Caroline

    2013-01-01

    Background Cardiovascular disease (CVD) and premature aging have been hypothesized as new risk factors for HIV associated neurocognitive disorders (HAND) in adults with virally-suppressed HIV infection. Moreover, their significance and relation to more classical HAND biomarkers remain unclear. Methods 92 HIV− infected (HIV+) adults stable on combined antiretroviral therapy (cART) and 30 age-comparable HIV-negative (HIV−) subjects underwent 1H Magnetic Resonance Spectroscopy (MRS) of the frontal white matter (targeting HIV, normal aging or CVD-related neurochemical injury), caudate nucleus (targeting HIV neurochemical injury), and posterior cingulate cortex (targeting normal/pathological aging, CVD-related neurochemical changes). All also underwent standard neuropsychological (NP) testing. CVD risk scores were calculated. HIV disease biomarkers were collected and cerebrospinal fluid (CSF) neuroinflammation biomarkers were obtained in 38 HIV+ individuals. Results Relative to HIV− individuals, HIV+ individuals presented mild MRS alterations: in the frontal white matter: lower N-Acetyl-Aspartate (NAA) (pHIV*age interaction was associated with lower frontal white matter NAA. CVD risk factors were associated with lower posterior cingulate cortex and caudate NAA in both groups. Past acute CVD events in the HIV+ group were associated with increased mIo in the posterior cingulate cortex. HIV duration was associated with lower caudate NAA; greater CNS cART penetration was associated with lower mIo in the posterior cingulate cortex and the degree of immune recovery on cART was associated with higher NAA in the frontal white matter. CSF neopterin was associated with higher mIo in the posterior cingulate cortex and frontal white matter. Conclusions In chronically HIV+ adults with long-term viral suppression, current CVD risk, past CVD and age are independent factors for neuronal injury and inflammation. This suggests a tripartite model of HIV, CVD and age likely driven by

  2. Transcranial direct current stimulation improves long-term memory deficits in an animal model of attention-deficit/hyperactivity disorder and modulates oxidative and inflammatory parameters.

    Science.gov (United States)

    Leffa, Douglas Teixeira; Bellaver, Bruna; Salvi, Artur Alban; de Oliveira, Carla; Caumo, Wolnei; Grevet, Eugenio Horacio; Fregni, Felipe; Quincozes-Santos, André; Rohde, Luis Augusto; Torres, Iraci L S

    2018-04-05

    Transcranial direct current stimulation (tDCS) is a technique that modulates neuronal activity and has been proposed as a potential therapeutic tool for attention-deficit/hyperactivity disorder (ADHD) symptoms. Although pilot studies have shown evidence of efficacy, its mechanism of action remains unclear. We evaluated the effects of tDCS on behavioral (working and long-term memory) and neurochemical (oxidative and inflammatory parameters) outcomes related to ADHD pathophysiology. We used the most widely accepted animal model of ADHD: spontaneously hypertensive rats (SHR). The selected behavioral outcomes have been shown to be altered in both ADHD patients and animal models, and were chosen for their relation to the proposed mechanistic action of tDCS. Adult male SHR and their control, the Wistar Kyoto rats (WKY), were subjected to 20 min of bicephalic tDCS or sham stimulation for 8 consecutive days. Working memory, long-term memory, and neurochemical outcomes were evaluated. TDCS improved long-term memory deficits presented by the SHR. No change in working memory performance was observed. In the hippocampus, tDCS increased both the production of reactive oxygen species in SHR and the levels of the antioxidant molecule glutathione in both strains. TDCS also modulated inflammatory response in the brains of WKY by downregulating pro-inflammatory cytokines. TDCS had significant effects that were specific for strain, type of behavioral and neurochemical outcomes. The long-term memory improvement in the SHR may point to a possible therapeutic role of tDCS in ADHD that does not seem to be mediated by inflammatory markers. Additionally, the anti-inflammatory effects observed in the brain of WKY after tDCS needs to be further explored. Copyright © 2018 Elsevier Inc. All rights reserved.

  3. The peptide NDP-MSH induces phenotype changes in the heart that resemble ischemic preconditioning.

    Science.gov (United States)

    Catania, Anna; Lonati, Caterina; Sordi, Andrea; Leonardi, Patrizia; Carlin, Andrea; Gatti, Stefano

    2010-01-01

    alpha-Melanocyte-stimulating hormone (alpha-MSH) is a pro-opiomelanocortin (POMC)-derived peptide that exerts multiple protective effects on host cells. Previous investigations showed that treatment with alpha-MSH or synthetic melanocortin agonists reduces heart damage in reperfusion injury and transplantation. The aim of this preclinical research was to determine whether melanocortin treatment induces preconditioning-like cardioprotection. In particular, the plan was to assess whether melanocortin administration causes phenotype changes similar to those induced by repetitive ischemic events. The idea was conceived because both ischemic preconditioning and melanocortin signaling largely depend on cAMP response element binding protein (CREB) phosphorylation. Rats received single i.v. injections of 750microg/kg of the alpha-MSH analogue Nle(4),DPhe(7)-alpha-MSH (NDP-MSH) or saline and were sacrificed at 0.5, 1, 3, or 5h. Western blot analysis showed that rat hearts expressed melanocortin 1 receptor (MC1R) protein. Treatment with NDP-MSH was associated with early and marked increase in interleukin 6 (IL-6) mRNA. This was followed by signal transducer and activator of transcription 3 (STAT3) phosphorylation and induction of suppressor of cytokine signaling 3 (SOCS3). There were no changes in expression of other cytokines of the IL-6 family. Expression of IL-10, IL-1beta, and TNF-alpha was likewise unaltered. In hearts of rats treated with NDP-MSH there was increased expression of the orphan nuclear receptor Nur77. The data indicate that NDP-MSH induces phenotype changes that closely resemble ischemic preconditioning and likely contribute to its established protection against reperfusion injury. In addition, the increased expression of Nur77 and SOCS3 could be part of a broader anti-inflammatory effect.

  4. Is the serotonergic system altered in romantic love? A literature review and research suggestions

    NARCIS (Netherlands)

    S.J.E. Langeslag (Sandra)

    2009-01-01

    textabstractInfatuated individuals think about their beloved a lot. The notions that these frequent thoughts resemble the obsessions of obsessive-compulsive disorder (OCD) patients and that those patients benefit from serotonin reuptake inhibitors (SSRIs), have led to the hypothesis that romantic

  5. Long-term testosterone treatment during pregnancy does not alter insulin or glucose profile in a sheep model of polycystic ovary syndrome.

    Science.gov (United States)

    Recabarren, Monica; Carrasco, Albert; Sandoval, Daniel; Diaz, Felipe; Sir-Petermann, Teresa; Recabarren, Sergio E

    2017-09-07

    The administration of testosterone to pregnant sheep to resemble fetal programming of the polycystic ovary syndrome could alter other hormones/factors of maternal origin with known effects on fetal growth. Hence, we studied the weekly profile of insulin, progesterone and glucose during a treatment with testosterone propionate given biweekly from weeks 5 to 17 of pregnancy (term at 21 weeks) and checked the outcome of their fetuses at 17 weeks of gestation after C-section. Control dams were only exposed to the vehicle of the hormone. The testosterone administration did not cause any significant change in the maternal weekly profile of insulin, progesterone or glucose concentration, although the plasma levels of testosterone in the treated dams were inversely correlated to the levels of progesterone. Testosterone treatment also induced an inverse correlation between mean maternal insulin levels and fetal insulin levels; however, the fetal zoometric parameters, body weight, or insulin levels did not differ between exposed and not exposed fetuses. Therefore, treatment with testosterone during pregnancy does not cause significant impact on insulin levels in the mother, leading to less effect on the programming of fetal growth.

  6. How aging affects sleep-dependent memory consolidation?

    Directory of Open Access Journals (Sweden)

    Caroline eHarand

    2012-02-01

    Full Text Available Sleep plays multiple functions among which energy conservation or recuperative processes. Besides, growing evidence indicate that sleep plays also a major role in memory consolidation, a process by which recently acquired and labile memory traces are progressively strengthened into more permanent and/or enhanced forms. Indeed, memories are not stored as they were initially encoded but rather undergo a gradual reorganization process, which is favoured by the neurochemical environment and the electrophysiological activity observed during sleep. Two putative, probably not exclusive, models (hippocampo-neocortical dialogue and synaptic homeostasis hypothesis have been proposed to explain the beneficial effect of sleep on memory processes. It is worth noting that all data gathered until now emerged from studies conducted in young subjects. The investigation of the relationships between sleep and memory in older adults has sparked off little interest until recently. Though, aging is characterized by memory impairment, changes in sleep architecture, as well as brain and neurochemical alterations. All these elements suggest that sleep-dependent memory consolidation may be impaired or occurs differently in older adults.Here, we give an overview of the mechanisms governing sleep-dependent memory consolidation, and the crucial points of this complex process that may dysfunction and result in impaired memory consolidation in aging.

  7. Alterations in glucocorticoid negative feedback following maternal Pb, prenatal stress and the combination: A potential biological unifying mechanism for their corresponding disease profiles

    International Nuclear Information System (INIS)

    Rossi-George, A.; Virgolini, M.B.; Weston, D.; Cory-Slechta, D.A.

    2009-01-01

    Combined exposures to maternal lead (Pb) and prenatal stress (PS) can act synergistically to enhance behavioral and neurochemical toxicity in offspring. Maternal Pb itself causes permanent dysfunction of the body's major stress system, the hypothalamic pituitary adrenal (HPA) axis. The current study sought to determine the potential involvement of altered negative glucocorticoid feedback as a mechanistic basis of the effects in rats of maternal Pb (0, 50 or 150 ppm in drinking water beginning 2 mo prior to breeding), prenatal stress (PS; restraint on gestational days 16-17) and combined maternal Pb + PS in 8 mo old male and female offspring. Corticosterone changes were measured over 24 h following an i.p. injection stress containing vehicle or 100 or 300 μg/kg (females) or 100 or 150 μg/kg (males) dexamethasone (DEX). Both Pb and PS prolonged the time course of corticosterone reduction following vehicle injection stress. Pb effects were non-monotonic, with a greater impact at 50 vs. 150 ppm, particularly in males, where further enhancement occurred with PS. In accord with these findings, the efficacy of DEX in suppressing corticosterone was reduced by Pb and Pb + PS in both genders, with Pb efficacy enhanced by PS in females, over the first 6 h post-administration. A marked prolongation of DEX effects was found in males. Thus, Pb, PS and Pb + PS, sometimes additively, produced hypercortisolism in both genders, followed by hypocortisolism in males, consistent with HPA axis dysfunction. These findings may provide a plausible unifying biological mechanism for the reported links between Pb exposure and stress-associated diseases and disorders mediated via the HPA axis, including obesity, hypertension, diabetes, anxiety, schizophrenia and depression. They also suggest broadening of Pb screening programs to pregnant women in high stress environments

  8. Romantic Love vs. Drug Addiction May Inspire a New Treatment for Addiction

    Science.gov (United States)

    Zou, Zhiling; Song, Hongwen; Zhang, Yuting; Zhang, Xiaochu

    2016-01-01

    Drug addiction is a complex neurological dysfunction induced by recurring drug intoxication. Strategies to prevent and treat drug addiction constitute a topic of research interest. Early-stage romantic love is characterized by some characteristics of addiction, which gradually disappear as the love relationship progresses. Therefore, comparison of the concordance and discordance between romantic love and drug addiction may elucidate potential treatments for addiction. This focused review uses the evidences from our recent studies to compare the neural alterations between romantic love and drug addiction, moreover we also compare the behavioral and neurochemical alterations between romantic love and drug addiction. From the behavioral comparisons we find that there are many similarities between the early stage of romantic love and drug addiction, and this stage romantic love is considered as a behavioral addiction, while significant differences exist between the later stage of romantic love and drug addiction, and this stage of romantic love eventually developed into a prosocial behavior. The neuroimaging comparisons suggest that romantic love and drug addiction both display the functional enhancement in reward and emotion regulation network. Except the similar neural changes, romantic love display special function enhancement in social cognition network, while drug addiction display special dysfunction in cognitive control network. The neurochemical comparisons show that there are many similarities in the dopamine (DA) system, while significant differences in oxytocin (OT) system for romantic love and drug addiction. These findings indicate that the functional alterations in reward and emotion regulation network and the DA system may be the neurophysiological basis of romantic love as a behavioral addiction, and the functional alterations in social cognition network and the OT system may be the neurophysiological basis of romantic love as a prosocial behavior. It

  9. Romantic love v.s. drug addiction may inspire a new treatment for addiction

    Directory of Open Access Journals (Sweden)

    Zhiling Zou

    2016-09-01

    Full Text Available Drug addiction is a complex neurological dysfunction induced by recurring drug intoxication. Strategies to prevent and treat drug addiction constitute a topic of research interest. Early-stage romantic love is characterized by some characteristics of addiction, which gradually disappear as the love relationship progresses. Therefore, comparison of the concordance and discordance between romantic love and drug addiction may elucidate potential treatments for addiction. This focused review uses the evidences from our recent studies to compare the neural alterations between romantic love and drug addiction, moreover we also compare the behavioral and neurochemical alterations between romantic love and drug addiction. From the behavioral comparisons we find that there are many similarities between the early stage of romantic love and drug addiction, and this stage romantic love is considered as a behavioral addiction, while significant differences exist between the later stage of romantic love and drug addiction, and this stage of romantic love eventually developed into a prosocial behavior. The neuroimaging comparisons suggest that romantic love and drug addiction both display the functional enhancement in reward and emotion regulation network. Except the similar neural changes, romantic love display special function enhancement in social cognition network, while drug addiction display special dysfunction in cognitive control network. The neurochemical comparisons show that there are many similarities in the dopamine (DA system, while significant differences in oxytocin (OT system for romantic love and drug addiction. These indicate that the functional alterations in reward and emotion regulation network and the DA system may be the neurophysiological basis of romantic love as a behavioral addiction, and the functional alterations in social cognition network and the OT system may be the neurophysiological basis of romantic love as a prosocial

  10. Smectite alteration

    International Nuclear Information System (INIS)

    Anderson, D.M.

    1984-11-01

    This report contains the proceedings of a second workshop in Washington DC December 8-9, 1983 on the alteration of smectites intended for use as buffer materials in the long-term containment of nuclear wastes. It includes extended summaries of all presentations and a transcript of the detailed scientific discussion. The discussions centered on three main questions: What is the prerequisite for and what is the precise mechanism by which smectite clays may be altered to illite. What are likly sources of potassium with respect to the KBS project. Is it likely that the conversion of smectite to illite will be of importance in the 10 5 to the 10 6 year time frame. The workshop was convened to review considerations and conclusions in connection to these questions and also to broaden the discussion to consider the use of smectite clays as buffer materials for similar applications in different geographical and geological settings. SKBF/KBS technical report 83-03 contains the proceedings from the first workshop on these matters that was held at the State University of New York, Buffalo May 26-27, 1982. (Author)

  11. Summability of alterations of convergent series

    Directory of Open Access Journals (Sweden)

    T. A. Keagy

    1981-01-01

    Full Text Available The effect of splitting, rearrangement, and grouping series alterations on the summability of a convergent series by ℓ−ℓ and cs−cs matrix methods is studied. Conditions are determined that guarantee the existence of alterations that are transformed into divergent series and into series with preassigned sums.

  12. Effects of Aging and Tocotrienol-Rich Fraction Supplementation on Brain Arginine Metabolism in Rats

    Directory of Open Access Journals (Sweden)

    Musalmah Mazlan

    2017-01-01

    Full Text Available Accumulating evidence suggests that altered arginine metabolism is involved in the aging and neurodegenerative processes. This study sought to determine the effects of age and vitamin E supplementation in the form of tocotrienol-rich fraction (TRF on brain arginine metabolism. Male Wistar rats at ages of 3 and 21 months were supplemented with TRF orally for 3 months prior to the dissection of tissue from five brain regions. The tissue concentrations of L-arginine and its nine downstream metabolites were quantified using high-performance liquid chromatography and liquid chromatography tandem mass spectrometry. We found age-related alterations in L-arginine metabolites in the chemical- and region-specific manners. Moreover, TRF supplementation reversed age-associated changes in arginine metabolites in the entorhinal cortex and cerebellum. Multiple regression analysis revealed a number of significant neurochemical-behavioral correlations, indicating the beneficial effects of TRF supplementation on memory and motor function.

  13. Central nervous system resuscitation

    DEFF Research Database (Denmark)

    McIntosh, T K; Garde, E; Saatman, K E

    1997-01-01

    Traumatic injury to the central nervous system induces delayed neuronal death, which may be mediated by acute and chronic neurochemical changes. Experimental identification of these injury mechanisms and elucidation of the neurochemical cascade following trauma may provide enhanced opportunities...

  14. Fetal mesenchymal stromal cells differentiating towards chondrocytes acquire a gene expression profile resembling human growth plate cartilage.

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    Sandy A van Gool

    Full Text Available We used human fetal bone marrow-derived mesenchymal stromal cells (hfMSCs differentiating towards chondrocytes as an alternative model for the human growth plate (GP. Our aims were to study gene expression patterns associated with chondrogenic differentiation to assess whether chondrocytes derived from hfMSCs are a suitable model for studying the development and maturation of the GP. hfMSCs efficiently formed hyaline cartilage in a pellet culture in the presence of TGFβ3 and BMP6. Microarray and principal component analysis were applied to study gene expression profiles during chondrogenic differentiation. A set of 232 genes was found to correlate with in vitro cartilage formation. Several identified genes are known to be involved in cartilage formation and validate the robustness of the differentiating hfMSC model. KEGG pathway analysis using the 232 genes revealed 9 significant signaling pathways correlated with cartilage formation. To determine the progression of growth plate cartilage formation, we compared the gene expression profile of differentiating hfMSCs with previously established expression profiles of epiphyseal GP cartilage. As differentiation towards chondrocytes proceeds, hfMSCs gradually obtain a gene expression profile resembling epiphyseal GP cartilage. We visualized the differences in gene expression profiles as protein interaction clusters and identified many protein clusters that are activated during the early chondrogenic differentiation of hfMSCs showing the potential of this system to study GP development.

  15. Epigenetic alteration of sedimentary rocks at hydrogenic uranium deposit

    International Nuclear Information System (INIS)

    Ding Wanlie; Shen Kefeng

    2001-01-01

    The author introduces the concept, the recognition criteria, the genesis and classification of the epigenetic alteration of sedimentary rocks in brief, and expounds the mineral-geochemical indications and characteristics of oxidation and reduction alterations in different geochemical zones in detail, and proposes the two models of ore-controlling zonation of epigenetic alteration. The authors finally introduce research methods of epigenetic alteration

  16. Development of gypsum alteration on marble and limestone

    Science.gov (United States)

    McGee, E.S.

    1996-01-01

    Blackened alteration crusts of gypsum plus particulates that form on sheltered areas on marble and limestone buildings pose a challenge for rehabilitation and cleaning. Fresh marble and limestone samples exposed at monitored exposure sites present conditions of simple geometry and well-documented exposures but have short exposure histories (one to five years). The gypsum alteration crusts that develop on these samples provide insight into the early stages and rate of alteration crust formation. Alteration crusts from buildings give a longer, but less well known exposure history and present much more complex surfaces for gypsum accumulation. Integrated observations and measurements of alteration crusts from exposure samples and from buildings identify four factors that are important in the formation and development of alteration crusts on marble and limestone: (1) pollution levels, (2) exposure to rain or washing, (3) geometry of exposure of the stone surface, and (4) permeability of the stone. The combination of these factors contributes to both the distribution and the physical characteristics of the gypsum crusts which may affect cleaning decisions.

  17. Mutations in ORC1, encoding the largest subunit of the origin recognition complex, cause microcephalic primordial dwarfism resembling Meier-Gorlin syndrome.

