Sample records for sandstone-hosted alteration system

  1. Assessment of undiscovered sandstone-hosted uranium resources in the Texas Coastal Plain, 2015 (United States)

    Mihalasky, Mark J.; Hall, Susan M.; Hammarstrom, Jane M.; Tureck, Kathleen R.; Hannon, Mark T.; Breit, George N.; Zielinski, Robert A.; Elliott, Brent


    The U.S. Geological Survey estimated a mean of 220 million pounds of recoverable uranium oxide (U3O8 ) remaining as potential undiscovered resources in southern Texas. This estimate used a geology-based assessment method for Tertiary sandstone-hosted uranium deposits in the Texas Coastal Plain sedimentary strata (fig.1).

  2. Uranium-Series Disequilibria in the Groundwater of the Shihongtan Sandstone-Hosted Uranium Deposit, NW China

    Directory of Open Access Journals (Sweden)

    Xinjian Peng


    Full Text Available Uranium (U concentration and the activities of 238U, 234U, and 230Th were determined for groundwaters, spring waters, and lake water collected from the Shihongtan sandstone-hosted U ore district and in the surrounding area, NW China. The results show that the groundwaters from the oxidizing aquifer with high dissolved oxygen concentration (O2 and oxidation-reduction potential (Eh are enriched in U. The high U concentration of groundwaters may be due to the interaction between these oxidizing groundwaters and U ore bodies, which would result in U that is not in secular equilibrium. Uranium is re-precipitated as uraninite on weathered surfaces and organic material, forming localized ore bodies in the sandstone-hosted aquifer. The 234U/238U, 230Th/234U, and 230Th/238U activity ratios (ARs for most water samples show obvious deviations from secular equilibrium (0.27–2.86, indicating the presence of water-rock/ore interactions during the last 1.7 Ma and probably longer. The 234U/238U AR generally increases with decreasing U concentrations in the groundwaters, suggesting that mixing of two water sources may occur in the aquifer. This is consistent with the fact that most of the U ore bodies in the deposit have a tabular shape originati from mixing between a relatively saline fluid and a more rapidly flowing U-bearing meteoric water.

  3. Multivariate approach to the chemical mapping of uranium in sandstone-hosted uranium ores analyzed using double pulse Laser-Induced Breakdown Spectroscopy (United States)

    Klus, Jakub; Mikysek, Petr; Prochazka, David; Pořízka, Pavel; Prochazková, Petra; Novotný, Jan; Trojek, Tomáš; Novotný, Karel; Slobodník, Marek; Kaiser, Jozef


    The goal of this work is to provide high resolution mapping of uranium in sandstone-hosted uranium ores using Laser-Induced Breakdown Spectroscopy (LIBS) technique. In order to obtain chemical image with highest possible spatial resolution, LIBS system in orthogonal double pulse (DP LIBS) arrangement was employed. Owing to this experimental arrangement the spot size of 50 μm in diameter resulting in lateral resolution of 100 μm was reached. Despite the increase in signal intensity in DP LIBS modification, the detection of uranium is challenging. The main cause is the high density of uranium spectral lines, which together with broadening of LIBS spectral lines overreaches the resolution of commonly used spectrometers. It results in increased overall background radiation with only few distinguishable uranium lines. Three different approaches in the LIBS data treatment for the uranium detection were utilized: i) spectral line intensity, ii) region of apparent background and iii) multivariate data analysis. By utilizing multivariate statistical methods, a specific specimen features (in our case uranium content) were revealed by processing complete spectral information obtained from broadband echelle spectrograph. Our results are in a good agreement with conventional approaches such as line fitting and show new possibilities of processing spectral data in mapping. As a reference technique to LIBS was employed X-ray Fluorescence (XRF). The XRF chemical images used in this paper have lower resolution (approximately 1-2 mm per image point), nevertheless the elemental distribution is apparent and corresponds to presented LIBS experiments.

  4. Experimental study on reduction of U (Ⅵ) by an anaerobic bacterium, Shewanella putrefaciens: Application to sandstone-hosted interlayer oxidation-zone type uranium deposits, China

    Institute of Scientific and Technical Information of China (English)

    MIN Maozhong; XU Huifang; L. L. Barton; PENG Xinjian; YIN Lin; WANG Rucheng


    An experimental study on reduction of U (Ⅵ) by anaerobic bacteria, Shewane//a putrefaciens, is first reported here in China. The experimental conditions were: 35℃ and pH =7.0-7.4, corresponding to a physicochemical environments in which the sandstone-hosted interlayer oxidation-zone type uranium deposit formed in Northwest China's Xinjiang. Bacteria adopted in the present experiment, Shewanella putrefaciens, occur extensively in natural environment. Our study shows that nano-crystal precipitates of uraninite quickly occurred on the surface of the cells within one week. It was found that the pitchblende was characterized by a random arrangement of uraninite nanocrystals (2-4 nm) in it, significantly different from natural pitchblende in which uraninite nanocrystals are arranged in order. Finally, a possible mechanism of uranium biomineralization by microorganisms in the deposits is discussed. Our investigation may supply a technical train of thoughts for bioremediation of nuclear-contaminated water environments and for underground dissolving extraction of the sandstone-hosted uranium ores.

  5. Porosity and Permeability Evolution in Cemented Rock Cores under Reactive Flowing Conditions: Comparative Analysis between Limestone and Sandstone Host Rocks (United States)

    Cao, P.; Karpyn, Z.; Li, L.


    CO2-brine has the potential to alter wellbore cement in depleted oil and gas reservoirs under geological CO2 sequestration conditions. A better understanding of CO2-brine-cement-rock interaction is needed to evaluate the seal integrity of candidate sequestration formation in the long run. This work investigates possible alteration of wellbore cement when bonded by different host formation rock upon exposure to CO2-saturated brine. Composite cement-sandstone and cement-limestone core samples were created to perform reactive coreflood experiments. After an eight-day dynamic flow-through period, both cores had a similar extent of porosity increase, while the cement-limestone core experienced a ten-fold higher increase in permeability. With the aid of X-ray Micro-CT imaging and Scanning Electron Microscopy, it is observed that cement underwent greater degradation at the cement-sandstone interface. Degradation of cement-limestone core mainly took place on the host rock matrix. Worm holes were developed and a solution channel was formed in the limestone, creating a dominant flow path that altered both flow and reaction behavior. Limestone buffered the injected acidic brine preventing further deterioration of cement near the core outlet. Changes in fluid chemistry of limestone and sandstone coreflood effluents are compared. Results from this work are aimed at assisting the development and validation of robust reactive transport models through direct measurement of cemented rock core porosity and permeability evolution as well as the effluent aqueous chemistry change. This will subsequently improve predictive capabilities of reactive transport models associated with CO2 sequestration in geologic environments. Permeability Evolution of Cement-Rock Core Sample during Dynamic Flow of CO2-Brine