    Science.gov (United States)

    Bicknell, Louise S; Walker, Sarah; Klingseisen, Anna; Stiff, Tom; Leitch, Andrea; Kerzendorfer, Claudia; Martin, Carol-Anne; Yeyati, Patricia; Al Sanna, Nouriya; Bober, Michael; Johnson, Diana; Wise, Carol; Jackson, Andrew P; O'Driscoll, Mark; Jeggo, Penny A

    2011-02-27

    Studies into disorders of extreme growth failure (for example, Seckel syndrome and Majewski osteodysplastic primordial dwarfism type II) have implicated fundamental cellular processes of DNA damage response signaling and centrosome function in the regulation of human growth. Here we report that mutations in ORC1, encoding a subunit of the origin recognition complex, cause microcephalic primordial dwarfism resembling Meier-Gorlin syndrome. We establish that these mutations disrupt known ORC1 functions including pre-replicative complex formation and origin activation. ORC1 deficiency perturbs S-phase entry and S-phase progression. Additionally, we show that Orc1 depletion in zebrafish is sufficient to markedly reduce body size during rapid embryonic growth. Our data suggest a model in which ORC1 mutations impair replication licensing, slowing cell cycle progression and consequently impeding growth during development, particularly at times of rapid proliferation. These findings establish a novel mechanism for the pathogenesis of microcephalic dwarfism and show a surprising but important developmental impact of impaired origin licensing.

  18. Cerebrospinal fluid space alterations in melancholic depression.

    Directory of Open Access Journals (Sweden)

    Esther Via

    Full Text Available Melancholic depression is a biologically homogeneous clinical entity in which structural brain alterations have been described. Interestingly, reports of structural alterations in melancholia include volume increases in Cerebro-Spinal Fluid (CSF spaces. However, there are no previous reports of CSF volume alterations using automated whole-brain voxel-wise approaches, as tissue classification algorithms have been traditionally regarded as less reliable for CSF segmentation. Here we aimed to assess CSF volumetric alterations in melancholic depression and their clinical correlates by means of a novel segmentation algorithm ('new segment', as implemented in the software Statistical Parametric Mapping-SPM8, incorporating specific features that may improve CSF segmentation. A three-dimensional Magnetic Resonance Image (MRI was obtained from seventy patients with melancholic depression and forty healthy control subjects. Although imaging data were pre-processed with the 'new segment' algorithm, in order to obtain a comparison with previous segmentation approaches, tissue segmentation was also performed with the 'unified segmentation' approach. Melancholic patients showed a CSF volume increase in the region of the left Sylvian fissure, and a CSF volume decrease in the subarachnoid spaces surrounding medial and lateral parietal cortices. Furthermore, CSF increases in the left Sylvian fissure were negatively correlated with the reduction percentage of depressive symptoms at discharge. None of these results were replicated with the 'unified segmentation' approach. By contrast, between-group differences in the left Sylvian fissure were replicated with a non-automated quantification of the CSF content of this region. Left Sylvian fissure alterations reported here are in agreement with previous findings from non-automated CSF assessments, and also with other reports of gray and white matter insular alterations in depressive samples using automated approaches

  19. Epigenetic Alterations in Alzheimer's Disease

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    Johannes eGräff

    2015-12-01

    Full Text Available Alzheimer’s disease (AD is the major cause of dementia in Western societies. It progresses asymptomatically during decades before being belatedly diagnosed when therapeutic strategies have become unviable. Although several genetic alterations have been associated with AD, the vast majority of AD cases do not show strong genetic underpinnings and are thus considered a consequence of non-genetic factors. Epigenetic mechanisms allow for the integration of long-lasting non-genetic inputs on specific genetic backgrounds, and recently, a growing number of epigenetic alterations in AD have been described. For instance, an accumulation of dysregulated epigenetic mechanisms in aging, the predominant risk factor of AD, might facilitate the onset of the disease. Likewise, mutations in several enzymes of the epigenetic machinery have been associated with neurodegenerative processes that are altered in AD such as impaired learning and memory formation. Genome-wide and locus-specific epigenetic alterations have also been reported, and several epigenetically dysregulated genes validated by independent groups. From these studies, a picture emerges of AD as being associated with DNA hypermethylation and histone deacetylation, suggesting a general repressed chromatin state and epigenetically reduced plasticity in AD. Here we review these recent findings and discuss several technical and methodological considerations that are imperative for their correct interpretation. We also pay particular focus on potential implementations and theoretical frameworks that we expect will help to better direct future studies aimed to unravel the epigenetic participation in AD.

  20. Epigenetic Alterations in Alzheimer's Disease.

    Science.gov (United States)

    Sanchez-Mut, Jose V; Gräff, Johannes

    2015-01-01

    Alzheimer's disease (AD) is the major cause of dementia in Western societies. It progresses asymptomatically during decades before being belatedly diagnosed when therapeutic strategies have become unviable. Although several genetic alterations have been associated with AD, the vast majority of AD cases do not show strong genetic underpinnings and are thus considered a consequence of non-genetic factors. Epigenetic mechanisms allow for the integration of long-lasting non-genetic inputs on specific genetic backgrounds, and recently, a growing number of epigenetic alterations in AD have been described. For instance, an accumulation of dysregulated epigenetic mechanisms in aging, the predominant risk factor of AD, might facilitate the onset of the disease. Likewise, mutations in several enzymes of the epigenetic machinery have been associated with neurodegenerative processes that are altered in AD such as impaired learning and memory formation. Genome-wide and locus-specific epigenetic alterations have also been reported, and several epigenetically dysregulated genes validated by independent groups. From these studies, a picture emerges of AD as being associated with DNA hypermethylation and histone deacetylation, suggesting a general repressed chromatin state and epigenetically reduced plasticity in AD. Here we review these recent findings and discuss several technical and methodological considerations that are imperative for their correct interpretation. We also pay particular focus on potential implementations and theoretical frameworks that we expect will help to better direct future studies aimed to unravel the epigenetic participation in AD.

  1. Differences in neurochemical profiles of two gadid species under ocean warming and acidification.

    Science.gov (United States)

    Schmidt, Matthias; Windisch, Heidrun Sigrid; Ludwichowski, Kai-Uwe; Seegert, Sean Lando Levin; Pörtner, Hans-Otto; Storch, Daniela; Bock, Christian

    2017-01-01

    Exposure to future ocean acidification scenarios may alter the behaviour of marine teleosts through interference with neuroreceptor functioning. So far, most studies investigated effects of ocean acidification on the behaviour of fish, either isolated or in combination with environmental temperature. However, only few physiological studies on this issue were conducted despite the putative neurophysiological origin of the CO 2 -induced behavioural changes. Here, we present the metabolic consequences of long-term exposure to projected ocean acidification (396-548 μatm P CO 2 under control and 915-1272 μatm under treatment conditions) and parallel warming in the brain of two related fish species, polar cod ( Boreogadus saida , exposed to 0 °C, 3 °C, 6 °C and 8 °C) and Atlantic cod ( Gadus morhua , exposed to 3 °C, 8 °C, 12 °C and 16 °C). It has been shown that B. saida is behaviourally vulnerable to future ocean acidification scenarios, while G. morhua demonstrates behavioural resilience. We found that temperature alters brain osmolyte, amino acid, choline and neurotransmitter concentrations in both species indicating thermal responses particularly in osmoregulation and membrane structure. In B. saida, changes in amino acid and osmolyte metabolism at the highest temperature tested were also affected by CO 2 , possibly emphasizing energetic limitations. We did not observe changes in neurotransmitters, energy metabolites, membrane components or osmolytes that might serve as a compensatory mechanism against CO 2 induced behavioural impairments. In contrast to B. saida , such temperature limitation was not detected in G. morhua ; however, at 8 °C, CO 2 induced an increase in the levels of metabolites of the glutamate/GABA-glutamine cycle potentially indicating greater GABAergic activity in G.morhua . Further, increased availability of energy-rich substrates was detected under these conditions. Our results indicate a change of GABAergic metabolism in

  2. Development of a mixed seawater-hydrothermal fluid geochemical signature during alteration of volcanic rocks in the Archean (∼2.7 Ga) Abitibi Greenstone Belt, Canada

    Science.gov (United States)

    Brengman, Latisha A.; Fedo, Christopher M.

    2018-04-01

    We investigated a group of silicified volcanic rocks from the ∼2.72 Ga Hunter Mine Group (HMG), Abitibi Greenstone Belt, Canada, in order to document progressive compositional change associated with alteration in a subaqueous caldera system. Rocks of the HMG divide into three groups based on mineralogy and texture for petrographic and geochemical analyses. Volcanic features (phenocrysts, pseudomorphs after primary glass shards, lapilli, volcanic clasts) are preserved in all groups, despite changing mineralogy from primarily quartz, feldspar, chlorite (Groups 1 and 2), to quartz, hematite and carbonate (Groups 2 and 3). Compositionally, Group 1 rocks resemble volcanic rocks in the region, while Group 2 and 3 rocks show a change in mineralogy to iron, silica, and carbonate minerals, which is associated with depletion of many major and trace elements associated with volcanic rocks (Al2O3, Na2O, K2O, Zr). In addition, rare earth elements display a clear progression from volcanic signatures in Group 1 (PrSN/YbSN = 1.7-2.96, EuSN/EuSN∗ = 0.84-1.72, Y/Ho = 25.20-27.41, LaSN/LaSN∗ = 0.97-1.29, and Zr/Hf = 38.38-42.09) to transitional mixed volcanic, hydrothermal, and seawater signatures in Group 2 (PrSN/YbSN 1.33-2.89, EuSN/EuSN∗ 1.33-2.5, Y/Ho = 23.94-30, LaSN/LaSN∗ 0.93-1.34, and Zr/Hf = 40-70), to mixed hydrothermal and seawater signatures in Group 3 (PrSN/YbSN 0.62-2.88, EuSN/EuSN∗ 1.30-7.15, LaSN/LaSN∗ 1.02-1.86, Y/Ho = 25.56-55, and Zr/Hf = 35-50). We interpret that silicification of volcanic rocks (Group 1) produced transitional altered volcanic rocks (Group 2), and siliceous and jaspilitic rocks (Group 3), based on preservation of delicate volcanic features. Building on this explanation, we interpret that major, trace- and rare-earth element mobility occurred during the process of silicification, during which siliceous and jaspilitic rocks (Group 3) acquired aspects of the rare-earth element geochemical signatures of marine chemical precipitates. We

  3. Gastric dysregulation induced by microinjection of 6-OHDA in the substantia nigra pars compacta of rats is determined by alterations in the brain-gut axis.

    Science.gov (United States)

    Toti, Luca; Travagli, R Alberto

    2014-11-15

    Idiopathic Parkinson's disease (PD) is a late-onset, chronic, and progressive motor dysfunction attributable to loss of nigrostriatal dopamine neurons. Patients with PD experience significant gastrointestinal (GI) issues, including gastroparesis. We aimed to evaluate whether 6-hydroxy-dopamine (6-OHDA)-induced degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc) induces gastric dysmotility via dysfunctions of the brain-gut axis. 6-OHDA microinjection into the SNpc induced a >90% decrease in tyrosine hydroxylase-immunoreactivity (IR) on the injection site. The [13C]-octanoic acid breath test showed a delayed gastric emptying 4 wk after the 6-OHDA treatment. In control rats, microinjection of the indirect sympathomimetic, tyramine, in the dorsal vagal complex (DVC) decreased gastric tone and motility; this inhibition was prevented by the fourth ventricular application of either a combination of α1- and α2- or a combination of D1 and D2 receptor antagonists. Conversely, in 6-OHDA-treated rats, whereas DVC microinjection of tyramine had reduced effects on gastric tone or motility, DVC microinjection of thyrotropin-releasing hormone induced a similar increase in motility as in control rats. In 6-OHDA-treated rats, there was a decreased expression of choline acetyl transferase (ChAT)-IR and neuronal nitric oxide synthase (NOS)-IR in DVC neurons but an increase in dopamine-β-hydroxylase-IR in the A2 area. Within the myenteric plexus of the esophagus, stomach, and duodenum, there were no changes in the total number of neurons; however, the percentage of NOS-IR neurons increased, whereas that of ChAT-IR decreased. Our data suggest that the delayed gastric emptying in a 6-OHDA rat model of PD may be caused by neurochemical and neurophysiological alterations in the brain-gut axis. Copyright © 2014 the American Physiological Society.

  4. Des Widerspenstigen Zähmung: Subjektives Alter(n, qualitativ erforscht

    Directory of Open Access Journals (Sweden)

    Stefanie Graefe

    2013-04-01

    Full Text Available Der Beitrag präsentiert Forschungsergebnisse einer qualitativen Interviewstudie zur subjektiven Alter(nserfahrung von Menschen in der zweiten Lebenshälfte sowie aus dem Forschungsprozess resultierende Überlegungen zur Frage, wie sich die soziale Erfahrung Alter(n methodologisch konzeptualisieren und empirisch erforschen lässt. Die Auswertung erfolgte angelehnt an die Grounded-Theory- Methodologie. Ausgehend von der "relativen (subjektiven Alterslosigkeit" als fallübergreifender Schlüsselkategorie wird im Folgenden eine Typologie von (Alters- Selbstkonzepten vorgestellt: das "wandlungsfähige", das "kontinuierliche" und das "verunsicherte" (Alters- Selbst. Skizziert wird eine methodologische Konzeption von Alter(n als eine zugleich prinzipiell unscharfe und erheblich normierte soziale Kategorie. Die Ergebnisse der Studie deuten darauf hin, dass – insbesondere vor dem Hintergrund der in jüngerer Zeit erfolgten sozialpolitischen Aufwertung der Lebensphase Alter – spezifische Sozialmilieus besonders prädestiniert scheinen, normative Anforderungen einer aktiven, produktiven und selbstverantwortlichen Gestaltung der Lebensphase Alter in ihr Selbstkonzept zu integrieren. URN: http://nbn-resolving.de/urn:nbn:de:0114-fqs1302114

  5. Hydrothermal alteration at Roosevelt Hot Springs KGRA: DDH 1976-1

    Energy Technology Data Exchange (ETDEWEB)

    Bryant, N.L.; Parry, W.T.

    1977-09-01

    Hot waters of the Roosevelt Thermal Area, Utah, have altered granitic rocks and detritus of the Mineral Range pluton, Utah. Alteration and mineral deposition recognized in a 200' drill core from DDH 1-76 is most intense in the upper 100 feet which consists of altered alluvium and opal deposits; the lower 100 feet is weakly altered quartz monzonite. Petrographic, x-ray, and chemical methods were used to characterize systematic changes in chemistry and mineralogy. Comparison of the alteration mineral assemblages with known water chemistry and equilibrium activity diagrams suggests that a simple solution equilibrium model cannot account for the alteration. A model is proposed in which upward moving thermal water supersaturated with respect to quartz and a downward moving cool water undersaturated with respect to quartz produces the observed alteration. An estimate of the heat flow contributions from hydrothermal alteration was made by calculating reaction enthalpies for alteration reactions at each depth. The estimated heat flow varied from .02 HFU (for 200' depth, 400,000 yr duration, and no sulfur oxidation) to 67 HFU (for 5,000' depth, 1,000 yr duration, and all sulfur oxidized from sulfide). Heat flow contributions from hydrothermal alteration are comparable with those from a cooling granitic magma.

  6. Chromosomal Alterations and Gene Expression Changes Associated with the Progression of Leukoplakia to Advanced Gingivobuccal Cancer

    Directory of Open Access Journals (Sweden)

    Priyanka G. Bhosale

    2017-06-01

    Full Text Available We present an integrative genome-wide analysis that can be used to predict the risk of progression from leukoplakia to oral squamous cell carcinoma (OSCC arising in the gingivobuccal complex (GBC. We find that the genomic and transcriptomic profiles of leukoplakia resemble those observed in later stages of OSCC and that several changes are associated with this progression, including amplification of 8q24.3, deletion of 8p23.2, and dysregulation of DERL3, EIF5A2, ECT2, HOXC9, HOXC13, MAL, MFAP5 and NELL2. Comparing copy number profiles of primary tumors with and without lymph-node metastasis, we identify alterations associated with metastasis, including amplifications of 3p26.3, 8q24.21, 11q22.1, 11q22.3 and deletion of 8p23.2. Integrative analysis reveals several biomarkers that have never or rarely been reported in previous OSCC studies, including amplifications of 1p36.33 (attributable to MXRA8, 3q26.31 (EIF5A2, 9p24.1 (CD274, and 12q13.2 (HOXC9 and HOXC13. Additionally, we find that amplifications of 1p36.33 and 11q22.1 are strongly correlated with poor clinical outcome. Overall, our findings delineate genomic changes that can be used in treatment management for patients with potentially malignant leukoplakia and OSCC patients with higher risk of lymph-node metastasis.

  7. Hypergravity-induced altered behavior in Drosophila

    Science.gov (United States)

    Hosamani, Ravikumar; Wan, Judy; Marcu, Oana; Bhattacharya, Sharmila

    2012-07-01

    Microgravity and mechanical stress are important factors of the spaceflight environment, and affect astronaut health and behavior. Structural, functional, and behavioral mechanisms of all cells and organisms are adapted to Earth's gravitational force, 1G, while altered gravity can pose challenges to their adaptability to this new environment. On ground, hypergravity paradigms have been used to predict and complement studies on microgravity. Even small changes that take place at a molecular and genetic level during altered gravity may result in changes in phenotypic behavior. Drosophila provides a robust and simple, yet very reliable model system to understand the complexity of hypergravity-induced altered behavior, due to availability of a plethora of genetic tools. Locomotor behavior is a sensitive parameter that reflects the array of molecular adaptive mechanisms recruited during exposure to altered gravity. Thus, understanding the genetic basis of this behavior in a hypergravity environment could potentially extend our understanding of mechanisms of adaptation in microgravity. In our laboratory we are trying to dissect out the cellular and molecular mechanisms underlying hypergravity-induced oxidative stress, and its potential consequences on behavioral alterations by using Drosophila as a model system. In the present study, we employed pan-neuronal and mushroom body specific knock-down adult flies by using Gal4/UAS system to express inverted repeat transgenes (RNAi) to monitor and quantify the hypergravity-induced behavior in Drosophila. We established that acute hypergravity (3G for 60 min) causes a significant and robust decrease in the locomotor behavior in adult Drosophila, and that this change is dependent on genes related to Parkinson's disease, such as DJ-1α , DJ-1β , and parkin. In addition, we also showed that anatomically the control of this behavior is significantly processed in the mushroom body region of the fly brain. This work links a molecular

  8. Neurochemical and behavioral characterization of neuronal glutamate transporter EAAT3 heterozygous mice

    Directory of Open Access Journals (Sweden)

    Luis F. González

    2017-10-01

    Full Text Available Abstract Background Obsessive–compulsive disorder (OCD is a severe neuropsychiatric condition affecting 1–3% of the worldwide population. OCD has a strong genetic component, and the SLC1A1 gene that encodes neuronal glutamate transporter EAAT3 is a strong candidate for this disorder. To evaluate the impact of reduced EAAT3 expression in vivo, we studied male EAAT3 heterozygous and wild-type littermate mice using a battery of behavioral paradigms relevant to anxiety (open field test, elevated plus maze and compulsivity (marble burying, as well as locomotor activity induced by amphetamine. Using high-performance liquid chromatography, we also determined tissue neurotransmitter levels in cortex, striatum and thalamus—brain areas that are relevant to OCD. Results Compared to wild-type littermates, EAAT3 heterozygous male mice have unaltered baseline anxiety-like, compulsive-like behavior and locomotor activity. Administration of acute amphetamine (5 mg/kg intraperitoneally increased locomotion with no differences across genotypes. Tissue levels of glutamate, GABA, dopamine and serotonin did not vary between EAAT3 heterozygous and wild-type mice. Conclusions Our results indicate that reduced EAAT3 expression does not impact neurotransmitter content in the corticostriatal circuit nor alter anxiety or compulsive-like behaviors.

  9. Geochemical behaviour of uranium in the cycle of alteration; Comportement geochimique de l'uranium dans le cycle d'alteration

    Energy Technology Data Exchange (ETDEWEB)

    Chervet, J; Coulomb, R [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires; Soudan, P [Centre d' Etude de Lalumine, Compagnie Pechiney (France)

    1958-07-01

    The investigation of the genesis of secondary mineralized accumulations, and the prospecting of deposits from microchemical anomalies in the surface material, is requiring a well-developed knowledge of the geochemical properties of the uranium during the alteration phase. In the present work, the authors tried to track the uranium history during a part of his natural creeping. a) They describe some most typical mineralogical observations of alteration phenomena and material migration, picked up in place on the deposits. b) They give experimental results concerning the solubilities of the uranium minerals and the factors affecting this solubility. c) They study the water circulation in granitic batholites, and the influence of the occurrence of the uranium deposits on their composition. d) They observe the amplitude of phenomena restricting the dispersions: fixations, precipitations, etc., and the behaviour of growth in uraniferous areas. e) Finally, the opposition chemical alteration-radioactive equilibrium results in an important imbalance in altered materials. The authors tried to use the measurement of this imbalance to explain geochemical processes. (author) [French] L'etude des conditions de genese des accumulations minerales secondaires, ainsi que la prospection des gisements a partir d'anomalies microchimiques dans les materiaux de surface, necessite une connaissance approfondie des proprietes geochimiques fondamentales de l'uranium dans la phase d'alteration. Nous essayons, dans ce travail, de suivre l'histoire de l'uranium dans une partie de son cheminement naturel. a) Nous decrivons quelques observations mineralogiques particulierement typiques de phenomenes d'alteration et de migration de matiere, prises 'in situ' dans les gisements. b) Nous donnons les resultats d'experiences de laboratoire sur les solubilites de mineraux d'uranium et sur les facteurs influen nt cette solubilite. c) Nous etudions les circulations d'eaux sur les massifs granitiques et

  10. Rare earth impact on glass structure and alteration kinetics

    International Nuclear Information System (INIS)

    Molieres, E.

    2012-01-01

    This work is related to the question of the geological deep repository of high-level waste glass. These wastes include fission products and minor actinides, elements which can be simulated by rare earths. As new glass compositions could enable increased rare earth concentrations, it is crucial to know and understand rare earth impact on glass structure on the one hand, and on glass alteration kinetics or their incorporation into an altered layer. This work studied simplified borosilicate glasses in order to limit synergetic effects between rare earths and other elements. Various complementary techniques were used to characterize pristine and altered glasses (solid-high resolution NMR, Raman spectroscopy, fluorescence, SIMS, SAXS). Firstly, the structural role of a rare earth is discussed and is compared to a calcium cation. The local environment of rare earths is also probed. Secondly, rare earth (nature and concentration) impact on several alteration regimes was studied (initial rate, rate drop). Then, after alteration, rare earth elements being retained within the altered layer, the structural impact of rare earth elements (and their local environment) in this alteration layer was also investigated. (author) [fr

  11. Do invasive plant species alter soil health?

    Science.gov (United States)

    Invasive species may alter soil characteristics or interact with the soil microbial community to yield a competitive advantage. Our objectives were to determine: if invasive plant species alter soil properties important to soil health; and the long-term effects of invasive plant species on soil pro...

  12. An Analysis of the Alteration Specialist Occupation.

    Science.gov (United States)

    Buerkel, Elaine; Rehling, Joseph H.

    The general purpose of the occupational analysis is to provide workable, basic information dealing with the many and varied duties performed in the textile service occupation. The industry needs properly trained alteration specialists, bushelmen and dressmakers, in the repairing, remodeling, altering or renovating of garments. Their personal…

  13. Smartphone-based assessment of blood alteration severity

    Science.gov (United States)

    Li, Xianglin; Xue, Jiaxin; Li, Wei; Li, Ting

    2018-02-01

    Blood quality and safety management is a critical issue for cold chain transportation of blood or blood-based biological reagent. The conventional methods of blood alteration severity assessment mainly rely on kit test or blood-gas analysis required opening the blood package to get samples, which cause possible blood pollution and are complicate, timeconsuming, and expensive. Here we proposed to develop a portable, real-time, safety, easy-operated and low cost method aimed at assessing blood alteration severity. Color images of the blood in transparent blood bags were collected with a smartphone and the alteration severity of the blood was assessed by the smartphone app offered analysis of RGB color values of the blood. The algorithm is based on a large number sample of RGB values of blood at different alteration degree. The blood quality results evaluated by the smartphone are in accordance with the actual data. This study indicates the potential of smart phone in real time, convenient, and reliable blood quality assessment.

  14. Microenvironment alters epigenetic and gene expression profiles in Swarm rat chondrosarcoma tumors

    International Nuclear Information System (INIS)

    Hamm, Christopher A; Wang, Deli; Malchenko, Sergey; Fatima Bonaldo, Maria de; Casavant, Thomas L; Hendrix, Mary JC; Soares, Marcelo B; Stevens, Jeff W; Xie, Hehuang; Vanin, Elio F; Morcuende, Jose A; Abdulkawy, Hakeem; Seftor, Elisabeth A; Sredni, Simone T; Bischof, Jared M

    2010-01-01

    Chondrosarcomas are malignant cartilage tumors that do not respond to traditional chemotherapy or radiation. The 5-year survival rate of histologic grade III chondrosarcoma is less than 30%. An animal model of chondrosarcoma has been established - namely, the Swarm Rat Chondrosarcoma (SRC) - and shown to resemble the human disease. Previous studies with this model revealed that tumor microenvironment could significantly influence chondrosarcoma malignancy. To examine the effect of the microenvironment, SRC tumors were initiated at different transplantation sites. Pyrosequencing assays were utilized to assess the DNA methylation of the tumors, and SAGE libraries were constructed and sequenced to determine the gene expression profiles of the tumors. Based on the gene expression analysis, subsequent functional assays were designed to determine the relevancy of the specific genes in the development and progression of the SRC. The site of transplantation had a significant impact on the epigenetic and gene expression profiles of SRC tumors. Our analyses revealed that SRC tumors were hypomethylated compared to control tissue, and that tumors at each transplantation site had a unique expression profile. Subsequent functional analysis of differentially expressed genes, albeit preliminary, provided some insight into the role that thymosin-β4, c-fos, and CTGF may play in chondrosarcoma development and progression. This report describes the first global molecular characterization of the SRC model, and it demonstrates that the tumor microenvironment can induce epigenetic alterations and changes in gene expression in the SRC tumors. We documented changes in gene expression that accompany changes in tumor phenotype, and these gene expression changes provide insight into the pathways that may play a role in the development and progression of chondrosarcoma. Furthermore, specific functional analysis indicates that thymosin-β4 may have a role in chondrosarcoma metastasis

  15. Microenvironment alters epigenetic and gene expression profiles in Swarm rat chondrosarcoma tumors

    Directory of Open Access Journals (Sweden)

    Hamm Christopher A

    2010-09-01

    Full Text Available Abstract Background Chondrosarcomas are malignant cartilage tumors that do not respond to traditional chemotherapy or radiation. The 5-year survival rate of histologic grade III chondrosarcoma is less than 30%. An animal model of chondrosarcoma has been established - namely, the Swarm Rat Chondrosarcoma (SRC - and shown to resemble the human disease. Previous studies with this model revealed that tumor microenvironment could significantly influence chondrosarcoma malignancy. Methods To examine the effect of the microenvironment, SRC tumors were initiated at different transplantation sites. Pyrosequencing assays were utilized to assess the DNA methylation of the tumors, and SAGE libraries were constructed and sequenced to determine the gene expression profiles of the tumors. Based on the gene expression analysis, subsequent functional assays were designed to determine the relevancy of the specific genes in the development and progression of the SRC. Results The site of transplantation had a significant impact on the epigenetic and gene expression profiles of SRC tumors. Our analyses revealed that SRC tumors were hypomethylated compared to control tissue, and that tumors at each transplantation site had a unique expression profile. Subsequent functional analysis of differentially expressed genes, albeit preliminary, provided some insight into the role that thymosin-β4, c-fos, and CTGF may play in chondrosarcoma development and progression. Conclusion This report describes the first global molecular characterization of the SRC model, and it demonstrates that the tumor microenvironment can induce epigenetic alterations and changes in gene expression in the SRC tumors. We documented changes in gene expression that accompany changes in tumor phenotype, and these gene expression changes provide insight into the pathways that may play a role in the development and progression of chondrosarcoma. Furthermore, specific functional analysis indicates that

  16. Aging and sex influence the permeability of the blood-brain barrier in the rat

    International Nuclear Information System (INIS)

    Saija, A.; Princi, P.; D'Amico, N.; De Pasquale, R.; Costa, G.

    1990-01-01

    The aim of the present study was to investigate the existence of aging- and sex-related alterations in the permeability of the blood-brain barrier (BBB) in the rat, by calculating a unidirectional blood-to-brain transfer constant (Ki) for the circulating tracer [ 14 C]-α-aminoisobutyric acid. The authors observed that: (a) the permeability of the BBB significantly increased within the frontal and temporo-parietal cortex, hypothalamus and cerebellum in 28-30 week old rats, in comparison with younger animals; (b) in several brain areas of female intact rats higher Ki values (even though not significantly different) were calculated at oestrus than at proestrus; (c) in 1-week ovariectomized rats there was a marked increase of Ki values at the level of the frontal, temporo-parietal and occipital cortex, cerebellum and brain-stem. One can speculate that aging and sex-related alterations in thee permeability of the BBB reflect respectively changes in brain neurochemical system activity and in plasma steroid hormone levels

  17. Delayed recall of childhood sexual abuse memories and the awakening rise and diurnal pattern of cortisol.

    Science.gov (United States)

    Smeets, Tom; Geraerts, Elke; Jelicic, Marko; Merckelbach, Harald

    2007-08-30

    Traumatic stress associated with childhood sexual abuse (CSA) may result in chronic alterations of stress-sensitive neurochemical systems (e.g., the hypothalamic-pituitary-adrenal axis and sympathetic-adrenal medullary activity). Some authors have suggested that these alterations might help explain why some individuals, after a period of inability to remember, demonstrate delayed recall of CSA memories (i.e., "recovered" memories). The present study is the first study that explored morning cortisol responses and circadian cortisol profiles among women with recovered (n=7), repressed (n=8), or continuous (n=6) memories of CSA and women without a history of CSA (n=9). Although there were group differences in current depression and post-traumatic stress symptoms, we found no differences in cortisol awakening response or daytime profile between women reporting recovered, repressed, or continuous memories of CSA as compared to women without a history of CSA. Implications for neurobiological models intended to explain the delayed recall of CSA are discussed.

  18. Hydrothermal alteration at Roosevelt Hot Springs KGRA - DDH 1976-1

    Energy Technology Data Exchange (ETDEWEB)

    Bryant, N.L.; Parry, W.T.

    1977-09-01

    Hot waters of the Roosevelt Thermal Area, Utah, have altered granitic rocks and detritus of the Mineral Range pluton, Utah. Petrographic, x-ray, and chemical methods were used to characterize systematic changes in chemistry and mineralogy. Major alteration zones include: 1) an advanced argillic zone in the upper 30 feet of altered detritus containing alunite, opal, vermiculite, and relic quartz; 2) an argillic zone from 30 feet to 105 feet containing kaolinite, muscovite, and minor alunite; and 3) a propylitic zone from 105 to 200 feet containing muscovite, pyrite, marcasite, montmorillonite, and chlorite in weakly altered quartz monzonite. Comparison of the alternation mineral assemblages with known water chemistry and equilibrium activity diagrams suggests that a simple solution equilibrium model cannot account for the alteration. A model is proposed in which upward moving thermal water supersaturated with respect to quartz and a downward moving cool water undersaturated with respect to quartz produces the observed alteration. An estimate of the heat flow contributions from hydrothermal alteration was made by calculating reaction enthalpies for alteration reactions at each depth.

  19. 46 CFR 115.700 - Permission for repairs and alterations.

    Science.gov (United States)

    2010-10-01

    ... replacement in kind, of electrical wiring, fuel lines, tanks, boilers and other pressure vessels, and steering... 46 Shipping 4 2010-10-01 2010-10-01 false Permission for repairs and alterations. 115.700 Section... AND CERTIFICATION Repairs and Alterations § 115.700 Permission for repairs and alterations. (a...

  20. Streamflow alteration at selected sites in Kansas

    Science.gov (United States)

    Juracek, Kyle E.; Eng, Ken

    2017-06-26

    An understanding of streamflow alteration in response to various disturbances is necessary for the effective management of stream habitat for a variety of species in Kansas. Streamflow alteration can have negative ecological effects. Using a modeling approach, streamflow alteration was assessed for 129 selected U.S. Geological Survey streamgages in the State for which requisite streamflow and basin-characteristic information was available. The assessment involved a comparison of the observed condition from 1980 to 2015 with the predicted expected (least-disturbed) condition for 29 streamflow metrics. The metrics represent various characteristics of streamflow including average flow (annual, monthly) and low and high flow (frequency, duration, magnitude).Streamflow alteration in Kansas was indicated locally, regionally, and statewide. Given the absence of a pronounced trend in annual precipitation in Kansas, a precipitation-related explanation for streamflow alteration was not supported. Thus, the likely explanation for streamflow alteration was human activity. Locally, a flashier flow regime (typified by shorter lag times and more frequent and higher peak discharges) was indicated for three streamgages with urbanized basins that had higher percentages of impervious surfaces than other basins in the State. The combination of localized reservoir effects and regional groundwater pumping from the High Plains aquifer likely was responsible, in part, for diminished conditions indicated for multiple streamflow metrics in western and central Kansas. Statewide, the implementation of agricultural land-management practices to reduce runoff may have been responsible, in part, for a diminished duration and magnitude of high flows. In central and eastern Kansas, implemented agricultural land-management practices may have been partly responsible for an inflated magnitude of low flows at several sites.

  1. Effects of environmental enrichment on behavioral deficits and alterations in hippocampal BDNF induced by prenatal exposure to morphine in juvenile rats.

    Science.gov (United States)

    Ahmadalipour, A; Sadeghzadeh, J; Vafaei, A A; Bandegi, A R; Mohammadkhani, R; Rashidy-Pour, A

    2015-10-01

    Prenatal morphine exposure throughout pregnancy can induce a series of neurobehavioral and neurochemical disturbances by affecting central nervous system development. This study was designed to investigate the effects of an enriched environment on behavioral deficits and changes in hippocampal brain-derived neurotrophic factor (BDNF) levels induced by prenatal morphine in rats. On pregnancy days 11-18, female Wistar rats were randomly injected twice daily with saline or morphine. Offspring were weaned on postnatal day (PND) 21. They were subjected to a standard rearing environment or an enriched environment on PNDs 22-50. On PNDs 51-57, the behavioral responses including anxiety and depression-like behaviors, and passive avoidance memory as well as hippocampal BDNF levels were investigated. The light/dark (L/D) box and elevated plus maze (EPM) were used for the study of anxiety, forced swimming test (FST) was used to assess depression-like behavior and passive avoidance task was used to evaluate learning and memory. Prenatal morphine exposure caused a reduction in time spent in the EPM open arms and a reduction in time spent in the lit side of the L/D box. It also decreased step-through latency and increased time spent in the dark side of passive avoidance task. Prenatal morphine exposure also reduced immobility time and increased swimming time in FST. Postnatal rearing in an enriched environment counteracted with behavioral deficits in the EPM and passive avoidance task, but not in the L/D box. This suggests that exposure to an enriched environment during adolescence period alters anxiety profile in a task-specific manner. Prenatal morphine exposure reduced hippocampal BDNF levels, but enriched environment significantly increased BDNF levels in both saline- and morphine-exposed groups. Our results demonstrate that exposure to an enriched environment alleviates behavioral deficits induced by prenatal morphine exposure and up-regulates the decreased levels of BDNF

  2. Tectonic resemblance of the Indian Platform, Pakistan with the Moesian Platform, Romania and strategy for exploration of hydrocarbons

    International Nuclear Information System (INIS)

    Memon, A.D.

    1994-01-01

    There is a remarkable tectonic resemblance between the indian Platform (Pakistan) and the Moesian Platform (Romania). As viewed in global tectonic perspective Moeslan and Indian Plates have played important role in Alpine Himalayan Orogeny; Moesian and Indian Platforms are extension of these respective plates. Characteristics features of both the platforms are block faulting which has effected not only the general tectonic framework but has also played important role in oil accumulation. Main producing rocks in the Moesian platform are Jurassic sandstones and cretaceous limestones while in the indian platform cretaceous sandstones are important reservoirs. The average geothermal gradient in the indian platform is 2.45 C/100m with the higher gradients in the central gas producing region. Geothermal gradients in the Moesian platform have an average value of 3 C/100m with higher gradients in the northern in the northern part. Some of the producing structures in both the platforms are remarkably similar, traps associated with normal faults are very important. Extensive exploration carried in the Moesian Platform makes it very important oil producing region of Romania. After the discovery of oil lower Sindh, serious exploration is being carried in the Indian platform. The paper deals with the similarities between these two important platforms. In the light of the studies of the Moesian platform, strategies or exploration of oil and gas in the Indian Platform are suggested. (author)

  3. The role of prefrontal catecholamines in attention and working memory

    Directory of Open Access Journals (Sweden)

    Behrad eNoudoost

    2014-04-01

    Full Text Available While much progress has been made in identifying the brain regions and neurochemical systems involved in the cognitive processes disrupted in mental illnesses, To date, the level of detail at which neurobiologists can describe the chain of events giving rise to cognitive functions is very rudimentary. Much of the intense interest in understanding cognitive functions is motivated by the hope that it might be possible to understand these complex functions at the level of neurons and neural circuits. Here, we review the current state of the literature regarding how modulations in catecholamine levels within the prefrontal cortex alter the neuronal and behavioral correlates of cognitive functions, particularly attention and working memory.

  4. The role of prefrontal catecholamines in attention and working memory

    Science.gov (United States)

    Clark, Kelsey L.; Noudoost, Behrad

    2014-01-01

    While much progress has been made in identifying the brain regions and neurochemical systems involved in the cognitive processes disrupted in mental illnesses, to date, the level of detail at which neurobiologists can describe the chain of events giving rise to cognitive functions is very rudimentary. Much of the intense interest in understanding cognitive functions is motivated by the hope that it might be possible to understand these complex functions at the level of neurons and neural circuits. Here, we review the current state of the literature regarding how modulations in catecholamine levels within the prefrontal cortex (PFC) alter the neuronal and behavioral correlates of cognitive functions, particularly attention and working memory. PMID:24782714

  5. ARID1B alterations identify aggressive tumors in neuroblastoma.

    Science.gov (United States)

    Lee, Soo Hyun; Kim, Jung-Sun; Zheng, Siyuan; Huse, Jason T; Bae, Joon Seol; Lee, Ji Won; Yoo, Keon Hee; Koo, Hong Hoe; Kyung, Sungkyu; Park, Woong-Yang; Sung, Ki W

    2017-07-11

    Targeted panel sequencing was performed to determine molecular targets and biomarkers in 72 children with neuroblastoma. Frequent genetic alterations were detected in ALK (16.7%), BRCA1 (13.9%), ATM (12.5%), and PTCH1 (11.1%) in an 83-gene panel. Molecular targets for targeted therapy were identified in 16 of 72 patients (22.2%). Two-thirds of ALK mutations were known to increase sensitivity to ALK inhibitors. Sequence alterations in ARID1B were identified in 5 of 72 patients (6.9%). Four of five ARID1B alterations were detected in tumors of high-risk patients. Two of five patients with ARID1B alterations died of disease progression. Relapse-free survival was lower in patients with ARID1B alterations than in those without (p = 0.01). In analysis confined to high-risk patients, 3-year overall survival was lower in patients with an ARID1B alteration (33.3 ± 27.2%) or MYCN amplification (30.0 ± 23.9%) than in those with neither ARID1B alteration nor MYCN amplification (90.5 ± 6.4%, p = 0.05). These results provide possibilities for targeted therapy and a new biomarker identifying a subgroup of neuroblastoma patients with poor prognosis.

  6. Hydrothermal Alteration of the Mt Unzen Conduit (Shimabara/Japan)

    Science.gov (United States)

    Yilmaz, T. I.; Mayer, K.; Hess, K. U.; Janots, E.; Gilg, H. A.; Dingwell, D. B.