  6. Genetic and grade and tonnage models for sandstone-hosted roll-type uranium deposits, Texas Coastal Plain, USA (United States)

    Hall, Susan M.; Mihalasky, Mark J.; Tureck, Kathleen; Hammarstrom, Jane M.; Hannon, Mark


    The coincidence of a number of geologic and climatic factors combined to create conditions favorable for the development of mineable concentrations of uranium hosted by Eocene through Pliocene sandstones in the Texas Coastal Plain. Here 254 uranium occurrences, including 169 deposits, 73 prospects, 6 showings and 4 anomalies, have been identified. About 80 million pounds of U3O8 have been produced and about 60 million pounds of identified producible U3O8 remain in place. The development of economic roll-type uranium deposits requires a source, large-scale transport of uranium in groundwater, and deposition in reducing zones within a sedimentary sequence. The weight of the evidence supports a source from thick sequences of volcanic ash and volcaniclastic sediment derived mostly from the Trans-Pecos volcanic field and Sierra Madre Occidental that lie west of the region. The thickest accumulations of source material were deposited and preserved south and west of the San Marcos arch in the Catahoula Formation. By the early Oligocene, a formerly uniformly subtropical climate along the Gulf Coast transitioned to a zoned climate in which the southwestern portion of Texas Coastal Plain was dry, and the eastern portion humid. The more arid climate in the southwestern area supported weathering of volcanic ash source rocks during pedogenesis and early diagenesis, concentration of uranium in groundwater and movement through host sediments. During the middle Tertiary Era, abundant clastic sediments were deposited in thick sequences by bed-load dominated fluvial systems in long-lived channel complexes that provided transmissive conduits favoring transport of uranium-rich groundwater. Groundwater transported uranium through permeable sandstones that were hydrologically connected with source rocks, commonly across formation boundaries driven by isostatic loading and eustatic sea level changes. Uranium roll fronts formed as a result of the interaction of uranium-rich groundwater

  7. Analysis of Rare Earth Elements (REE) in vein quartz and quartz-sandstone host rock in the Zhelannoe high purity quartz deposit, Russia (United States)

    Zemskova, Marina; Prokofiev, Vsevolod; Bychkov, Andrey


    The Zhelannoe high purity quartz deposit is located on the western slope of the Polar Urals. It is one of the largest deposits of vein quartz and rock crystal in Russia. Most of the mineralization is hosted within a single horizon of very firm quartz-sandstone, where plastic deformation did not occur almost entirely. All tectonic stress was released by the development of numerous thrust faults of different scales. Cavities formed during this process were later filled with quartz and rock crystal. In order to obtain more details on conditions under which mineralization took place, analysis of trace element contents in vein quartz and host rocks, and the micro-thermometric study of fluid inclusions in quartz have been carried out. The trace element composition of vein quartz and of the host rock has been determined by ICP-MS. The results have shown that concentrations of most of the 46 studied elements in quartz are two orders of magnitude lower than in chondrite, and more than three orders of magnitude lower than in the upper crust. Even though Pb and Li have the highest concentrations in quartz samples, levels are only nearly comparable in chondrite, and substantially lower in the upper crust. At the same time, negative anomalies of Pb and Li concentrations in the host rock may indicate the removal of these elements during vein quartz formation. Contents of most REEs are two orders of magnitude lower than in chondrite, and three orders of magnitude lower than in the host rock. Generally, the patterns of REE distribution in vein quartz and the host rock express a clear correlation; confirming the genetic link between vein quartz and quartz-sandstone host rock. However, the process of quartz recrystallization led to an intense decrease of REEs content, and of all other impurities, which consequently influenced industrial value of the Zhelannoe deposit. As a result of the micro-thermometric study of fluid inclusions in quartz, the following physical

  8. Inflammation and immune system alterations in frailty. (United States)

    Yao, Xu; Li, Huifen; Leng, Sean X


    Frailty is an important geriatric syndrome characterized by multisystem dysregulation. Substantial evidence suggests heightened inflammatory state and significant immune system alterations in frailty. A heightened inflammatory state is marked by increases in levels of inflammatory molecules (interleukin 6 and C-reactive protein) and counts of white blood cell and its subpopulations, which may play an important role in the pathogenesis of frailty, directly or through its detrimental influence on other physiologic systems. Alterations in the innate immune system include decreased proliferation of the peripheral blood mononuclear cells and upregulated monocytic expression of specific stress-responsive inflammatory pathway genes. In the adaptive immune system, although little information is available about potential B-cell changes, significant alterations have been identified in the T-cell compartment, including increased counts of CD8+, CD8+CD28-, CCR5+T cells, above and beyond age-related senescent immune remodeling.

  9. 全国砂岩型铀矿资源潜力评价%The Potential Evaluation of Sandstone-Hosted Uranium Resources in China

    Institute of Scientific and Technical Information of China (English)

    刘武生; 贾立城; 刘红旭


    Based on systematic study on structural environment and metallogenic pattern of uraniferous formation of marine carbonaceous-siliceous-argillaceous rocks in China, four types of mineralization systems was proposed, which include margin rift valley system, epicontinental rift-deep fracture zone system, borderland basin system and epicontinental active downfaulted aulacogen system. Large-scale uranium mineralization of carbonaceous-siliceous-argillaceous rock is believed to be controlled by uraniferous marine carbonaceous-siliceous-argillaceous rocks which were settled down with submarine backwash and submarine volcanic-eruption in margin rift valley and continental margin rifting environment. Characteristic parameter group of large-size mineralization cluster was applied to establish the evaluation and prediction system for typical carbonaceous-siliceous-argillaceous rock type mineralization area so as to generally evaluate the uranium resource of this type in China.%文章在充分借鉴和应用国内外砂岩型铀矿的成矿理论、成果认识的基础上,通过对中国构造地质背景分析和成矿规律总结,厘定出8条砂岩型铀矿的成矿要素和12种预测类型(矿床式).同时,采用固体矿产矿床模型综合地质信息预测技术,全过程在GIS平台上圈定了预测区88片、预测靶区709片;采用修正体积法估算资源量,对全国砂岩型铀矿作出全面、客观评价,为今后找矿战略部署和战略选区提供科学依据.