    2016-12-01

    Investigations were carried out on hydrothermally altered coherent dacitic dykes samples from (USDP-4) drill core at Mt Unzen stratovolcano (Shimabara/Japan). XRF, XRD, EMPA, and C-O-isotope analysis led to insights concerning chemistry, mineralogy, and intensity of alteration as well as the origin of carbonate-precipitating fluids. Additionally a textural characterization of the occurring replacement features in the magma conduit zone was performed. The occurrence of the main secondary phases such as chlorite, pyrite, carbonates, and R1 (Reichweite parameter) illite-smectite indicate a weak to moderate propylitic to phyllic hydrothermal alteration. The dacitic samples of the dykes show different hydrothermal alteration features: (i) carbonate pseudomorphs after hornblende as well as core and zonal textures due to replacement of plagioclase by R1 illite-smectite, (ii) colloform banded fracture fillings and fillings in dissolution vugs, and (iii) chlorite and R1 illite-smectite in the groundmass. Carbonates in fractures comprise iron-rich dolomite solid solutions ("ankerite") and calcite. Isotopic values of d13Cvpdb = -4.59 ± 0.6‰ and d18Ovpdb = -21.73 ± 0.5‰ indicate a hydrothermal-magmatic origin for the carbonate formation. The chlorite-carbonate-pyrite index (CCPI) and the Ishikawa alteration index (AI), applied to the investigated samples show significant differences (CCPI=52.7-57.8; AI=36.1-40.6) indicating their different degree of alteration. According to Nakada et al., 2005, the C13 to C16 dykes represent the feeder dyke from the latest eruption (1991-1995) whereas C8 represents an earlier dyke feeder dyke from an older eruption. Weakest conduit alteration, which was obtained in samples C16-1-5 and C13-2-5, correlates with the alteration degree of the pristine dome rocks. Highest CCPI value was determined for sample C14-1-5 and the highest AI value was determined for sample C15-2-6. The degrees of alteration do not indicate highest alteration of the

  7. Buccal alterations in diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Negrato Carlos

    2010-01-01

    Full Text Available Abstract Long standing hyperglycaemia besides damaging the kidneys, eyes, nerves, blood vessels, heart, can also impair the function of the salivary glands leading to a reduction in the salivary flow. When salivary flow decreases, as a consequence of an acute hyperglycaemia, many buccal or oral alterations can occur such as: a increased concentration of mucin and glucose; b impaired production and/or action of many antimicrobial factors; c absence of a metalloprotein called gustin, that contains zinc and is responsible for the constant maturation of taste papillae; d bad taste; e oral candidiasis f increased cells exfoliation after contact, because of poor lubrication; g increased proliferation of pathogenic microorganisms; h coated tongue; i halitosis; and many others may occur as a consequence of chronic hyperglycaemia: a tongue alterations, generally a burning mouth; b periodontal disease; c white spots due to demineralization in the teeth; d caries; e delayed healing of wounds; f greater tendency to infections; g lichen planus; h mucosa ulcerations. Buccal alterations found in diabetic patients, although not specific of this disease, have its incidence and progression increased when an inadequate glycaemic control is present.

  8. Buccal alterations in diabetes mellitus.

    Science.gov (United States)

    Negrato, Carlos Antonio; Tarzia, Olinda

    2010-01-15

    Long standing hyperglycaemia besides damaging the kidneys, eyes, nerves, blood vessels, heart, can also impair the function of the salivary glands leading to a reduction in the salivary flow. When salivary flow decreases, as a consequence of an acute hyperglycaemia, many buccal or oral alterations can occur such as: a) increased concentration of mucin and glucose; b) impaired production and/or action of many antimicrobial factors; c) absence of a metalloprotein called gustin, that contains zinc and is responsible for the constant maturation of taste papillae; d) bad taste; e) oral candidiasis f) increased cells exfoliation after contact, because of poor lubrication; g) increased proliferation of pathogenic microorganisms; h) coated tongue; i) halitosis; and many others may occur as a consequence of chronic hyperglycaemia: a) tongue alterations, generally a burning mouth; b) periodontal disease; c) white spots due to demineralization in the teeth; d) caries; e) delayed healing of wounds; f) greater tendency to infections; g) lichen planus; h) mucosa ulcerations. Buccal alterations found in diabetic patients, although not specific of this disease, have its incidence and progression increased when an inadequate glycaemic control is present.

  9. Alter(n – ein vielschichtiger Begriff

    Directory of Open Access Journals (Sweden)

    Nicole Maly-Lukas

    2005-07-01

    Full Text Available Diese Veröffentlichung, die aus einer Vortragsreihe an der katholischen Fachhochschule Freiburg entstanden ist, führt die Leserinnen und Leser in die verschiedenen Sichtweisen des Alter(ns in der modernen Gesellschaft ein. Es handelt sich um eine gelungene Zusammenstellung von Beiträgen aus unterschiedlichen Disziplinen, die sich alle aus ihrer Sicht dem Thema Alter(n widmen. Die einzelnen Artikel sind zwischen 8 und 38 Seiten lang und recht schnell und einfach zu lesen. Je nach Hintergrund und Interessen werden die einzelnen Leserinnen und Leser dabei sicher unterschiedliche Beiträge favorisieren. Schade ist nur, dass durch die ungleichen Längen der Beiträge bestimmte thematische Schwerpunkte – ob gewollt oder nicht – gesetzt werden. Dies sollte die Leserinnen und Leser, die offen für unterschiedlichste Sichtweisen des Alter(ns sind, jedoch nicht davon abhalten, dieses Buch zu lesen.

  10. Impairment of lysophospholipid metabolism in obesity: altered plasma profile and desensitization to the modulatory properties of n-3 polyunsaturated fatty acids in a randomized controlled trial.

    Science.gov (United States)

    Del Bas, Josep M; Caimari, Antoni; Rodriguez-Naranjo, Maria Isabel; Childs, Caroline E; Paras Chavez, Carolina; West, Annette L; Miles, Elizabeth A; Arola, Lluis; Calder, Philip C

    2016-08-01

    Plasma lysophospholipids have emerged as signaling molecules with important effects on inflammation, insulin resistance, and fatty liver disease, each of which is linked closely to obesity. Dietary n-3 (ω-3) polyunsaturated fatty acids (PUFAs) may be able to improve these conditions. The objective of this study was to assess the response of plasma lysophospholipids to obesity, n-3 PUFA consumption, and a high-fat meal challenge to better understand the role of lysophospholipid metabolism in the progression of obesity-related disorders. We determined the concentrations of 8 lysophosphatidylcholines, 11 lysophosphatidylethanolamines, and 7 lysophosphatidylinositols in the plasma of 34 normal-weight and 38 obese subjects randomly assigned to consume corn oil (control) or n-3 PUFA-rich fish oil (3 g/d; n = 15-19/group) for 90 d. Blood samples were collected on the last day of the study under fasting conditions and 6 h after a high-fat meal (1135 kcal, 86 g fat) challenge. The profile of secreted lysophospholipids was studied in HepG2 cells under palmitate-induced steatosis. Obese and normal-weight subjects had different profiles of plasma lysophospholipids. A multivariate combination of the 26 lysophospholipids could discriminate between normal-weight and obese subjects with an accuracy of 98%. The high-fat meal challenge altered the concentration of plasma lysophosphatidylcholines in an oil treatment-dependent manner in normal-weight but not obese subjects, suggesting that obesity impairs the sensitivity of lysophospholipid metabolism to n-3 PUFAs. Noncytotoxic steatosis in HepG2 cells affected the secretion pattern of lysophospholipids, partially resembling the changes observed in the plasma of obese subjects. Obesity has a substantial impact on lysophospholipid metabolism, altering the plasma lysophospholipid profile and abolishing its sensitivity to dietary n-3 PUFAs. These effects could contribute to the onset or progression of alterations associated with obesity

  11. CADDIS Volume 2. Sources, Stressors and Responses: Flow Alteration - Detailed Conceptual Diagram

    Science.gov (United States)

    Introduction to the flow alteration module, when to list flow alteration as a candidate cause, ways to measure flow alteration, simple and detailed conceptual model diagrams for flow alteration, flow alteration module references and literature reviews.

  12. CADDIS Volume 2. Sources, Stressors and Responses: Flow Alteration - Simple Conceptual Diagram

    Science.gov (United States)

    Introduction to the flow alteration module, when to list flow alteration as a candidate cause, ways to measure flow alteration, simple and detailed conceptual model diagrams for flow alteration, flow alteration module references and literature reviews.

  13. State-related alterations of gene expression in bipolar disorder

    DEFF Research Database (Denmark)

    Munkholm, Klaus; Vinberg, Maj; Berk, Michael

    2012-01-01

    Munkholm K, Vinberg M, Berk M, Kessing LV. State-related alterations of gene expression in bipolar disorder: a systematic review. Bipolar Disord 2012: 14: 684-696. © 2012 The Authors. Journal compilation © 2012 John Wiley & Sons A/S. Objective:  Alterations in gene expression in bipolar disorder...... have been found in numerous studies. It is unclear whether such alterations are related to specific mood states. As a biphasic disorder, mood state-related alterations in gene expression have the potential to point to markers of disease activity, and trait-related alterations might indicate...... vulnerability pathways. This review therefore evaluated the evidence for whether gene expression in bipolar disorder is state or trait related. Methods:  A systematic review, using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guideline for reporting systematic reviews, based...

  14. Roentgenological findings in muscular alterations of extremities

    International Nuclear Information System (INIS)

    Palvoelgyi, R.

    1978-01-01

    A survey of roentgenological findings in muscular alterations of extremities based on the author's experiences and on the literature is presented. Following a description of the normal roentgen anatomy, the alterations in different diseases of interstitial lipomatosis are demonstrated. By roentgenological examinations differt muscular lesions of the extremities can be differentiated and the clinical follow-up verified. (orig.) [de

  15. Antiherbivore defenses alter natural selection on plant reproductive traits.

    Science.gov (United States)

    Thompson, Ken A; Johnson, Marc T J

    2016-04-01

    While many studies demonstrate that herbivores alter selection on plant reproductive traits, little is known about whether antiherbivore defenses affect selection on these traits. We hypothesized that antiherbivore defenses could alter selection on reproductive traits by altering trait expression through allocation trade-offs, or by altering interactions with mutualists and/or antagonists. To test our hypothesis, we used white clover, Trifolium repens, which has a Mendelian polymorphism for the production of hydrogen cyanide-a potent antiherbivore defense. We conducted a common garden experiment with 185 clonal families of T. repens that included cyanogenic and acyanogenic genotypes. We quantified resistance to herbivores, and selection on six floral traits and phenology via male and female fitness. Cyanogenesis reduced herbivory but did not alter the expression of reproductive traits through allocation trade-offs. However, the presence of cyanogenic defenses altered natural selection on petal morphology and the number of flowers within inflorescences via female fitness. Herbivory influenced selection on flowers and phenology via female fitness independently of cyanogenesis. Our results demonstrate that both herbivory and antiherbivore defenses alter natural selection on plant reproductive traits. We discuss the significance of these results for understanding how antiherbivore defenses interact with herbivores and pollinators to shape floral evolution. © 2016 The Author(s). Evolution © 2016 The Society for the Study of Evolution.

  16. Bacillus subtilis alters the proportion of major membrane phospholipids in response to surfactin exposure.

    Science.gov (United States)

    Uttlová, Petra; Pinkas, Dominik; Bechyňková, Olga; Fišer, Radovan; Svobodová, Jaroslava; Seydlová, Gabriela

    2016-12-01

    Surfactin, an anionic lipopeptide produced by Bacillus subtilis, is an antimicrobial that targets the cytoplasmic membrane. Nowadays it appears increasingly apparent that the mechanism of resistance against these types of antibiotics consists of target site modification. This prompted us to investigate whether the surfactin non-producing strain B. subtilis 168 changes its membrane composition in response to a sublethal surfactin concentration. Here we show that the exposure of B. subtilis to surfactin at concentrations of 350 and 650 μg/ml (designated as SF350 and SF650, respectively) leads to a concentration-dependent growth arrest followed by regrowth with an altered growth rate. Analysis of the membrane lipid composition revealed modifications both in the polar head group and the fatty acid region. The presence of either surfactin concentration resulted in a reduction in the content of the major membrane phospholipid phosphatidylglycerol (PG) and increase in phosphatidylethanolamine (PE), which was accompanied by elevated levels of phosphatidic acid (PA) in SF350 cultures. The fatty acid analysis of SF350 cells showed a marked increase in non-branched high-melting fatty acids, which lowered the fluidity of the membrane interior measured as the steady-state fluorescence anisotropy of DPH. The liposome leakage of carboxyfluorescein-loaded vesicles resembling the phospholipid composition of surfactin-adapted cells showed that the susceptibility to surfactin-induced leakage is strongly reduced when the PG/PE ratio decreases and/or PA is included in the target bilayer. We concluded that the modifications of the phospholipid content of B. subtilis cells might provide a self-tolerance of the membrane active surfactin. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Antagonist effects of calcium on borosilicate glass alteration

    Energy Technology Data Exchange (ETDEWEB)

    Mercado-Depierre, S. [CEA Marcoule, DTCD SPDE LCLT, 30207 Bagnols sur Cèze (France); Angeli, F., E-mail: frederic.angeli@cea.fr [CEA Marcoule, DTCD SPDE LCLT, 30207 Bagnols sur Cèze (France); Frizon, F. [CEA Marcoule, DTCD SECM LP2C, 30207 Bagnols sur Cèze (France); Gin, S. [CEA Marcoule, DTCD SPDE LCLT, 30207 Bagnols sur Cèze (France)

    2013-10-15

    Graphical abstract: Display Omitted -- Highlights: •Kinetic study of glass alteration is investigated in calcium-enriched solutions. •New insights into silicon–calcium interactions in glass/cement systems are proposed. •Glass alteration is controlled by pH, Ca concentration and reaction progress. •Evidence of antagonist effects according to the importance of these parameters. -- Abstract: Numerous studies have been conducted on glass and cement durability in contact with water, but very little work to date has focused directly on interactions between the two materials. These interactions are mostly controlled by silicon–calcium reactivity. However, the physical and chemical processes involved remain insufficiently understood to predict the evolution of coupled glass–cement systems used in several industrial applications. Results are reported from borosilicate glass alteration in calcium-rich solutions. Our data show that four distinct behaviors can be expected according to the relative importance of three key parameters: the pH, the reaction progress (short- or long-term alteration) and the calcium concentration. Glass alteration is thus controlled by specific mechanisms depending on the solution chemistry: calcium complexation at the glass surface, precipitation of calcium silicate hydrates (C–S–H) or calcium incorporation in the altered layer. These findings highlight the impact of silicon–calcium interactions on glass durability and open the way for a better understanding of glass–cement mixing in civil engineering applications as well as in nuclear waste storage.

  18. Antagonist effects of calcium on borosilicate glass alteration

    International Nuclear Information System (INIS)

    Mercado-Depierre, S.; Angeli, F.; Frizon, F.; Gin, S.

    2013-01-01

    Graphical abstract: Display Omitted -- Highlights: •Kinetic study of glass alteration is investigated in calcium-enriched solutions. •New insights into silicon–calcium interactions in glass/cement systems are proposed. •Glass alteration is controlled by pH, Ca concentration and reaction progress. •Evidence of antagonist effects according to the importance of these parameters. -- Abstract: Numerous studies have been conducted on glass and cement durability in contact with water, but very little work to date has focused directly on interactions between the two materials. These interactions are mostly controlled by silicon–calcium reactivity. However, the physical and chemical processes involved remain insufficiently understood to predict the evolution of coupled glass–cement systems used in several industrial applications. Results are reported from borosilicate glass alteration in calcium-rich solutions. Our data show that four distinct behaviors can be expected according to the relative importance of three key parameters: the pH, the reaction progress (short- or long-term alteration) and the calcium concentration. Glass alteration is thus controlled by specific mechanisms depending on the solution chemistry: calcium complexation at the glass surface, precipitation of calcium silicate hydrates (C–S–H) or calcium incorporation in the altered layer. These findings highlight the impact of silicon–calcium interactions on glass durability and open the way for a better understanding of glass–cement mixing in civil engineering applications as well as in nuclear waste storage

  19. Acetylene Resembling Effect of Ethylene on Seed Germination: Evaluating the Effect of Acetylene Released from Calcium Carbide

    Directory of Open Access Journals (Sweden)

    Kambiz MASHAYEKHI

    2015-09-01

    Full Text Available Some vegetable seeds need a very long time to germinate. In these kinds of seeds the second phase of germination is very long. As acetylene’s chemical structure is almost similar to the gaseous hormone ethylene, its’ physiological effect on seed germination should be very similar as well. Therefore, an experiment was established in order to enhance seed germination, by treating seeds with acetylene released from interaction of calcium carbide (CaC2 with water (H2O. A simple system was designed for efficient and proper use of gaseous acetylene resulted from the two substrates interaction, which conducted the produced gas obtained inside the interaction chamber into a sealed container wherein seeds were floating in water. This experiment aimed to evaluate the effect of one concentration of acetylene with different exposure periods (between 1 to 8 hours on parsley, celery and Swees chard seeds’ germination (chosen as late germinating vegetables. The effect of acetylene on seed germination speed and percent was investigated. There were significant differences in both percent and speed of germination within the various treatments. By floating for 3, 5 and 3 hours for parsley, celery and Swiss chard respectively, the highest germination rates were observed. The highest germination speed was achieved by 5, 5 and 3 hours floating respectively for parsley, celery and Swiss chard. Based on the results obtained, the current experiment suggests that acetylene has positive effect on enhancing seed germination of named vegetables, and played the role of ethylene, its effects resembling in regard to seed germination process.

  20. Geothermal alteration of clay minerals and shales: diagenesis

    Energy Technology Data Exchange (ETDEWEB)

    Weaver, C.E.

    1979-07-01

    The objective of this report is to perform a critical review of the data on the mineral and chemical alterations that occur during diagenesis and low-grade metamorphism of shale and other clay-rich rocks - conditions similar to those expected from emplacement of heat-producing radioactive waste in a geologic repository. The conclusions drawn in this document are that the following type of alterations could occur: smectite alteration, ion mobilization, illitic shales, kaolinite reactions, chlorite reactions, organic reactions, paleotemperatures, low temperature shales, high temperature shales, and phase equilibrium changes.

  1. Geothermal alteration of clay minerals and shales: diagenesis

    International Nuclear Information System (INIS)

    Weaver, C.E.

    1979-07-01

    The objective of this report is to perform a critical review of the data on the mineral and chemical alterations that occur during diagenesis and low-grade metamorphism of shale and other clay-rich rocks - conditions similar to those expected from emplacement of heat-producing radioactive waste in a geologic repository. The conclusions drawn in this document are that the following type of alterations could occur: smectite alteration, ion mobilization, illitic shales, kaolinite reactions, chlorite reactions, organic reactions, paleotemperatures, low temperature shales, high temperature shales, and phase equilibrium changes

  2. The genetic alteration of p53 in esophageal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Jae Il; Baik, Hee Jong; Kim, Chang Min; Kim, Mi Hee [Korea Cancer Center Hospital, Seoul (Korea, Republic of)

    1996-01-01

    Genetic alterations in the p53 gene have been detected in various human malignancies, and its alterations inactive the function of p53 as a tumor suppressor. Point mutation and gene deletion are the main mechanisms of p53 inactivation. To determine the incidence of genetic alteration of p53 and their clinical implications in Korean patients of esophageal cancer, we investigated p53 alterations in 26 esophageal cancer tissues paired with its normal tissue by Southern blot analysis, PCR-SSCP, and direct sequencing. Allelic loss of chromosome 17p occurred in 12 out of 21 informative cases(57%) by Southern blot analysis, and 16 cases showed mobility shift in PCR-SSCP, so overall incidence of p53 gene alterations was 77%(20/26). The mutations detected was randomly dispersed over exon4-8 and was frequently G-T transversion and C:T transitions. Three identical mutations were clustered at codon 213 suggested the same etiologic agents in this cases. The p53 gene alterations play a significant role in the development of esophageal cancers, however, no relationship between p53 mutation and clinical data was detected so far. 9 refs. (Author).

  3. Analysis of SHIP1 expression and activity in Crohn’s disease patients

    NARCIS (Netherlands)

    R. Somasundaram (Rajesh); S. Fernandes (Sandra); J.J. Deuring (Jasper); C.J. de Haar (Colin); E.J. Kuipers (Ernst); L. Vogelaar (Lauran); F.A. Middleton (Frank A.); C.J. van der Woude (Janneke); M.P. Peppelenbosch (Maikel); W.G. Kerr (William ); G.M. Fuhler (Gwenny)

    2017-01-01

    markdownabstract_Background_ SH2 domain containing inositol-5-phosphatase (SHIP1) is an important modulator of innate and adaptive immunity. In mice, loss of SHIP1 provokes severe ileitis resembling Crohn's disease (CD), as a result of deregulated immune responses, altered cytokine

  4. Ceramide profile in hypohidrotic ectodermal dysplasia

    DEFF Research Database (Denmark)

    Jungersted, J. M.; Høgh, Julie Kaae; Hellgren, Lars

    2012-01-01

    Background. Hypohidrotic ectodermal dysplasia (HED) is a rare genetic disease. The clinical presentation includes lack of sweating ability, and an often widely spread dermatitis resembling atopic dermatitis (AD). In AD, the skin‐barrier defect is partly ascribed to the altered lipid profile...

  5. Protective effect of Curcumin, the active principle of turmeric (Curcuma longa) in haloperidol-induced orofacial dyskinesia and associated behavioural, biochemical and neurochemical changes in rat brain.

    Science.gov (United States)

    Bishnoi, Mahendra; Chopra, Kanwaljit; Kulkarni, Shrinivas K

    2008-02-01

    Tardive dyskinesia (TD) is a motor disorder of the orofacial region resulting from chronic neuroleptic treatment. A high incidence and irreversibility of this hyperkinetic disorder has been considered a major clinical issue in the treatment of schizophrenia. The molecular mechanism related to the pathophysiology of tardive dyskinesia is not completely known. Various animal studies have demonstrated an enhanced oxidative stress and increased glutamatergic transmission as well as inhibition in the glutamate uptake after the chronic administration of haloperidol. The present study investigated the effect of curcumin, an antioxidant, in haloperidol-induced tardive dyskinesia by using different behavioural (orofacial dyskinetic movements, stereotypy, locomotor activity, % retention), biochemical (lipid peroxidation, reduced glutathione levels, antioxidant enzyme levels (SOD and catalase) and neurochemical (neurotransmitter levels) parameters. Chronic administration of haloperidol (1 mg/kg i.p. for 21 days) significantly increased vacuous chewing movements (VCM's), tongue protrusions, facial jerking in rats which was dose-dependently inhibited by curcumin. Chronic administration of haloperidol also resulted in increased dopamine receptor sensitivity as evident by increased locomotor activity and stereotypy and also decreased % retention time on elevated plus maze paradigm. Pretreatment with curcumin reversed these behavioral changes. Besides, haloperidol also induced oxidative damage in all major regions of brain which was attenuated by curcumin, especially in the subcortical region containing striatum. On chronic administration of haloperidol, there was a decrease in turnover of dopamine, serotonin and norepinephrine in both cortical and subcortical regions which was again dose-dependently reversed by treatment with curcumin. The findings of the present study suggested for the involvement of free radicals in the development of neuroleptic-induced tardive dyskinesia and

  6. Metabolic cost and mechanics of walking in women with fibromyalgia syndrome

    OpenAIRE

    MacPhee, Ren?e S; McFall, Kristen; Perry, Stephen D; Tiidus, Peter M

    2013-01-01

    Background Fibromyalgia syndrome (FS) is characterized by the presence of widespread pain, fatigue, muscle weakness and reduced work capacity. Previous research has demonstrated that women with fibromyalgia have altered walking (gait) patterns, which may be a consequence of muscular pain. This altered gait is characterized by greater reliance on hip flexors rather than ankle plantar flexors and resembles gait patterns seen in normal individuals walking at higher speeds, suggesting that gait o...

  7. Radiological forms of pneumonia appearing in ornithosis

    International Nuclear Information System (INIS)

    Soltz, G.; Simay, A.; Muennich, D.

    1980-01-01

    The clinical and radiological symptoms of ornithosis are reviewed. 102 patients were examined. In 80 cases radiological alterations were found in the lungs: in 78 cases reticular infiltrations and in two cases shadows resembling to milk-glass. In most cases the infiltration was localized in the basal segments. In three cases the alterations of the lungs were accompanied by enlarged lymph nodes in the hilus, and in six cases by intrapleural fluid. (L.E.)

  8. Effect of the novel synthetic cannabinoids AKB48 and 5F-AKB48 on "tetrad", sensorimotor, neurological and neurochemical responses in mice. In vitro and in vivo pharmacological studies.

    Science.gov (United States)

    Canazza, Isabella; Ossato, Andrea; Trapella, Claudio; Fantinati, Anna; De Luca, Maria Antonietta; Margiani, Giulia; Vincenzi, Fabrizio; Rimondo, Claudia; Di Rosa, Fabiana; Gregori, Adolfo; Varani, Katia; Borea, Pier Andrea; Serpelloni, Giovanni; Marti, Matteo

    2016-10-01

    AKB48 and its fluorinate derivate 5F-AKB48 are two novel synthetic cannabinoids belonging to a structural class with an indazole core structure. They are marketed as incense, herbal preparations or chemical supply for their psychoactive Cannabis-like effects. The present study was aimed at investigating the in vitro and in vivo pharmacological activity of AKB48 and 5F-AKB48 in male CD-1 mice and comparing their in vivo effects with those caused by the administration of Δ 9 -THC and JWH-018. In vitro competition binding experiments performed on mouse and human CB 1 and CB 2 receptors revealed a nanomolar affinity and potency of the AKB48 and 5F-AKB48. In vivo studies showed that AKB48 and 5F-AKB48, induced hypothermia, increased pain threshold to both noxious mechanical and thermal stimuli, caused catalepsy, reduced motor activity, impaired sensorimotor responses (visual, acoustic and tactile), caused seizures, myoclonia, hyperreflexia and promoted aggressiveness in mice. Moreover, microdialysis study in freely moving mice showed that systemic administration of AKB48 and 5F-AKB48 stimulated dopamine release in the nucleus accumbens. Behavioural, neurological and neurochemical effects were fully prevented by the selective CB 1 receptor antagonist/inverse agonist AM 251. For the first time, the present study demonstrates the overall pharmacological effects induced by the administration of AKB48 and 5F-AKB48 in mice and suggests that the fluorination can increase the power and/or effectiveness of SCBs. Furthermore, this study outlines the potential detrimental effects of SCBs on human health.

  9. Epigenetic Alterations in Alzheimer’s Disease

    Science.gov (United States)

    Sanchez-Mut, Jose V.; Gräff, Johannes

    2015-01-01

    Alzheimer’s disease (AD) is the major cause of dementia in Western societies. It progresses asymptomatically during decades before being belatedly diagnosed when therapeutic strategies have become unviable. Although several genetic alterations have been associated with AD, the vast majority of AD cases do not show strong genetic underpinnings and are thus considered a consequence of non-genetic factors. Epigenetic mechanisms allow for the integration of long-lasting non-genetic inputs on specific genetic backgrounds, and recently, a growing number of epigenetic alterations in AD have been described. For instance, an accumulation of dysregulated epigenetic mechanisms in aging, the predominant risk factor of AD, might facilitate the onset of the disease. Likewise, mutations in several enzymes of the epigenetic machinery have been associated with neurodegenerative processes that are altered in AD such as impaired learning and memory formation. Genome-wide and locus-specific epigenetic alterations have also been reported, and several epigenetically dysregulated genes validated by independent groups. From these studies, a picture emerges of AD as being associated with DNA hypermethylation and histone deacetylation, suggesting a general repressed chromatin state and epigenetically reduced plasticity in AD. Here we review these recent findings and discuss several technical and methodological considerations that are imperative for their correct interpretation. We also pay particular focus on potential implementations and theoretical frameworks that we expect will help to better direct future studies aimed to unravel the epigenetic participation in AD. PMID:26734709

  10. Voluntary Ethanol Consumption Induced by Social Isolation Reverses the Increase of α4/δ GABAA Receptor Gene Expression and Function in the Hippocampus of C57BL/6J Mice

    Science.gov (United States)

    Sanna, Enrico; Talani, Giuseppe; Obili, Nicola; Mascia, Maria Paola; Mostallino, Maria Cristina; Secci, Pietro Paolo; Pisu, Maria Giuseppina; Biggio, Francesca; Utzeri, Cinzia; Olla, Pierluigi; Biggio, Giovanni; Follesa, Paolo

    2011-01-01

    Post-weaning social isolation (SI) is a model of prolonged mild stress characterized by behavioral and neurochemical alterations. We used SI in C57BL/6J mice to investigate the effects of ethanol (EtOH) in the free-choice drinking paradigm on gene expression and function of γ-aminobutyric acid type A receptors (GABAARs) and the role of neuroactive steroids in the actions of EtOH in the hippocampus. SI stress induced a marked reduction in hippocampal 3α-hydroxy-5α-pregnan-20-one (3α,5α-TH PROG) and was associated with molecular and functional changes of the GABAAR. The gene expression of the α4 and δ subunits was increased in the hippocampus of SI C57BL/6J mice; the expression of the γ2 subunit was decreased whereas that of the α1 did not change. Patch-clamp recordings in dentate gyrus (DG) granule cells obtained from SI C57BL/6J mice revealed a greater enhancement of tonic currents induced by α-(4,5,6,7-tetrahydroisoxazolo[5,4-c] pyridin-3-ol (THIP) compared to that in control C57BL/6J mice. These neurochemical, molecular and functional changes observed in SI C57BL/6J mice were associated with an increased EtOH intake and EtOH preference. Nevertheless, the increase in EtOH consumption did not restore the reduction in hippocampal 3α,5α-TH PROG induced by SI. EtOH self-administration blocked the changes in gene expression of the α4 subunit but not those of the δ and γ2 subunits induced by SI. In addition, EtOH self-administration did not block the SI-induced changes in GABAAR-mediated tonic inhibition in hippocampal granule cells but increased the frequency of basal GABAergic sIPSCs in DG granule cells. We conclude that self-administration of EtOH selectively abolishes the increase of α4 subunit but not other neurochemical, molecular, and functional modifications induced by SI prolonged mild stress. PMID:21347217

  11. The alteration of intracellular enzymes. III. The effect of temperature on the kinetics of altered and unaltered yeast catalase.

    Science.gov (United States)

    FRASER, M J; KAPLAN, J G

    1955-03-20

    1. The very large increase in catalase activity (Euler effect) which follows treatment of yeast cells with CHCl(3), UV and n-propanol is accompanied by highly significant changes in kinetic properties. With respect to the enzymatic decomposition of H(2)O(2), the thermodynamic constants of the activation process micro, DeltaHdouble dagger, DeltaSdouble dagger, DeltaFdouble dagger, decrease, following treatment of the intracellular enzyme, by 4.5 kcal., 4.5 kcal., 10.1 e.u. and 1.7 kcal., respectively, all these differences being significant at the 1 per cent level. 2. Similar differences exist between the untreated, intracellular enzyme on the one hand, and the extracted yeast and crystalline beef liver catalases on the other. Significant differences in these thermodynamic constants do not exist among the treated intracellular, extracted yeast, and crystalline liver catalases. 3. These data provide unequivocal confirmation of the phenomenon of enzyme alteration reported previously, and confirm previous evidence that the extracted and crystalline enzymes have also undergone enzyme alteration and have properties which are identical with, or very similar to, those of the catalase altered in situ. 4. With respect to the process of heat destruction of catalase, the greatly diminished stability to heat of the altered enzymes, previously reported, has been confirmed. The thermodynamic constants of activation of this process have likewise changed following alteration, in the case of micro, DeltaHdouble dagger, and DeltaSdouble dagger an increase of 20.6 kcal., 20.6 kcal., and 70 e.u., respectively, and of DeltaFdouble dagger a decrease of 2.8 kcal. 5. All these data have been shown to be consistent with, and in some cases predictable from, the interfacial hypothesis, which states that the unaltered catalase exists within the cell adsorbed to some interface, in a partially, but reversibly, unfolded configuration of relatively low specificity; enzyme alteration consists, in

  12. Timescales and settings for alteration of chondritic meteorites

    Energy Technology Data Exchange (ETDEWEB)

    Krot, A N; Hutcheon, I D; Brearley, A J; Pravdivtseva, O V; Petaev, M I; Hohenberg, C M

    2005-11-16

    Most groups of chondritic meteorites experienced diverse styles of secondary alteration to various degrees that resulted in formation of hydrous and anhydrous minerals (e.g., phyllosilicates, magnetite, carbonates, ferrous olivine, hedenbergite, wollastonite, grossular, andradite, nepheline, sodalite, Fe,Ni-carbides, pentlandite, pyrrhotite, Ni-rich metal). Mineralogical, petrographic, and isotopic observations suggest that the alteration occurred in the presence of aqueous solutions under variable conditions (temperature, water/rock ratio, redox conditions, and fluid compositions) in an asteroidal setting, and, in many cases, was multistage. Although some alteration predated agglomeration of the final chondrite asteroidal bodies (i.e. was pre-accretionary), it seems highly unlikely that the alteration occurred in the solar nebula, nor in planetesimals of earlier generations. Short-lived isotope chronologies ({sup 26}Al-{sup 26}Mg, {sup 53}Mn-{sup 53}Cr, {sup 129}I-{sup 129}Xe) of the secondary minerals indicate that the alteration started within 1-2 Ma after formation of the Ca,Al-rich inclusions and lasted up to 15 Ma. These observations suggest that chondrite parent bodies must have accreted within the first 1-2 Ma after collapse of the protosolar molecular cloud and provide strong evidence for an early onset of aqueous activity on these bodies.

  13. Alteration, slope-classified alteration, and potential lahar inundation maps of volcanoes for the Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) Volcano Archive

    Science.gov (United States)

    Mars, John C.; Hubbard, Bernard E.; Pieri, David; Linick, Justin

    2015-01-01

    This study identifies areas prone to lahars from hydrothermally altered volcanic edifices on a global scale, using visible and near infrared (VNIR) and short wavelength infrared (SWIR) reflectance data from the Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) and digital elevation data from the ASTER Global Digital Elevation Model (GDEM) dataset. This is the first study to create a global database of hydrothermally altered volcanoes showing quantitatively compiled alteration maps and potentially affected drainages, as well as drainage-specific maps illustrating modeled lahars and their potential inundation zones. We (1) identified and prioritized 720 volcanoes based on population density surrounding the volcanoes using the Smithsonian Institution Global Volcanism Program database (GVP) and LandScan™ digital population dataset; (2) validated ASTER hydrothermal alteration mapping techniques using Airborne Visible and Infrared Imaging Spectrometer (AVIRIS) and ASTER data for Mount Shasta, California, and Pico de Orizaba (Citlaltépetl), Mexico; (3) mapped and slope-classified hydrothermal alteration using ASTER VNIR-SWIR reflectance data on 100 of the most densely populated volcanoes; (4) delineated drainages using ASTER GDEM data that show potential flow paths of possible lahars for the 100 mapped volcanoes; (5) produced potential alteration-related lahar inundation maps using the LAHARZ GIS code for Iztaccíhuatl, Mexico, and Mount Hood and Mount Shasta in the United States that illustrate areas likely to be affected based on DEM-derived volume estimates of hydrothermally altered rocks and the ~2x uncertainty factor inherent within a statistically-based lahar model; and (6) saved all image and vector data for 3D and 2D display in Google Earth™, ArcGIS® and other graphics display programs. In addition, these data are available from the ASTER Volcano Archive (AVA) for distribution (available at http://ava.jpl.nasa.gov/recent_alteration_zones.php).

  14. Contribution of altered signal transduction associated to glutamate receptors in brain to the neurological alterations of hepatic encephalopathy

    Institute of Scientific and Technical Information of China (English)

    Vicente Felipo

    2006-01-01

    Patients with liver disease may present hepatic encephalopathy (HE), a complex neuropsychiatric syndrome covering a wide range of neurological alterations,including cognitive and motor disturbances. HE reduces the quality of life of the patients and is associated with poor prognosis. In the worse cases HE may lead to coma or death.The mechanisms leading to HE which are not well known are being studied using animal models. The neurological alterations in HE are a consequence of impaired cerebral function mainly due to alterations in neurotransmission. We review here some studies indicating that alterations in neurotransmission associated to different types of glutamate receptors are responsible for some of the cognitive and motor alterations present in HE.These studies show that the function of the signal transduction pathway glutamate-nitric oxide-cGMP associated to the NMDA type of glutamate receptors is impaired in brain in vivo in HE animal models as well as in brain of patients died of HE. Activation of NMDA receptors in brain activates this pathway and increases cGMP. In animal models of HE this increase in cGMP induced by activation of NMDA receptors is reduced,which is responsible for the impairment in learning ability in these animal models. Increasing cGMP by pharmacological means restores learning ability in rats with HE and may be a new therapeutic approach to improve cognitive function in patients with HE.However, it is necessary to previously assess the possible secondary effects.Patients with HE may present psychomotor slowing,hypokinesia and bradykinesia. Animal models of HE also show hypolocomotion. It has been shown in rats with HE that hypolocomotion is due to excessive activation of metabotropic glutamate receptors (mGluRs) in substantia nigra pars reticulata. Blocking mGluR1 in this brain area normalizes motor activity in the rats, suggesting that a similar treatment for patients with HE could be useful to treat psychomotor slowing and

  15. Alteration of nuclear glass in contact with iron and claystone at 90 °C under anoxic conditions: Characterization of the alteration products after two years of interaction

    International Nuclear Information System (INIS)

    Schlegel, Michel L.; Martin, Christelle; Brucker, Florence; Bataillon, Christian; Blanc, Cécile; Chorro, Matthieu; Jollivet, Patrick

    2016-01-01

    The present study investigates the alteration of a fractured glass block in contact with iron and Callovo-Oxfordian claystone at 90 °C under anoxic and water-saturated conditions. The alteration rates and the nature of glass alteration products at the different compact interfaces (glass-clay, glass-iron) and in cracks were assessed by solution chemistry and microscopic-scale techniques (scanning electron microscopy coupled with energy-dispersive X-ray microscopy, microRaman spectroscopy, and X-ray absorption fine structure spectroscopy). A significant but modest (two-fold) increase in glass alteration in contact with steel was observed, leading to an average alteration rate over the experiment of about 0.007–0.014 g/m"2/d. This rate is significantly lower than forward rate r_0 in clay-equilibrated groundwater (1.7 g/m"2/d), indicating that a decrease of the alteration rate was not hindered by the steel presence. The corrosion–alteration interface was made up of successive layers of corrosion products in contact with iron, a layer of Fe silicates, and an altered glass layer enriched in Fe. Characterization of the glass block in direct contact with claystone revealed that the thickness of altered glass was much more important than at the glass-iron interface. The altered glass layer in contact with clay was slightly enriched in Fe and Mg, and depleted in alkali cations. Altered glass layers in cracks were usually limited to fringes thinner than 2 μm, with a thickness decreasing from the crack mouth, indicating that alteration is controlled by transport in the cracks. The fractures were partially filled with calcite and lanthanide hydroxocarbonate precipitates. These results contribute to the understanding of nuclear vitrified waste-iron-corrosion products interactions in a deep geological repository. - Highlights: • Anoxic alteration of glass in contact with iron and clay at 90 °C for two-years. • Alteration rates of 0.015 and 0.5 g/m"2/d at glass

  16. Altered Global Signal Topography in Schizophrenia.

    Science.gov (United States)

    Yang, Genevieve J; Murray, John D; Glasser, Matthew; Pearlson, Godfrey D; Krystal, John H; Schleifer, Charlie; Repovs, Grega; Anticevic, Alan

    2017-11-01

    Schizophrenia (SCZ) is a disabling neuropsychiatric disease associated with disruptions across distributed neural systems. Resting-state functional magnetic resonance imaging has identified extensive abnormalities in the blood-oxygen level-dependent signal in SCZ patients, including alterations in the average signal over the brain-i.e. the "global" signal (GS). It remains unknown, however, if these "global" alterations occur pervasively or follow a spatially preferential pattern. This study presents the first network-by-network quantification of GS topography in healthy subjects and SCZ patients. We observed a nonuniform GS contribution in healthy comparison subjects, whereby sensory areas exhibited the largest GS component. In SCZ patients, we identified preferential GS representation increases across association regions, while sensory regions showed preferential reductions. GS representation in sensory versus association cortices was strongly anti-correlated in healthy subjects. This anti-correlated relationship was markedly reduced in SCZ. Such shifts in GS topography may underlie profound alterations in neural information flow in SCZ, informing development of pharmacotherapies. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  17. Autoradiography in Studying the Alteration of Rocks; L'Autoradiographie dans l'Etude de l'Alteration des Roches

    Energy Technology Data Exchange (ETDEWEB)

    Leveque, P.; Vigneaux, M. [Institut de Geologie du Bassin d' Aquitaine, Faculte des Sciences de l' Universite de Bordeaux (France)

    1967-06-15

    The alteration of rocks intended for use as the foundations of large-scale civil-engineering projects, for building construction and for rock piling has been studied and numerous tests carried out; some of these tests have been standardized in varying degrees. The conventional method of autoradiography has been used to develop one of the processes for estimating alteration due, in particular, to thermal shocks. By using {sup 35}S and {sup 32}P, the authors were able to follow the progressive alteration of different rocks in the form of microfissurations. This process is considerably more accurate than that based solely on utilization of the characteristics of rocks in normal or polarized light. In addition, it permits absolute comparison of the initial microfissuration conditions of the sample and the microfissuration found after an increasing number of thermal shock cycles. The results of the process are given in the paper. (author) [French] L'alterabilite des roches destinees, soit a des fondations de grands travaux de genie civil, soit a la construction d'immeubles, soit enfin a l'etablissement d'enrochements, a fait l'objet de nombreux essais dont certains ont ete normalises, ou tout au moins ont subi un debut de normalisation. Un des procedes de determination du processus d'alteration du notamment aux chocs thermiques a ete mis au point a partir de la methode classique d'autoradiographie. L'utilisation de {sup 35}S et de {sup 32}P a permis de suivre la progression de l'alteration par microfissuration dans des roches diverses. Ce procede est notablement plus precis que celui qui est fonde sur la seule utilisation des caracteristiques des roches en lumiere naturelle ou polarisee. De plus, il permet la comparaison en valeur absolue de l'etat de microfissuration initial de l'echantillon avec la microfissuration obtenue apres un nombre croissant de cycles de chocs thermiques. Les resultats obtenus grace a ce procede sont donnes dans le memoire. (author)

  18. Behavioral effects of heavy ions and protons and potential countermeasure agents

    Science.gov (United States)

    Vazquez, M.; Gatley, J.; Bruneus, M.; Koslosky, S.; Billups, A.