  10. Glaucoma alters the circadian timing system.

    Directory of Open Access Journals (Sweden)

    Elise Drouyer

    Full Text Available Glaucoma is a widespread ocular disease and major cause of blindness characterized by progressive, irreversible damage of the optic nerve. Although the degenerative loss of retinal ganglion cells (RGC and visual deficits associated with glaucoma have been extensively studied, we hypothesize that glaucoma will also lead to alteration of the circadian timing system. Circadian and non-visual responses to light are mediated by a specialized subset of melanopsin expressing RGCs that provide photic input to mammalian endogenous clock in the suprachiasmatic nucleus (SCN. In order to explore the molecular, anatomical and functional consequences of glaucoma we used a rodent model of chronic ocular hypertension, a primary causal factor of the pathology. Quantitative analysis of retinal projections using sensitive anterograde tracing demonstrates a significant reduction (approximately 50-70% of RGC axon terminals in all visual and non-visual structures and notably in the SCN. The capacity of glaucomatous rats to entrain to light was challenged by exposure to successive shifts of the light dark (LD cycle associated with step-wise decreases in light intensity. Although glaucomatous rats are able to entrain their locomotor activity to the LD cycle at all light levels, they require more time to re-adjust to a shifted LD cycle and show significantly greater variability in activity onsets in comparison with normal rats. Quantitative PCR reveals the novel finding that melanopsin as well as rod and cone opsin mRNAs are significantly reduced in glaucomatous retinas. Our findings demonstrate that glaucoma impacts on all these aspects of the circadian timing system. In light of these results, the classical view of glaucoma as pathology unique to the visual system should be extended to include anatomical and functional alterations of the circadian timing system.

  11. Alterations of the Thioredoxin System by Hyperoxia (United States)

    Tipple, Trent E.; Welty, Stephen E.; Nelin, Leif D.; Hansen, Jason M.; Rogers, Lynette K.


    Alterations in vascular endothelial growth factor (VEGF) contribute to alveolar simplification seen in animal models of bronchopulmonary dysplasia, and VEGF expression is redox regulated by thioredoxin (Trx)-1 in other diseases. The present studies tested the hypothesis that exposure to 85% O2 negatively impacts the Trx1 system and VEGF expression in the lungs of newborn mice. There was no effect of fraction of inspired oxygen on lung Trx1 or Trx reductase-1 protein levels; however, lung Trx1 protein was predominantly oxidized in the lungs of newborn mice exposed to 85% O2 by 24 hours of exposure. In room air (RA), lung Trx interacting protein (Txnip) levels decreased developmentally through Day 7 (1.0 ± 0.06 [Day 1] vs. 0.49 ± 0.10 [Day 3] vs. 0.29 ± 0.03 [Day 7]; P < 0.01), whereas VEGF expression increased (1.25 ± 0.16 [Day 1] vs. 4.35 ± 1.51 [Day 3] vs. 13.23 ± 0.37 [Day 7]; P < 0.01). Newborn mice exposed to 85% O2 had no developmental decrease in Txnip protein levels and a delayed increase in VEGF protein levels. Lung Txnip and VEGF protein levels were different than in corresponding RA controls at Day 3, before the detection of lung morphologic abnormalities in our model. Txnip and VEGF protein levels were inversely correlated in both the RA and hyperoxia-exposed groups (n = 18; R = −0.66; P = 0.003). In conclusion, oxidation of Trx1 and sustained Txnip expression in the lungs of newborn mice exposed to 85% oxygen is likely to severely attenuate normal Trx1 function. The inverse correlation of Txnip with VEGF expression suggests that decreased Trx1 function contributes to the observed lung developmental abnormalities. PMID:19244202

  12. Altered anterior visual system development following early monocular enucleation

    Directory of Open Access Journals (Sweden)

    Krista R. Kelly


    Conclusions: The novel finding of an asymmetry in morphology of the anterior visual system following long-term survival from early monocular enucleation indicates altered postnatal visual development. Possible mechanisms behind this altered development include recruitment of deafferented cells by crossing nasal fibres and/or geniculate cell retention via feedback from primary visual cortex. These data highlight the importance of balanced binocular input during postnatal maturation for typical anterior visual system morphology.

  13. Immune system alterations in amyotrophic lateral sclerosis

    DEFF Research Database (Denmark)

    Hovden, H; Frederiksen, J L; Pedersen, S W


    Amyotrophic lateral sclerosis is a disease of which the underlying cause and pathogenesis are unknown. Cumulatative data clearly indicates an active participation by the immune system in the disease. An increasingly recognized theory suggests a non-cell autonomous mechanism, meaning that multiple...

  14. Mephedrone alters basal ganglia and limbic dynorphin systems. (United States)

    German, Christopher L; Alburges, Mario E; Hoonakker, Amanda J; Fleckenstein, Annette E; Hanson, Glen R


    Mephedrone (4-methymethcathinone) is a synthetic cathinone designer drug that disrupts central nervous system (CNS) dopamine (DA) signaling. Numerous central neuropeptide systems reciprocally interact with dopaminergic neurons to provide regulatory counterbalance, and are altered by aberrant DA activity associated with stimulant exposure. Endogenous opioid neuropeptides are highly concentrated within dopaminergic CNS regions and facilitate many rewarding and aversive properties associated with drug use. Dynorphin, an opioid neuropeptide and kappa receptor agonist, causes dysphoria and aversion to drug consumption through signaling within the basal ganglia and limbic systems, which is affected by stimulants. This study evaluated how mephedrone alters basal ganglia and limbic system dynorphin content, and the role of DA signaling in these changes. Repeated mephedrone administrations (4 × 25 mg/kg/injection, 2-h intervals) selectively increased dynorphin content throughout the dorsal striatum and globus pallidus, decreased dynorphin content within the frontal cortex, and did not alter dynorphin content within most limbic system structures. Pretreatment with D1 -like (SCH-23380) or D2 -like (eticlopride) antagonists blocked mephedrone-induced changes in dynorphin content in most regions examined, indicating altered dynorphin activity is a consequence of excessive DA signaling. Synapse, 2014. © 2014 Wiley Periodicals, Inc.