    Space travel beyond the Earth's protective magnetic field (for example, to Mars) will involve exposure of astronauts to irradiation by high-energy nuclei such as 56 Fe, which are a component of galactic cosmic rays. These particles have high linear energy transfer (LET) and are expected to irreversibly damage cells they traverse. Exposure to HZE radiation may therefore cause progressive deterioration of brain function, adding to other inescapable damage involved in normal aging. We propose a study of the hypothesis that long-term behavioral alterations are induced after exposure of the brain to 1 GeV/n iron and silicon particles with fluences of 1 to 8 particles/cell targets. Previous studies support this notion but are not definitive, especially with regard to long-term effects. Our principal goal is to examine the neurological effects of high-LET radiation on C57BL/6 mice using a series of behavioral tests to unveil the temporal expression of altered behaviors in the radiation response, as well as the means, which can modulate these responses. The studies planned in this project are designed to: 1) Characterize the behavioral consequences after exposure to low-fluences of heavy ions and protons on C57BL/6 mice. The main behavioral endpoints to be used in these studies are locomotor activity to evaluate the integrity of striatal dopaminergic pathways, and spatial reference memory to probe hippocampal cholinergic pathways. 2) Characterize the neurochemical and structural changes induced by heavy ions and protons. 3) To develop countermeasures to protect neural cell populations exposed to low fluences of heavy ions and protons. The project will test methods to protect injured neural cells based on their molecular and cellular mechanisms that may regulate neural cell survival in the central nervous system. Among the methods that will be studied is the direct administration of neuroprotective molecules as well as the modulation of apoptotic pathways by pharmacological

  19. Characterizing genomic alterations in cancer by complementary functional associations.

    Science.gov (United States)

    Kim, Jong Wook; Botvinnik, Olga B; Abudayyeh, Omar; Birger, Chet; Rosenbluh, Joseph; Shrestha, Yashaswi; Abazeed, Mohamed E; Hammerman, Peter S; DiCara, Daniel; Konieczkowski, David J; Johannessen, Cory M; Liberzon, Arthur; Alizad-Rahvar, Amir Reza; Alexe, Gabriela; Aguirre, Andrew; Ghandi, Mahmoud; Greulich, Heidi; Vazquez, Francisca; Weir, Barbara A; Van Allen, Eliezer M; Tsherniak, Aviad; Shao, Diane D; Zack, Travis I; Noble, Michael; Getz, Gad; Beroukhim, Rameen; Garraway, Levi A; Ardakani, Masoud; Romualdi, Chiara; Sales, Gabriele; Barbie, David A; Boehm, Jesse S; Hahn, William C; Mesirov, Jill P; Tamayo, Pablo

    2016-05-01

    Systematic efforts to sequence the cancer genome have identified large numbers of mutations and copy number alterations in human cancers. However, elucidating the functional consequences of these variants, and their interactions to drive or maintain oncogenic states, remains a challenge in cancer research. We developed REVEALER, a computational method that identifies combinations of mutually exclusive genomic alterations correlated with functional phenotypes, such as the activation or gene dependency of oncogenic pathways or sensitivity to a drug treatment. We used REVEALER to uncover complementary genomic alterations associated with the transcriptional activation of β-catenin and NRF2, MEK-inhibitor sensitivity, and KRAS dependency. REVEALER successfully identified both known and new associations, demonstrating the power of combining functional profiles with extensive characterization of genomic alterations in cancer genomes.

  20. Hydrothermal alteration in Dumoga Barat, Bolaang Mongondow area North Sulawesi

    International Nuclear Information System (INIS)

    Agus Harjanto' Sutanto; Sutarto; Achmad Subandrio; I Made Suasta; Juanito Salamat; Giri Hartono; Putu Suputra; I Gde Basten; Muhammad Fauzi; Rosdiana

    2016-01-01

    Bolaang Mongondow is located in central north Sulawesi arm, which is composed of Neogen magmatic arc and potentially contain economic minerals. This condition is behind the research purpose to study the mineral resources potencies. Research aim is to study alteration caused by hydrothermal process and its relation with gold (Au) deposit based on field study and laboratory analysis. Methodologies used for the research are literature study, geological survey, rocks sampling, laboratory analysis, and data processing. Research area is a multiply diorite intrusion complex. Andesite, volcaniclastic rocks, and dacite, the older rocks, were intruded by this complex. Later, dacitic tuff, volcanic sandstone, and alluvium deposited above them. There are three measured and mapped major faults heading NE-SW crossed by E-W fault and NW-SE fault lately crossed all the older faults. Early stage hydrothermal alteration related to the existence of young quartz diorite, showing alteration stage from the potassic center to distal prophylatic. Final stage hydrothermal alteration consist of argilic, advanced argilic, and silica-clay mineral±magnetite±chlorite alteration overlapping the earlier alteration. Mineralization of Cu-Au±Ag in central part of research area or Tayap-Kinomaligan area is mostly associated with potassic altered young quartz diorite and crossed by parallel and stock worked quartz-magnetite-chalcopyrite±bornite vein. (author)

  1. A dioxin-like compound induces hyperplasia and branching morphogenesis in mouse mammary gland, through alterations in TGF-β1 and aryl hydrocarbon receptor signaling.

    Science.gov (United States)

    Miret, Noelia; Rico-Leo, Eva; Pontillo, Carolina; Zotta, Elsa; Fernández-Salguero, Pedro; Randi, Andrea

    2017-11-01

    Hexachlorobenzene (HCB) is a widespread environmental pollutant and a dioxin-like compound that binds weakly to the aryl hydrocarbon receptor (AhR). Because AhR and transforming growth factor β1 (TGF-β1) converge to regulate common signaling pathways, alterations in this crosstalk might contribute to developing preneoplastic lesions. The aim of this study was to evaluate HCB action on TGF-β1 and AhR signaling in mouse mammary gland, through AhR+/+ and AhR-/- models. Results showed a differential effect in mouse mammary epithelial cells (NMuMG), depending on the dose: 0.05μM HCB induced cell migration and TGF-β1 signaling, whereas 5μM HCB reduced cell migration, promoted cell cycle arrest and stimulated the dioxin response element (DRE) -dependent pathway. HCB (5μM) enhanced α-smooth muscle actin expression and decreased TGF-β receptor II mRNA levels in immortalized mouse mammary fibroblasts AhR+/+, resembling the phenotype of transformed cells. Accordingly, their conditioned medium was able to enhance NMuMG cell migration. Assays in C57/Bl6 mice showed HCB (3mg/kg body weight) to enhance ductal hyperplasia, cell proliferation, estrogen receptor α nuclear localization, branch density, and the number of terminal end buds in mammary gland from AhR+/+ mice. Primary culture of mammary epithelial cells from AhR+/+ mice showed reduced AhR mRNA levels after HCB exposure (0.05 and 5μM). Interestingly, AhR-/- mice exhibited an increase in ductal hyperplasia and mammary growth in the absence of HCB treatment, thus revealing the importance of AhR in mammary development. Our findings show that environmental HCB concentrations modulate AhR and TGF-β1 signaling, which could contribute to altered mammary branching morphogenesis, likely leading to preneoplastic lesions and retaining terminal end buds. Copyright © 2017. Published by Elsevier Inc.

  2. Narcissism Guides Mate Selection: Humans Mate Assortatively, as Revealed by Facial Resemblance, following an Algorithm of “Self Seeking Like”

    Directory of Open Access Journals (Sweden)

    Liliana Alvarez

    2004-01-01

    Full Text Available Theoretical studies suggest that mating and pair formation is not likely to be random. Computer simulations suggested that sex among genetically complex organisms requires mate choice strategies for its evolutionary maintenance, to reduce excessive genetic variance produced by out-crossing. One strategy achieving this aim efficiently in computer simulations is assortative mating modeled as “self seeking like”. Another one is selection of “good genes”. Assortative mating increases the probability of finding a genetically similar mate, without fomenting inbreeding, achieving assortative mating without hindering the working of other mate selection strategies which aim to maximize the search for “good genes”, optimizing the working of sex in evolutionary terms. Here we present indirect evidence that in a significant proportion of human reproductive couples, the partners show much higher facial resemblances than can be expected by random pair formation, or as the outcome of “matching for attractiveness” or the outcome of competition for the most attractive partner accessible, as had been previously assumed. The data presented is compatible with the hypothesis derived from computer simulations, that human mate selection strategies achieve various aims: “self seeking like” (including matching for attractiveness and mating with the best available genes.

  3. SEDAH. Data Server for hydrologic alteration evaluation

    International Nuclear Information System (INIS)

    Martinez Romero, R.; Magdaleno Mas, F.; Ortiz Rodriguez, J.; Fernandez Yuste, J. A.; Martinez Santa-Maria, C.

    2011-01-01

    Several tasks and studies have been developed from 2008 till 2010 all around the country in order to evaluate the hydrologic alteration of water bodies. In most cases this alteraction has been evaluated through IAHRIS (Martinez and Fernandez, 2006). The necessity of creating a new toll that allowed a better performance of the National Flow-Stage Stations Network data was showed up by developing these works. The output data series should match IAHRIS and IHA. SEDAH (Data Server for Evaluating Hydrologic Alteration) Helps to solve some of these problems by supplying an easy way to select flow stations, dates, flow series typology, etc. Moreover, other useful utilities are: a preliminary appraisement of quality data, calssification of altered or reference flow series and exportation of data in different file formats. The web application works with different data bases, daily, monthly and annual series belonging to, wither actual series from flow station data or completed series by statistical procedures. Through SEDAH the user has easy access to all this huge information ready for being applied in hydrologic alteration assessment, environmental fows regime, river restoration projects, etc. Furthermore, this first phase of the application constitute the basis for future powerful functionalities related to the natural flow series obtaining. (Author) 5 refs.

  4. White matter alterations in neurodegenerative and vascular dementia

    International Nuclear Information System (INIS)

    Supprian, T.; Kessler, H.; Falkai, P.; Retz, W.; Roesler, M.; Grunwald, I.; Reith, W.

    2003-01-01

    Due to a significant overlap of the two syndromes, differentiation of degenerative dementia of the Alzheimer-type from vascular dementia may be difficult even when imaging studies are available. White matter changes occur in many patients suffering from Alzheimer's disease. Little is known about the impact of white matter changes on the course and clinical presentation of Alzheimer's disease. High sensitivity of MRI in the detection of white matter alterations may account for over-diagnosing vascular dementia. The clinical significance of white matter alterations in dementia is still a matter of debate. The article reviews current concepts about the role of white matter alterations in dementia. (orig.) [de

  5. Valuing hydrological alteration in Multi-Objective reservoir management

    Science.gov (United States)

    Bizzi, S.; Pianosi, F.; Soncini-Sessa, R.

    2012-04-01

    Water management through dams and reservoirs is worldwide necessary to support key human-related activities ranging from hydropower production to water allocation for agricultural production, and flood risk mitigation. Advances in multi-objectives (MO) optimization techniques and ever growing computing power make it possible to design reservoir operating policies that represent Pareto-optimal tradeoffs between the multiple interests analysed. These progresses if on one hand are likely to enhance performances of commonly targeted objectives (such as hydropower production or water supply), on the other risk to strongly penalize all the interests not directly (i.e. mathematically) optimized within the MO algorithm. Alteration of hydrological regime, although is a well established cause of ecological degradation and its evaluation and rehabilitation are commonly required by recent legislation (as the Water Framework Directive in Europe), is rarely embedded as an objective in MO planning of optimal releases from reservoirs. Moreover, even when it is explicitly considered, the criteria adopted for its evaluation are doubted and not commonly trusted, undermining the possibility of real implementation of environmentally friendly policies. The main challenges in defining and assessing hydrological alterations are: how to define a reference state (referencing); how to define criteria upon which to build mathematical indicators of alteration (measuring); and finally how to aggregate the indicators in a single evaluation index that can be embedded in a MO optimization problem (valuing). This paper aims to address these issues by: i) discussing benefits and constrains of different approaches to referencing, measuring and valuing hydrological alteration; ii) testing two alternative indices of hydrological alteration in the context of MO problems, one based on the established framework of Indices of Hydrological Alteration (IHA, Richter et al., 1996), and a novel satisfying the

  6. Neuroblastoma cells undergo transcriptomic alterations upon dissemination into the bone marrow and subsequent tumor progression.

    Science.gov (United States)

    Rifatbegovic, Fikret; Frech, Christian; Abbasi, M Reza; Taschner-Mandl, Sabine; Weiss, Tamara; Schmidt, Wolfgang M; Schmidt, Iris; Ladenstein, Ruth; Ambros, Inge M; Ambros, Peter F

    2018-01-15

    Neuroblastoma is the most common extracranial solid tumor in childhood. The vast majority of metastatic (M) stage patients present with disseminated tumor cells (DTCs) in the bone marrow (BM) at diagnosis and relapse. Although these cells represent a major obstacle in the treatment of neuroblastoma patients, insights into their expression profile remained elusive. The present RNA-Seq study of stage 4/M primary tumors, enriched BM-derived diagnostic and relapse DTCs, as well as the corresponding BM-derived mononuclear cells (MNCs) from 53 patients revealed 322 differentially expressed genes in DTCs as compared to the tumors (q 2). Particularly, the levels of transcripts encoded by mitochondrial DNA were elevated in DTCs, whereas, for example, genes involved in angiogenesis were downregulated. Furthermore, 224 genes were highly expressed in DTCs and only slightly, if at all, in MNCs (q  6). Interestingly, we found the transcriptome of relapse DTCs largely resembling those of diagnostic DTCs with only 113 differentially expressed genes under relaxed cut-offs (q 0.5). Notably, relapse DTCs showed a positional enrichment of 31 downregulated genes on chromosome 19, including five tumor suppressor genes: SIRT6, BBC3/PUMA, STK11, CADM4 and GLTSCR2. This first RNA-Seq analysis of neuroblastoma DTCs revealed their unique expression profile in comparison to the tumors and MNCs, and less pronounced differences between diagnostic and relapse DTCs. The latter preferentially affected downregulation of genes encoded by chromosome 19. As these alterations might be associated with treatment failure and disease relapse, further functional studies on DTCs should be considered. © 2017 The Authors International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.

  7. Hydrothermal surface alteration in the Copahue Geothermal Field (Argentina)

    Energy Technology Data Exchange (ETDEWEB)

    Mas, Graciela R.; Mas, Luis C.; Bengochea, Leandro

    1996-01-24

    In the area of the Copahue Geothermal Field, there are five active geothermal manifestations, which mainly consist of fumaroles, hot springs and mud pots. Four of these manifestations are located in Argentina: Las Máquinas, Termas de Copahue, Las Maquinitas and El Anfiteatro, and the fifth on the Chilean side: Chancho Co. All of them present a strong acid sulfate country rock alteration, characterized by the assemblage alunite + kaolinite + quartz + cristobalite + pyrite + sulfur + jarosite, as the result of the base leaching by fluids concentrated in H2SO4 by atmospheric oxidation at the water table in a steam heated environment of H2S released by deeper boiling fluids. Another alteration zone in this area, called COP-2, is a fossil geothermal manifestation which shows characteristics of neutral to alkaline alteration represented mainly by the siliceous sinter superimposed over the acid alteration. The mineralogy and zoning of these alteration zones, and their relation with the hidrothermal solutions and the major structures of the area are analized.

  8. Mechanisms for altered carnitine content in hypertrophied rat hearts

    International Nuclear Information System (INIS)

    Reibel, D.K.; O'Rourke, B.; Foster, K.A.

    1987-01-01

    Carnitine levels are reduced in hypertrophied hearts of rats subjected to aortic constriction (banding) and evaluated in hypertrophied hearts of spontaneously hypertensive rats (SHR). In an attempt to determine the mechanisms for these alterations, L-[ 14 C]carnitine transport was examined in isolated perfused hearts. Total carnitine uptake was significantly reduced by ∼20% in hypertrophied hearts of banded rats at all perfusate carnitine concentrations employed. The reduction in total uptake was due to a 40% reduction in carrier-mediated carnitine uptake with no difference in uptake by diffusion. In contrast, carnitine uptake was not altered in isolated hypertrophied hearts of SHR. However, serum carnitine levels were elevated in SHR, which could result in increased myocardial carnitine uptake in vivo. The data suggest that altered carnitine content in hypertrophied hearts of aortic-banded rats is due to an alteration in the carrier-mediated carnitine transport system in the myocardium. However, altered carnitine content in hypertrophied hearts of SHR is not due to a change in the carnitine transport system per se but may rather be due to a change in serum carnitine levels

  9. R7T7 glass alteration mechanism in an aqueous closed system: understanding and modelling the long term alteration kinetic

    International Nuclear Information System (INIS)

    Chave, T.