  15. A highly specific coding system for structural chromosomal alterations. (United States)

    Martínez-Frías, M L; Martínez-Fernández, M L


    The Spanish Collaborative Study of Congenital Malformations (ECEMC, from the name in Spanish) has developed a very simple and highly specific coding system for structural chromosomal alterations. Such a coding system would be of value at present due to the dramatic increase in the diagnosis of submicroscopic chromosomal deletions and duplications through molecular techniques. In summary, our new coding system allows the characterization of: (a) the type of structural anomaly; (b) the chromosome affected; (c) if the alteration affects the short or/and the long arm, and (d) if it is a non-pure dicentric, a non-pure isochromosome, or if it affects several chromosomes. We show the distribution of 276 newborn patients with these types of chromosomal alterations using their corresponding codes according to our system. We consider that our approach may be useful not only for other registries, but also for laboratories performing these studies to store their results on case series. Therefore, the aim of this article is to describe this coding system and to offer the opportunity for this coding to be applied by others. Moreover, as this is a SYSTEM, rather than a fixed code, it can be implemented with the necessary modifications to include the specific objectives of each program. Copyright © 2013 Wiley Periodicals, Inc.

  16. The sympathetic nervous system alterations in human hypertension. (United States)

    Grassi, Guido; Mark, Allyn; Esler, Murray


    Several articles have dealt with the importance and mechanisms of the sympathetic nervous system alterations in experimental animal models of hypertension. This review addresses the role of the sympathetic nervous system in the pathophysiology and therapy of human hypertension. We first discuss the strengths and limitations of various techniques for assessing the sympathetic nervous system in humans, with a focus on heart rate, plasma norepinephrine, microneurographic recording of sympathetic nerve traffic, and measurements of radiolabeled norepinephrine spillover. We then examine the evidence supporting the importance of neuroadrenergic factors as promoters and amplifiers of human hypertension. We expand on the role of the sympathetic nervous system in 2 increasingly common forms of secondary hypertension, namely hypertension associated with obesity and with renal disease. With this background, we examine interventions of sympathetic deactivation as a mode of antihypertensive treatment. Particular emphasis is given to the background and results of recent therapeutic approaches based on carotid baroreceptor stimulation and radiofrequency ablation of the renal nerves.

  17. Method and Apparatus Providing Deception and/or Altered Operation in an Information System Operating System (United States)

    Cohen, Fred; Rogers, Deanna T.; Neagoe, Vicentiu


    A method and/or system and/or apparatus providing deception and/or execution alteration in an information system. In specific embodiments, deceptions and/or protections are provided by intercepting and/or modifying operation of one or more system calls of an operating system.

  18. 76 FR 4449 - Privacy Act of 1974; Report of Modified or Altered System of Records (United States)


    ... Altered System of Records AGENCY: Scientific Resources Program, Material, Data and Specimen Handling...). ACTION: Notification of Proposed Altered System of Records. SUMMARY: The Department of Health and Human..., Federal holidays excepted. SUPPLEMENTARY INFORMATION: NCID proposes to alter System of Records, No....

  19. Mephedrone alters basal ganglia and limbic neurotensin systems. (United States)

    German, Christopher L; Hoonakker, Amanda H; Fleckenstein, Annette E; Hanson, Glen R


    Mephedrone (4-methylmethcathinone) is a synthetic cathinone designer drug that alters pre-synaptic dopamine (DA) activity like many psychostimulants. However, little is known about the post-synaptic dopaminergic impacts of mephedrone. The neuropeptide neurotensin (NT) provides inhibitory feedback for basal ganglia and limbic DA pathways, and post-synaptic D1 -like and D2 -like receptor activity affects NT tissue levels. This study evaluated how mephedrone alters basal ganglia and limbic system NT content and the role of NT receptor activation in drug consumption behavior. Four 25 mg/kg injections of mephedrone increased NT content in basal ganglia (striatum, substantia nigra and globus pallidus) and the limbic regions (nucleus accumbens core), while a lower dosage (5 mg/kg/injection) only increased striatal NT content. Mephedrone-induced increases in basal ganglia NT levels were mediated by D1 -like receptors in the striatum and the substantia nigra by both D1 -like and D2 -like receptors in the globus pallidus. Mephedrone increased substance P content, another neuropeptide, in the globus pallidus, but not in the dorsal striatum or substantia nigra. Finally, the NT receptor agonist PD149163 blocked mephedrone self-administration, suggesting reduced NT release, as indicated by increased tissue levels, likely contributing to patterns of mephedrone consumption.

  20. BACE1-Deficient Mice Exhibit Alterations in Immune System Pathways. (United States)

    Stertz, L; Contreras-Shannon, V; Monroy-Jaramillo, N; Sun, J; Walss-Bass, C


    BACE1 encodes for the beta-site amyloid precursor protein cleaving enzyme 1 or β-secretase. Genetic deletion of Bace1 leads to behavioral alterations and affects midbrain dopaminergic signaling and memory processes. In order to further understand the role of BACE1 in brain function and behavior, we performed microarray transcriptome profiling and gene pathway analysis in the hippocampus of BACE1-deficient mice compared to wild type. We identified a total of 91 differentially expressed genes (DEGs), mostly enriched in pathways related to the immune and inflammation systems, particularly IL-9 and NF-κB activation pathways. Serum levels of IL-9 were elevated in BACE1-deficient mice. Our network analysis supports an intimate connection between immune response via NF-κB and BACE1 signaling through the NRG1/Akt1 pathway. Our findings warrant future mechanistic studies to determine if BACE1 signaling and the IL-9 pathway interact to alter behavior and brain function. This study opens new avenues in the investigation of hippocampus-related neuroimmunological and neuroinflammation-associated disorders.


    Grassi, Guido; Mark, Allyn; Esler, Murray


    A number of articles have dealt with the importance and mechanisms of the sympathetic nervous system alterations in experimental animal models of hypertension. This review addresses the role of the sympathetic nervous system in the pathophysiology and therapy of human hypertension. We first discuss the strengths and limitations of various techniques for assessing the sympathetic nervous system in humans, with a focus on heart rate, plasma norepinephrine, microneurographic recording of sympathetic nerve traffic, and measurements of radiolabeled norepinephrine spillover. We then examine the evidence supporting the importance of neuroadrenergic factors as “promoters” and “amplifiers” of human hypertension. We expand on the role of the sympathetic nervous system in two increasingly common forms of secondary hypertension, namely hypertension associated with obesity and with renal disease. With this background, we examine interventions of sympathetic deactivation as a mode of antihypertensive treatment. Particular emphasis is given to the background and results of recent therapeutic approaches based on carotid baroreceptor stimulation and radiofrequency ablation of the renal nerves. PMID:25767284

  2. Altered balance in the autonomic nervous system in schizophrenic patients

    DEFF Research Database (Denmark)

    Nielsen, B M; Mehlsen, J; Behnke, K


    healthy subjects (32 +/- 7 years) served as controls. Immediate heart-rate responses to a single deep inspiration was used as a measure of parasympathetic function. Heart-rate response to standing was used as a measure of sympathetic function. Supine blood pressure, heart-rate and orthostatic changes...... in blood pressure did not differ between groups. Heart-rate response to standing was greater in both medicated and non-medicated schizophrenics compared to normal subjects (P less than 0.01). Heart-rate response to standing was greater in non-medicated compared to medicated schizophrenics (P less than 0.......05). Heart-rate response to inspiration was greater in non-medicated schizophrenics compared to normal subjects (P less than 0.05), whereas no difference was found between medicated and non-medicated schizophrenics. The results show that the balance in the autonomic nervous system is altered in schizophrenic...

  3. Thermodynamics of Organic Compound Alteration in Hydrothermal Systems (United States)

    Shock, E. L.


    Organic compounds enter hydrothermal systems through infiltrating surface waters, zones of microbial productivity in the subsurface, extracts of organic matter in surrounding host rocks, and abiotic synthesis. Owing to variations in pH, oxidation state, composition, temperature, and pressure throughout the changing pathways of fluid migration over the duration of the system, organic compounds from all of these sources are introduced to conditions where their relative stabilities and reactivities can be dramatically transformed. If those transformations were predictable, then the extent to which organic alteration reactions have occurred could be used to reveal flowpaths and histories of hydrothermal systems. Speciation and mass transfer calculations permit some insight into the underlying thermodynamic driving forces that result in organic compound alteration. As an example, the speciation of many geochemist's canonical organic matter: CH2O depends strongly on oxidation state, temperature, and total concentration of dissolved organic matter. Calculations show that at oxidation states buffered by iron-bearing mineral assemblages, organic acids dominate the speciation of CH2O throughout hydrothermal systems, with acetic acid (itself equivalent to 2 CH2O by bulk composition) and propanoic acid generally the most abundant compounds. However, at more reduced conditions, which may prevail in organic-rich iron-poor sediments, the drive is to form ketones and especially alcohols at the expense of organic acids. The distribution of organic carbon among the various members of these compound classes is strongly dependent on the total concentration of dissolved organic matter. As an example, at a bulk concentration equivalent to average dissolved organic matter in seawater (45μm), the dominant alcohols at 100°C are small compounds like ethanol and 1-propanol. In contrast, at a higher bulk concentration of 500μm, there is a drive to shift large percentages of dissolved

  4. Acute systemic rapamycin induces neurobehavioral alterations in rats. (United States)

    Hadamitzky, Martin; Herring, Arne; Keyvani, Kathy; Doenlen, Raphael; Krügel, Ute; Bösche, Katharina; Orlowski, Kathrin; Engler, Harald; Schedlowski, Manfred


    Rapamycin is a drug with antiproliferative and immunosuppressive properties, widely used for prevention of acute graft rejection and cancer therapy. It specifically inhibits the activity of the mammalian target of rapamycin (mTOR), a protein kinase known to play an important role in cell growth, proliferation and antibody production. Clinical observations show that patients undergoing therapy with immunosuppressive drugs frequently suffer from affective disorders such as anxiety or depression. However, whether these symptoms are attributed to the action of the distinct compounds remains rather elusive. The present study investigated in rats neurobehavioral consequences of acute rapamycin treatment. Systemic administration of a single low dose rapamycin (3mg/kg) led to enhanced neuronal activity in the amygdala analyzed by intracerebral electroencephalography and FOS protein expression 90min after drug injection. Moreover, behavioral investigations revealed a rapamycin-induced increase in anxiety-related behaviors in the elevated plus-maze and in the open-field. The behavioral alterations correlated to enhanced amygdaloid expression of KLK8 and FKBP51, proteins that have been implicated in the development of anxiety and depression. Together, these results demonstrate that acute blockade of mTOR signaling by acute rapamycin administration not only causes changes in neuronal activity, but also leads to elevated protein expression in protein kinase pathways others than mTOR, contributing to the development of anxiety-like behavior. Given the pivotal role of the amygdala in mood regulation, associative learning, and modulation of cognitive functions, our findings raise the question whether therapy with rapamycin may induce alterations in patients neuropsychological functioning.

  5. Maternal bisphenol A alters fetal endocrine system: Thyroid adipokine dysfunction. (United States)

    Ahmed, R G


    Because bisphenol A (BPA) has been detected in animals, the aim of this study was to investigate the possible effects of maternal BPA exposure on the fetal endocrine system (thyroid-adipokine axis). BPA (20 or 40 μg/kg body weight) was orally administered to pregnant rats from gestation day (GD) 1-20. In both treated groups, the dams and their fetuses had lower serum thyroxine (T4) and triiodothyronine (T3) levels, and higher thyrotropin (TSH) level than control dams and fetuses at GD 20. Some histopathological changes in fetal thyroid glands were observed in both maternal BPA groups at embryonic day (ED) 20, including fibroblast proliferation, hyperplasia, luminal obliteration, oedema, and degeneration. These disorders resulted in the suppression of fetal serum growth hormone (GH), insulin growth factor-1 (IGF1) and adiponectin (ADP) levels, and the elevation of fetal serum leptin, insulin and tumor necrosis factor-alpha (TNFα) levels in both treated groups with respect to control. The depraved effects of both treated groups were associated with reduced maternal and fetal body weight compared to the control group. These alterations were dose dependent. Thus, BPA might penetrate the placental barrier and perturb the fetal thyroid adipokine axis to influence fat metabolism and the endocrine system.

  6. Molecular alteration of a muscarinic acetylcholine receptor system during synaptogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Large, T.H.; Cho, N.J.; De Mello, F.G.; Klein, W.L.