    2007-10-01

    The long term alteration rate of the French R7T7 nuclear glass has been investigated since many years because it will define the overall resistance of the radionuclide containment matrix. Recent studies have shown that the final rate remains constant or is slightly decreasing with time. It never reaches zero. Though this residual rate is very low, only 5 nm per year at 50 C, it would be the dominant alteration phenomenon in a geological repository. Two mechanisms are suggested for explaining such behaviour: diffusion in solution of elements from glass through an amorphous altered layer and precipitation of neo-formed phases. The diffusion processes are in agreement with a solid state diffusion mechanism and can lead to secondary phase precipitation due to solution concentration increases. Observed phases are mainly phyllosilicates and zeolites, in specific conditions. Phyllosilicates are expected to maintain the residual kinetic rate whereas alteration resumption could be observed in presence of zeolites at very high pH or temperature (10.5 at 90 C or temperature above 150 C). Both diffusion and neo-formed phase precipitation have been investigated in order to better understand their impact on the residual alteration rate and have then been modelled by a calculation code, coupling chemistry and transport, in order to be able to better anticipate the long term behaviour of the glass R7T7 in an aqueous closed system. (author)

  10. Gesundheit und Pflege im Alter

    OpenAIRE

    Pfaff, Martin

    1989-01-01

    Gesundheit und Pflege im Alter : d. Gesundheitsreformgesetz (GRG) ; Möglichkeiten, Grenzen u. weitere Vorschläge / Martin Pfaff ; Klaus Deimer. - In: Expertengespräch "Pflege in der Familie". - Augsburg, 1989. - Getr. Zählung

  11. New insight into atmospheric alteration of alkali-lime silicate glasses

    International Nuclear Information System (INIS)

    Alloteau, Fanny; Lehuédé, Patrice; Majérus, Odile; Biron, Isabelle; Dervanian, Anaïs; Charpentier, Thibault; Caurant, Daniel

    2017-01-01

    Highlights: •Glass silicate network hydrolysis is by far the predominant reaction at 80 °C. •Atmospheric conditions yield different altered layer structure than in immersion. •The altered layer bears about 10 wt% of water mainly as H-bonded SiOH groups. •Alkali ions stay embedded into the altered layer closed to SiOH and H 2 O species. -- Abstract: A mixed alkali lime silicate glass altered in atmospheric conditions (80 °C/85%RH, Relative Humidity) for various lengths of time was characterized at all scales. The altered glass forms a hydrated solid phase bearing about 10 wt% of H 2 O in the form of Si-OH groups and molecular water. No alkali depletion was observed after ageing tests. Structural results from 1 H, 23 Na and 29 Si MAS NMR point out the close proximity of Si-OH, H 2 O and Na + species. This study gives new insight into the mechanisms of the atmospheric alteration, essential to conservation strategies in industry and cultural heritage.

  12. Learning Arm/Hand Coordination with an Altered Visual Input

    Directory of Open Access Journals (Sweden)

    Simona Denisia Iftime Nielsen

    2010-01-01

    Full Text Available The focus of this study was to test a novel tool for the analysis of motor coordination with an altered visual input. The altered visual input was created using special glasses that presented the view as recorded by a video camera placed at various positions around the subject. The camera was positioned at a frontal (F, lateral (L, or top (T position with respect to the subject. We studied the differences between the arm-end (wrist trajectories while grasping an object between altered vision (F, L, and T conditions and normal vision (N in ten subjects. The outcome measures from the analysis were the trajectory errors, the movement parameters, and the time of execution. We found substantial trajectory errors and an increased execution time at the baseline of the study. We also found that trajectory errors decreased in all conditions after three days of practice with the altered vision in the F condition only for 20 minutes per day, suggesting that recalibration of the visual systems occurred relatively quickly. These results indicate that this recalibration occurs via movement training in an altered condition. The results also suggest that recalibration is more difficult to achieve for altered vision in the F and L conditions compared to the T condition. This study has direct implications on the design of new rehabilitation systems.

  13. Zeolitization of intracaldera sediments and rhyolitic rocks in the 1.25 Ma lake of Valles caldera, New Mexico, USA

    Science.gov (United States)

    Chipera, Steve J.; Goff, Fraser; Goff, Cathy J.; Fittipaldo, Melissa

    2008-12-01

    Quantitative X-ray diffraction analysis of about 80 rhyolite and associated lacustrine rocks has characterized previously unrecognized zeolitic alteration throughout the Valles caldera resurgent dome. The alteration assemblage consists primarily of smectite-clinoptilolite-mordenite-silica, which replaces groundmass and fills voids, especially in the tuffs and lacustrine rocks. Original rock textures are routinely preserved. Mineralization typically extends to depths of only a few tens of meters and resembles shallow "caldera-type zeolitization" as defined by Utada et al. [Utada, M., Shimizu, M., Ito, T., Inoue, A., 1999. Alteration of caldera-forming rocks related to the Sanzugawa volcanotectonic depression, northeast Honshu, Japan — with special reference to "caldera-type zeolitization." Resource Geol. Spec. Issue No. 20, 129-140]. Geology and 40Ar/ 39Ar dates limit the period of extensive zeolite growth to roughly the first 30 kyr after the current caldera formed (ca. 1.25 to 1.22 Ma). Zeolitic alteration was promoted by saturation of shallow rocks with alkaline lake water (a mixture of meteoric waters and degassed hydrothermal fluids) and by high thermal gradients caused by cooling of the underlying magma body and earliest post-caldera rhyolite eruptions. Zeolitic alteration of this type is not found in the later volcanic and lacustrine rocks of the caldera moat (≤ 0.8 Ma) suggesting that later lake waters were cooler and less alkaline. The shallow zeolitic alteration does not have characteristics resembling classic, alkaline lake zeolite deposits (no analcime, erionite, or chabazite) nor does it contain zeolites common in high-temperature hydrothermal systems (laumontite or wairakite). Although aerially extensive, the early zeolitic alteration does not form laterally continuous beds and are consequently, not of economic significance.

  14. Modifications of Poly(o-phenylenediamine Permselective Layer on Pt-Ir for Biosensor Application in Neurochemical Monitoring

    Directory of Open Access Journals (Sweden)

    Robert D. O’Neill

    2007-04-01

    Full Text Available Reports that globular proteins could enhance the interference blocking ability ofthe PPD (poly(o-phenylenediamine layer used as a permselective barrier in biosensordesign, prompted this study where a variety of modifying agents were incorporated into PPDduring its electrosynthesis on Pt-Ir electrodes. Trapped molecules, including fibrous proteinsand β-cyclodextrin, altered the polymer/modifier composite selectivity by affecting thesensitivity to both H2O2 (signal molecule in many enzyme-based biosensors and thearchetypal interference species, ascorbic acid. A comparison of electrochemical properties ofPt and a Pt-Ir alloy suggests that the benefits of the latter, more rigid, metal can be exploitedin PPD-based biosensor design without significant loss of backward compatibility withstudies involving pure Pt.

  15. Altered states, altered spaces : architecture, space and landscape in the film and television of Stanley Kubrick and Ken Russell

    OpenAIRE

    Melia, Matthew

    2017-01-01

    Altered States, Altered Spaces: Architecture, Landscape and Space in the work of Stanley Kubrick and Ken Russell.\\ud \\ud Stanley Kubrick and Ken Russell, at first, seem like unlikely bedfellows for a critical comparison: the combined Baroque, Mannerist, frequently excessive and romantic nature of Russell’s screen standing in apparent contrast to the structure, order, organisation, Brutalism and spatial complexity of Kubrick’s.\\ud \\ud In an online blogpost1 (2007) Russell biographer Paul Sutto...

  16. Acute Stress Induces Selective Alterations in Cost/Benefit Decision-Making

    Science.gov (United States)

    Shafiei, Naghmeh; Gray, Megan; Viau, Victor; Floresco, Stan B

    2012-01-01

    Acute stress can exert beneficial or detrimental effects on different forms of cognition. In the present study, we assessed the effects of acute restraint stress on different forms of cost/benefit decision-making, and some of the hormonal and neurochemical mechanisms that may underlie these effects. Effort-based decision-making was assessed where rats chose between a low effort/reward (1 press=2 pellets) or high effort/reward option (4 pellets), with the effort requirement increasing over 4 blocks of trials (2, 5, 10, and 20 lever presses). Restraint stress for 1 h decreased preference for the more costly reward and induced longer choice latencies. Control experiments revealed that the effects on decision-making were not mediated by general reductions in motivation or preference for larger rewards. In contrast, acute stress did not affect delay-discounting, when rats chose between a small/immediate vs larger/delayed reward. The effects of stress on decision-making were not mimicked by treatment with physiological doses of corticosterone (1–3 mg/kg). Blockade of dopamine receptors with flupenthixol (0.25 mg/kg) before restraint did not attenuate stress-induced effects on effort-related choice, but abolished effects on choice latencies. These data suggest that acute stress interferes somewhat selectively with cost/benefit evaluations concerning effort costs. These effects do not appear to be mediated solely by enhanced glucocorticoid activity, whereas dopaminergic activation may contribute to increased deliberation times induced by stress. These findings may provide insight into impairments in decision-making and anergia associated with stress-related disorders, such as depression. PMID:22569506

  17. Acute stress induces selective alterations in cost/benefit decision-making.

    Science.gov (United States)

    Shafiei, Naghmeh; Gray, Megan; Viau, Victor; Floresco, Stan B

    2012-09-01

    Acute stress can exert beneficial or detrimental effects on different forms of cognition. In the present study, we assessed the effects of acute restraint stress on different forms of cost/benefit decision-making, and some of the hormonal and neurochemical mechanisms that may underlie these effects. Effort-based decision-making was assessed where rats chose between a low effort/reward (1 press=2 pellets) or high effort/reward option (4 pellets), with the effort requirement increasing over 4 blocks of trials (2, 5, 10, and 20 lever presses). Restraint stress for 1 h decreased preference for the more costly reward and induced longer choice latencies. Control experiments revealed that the effects on decision-making were not mediated by general reductions in motivation or preference for larger rewards. In contrast, acute stress did not affect delay-discounting, when rats chose between a small/immediate vs larger/delayed reward. The effects of stress on decision-making were not mimicked by treatment with physiological doses of corticosterone (1-3 mg/kg). Blockade of dopamine receptors with flupenthixol (0.25 mg/kg) before restraint did not attenuate stress-induced effects on effort-related choice, but abolished effects on choice latencies. These data suggest that acute stress interferes somewhat selectively with cost/benefit evaluations concerning effort costs. These effects do not appear to be mediated solely by enhanced glucocorticoid activity, whereas dopaminergic activation may contribute to increased deliberation times induced by stress. These findings may provide insight into impairments in decision-making and anergia associated with stress-related disorders, such as depression.

  18. Neural Alterations in Acquired Age-Related Hearing Loss

    Directory of Open Access Journals (Sweden)

    Raksha Anand Mudar

    2016-06-01

    Full Text Available Hearing loss is one of the most prevalent chronic health conditions in older adults. Growing evidence suggests that hearing loss is associated with reduced cognitive functioning and incident dementia. In this mini-review, we briefly examine literature on anatomical and functional alterations in the brains of adults with acquired age-associated hearing loss, which may underlie the cognitive consequences observed in this population, focusing on studies that have used structural and functional magnetic resonance imaging, diffusion tensor imaging, and event-related electroencephalography. We discuss structural and functional alterations observed in the temporal and frontal cortices and the limbic system. These neural alterations are discussed in the context of common cause, information-degradation, and sensory-deprivation hypotheses, and we suggest possible rehabilitation strategies. Although we are beginning to learn more about changes in neural architecture and functionality related to age-associated hearing loss, much work remains to be done. Understanding the neural alterations will provide objective markers for early identification of neural consequences of age-associated hearing loss and for evaluating benefits of intervention approaches.

  19. Antibiotic treatment attenuates behavioral and neurochemical changes induced by exposure of rats to group a streptococcal antigen.

    Directory of Open Access Journals (Sweden)

    Dafna Lotan

    Full Text Available Post-streptococcal A (GAS sequelae including movement and neuropsychiatric disorders have been associated with improvement in response to antibiotic therapy. Besides eradication of infection, the underlying basis of attenuation of neuropsychiatric symptoms following antibiotic treatment is not known. The aim of the present study was to test the efficacy of antibiotic treatment in a rat model of GAS-related neuropsychiatric disorders. In the model, rats were not infected but were exposed to GAS-antigen or to adjuvants only (Control rats and treated continuously with the antibiotic ampicillin in their drinking water from the first day of GAS-antigen exposure. Two additional groups of rats (GAS and Control did not receive ampicillin in their drinking water. Behavior of the four groups was assessed in the forced swim, marble burying and food manipulation assays. We assessed levels of D1 and D2 dopamine receptors and tyrosine hydroxylase in the prefrontal cortex and striatum, and IgG deposition in the prefrontal cortex, striatum and thalamus. Ampicillin treatment prevented emergence of the motor and some of the behavioral alterations induced by GAS-antigen exposure, reduced IgG deposition in the thalamus of GAS-exposed rats, and tended to attenuate the increase in the level of TH and D1 and D2 receptors in their striatum, without concomitantly reducing the level of sera anti-GAS antibodies. Our results reinforce the link between exposure to GAS antigen, dysfunction of central dopaminergic pathways and motor and behavioral alterations. Our data further show that some of these deleterious effects can be attenuated by antibiotic treatment, and supports the latter's possible efficacy as a prophylactic treatment in GAS-related neuropsychiatric disorders.

  20. Mortar alteration: experimental study and ancient analogues

    International Nuclear Information System (INIS)

    Rassineux, Francois

    1987-01-01

    As the durability of cemented matrices is a matter of great importance in numerous domains, notably for the long term reliability of surface storages of radioactive wastes, the objective of this research thesis is to define mechanisms of evolution of cemented matrices when in contact with diluted aqueous solutions. The author notably studied the influence of the lixiviation mode on the evolution of two mortars having different compositions (pH, CO 2 pressure, system containment, and cement mineralogical nature appear to be the main governing parameters), the alteration (dissolution is the prevailing process in the interaction between cemented matrices and a diluted solution such as rain water), and ancient binders (archaeological binders containing mineral phases such as hydrated calcium silicates or hydro-grossulars). The obtained results lead to the definition of alteration mechanisms in modern cements, and highlight factors governing the durability of these materials when submitted to meteoric alteration [fr

  1. Neuro-chemical activation of brain reward meso-limbic circuitry is associated with relapse prevention and drug hunger: a hypothesis.

    Science.gov (United States)

    Blum, Kenneth; Gold, Mark S

    2011-04-01

    It is no surprise that it has taken over four decades to confirm and extend the crucial role of dopamine and related genes and gene deficits in the etiology of risk for drug dependence. Hundreds of studies, enabled by neuroscience neuroimaging and genetic advances, have been reported. While dopamine theories have been reported, confirmed, replicated and replicated again, changes have been slow to move from the bench to the bedside. Unlike penicillin used to target certain infections, addiction requires the consent, motivation and enthusiastic participation of the patient. Clearly, current treatment has not caught up with advances in the science. In-patient and out-patient treatment still relies on detoxification, abstinence and 12 step programs. Addiction is a chronic and relapsing disease. Addiction treatment can be reported as cures at 3 or 6 weeks, only to be clearly failures at 1 or 5 years. The logical standard of care should focus on detoxifying, stabilizing and returning the patient to the pre-loss of control or pre-addiction neurochemical state. Pre-clinical and clinical data on neurochemistry and neurogenetics of Substance Use Disorder (SUD) as it relates to both relapse and drug hunger has been reviewed. We are proposing herein that efforts to physiologically integrate known neural mechanisms with other psychotherapeutic treatment options to combat relapse should be encouraged. It is well known that after prolonged abstinence, recovered addicts are particularly vulnerable to relapse. Individuals who use their drug of choice after abstinence experience a powerful euphoria that can quickly precipitate a full-blown relapse. While a biological explanation for this conundrum has remained elusive, we hypothesize that this clinically observed "supersensitivity" might be the result of pre-morbid or state genetic hypodopaminergic polymorphisms. We are proposing that recent studies have indicated that genetic, personality and environmental factors are predictors of

  2. Lymphoid Aggregates That Resemble Tertiary Lymphoid Organs Define a Specific Pathological Subset in Metal-on-Metal Hip Replacements

    Science.gov (United States)

    Barone, Francesca; Hardie, Debbie L.; Matharu, Gulraj S.; Davenport, Alison J.; Martin, Richard A.; Grant, Melissa; Mosselmans, Frederick; Pynsent, Paul; Sumathi, Vaiyapuri P.; Addison, Owen; Revell, Peter A.; Buckley, Christopher D.

    2013-01-01

    Aseptic lymphocyte-dominated vasculitis-associated lesion (ALVAL) has been used to describe the histological lesion associated with metal-on-metal (M-M) bearings. We tested the hypothesis that the lymphoid aggregates, associated with ALVAL lesions resemble tertiary lymphoid organs (TLOs). Histopathological changes were examined in the periprosthetic tissue of 62 M-M hip replacements requiring revision surgery, with particular emphasis on the characteristics and pattern of the lymphocytic infiltrate. Immunofluorescence and immunohistochemistry were used to study the classical features of TLOs in cases where large organized lymphoid follicles were present. Synchrotron X-ray fluorescence (XRF) measurements were undertaken to detect localisation of implant derived ions/particles within the samples. Based on type of lymphocytic infiltrates, three different categories were recognised; diffuse aggregates (51%), T cell aggregates (20%), and organised lymphoid aggregates (29%). Further investigation of tissues with organised lymphoid aggregates showed that these tissues recapitulate many of the features of TLOs with T cells and B cells organised into discrete areas, the presence of follicular dendritic cells, acquisition of high endothelial venule like phenotype by blood vessels, expression of lymphoid chemokines and the presence of plasma cells. Co-localisation of implant-derived metals with lymphoid aggregates was observed. These findings suggest that in addition to the well described general foreign body reaction mediated by macrophages and a T cell mediated type IV hypersensitivity response, an under-recognized immunological reaction to metal wear debris involving B cells and the formation of tertiary lymphoid organs occurs in a distinct subset of patients with M-M implants. PMID:23723985

  3. Chromite alteration processes within Vourinos ophiolite

    Science.gov (United States)

    Grieco, Giovanni; Merlini, Anna

    2012-09-01

    The renewed interest in chromite ore deposits is directly related to the increase in Cr price ruled by international market trends. Chromite, an accessory mineral in peridotites, is considered to be a petrogenetic indicator because its composition reflects the degree of partial melting that the mantle experienced while producing the chromium spinel-bearing rock (Burkhard in Geochim Cosmochim Acta 57:1297-1306, 1993). However, the understanding of chromite alteration and metamorphic modification is still controversial (e.g. Evans and Frost in Geochim Cosmochim Acta 39:959-972, 1975; Burkhard in Geochim Cosmochim Acta 57:1297-1306, 1993; Oze et al. in Am J Sci 304:67-101, 2004). Metamorphic alteration leads to major changes in chromite chemistry and to the growth of secondary phases such as ferritchromite and chlorite. In this study, we investigate the Vourinos complex chromitites (from the mines of Rizo, Aetoraches, Xerolivado and Potamia) with respect to textural and chemical analyses in order to highlight the most important trend of alteration related to chromite transformation. The present study has been partially funded by the Aliakmon project in collaboration between the Public Power Corporation of Greece and Institute of Geology and Mineral Exploration of Kozani.

  4. Epidermal growth factor receptor structural alterations in gastric cancer

    International Nuclear Information System (INIS)

    Moutinho, Cátia; Mateus, Ana R; Milanezi, Fernanda; Carneiro, Fátima; Seruca, Raquel; Suriano, Gianpaolo

    2008-01-01

    EGFR overexpression has been described in many human tumours including gastric cancer. In NSCLC patients somatic EGFR mutations, within the kinase domain of the protein, as well as gene amplification were associated with a good clinical response to EGFR inhibitors. In gastric tumours data concerning structural alterations of EGFR remains controversial. Given its possible therapeutic relevance, we aimed to determine the frequency and type of structural alterations of the EGFR gene in a series of primary gastric carcinomas. Direct sequencing of the kinase domain of the EGFR gene was performed in a series of 77 primary gastric carcinomas. FISH analysis was performed in 30 cases. Association studies between EGFR alterations and the clinical pathological features of the tumours were performed. Within the 77 primary gastric carcinomas we found two EGFR somatic mutations and several EGFR polymorphisms in exon 20. Six different intronic sequence variants of EGFR were also found. Four gastric carcinomas showed balanced polysomy or EGFR gene amplification. We verified that gastric carcinoma with alterations of EGFR (somatic mutations or copy number variation) showed a significant increase of tumour size (p = 0.0094) in comparison to wild-type EGFR carcinomas. We demonstrate that EGFR structural alterations are rare in gastric carcinoma, but whenever present, it leads to tumour growth. We considered that searching for EGFR alterations in gastric cancer is likely to be clinically important in order to identify patients susceptible to respond to tyrosine kinase inhibitors

  5. Detection Of Alterations In Audio Files Using Spectrograph Analysis

    Directory of Open Access Journals (Sweden)

    Anandha Krishnan G

    2015-08-01

    Full Text Available The corresponding study was carried out to detect changes in audio file using spectrograph. An audio file format is a file format for storing digital audio data on a computer system. A sound spectrograph is a laboratory instrument that displays a graphical representation of the strengths of the various component frequencies of a sound as time passes. The objectives of the study were to find the changes in spectrograph of audio after altering them to compare altering changes with spectrograph of original files and to check for similarity and difference in mp3 and wav. Five different alterations were carried out on each audio file to analyze the differences between the original and the altered file. For altering the audio file MP3 or WAV by cutcopy the file was opened in Audacity. A different audio was then pasted to the audio file. This new file was analyzed to view the differences. By adjusting the necessary parameters the noise was reduced. The differences between the new file and the original file were analyzed. By adjusting the parameters from the dialog box the necessary changes were made. The edited audio file was opened in the software named spek where after analyzing a graph is obtained of that particular file which is saved for further analysis. The original audio graph received was combined with the edited audio file graph to see the alterations.