    Biochemical properties of the muscarinic acetylcholine receptor system of the avian retina were found to change during the period when synapses form in ovo. Comparison of ligand binding to membranes obtained before and after synaptogenesis showed a significant increase in the affinity, but not proportion, of the high affinity agonist-binding state. There was no change in receptor sensitivity to antagonists during this period. Pirenzepine binding, which can discriminate muscarinic receptor subtypes, showed the presence of a single population of low affinity sites (M2) before and after synaptogenesis. The change in agonist binding was not due to the late development of receptor function. However, detergent-solubilization of membranes eliminated differences in agonist binding between receptors from embryos and hatched chicks, suggesting a developmental change in interactions of the receptor with functionally related membrane components. A possible basis for altered interactions was obtained from isoelectric point data showing that the muscarinic receptor population underwent a transition from a predominantly low pI form (4.25) in 13 day embryos to a predominantly high pI form (4.50) in newly hatched chicks. The possibility that biochemical changes in the muscarinic receptor play a role in differentiation of the system by controlling receptor position on the surface of nerve cells is discussed.

  7. Computational Hemodynamic Simulation of Human Circulatory System under Altered Gravity (United States)

    Kim. Chang Sung; Kiris, Cetin; Kwak, Dochan


    A computational hemodynamics approach is presented to simulate the blood flow through the human circulatory system under altered gravity conditions. Numerical techniques relevant to hemodynamics issues are introduced to non-Newtonian modeling for flow characteristics governed by red blood cells, distensible wall motion due to the heart pulse, and capillary bed modeling for outflow boundary conditions. Gravitational body force terms are added to the Navier-Stokes equations to study the effects of gravity on internal flows. Six-type gravity benchmark problems are originally presented to provide the fundamental understanding of gravitational effects on the human circulatory system. For code validation, computed results are compared with steady and unsteady experimental data for non-Newtonian flows in a carotid bifurcation model and a curved circular tube, respectively. This computational approach is then applied to the blood circulation in the human brain as a target problem. A three-dimensional, idealized Circle of Willis configuration is developed with minor arteries truncated based on anatomical data. Demonstrated is not only the mechanism of the collateral circulation but also the effects of gravity on the distensible wall motion and resultant flow patterns.

  8. Altered signaling in systemic juvenile idiopathic arthritis monocytes. (United States)

    Macaubas, Claudia; Wong, Elizabeth; Zhang, Yujuan; Nguyen, Khoa D; Lee, Justin; Milojevic, Diana; Shenoi, Susan; Stevens, Anne M; Ilowite, Norman; Saper, Vivian; Lee, Tzielan; Mellins, Elizabeth D


    Systemic juvenile idiopathic arthritis (sJIA) is characterized by systemic inflammation and arthritis. Monocytes are implicated in sJIA pathogenesis, but their role in disease is unclear. The response of sJIA monocytes to IFN may be dysregulated. We examined intracellular signaling in response to IFN type I (IFNα) and type II (IFNγ) in monocytes during sJIA activity and quiescence, in 2 patient groups. Independent of disease activity, monocytes from Group 1 (collected between 2002 and 2009) showed defective STAT1 phosphorylation downstream of IFNs, and expressed higher transcript levels of SOCS1, an inhibitor of IFN signaling. In the Group 2 (collected between 2011 and 2014), monocytes of patients with recent disease onset were IFNγ hyporesponsive, but in treated, quiescent subjects, monocytes were hyperresponsive to IFNγ. Recent changes in medication in sJIA may alter the IFN hyporesponsiveness. Impaired IFN/pSTAT1 signaling is consistent with skewing of sJIA monocytes away from an M1 phenotype and may contribute to disease pathology.

  9. A refined genetic model for the Laisvall and Vassbo Mississippi Valley-type sandstone-hosted deposits, Sweden: constraints from paragenetic studies, organic geochemistry, and S, C, N, and Sr isotope data (United States)

    Saintilan, Nicolas J.; Spangenberg, Jorge E.; Samankassou, Elias; Kouzmanov, Kalin; Chiaradia, Massimo; Stephens, Michael B.; Fontboté, Lluís


    The current study has aimed to refine the previously proposed two-fluid mixing model for the Laisvall (sphalerite Rb-Sr age of 467 ± 5 Ma) and Vassbo Mississippi Valley-type deposits hosted in Ediacaran to Cambrian sandstone, Sweden. Premineralization cements include authigenic monazite, fluorapatite, and anatase in the Upper Sandstone at Laisvall, reflecting anoxic conditions during sandstone burial influenced by the euxinic character of the overlying carbonaceous middle Cambrian to Lower Ordovician Alum Shale Formation ( δ 13Corg = -33.0 to -29.5 ‰, δ 15Norg = 1.5 to 3.3 ‰, 0.33 to 3.03 wt% C, 0.02 to 0.08 wt% N). The available porosity for epigenetic mineralization, including that produced by subsequent partial dissolution of pre-Pb-Zn sulfide calcite and barite cements, was much higher in calcite- and barite-cemented sandstone paleoaquifers (29 % by QEMSCAN mapping) than in those mainly cemented by quartz (8 %). A major change in the Laisvall plumbing system is recognized by the transition from barite cementation to Pb-Zn sulfide precipitation in sandstone. Ba-bearing, reduced, and neutral fluids had a long premineralization residence time (highly radiogenic 87S/86Sr ratios of 0.718 to 0.723) in basement structures. As a result of an early Caledonian arc-continent collision and the development of a foreland basin, fluids migrated toward the craton and expelled Ba-bearing fluids from their host structures into overlying sandstone where they deposited barite upon mixing with a sulfate pool ( δ 34Sbarite = 14 to 33 ‰). Subsequently, slightly acidic brines initially residing in pre-Ediacaran rift sediments in the foredeep of the early Caledonian foreland basin migrated through the same plumbing system and acquired metals on the way. The bulk of Pb-Zn mineralization formed at temperatures between 120 and 180 °C by mixing of these brines with a pool of H2S ( δ 34S = 24 to 29 ‰) produced via thermochemical sulfate reduction (TSR) with oxidation of

  10. Altered B cell receptor signaling in human systemic lupus erythematosus (United States)

    Jenks, Scott A.; Sanz, Iñaki


    Regulation of B cell receptor signaling is essential for the development of specific immunity while retaining tolerance to self. Systemic lupus erythematosus (SLE) is characterized by a loss of B cell tolerance and the production of anti-self antibodies. Accompanying this break down in tolerance are alterations in B cell receptor signal transduction including elevated induced calcium responses and increased protein phosphorylation. Specific pathways that negatively regulate B cell signaling have been shown to be impaired in some SLE patients. These patients have reduced levels of the kinase Lyn in lipid raft microdomains and this reduction is inversely correlated with increased CD45 in lipid rafts. Function and expression of the inhibitory immunoglobulin receptor FcγRIIB is also reduced in Lupus IgM- CD27+ memory cells. Because the relative contribution of different memory and transitional B cell subsets can be abnormal in SLE patients, we believe studies targeted to well defined B cell subsets will be necessary to further our understanding of signaling abnormalities in SLE. Intracellular flow cytometric analysis of signaling is a useful approach to accomplish this goal. PMID:18723129

  11. 76 FR 4451 - Privacy Act of 1974; Report of Modified or Altered System of Records (United States)


    ... Altered System of Records AGENCY: Executive Systems and Fellowship Staff, Atlanta Human Resources Center... Health and Human Services (HHS) may disclose information from this system of records to the Department of...). ACTION: Notification of Proposed Altered System of Records. SUMMARY: The Department of Health and...

  12. Altered Systemic Adipokines in Patients with Chronic Urticaria. (United States)

    Trinh, Hoang Kim Tu; Pham, Duy Le; Ban, Ga-Young; Lee, Hyun-Young; Park, Hae-Sim; Ye, Young-Min


    Increasing evidence suggests that adipokines affect immune responses and chronic urticaria (CU) is associated with an altered immune response related to chronic systemic inflammation. Our objectives were to investigate whether adipokines are involved in CU pathogenesis and to outline relationships between adipokines and urticaria severity and quality of life. Serum adiponectin, leptin, lipocalin-2 (LCN2), interleukin (IL)-10, IL-6, and tumor necrosis factor (TNF)-α concentrations were measured by enzyme-linked immunosorbent assays in 191 CU patients and 89 healthy controls. The effect of LCN2 on N-formyl-methionine-leucine-phenylalanine (fMLP)-induced neutrophil chemotaxis was assessed using migration assays. CU severity was assessed based on the urticaria activity score (UAS). To explore relationships between adipokines and UAS and the chronic urticaria-specific quality of life (CU-QoL) questionnaire, a structural equation model was used. Mean levels of serum LCN2, TNF-α, IL-6, and IL-10 were significantly higher in CU patients than in controls. Adiponectin levels were significantly lower in patients with CU than in controls. While serum IL-6 levels were significantly higher in refractory CU patients, compared to responsive CU individuals, LCN2 levels were significantly lower. LCN2 inhibited fMLP-induced neutrophil migration. LCN2 showed a direct relationship with UAS (β = -0.274, p < 0.001), and UAS was found to contribute to CU-QoL (β = 0.417, p < 0.001). Our results highlighted an imbalance in pro- and anti-inflammatory adipokines in CU patients. We suggest that LCN2 could be a differential marker for disease activity and the clinical responses to antihistamine treatment in CU patients. Modulation of systemic inflammation may be a therapeutic strategy for treating severe, refractory CU. © 2016 S. Karger AG, Basel.

  13. Primitive Liquid Water of the Solar System in an Aqueous Altered Carbonaceous Chondrite (United States)

    Tsuchiyama, A.; Miyake, A.; Kitayama, A.; Matsuno, J.; Takeuchi, A.; Uesugi, K.; Suzuki, Y.; Nakano, T.; Zolensky, M. E.


    Non-destructive 3D observations of the aqueous altered CM chondrite Sutter's Mill using scanning imaging x-ray microscopy (SIXM) showed that some of calcite and enstatite grains contain two-phase inclusion, which is most probably composed of liquid water and bubbles. This water should be primitive water responsible for aqueous alteration in an asteroid in the early solar system.

  14. 75 FR 60468 - Privacy Act of 1974; Report of an Altered System of Records (United States)


    ... HUMAN SERVICES Health Resources and Services Administration Privacy Act of 1974; Report of an Altered... requirements of the Privacy Act of 1974, the Health Resources and Services Administration (HRSA) is proposing... alterations are to update the system name, authority, and location; make a minor change to the purposes,...

  15. 78 FR 32256 - Privacy Act of 1974; Report of an Altered CMS System of Records Notice (United States)


    ... HUMAN SERVICES Centers for Medicare & Medicaid Services Privacy Act of 1974; Report of an Altered CMS System of Records Notice AGENCY: Centers for Medicare & Medicaid Services (CMS), Department of Health and... requirements of the Privacy Act of 1974 (5 USC 552a), CMS proposes the following alterations to existing...

  16. 78 FR 64196 - Privacy Act Altered System of Records (United States)


    ..., Biographical Files (78 FR 171). In that notice, the Department announced its intent to amend that system of..., Biographical Files. The notice of proposed amendment to this system of records was published in the Federal..., Biographical Files and Social Networks. The amendment serves to modify the system of records by...

  17. Chemical transport in geothermal systems in Iceland: Evidence from hydrothermal alteration (United States)

    Franzson, Hjalti; Zierenberg, Robert; Schiffman, Peter


    This study focuses on the chemical changes in basaltic rocks in fossil low- and high-temperature hydrothermal systems in Iceland. The method used takes into account the amount of dilution caused by vesicle and vein fillings in the rocks. The amount of dilution allows a calculation of the primary concentration of the immobile element Zr, and by multiplying the composition of the altered rock by the ratio of Zr (protolith)/Zr (altered rock) one can compute the mass addition caused by the dilution of the void fillings, and also make a direct comparison with the likely protoliths from the same areas. The samples were divided into three groups; two from Tertiary fossil high-temperature systems (Hafnarfjall, Geitafell), and the third group from a low temperature, zeolite-altered plateau basalt succession. The results show that hydrothermally altered rocks are enriched in Si, Al, Fe, Mg and Mn, and that Na, K and Ca are mobile but show either depletion or enrichment. The elements that are immobile include Zr, Y, Nb and probably Ti. The two high-temperature systems show quite similar chemical alteration trends, an observation which may apply to Icelandic fresh water high-temperature systems in general. The geochemical data show that the major changes in the altered rocks from Icelandic geothermal systems may be attributed to addition of elements during deposition of pore-filling alteration minerals. A comparison with seawater-dominated basalt-hosted hydrothermal systems shows much greater mass flux within the seawater systems, even though both systems have similar alteration assemblages. The secondary mineral assemblages seem to be controlled predominantly by the thermal stability of the alteration phases and secondarily by the composition of the hydrothermal fluids.