  6. Anatomical study of minor alterations in neonate vocal folds.

    Science.gov (United States)

    Silva, Adriano Rezende; Machado, Almiro José; Crespo, Agrício Nubiato

    2014-01-01

    Minor structural alterations of the vocal fold cover are frequent causes of voice abnormalities. They may be difficult to diagnose, and are expressed in different manners. Cases of intracordal cysts, sulcus vocalis, mucosal bridge, and laryngeal micro-diaphragm form the group of minor structural alterations of the vocal fold cover investigated in the present study. The etiopathogenesis and epidemiology of these alterations are poorly known. To evaluate the existence and anatomical characterization of minor structural alterations in the vocal folds of newborns. 56 larynxes excised from neonates of both genders were studied. They were examined fresh, or defrosted after conservation via freezing, under a microscope at magnifications of 25× and 40×. The vocal folds were inspected and palpated by two examiners, with the aim of finding minor structural alterations similar to those described classically, and other undetermined minor structural alterations. Larynges presenting abnormalities were submitted to histological examination. Six cases of abnormalities were found in different larynges: one (1.79%) compatible with a sulcus vocalis and five (8.93%) compatible with a laryngeal micro-diaphragm. No cases of cysts or mucosal bridges were found. The observed abnormalities had characteristics similar to those described in other age groups. Abnormalities similar to sulcus vocalis or micro-diaphragm may be present at birth. Copyright © 2014 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

  7. Ultrastructural alterations in adult Schistosoma mansoni caused by artemether

    Directory of Open Access Journals (Sweden)

    Shuhua Xiao

    2002-07-01

    Full Text Available Progress has been made over the last decade with the development and clinical use of artemether as an agent against major human schistosome parasites. The tegument has been identified as a key target of artemether, implying detailed studies on ultrastructural damage induced by this compound. We performed a temporal examination, employing a transmission electron microscope to assess the pattern and extent of ultrastructural alterations in adult Schistosoma mansoni harboured in mice treated with a single dose of 400 mg/kg artemether. Eight hours post-treatment, damage to the tegument and subtegumental structures was seen. Tegumental alterations reached a peak 3 days after treatment and were characterized by swelling, fusion of distal cytoplasma, focal lysis of the tegumental matrix and vacuolisation. Tubercles and sensory organelles frequently degenerated or collapsed. Typical features of subtegumental alterations, including muscle fibres, syncytium and parenchyma tissues, were focal or extensive lysis, vacuolisation and degeneration of mitochondria. Severe alterations were also observed in gut epithelial cells and vitelline cells of female worms. Our findings of artemether-induced ultrastructural alterations in adult S. mansoni confirm previous results obtained with juvenile S. mansoni and S. japonicum of different ages.

  8. Bone alterations by stress in athletes

    International Nuclear Information System (INIS)

    Doege, H.

    1990-01-01

    This report describes our experiences with the bone imaging in athletes. We studied 10 athletes and 10 other patients with spondylolisthesis of the lumbar spine and 16 athletes with suspicion of alterations of extremities. An increased uptake of this radiopharmaceutical was detected in six of 10 athletes with spondylolisthesis caused probably by stress fracture. Bone scans were negative in seven of 16 athletes with suspicion of lesion of extremities. In the remaining 9 patients scans were abnormal and showed periosteal injuries, epiphyseal alteration, joint abnormalities, tibial stress fractures and couvert fracture. It was also abnormal in bone injuries not evident in radiography. (orig.) [de

  9. Altered States of Consciousness during an Extreme Ritual

    Science.gov (United States)

    Loewald, Tonio; Comber, Evelyn M.; Hanson, Sarah A.; Pruitt, Bria

    2016-01-01

    Extreme rituals (body-piercing, fire-walking, etc.) are anecdotally associated with altered states of consciousness—subjective alterations of ordinary mental functioning (Ward, 1984)—but empirical evidence of altered states using both direct and indirect measures during extreme rituals in naturalistic settings is limited. Participants in the “Dance of Souls”, a 3.5-hour event during which participants received temporary piercings with hooks or weights attached to the piercings and danced to music provided by drummers, responded to measures of two altered states of consciousness. Participants also completed measures of positive and negative affect, salivary cortisol (a hormone associated with stress), self-reported stress, sexual arousal, and intimacy. Both pierced participants (pierced dancers) and non-pierced participants (piercers, piercing assistants, observers, drummers, and event leaders) showed evidence of altered states aligned with transient hypofrontality (Dietrich, 2003; measured with a Stroop test) and flow (Csikszentmihalyi, 1990; Csikszentmihalyi & Csikszentmihalyi, 1990; measured with the Flow State Scale). Both pierced and non-pierced participants also reported decreases in negative affect and psychological stress and increases in intimacy from before to after the ritual. Pierced and non-pierced participants showed different physiological reactions, however, with pierced participants showing increases in cortisol and non-pierced participants showing decreases from before to during the ritual. Overall, the ritual appeared to induce different physiological effects but similar psychological effects in focal ritual participants (i.e., pierced dancers) and in participants adopting other roles. PMID:27175897

  10. Altered States of Consciousness during an Extreme Ritual.

    Directory of Open Access Journals (Sweden)

    Ellen M Lee

    Full Text Available Extreme rituals (body-piercing, fire-walking, etc. are anecdotally associated with altered states of consciousness-subjective alterations of ordinary mental functioning (Ward, 1984-but empirical evidence of altered states using both direct and indirect measures during extreme rituals in naturalistic settings is limited. Participants in the "Dance of Souls", a 3.5-hour event during which participants received temporary piercings with hooks or weights attached to the piercings and danced to music provided by drummers, responded to measures of two altered states of consciousness. Participants also completed measures of positive and negative affect, salivary cortisol (a hormone associated with stress, self-reported stress, sexual arousal, and intimacy. Both pierced participants (pierced dancers and non-pierced participants (piercers, piercing assistants, observers, drummers, and event leaders showed evidence of altered states aligned with transient hypofrontality (Dietrich, 2003; measured with a Stroop test and flow (Csikszentmihalyi, 1990; Csikszentmihalyi & Csikszentmihalyi, 1990; measured with the Flow State Scale. Both pierced and non-pierced participants also reported decreases in negative affect and psychological stress and increases in intimacy from before to after the ritual. Pierced and non-pierced participants showed different physiological reactions, however, with pierced participants showing increases in cortisol and non-pierced participants showing decreases from before to during the ritual. Overall, the ritual appeared to induce different physiological effects but similar psychological effects in focal ritual participants (i.e., pierced dancers and in participants adopting other roles.

  11. Chemosensory alterations and cancer therapies

    International Nuclear Information System (INIS)

    Bartoshuk, L.M.

    1990-01-01

    Taste and olfaction provide sensory information and sensory pleasure. Cancer therapies affect both. Chemotherapy has not been shown to produce dramatic losses of taste or smell, but systematic studies on various chemotherapeutic agents and types of cancer are lacking. Radiation therapy does produce clear losses of both taste and smell. Both chemotherapy and radiation therapy alter the pleasure produced by taste and smell through the formation of conditioned aversions. That is, foods consumed in proximity with the nausea of therapy come to be unpleasant. The impact of conditioned aversions can be diminished by providing a scapegoat food just before therapy. Alterations in foods may be beneficial to the cancer patient. Increasing the concentrations of flavor ingredients can compensate for sensory losses, and providing pureed foods that retain the cognitive integrity of a meal can benefit the patient who has chewing or swallowing problems

  12. Alteration zones: are they a good target for gold deposits in Egypt

    International Nuclear Information System (INIS)

    Botros, N.S.

    2002-01-01

    Extensive rock alterations are a clearly visible characteristic of most Egyptian gold deposits and occurrences. The alterations occur either surrounding the auriferous quartz veins and/or structurally controlled by specific structural features, such as fractures and shear surfaces. Some samples of these alteration zones have proved to be anomalously enriched in gold while others are completely barren. Accordingly there is a controversy on the merit of alteration zones as good lead to gold. Here, the various types of wall rocks wall-rock alteration are reviewed with a discussion on the possible reaction that could have generated them. It is concluded that two main styles of alterations could be recognized in the field. The first results during the liberation of gold from the source rocks, and is characterized by being widely distributed and spatial relation to major structures. The second style, however, is related to the deposition of gold and is recognizable only within a few meters of the auriferous quartz veins. The potentiality of each style is discussed and applications of concept are offered. In general, alterations accompanying the liberation of gold are not completely devoid of gold, but may still retain some gold depending on the mineralogical siting of gold in the source rocks. Moreover, this type of alteration is a good criterion for the presence of gold in the nearby sites. Alterations accompanying deposition of gold, on the other hand, constitute a good target for gold particularly the portions that are dissected by minor quartz veins, veinlets and stockworks (silicification) where gold is believed to migrate to such sites with silica liberated during the different types of alterations. The presence of some efficient precipitants, such as sulphides, carbonates, clay minerals, sericites, iron oxides, chlorite and graphite in the alteration zones is a good indicator of the alteration zone. (author)

  13. Marijuana exposure and pulmonary alterations in primates.

    Science.gov (United States)

    Fligiel, S E; Beals, T F; Tashkin, D P; Paule, M G; Scallet, A C; Ali, S F; Bailey, J R; Slikker, W

    1991-11-01

    As part of a large multidisciplinary study, we examined lungs from 24 periadolescent male rhesus monkeys that were sacrificed seven months after daily marijuana smoke inhalation of 12 months duration. Animals were divided into four exposure groups: A) high-dose (one marijuana cigarette 7 days/week), B) low-dose (one marijuana cigarette 2 days/week and sham smoke 5 days/week), C) placebo (one extracted marijuana cigarette 7 days/week), and D) sham (sham smoke 7 days/week). Lungs, removed intact, were formalin inflated, sectioned and examined. Several pathological alterations, including alveolitis, alveolar cell hyperplasia and granulomatous inflammation, were found with higher frequency in all cigarette-smoking groups. Other alterations, such as bronchiolitis, bronchiolar squamous metaplasia and interstitial fibrosis, were found most frequently in the marijuana-smoking groups. Alveolar cell hyperplasia with focal atypia was seen only in the marijuana-smoking animals. These changes represent mostly early alterations of small airways. Additional follow-up studies are needed to determine their long-term prognostic significance.

  14. Alterations in physiology and anatomy during pregnancy.

    Science.gov (United States)

    Tan, Eng Kien; Tan, Eng Loy

    2013-12-01

    Pregnant women undergo profound anatomical and physiological changes so that they can cope with the increased physical and metabolic demands of their pregnancies. The cardiovascular, respiratory, haematological, renal, gastrointestinal and endocrine systems all undergo important physiological alterations and adaptations needed to allow development of the fetus and to allow the mother and fetus to survive the demands of childbirth. Such alterations in anatomy and physiology may cause difficulties in interpreting signs, symptoms, and biochemical investigations, making the clinical assessment of a pregnant woman inevitably confusing but challenging. Understanding these changes is important for every practicing obstetrician, as the pathological deviations from the normal physiological alterations may not be clear-cut until an adverse outcome has resulted. Only with a sound knowledge of the physiology and anatomy changes can the care of an obstetric parturient be safely optimized for a better maternal and fetal outcome. Copyright © 2013 Elsevier Ltd. All rights reserved.

  15. The effects of proton exposure on neurochemistry and behavior

    Science.gov (United States)

    Shukitt-Hale, B.; Szprengiel, A.; Pluhar, J.; Rabin, B. M.; Joseph, J. A.

    2004-01-01

    Future space missions will involve long-term travel beyond the magnetic field of the Earth, where astronauts will be exposed to radiation hazards such as those that arise from galactic cosmic rays. Galactic cosmic rays are composed of protons, α particles, and particles of high energy and charge (HZE particles). Research by our group has shown that exposure to HZE particles, primarily 600 MeV/n and 1 GeV/n 56Fe, can produce significant alterations in brain neurochemistry and behavior. However, given that protons can make up a significant portion of the radiation spectrum, it is important to study their effects on neural functioning and on related performance. Therefore, these studies examined the effects of exposure to proton irradiation on neurochemical and behavioral endpoints, including dopaminergic functioning, amphetamine-induced conditioned taste aversion learning, and spatial learning and memory as measured by the Morris water maze. Male Sprague-Dawley rats received a dose of 0, 1.5, 3.0 or 4.0 Gy of 250 MeV protons at Loma Linda University and were tested in the different behavioral tests at various times following exposure. Results showed that there was no effect of proton irradiation at any dose on any of the endpoints measured. Therefore, there is a contrast between the insignificant effects of high dose proton exposure and the dramatic effectiveness of low dose (<0.1 Gy) exposures to 56Fe particles on both neurochemical and behavioral endpoints.

  16. Neuroimaging in nuclear medicine: drug addicted brain

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Yong-An; Kim, Dae-Jin [The Catholic University of Korea, Seoul (Korea, Republic of)

    2006-02-15

    Addiction to illicit drugs in one of today's most important social issues. Most addictive drugs lead to irreversible parenchymal changes in the human brain. Neuroimaging data bring to light the pharmacodynamics and pharmacokinetics of the abused drugs, and demonstrate that addiction is a disease of the brain. Continuous researches better illustrate the neurochemical alterations in brain function, and attempt to discover the links to consequent behavioral changes. Newer hypotheses and theories follow the numerous results, and more rational methods of approaching therapy are being developed. Substance abuse is on the rise in Korea, and social interest in the matter as well. On the other hand, diagnosis and treatment of drug addiction is still very difficult, because how the abused substance acts in the brain, or how it leads to behavioral problems in not widely known. Therefore, understanding the mechanism of drug addiction can improve the process of diagnosing addict patients, planning therapy, and predicting the prognosis . Neuroimaging approaches by nuclear medicine methods are expected to objectively judge behavioral and neurochemical changes, and response to treatment. In addition, as genes associated with addictive behavior are discovered, functional nuclear medicine images will aid in the assessment of individuals. Reviewing published literature on neuroimaging regarding nuclear medicine is expected to be of assistance to the management of drug addict patients. What's more, means of applying nuclear medicine to the care of drug addict patients should be investigated further.

  17. Neuroimaging in nuclear medicine: drug addicted brain

    International Nuclear Information System (INIS)

    Chung, Yong-An; Kim, Dae-Jin

    2006-01-01

    Addiction to illicit drugs in one of today's most important social issues. Most addictive drugs lead to irreversible parenchymal changes in the human brain. Neuroimaging data bring to light the pharmacodynamics and pharmacokinetics of the abused drugs, and demonstrate that addiction is a disease of the brain. Continuous researches better illustrate the neurochemical alterations in brain function, and attempt to discover the links to consequent behavioral changes. Newer hypotheses and theories follow the numerous results, and more rational methods of approaching therapy are being developed. Substance abuse is on the rise in Korea, and social interest in the matter as well. On the other hand, diagnosis and treatment of drug addiction is still very difficult, because how the abused substance acts in the brain, or how it leads to behavioral problems in not widely known. Therefore, understanding the mechanism of drug addiction can improve the process of diagnosing addict patients, planning therapy, and predicting the prognosis . Neuroimaging approaches by nuclear medicine methods are expected to objectively judge behavioral and neurochemical changes, and response to treatment. In addition, as genes associated with addictive behavior are discovered, functional nuclear medicine images will aid in the assessment of individuals. Reviewing published literature on neuroimaging regarding nuclear medicine is expected to be of assistance to the management of drug addict patients. What's more, means of applying nuclear medicine to the care of drug addict patients should be investigated further

  18. Neuroprotective Activity of Curcumin in Combination with Piperine against Quinolinic Acid Induced Neurodegeneration in Rats.

    Science.gov (United States)

    Singh, Shamsher; Kumar, Puneet

    2016-01-01

    Quinolinic acid (QA) is an excitotoxin that induces Huntington's-like symptoms in animals and humans. Curcumin (CMN) is a well-known antioxidant but the major problem is its bioavailability. Therefore, the present study was designed to investigate the effect of CMN in the presence of piperine against QA-induced excitotoxic cell death in rats. QA was administered intrastriatally at a dose of 200 nmol/2 µl saline, bilaterally. CMN (25 and 50 mg/kg/day, p.o.) and combination of CMN (25 mg/kg/day, p.o.) and with piperine (2.5 mg/kg/day, p.o.) was administered daily for the next 21 days. Body weight and behavioral parameters were observed on 1st, 7th, 14th and 21st day. On the 22nd day, animals were sacrificed and striatum was isolated for biochemical (LPO, nitrite and GSH), neuroinflammatory (interleukin (IL)-1β, IL-6 and TNF-α) and neurochemical (dopamine, norepinephrine, GABA, glutamate, 5-HT, 3,4-dihydroxyphenylacetic acid and homovanillic acid) estimation. CMN treatment showed beneficial effect against QA-induced motor deficit, biochemical and neurochemical abnormalities in rats. Combination of piperine (2.5 mg/kg/day, p.o.) with CMN (25 mg/kg/day, p.o.) significantly enhanced its protective effect as compared to treatment with CMN alone. This study has revealed that the combination of CMN and piperine showed strong antioxidant and protective effect against QA-induced behavioral and neurological alteration in rats. © 2016 S. Karger AG, Basel.

  19. Piperine Enhances the Protective Effect of Curcumin Against 3-NP Induced Neurotoxicity: Possible Neurotransmitters Modulation Mechanism.

    Science.gov (United States)

    Singh, Shamsher; Jamwal, Sumit; Kumar, Puneet

    2015-08-01

    3-Nitropropionic acid (3-NP) is a fungal toxin well established model used for inducing symptoms of Huntington's disease. Curcumin a natural polyphenol has been reported to possess neuroprotective activity by decreasing oxidative stress. The aim of present study was to investigate neuroprotective effect of curcumin with piperine (bioavailability enhancer) against 3-NP induced neurotoxicity in rats. Administration of 3-NP (10 mg/kg for 21 days) showed loss in body weight, declined motor function and changes in biochemical (LPO, nitrite and glutathione level), neuroinflammatory (TNF-α and IL-1β level) and neurochemical (DA, NE, 5-HT, DOPAC, 5-HIAA and HVA). Chronic treatment with curcumin (25 and 50 mg/kg) and curcumin (25 mg/kg) with piperine (2.5 mg/kg) once daily for 21 days prior to 3-NP administration. All the behavioral parameters were studied at 1st, 7th, 14th, and 21st day. On 22nd day all the animals was scarified and striatum was separated. Curcumin alone and combination (25 mg/kg) with piperine (2.5 mg/kg) showed beneficial effect against 3-NP induced motor deficit, biochemical and neurochemical abnormalities in rats. Piperine (2.5 mg/kg) with curcumin (25 mg/kg) significantly enhances its protective effect as compared with curcumin alone treated group. The results of the present study indicate that protective effect of curcumin potentiated in the presence of piperine (bioavailability enhancer) against 3-NP-induced behavioral and molecular alteration.

  20. Benign Bone Conditions That May Be FDG-avid and Mimic Malignancy

    NARCIS (Netherlands)

    Kwee, Thomas C.; de Klerk, John M. H.; Nix, Maarten; Heggelman, Ben G. F.; Dubois, Stefan V.; Adams, Hugo J. A.

    Positron emission tomography with the radiotracer F-18-fluoro-2-deoxy-D-glucose (FDG) plays an important role in the evaluation of bone pathology. However, FDG is not a cancer-specific agent, and knowledge of the differential diagnosis of benign FDG-avid bone alterations that may resemble malignancy