  18. Alterations in the Coagulation System during Major Visceral Surgery in Children

    DEFF Research Database (Denmark)

    Kordjian, Hayarpi H; Nybo, Mads; Qvist, Niels


    Purpose. The description of the alterations in the hemostatic system in children undergoing abdominal surgery is sparse. Enhanced clinical outcomes for previously untreatable conditions have led to an increased incidence of venous thromboembolic complications. Alterations in children's coagulation...... system during major abdominal operations compared to minor procedures were examined. Methods. Children (0-12 years) undergoing either laparotomy, thoracotomy, or minor surgery were included. Participants were divided into two groups: group 1 was open laparotomy including operations for solid abdominal...

  19. A Palaeoproterozoic multi-stage hydrothermal alteration system at Nalunaq gold deposit, South Greenland

    DEFF Research Database (Denmark)

    Bell, Robin-Marie; Kolb, Jochen; Waight, Tod Earle


    closure in 2014, having produced 10.67 t of gold. This study uses a combination of field investigation, petrography and U/Pb zircon and titanite geochronology to define a multistage hydrothermal alteration system at Nalunaq. A clinopyroxene-plagioclase-garnet(-sulphide) alteration zone (CPGZ) developed...... in the Nanortalik Peninsula, close to regional peak metamorphism and prior to gold-quartz vein formation. The ca. 1783–1762-Ma gold-quartz veins are hosted in reactivated shear zones with a hydrothermal alteration halo of biotite-arsenopyrite-sericite-actinolite-pyrrhotite(-chloriteplagioclase- löllingite......-tourmaline-titanite), which is best developed in areas of exceptionally high gold grades. Aplite dykes dated to ca. 1762 Ma cross-cut the gold-quartz veins, providing a minimum age for mineralisation. A hydrothermal calcite-titanite alteration assemblage is dated to ca. 1766 Ma; however, this alteration is highly isolated...

  20. 76 FR 4480 - Privacy Act of 1974; Report of Modified or Altered System of Records (United States)


    ... sprinkler system, numerous automatic sensors (e.g., water, heat, smoke, etc.) are installed, and a proper... room is controlled by a cardkey and security code (numeric keypad) system. The local fire department is... Altered System of Records AGENCY: National Center for Environmental Health (NCEH), Coordinating Center...

  1. 75 FR 5604 - Privacy Act of 1974; Report of an Altered System of Records (United States)


    ... HUMAN SERVICES Health Resources and Services Administration Privacy Act of 1974; Report of an Altered... requirements of the Privacy Act of 1974, the Health Resources and Services Administration (HRSA) is proposing... of the system, the system location, categories of individuals covered by the system, categories...

  2. Hydrothermal alteration in the Reykjanes geothermal system: Insights from Iceland deep drilling program well RN-17 (United States)

    Marks, Naomi; Schiffman, Peter; Zierenberg, Robert A.; Franzson, Hjalti; Fridleifsson, Gudmundur Ó.


    The Reykjanes geothermal system is a seawater-recharged hydrothermal system that appears to be analogous to seafloor hydrothermal systems in terms of host rock type and low water/rock alteration. The similarities make the Reykjanes system a useful proxy for seafloor vents. At some time during the Pleistocene, the system was dominated by meteoric water recharge, and fluid composition at Reykjanes has evolved through time as a result of changing proportions of meteoric water influx as well as differing pressure and temperature conditions. The purpose of this study is to characterize secondary mineralization, degree of metasomatic alteration, and bulk composition of cuttings from well RN-17 from the Reykjanes geothermal system. The basaltic host rock includes hyaloclastite, breccia, tuff, extrusive basalt, diabase, as well as a marine sedimentary sequence. The progressive hydrothermal alteration sequence observed with increasing depth results from reaction of geothermal fluids with the basaltic host rock. An assemblage of greenschist facies alteration minerals, including actinolite, prehnite, epidote and garnet, occurs at depths as shallow as 350 m; these minerals are commonly found in Icelandic geothermal systems at temperatures above 250 °C (Bird and Spieler, 2004). This requires hydrostatic pressures that exceed the present-day depth to boiling point curve, and therefore must record alteration at higher fluid pressures, perhaps as a result of Pleistocene glaciation. Major, minor, and trace element profiles of the cuttings indicate transitional MORB to OIB composition with limited metasomatic shifts in easily mobilized elements. Changes in MgO, K 2O and loss on ignition indicate that metasomatism is strongly correlated with protolith properties. The textures of alteration minerals reveal alteration style to be strongly dependent on protolith as well. Hyaloclastites are intensely altered with calc-silicate alteration assemblages comprising calcic hydrothermal

  3. Vascular Alterations and Sexual Function in Systemic Sclerosis

    Directory of Open Access Journals (Sweden)

    Ann Julie Impens


    Full Text Available Sexual dysfunction is common in systemic sclerosis (SSc. Male erectile dysfunction (MED has been reported in around 80% of subjects and more than half of female patients fulfill criteria for diagnosis as female sexual arousal Disorder (FSAD. While some evidence supports a role for cavernosal fibrosis, abundant data suggest that MED is yet another clinical feature of SSc related to vasculopathy. The contribution of vasculopathy to the more complex issues of female sexual dysfunction is less clear. Inhibitors of Type V phosphodiesterase are effective in men with MED secondary to SSc. Limited study in women suggests inconsistent effects on behavior (frequency but not on measures related to perfusion. Sexual activity is an important component of quality of life and an important domain for the caregiver to address; it is not clear that it warrants primary consideration as a consistent measure of scleroderma-related vasculopathy.

  4. Motivation alters impression formation and related neural systems. (United States)

    Hughes, Brent L; Zaki, Jamil; Ambady, Nalini


    Observers frequently form impressions of other people based on complex or conflicting information. Rather than being objective, these impressions are often biased by observers' motives. For instance, observers often downplay negative information they learn about ingroup members. Here, we characterize the neural systems associated with biased impression formation. Participants learned positive and negative information about ingroup and outgroup social targets. Following this information, participants worsened their impressions of outgroup, but not ingroup, targets. This tendency was associated with a failure to engage neural structures including lateral prefrontal cortex, dorsal anterior cingulate cortex, temporoparietal junction, Insula and Precuneus when processing negative information about ingroup (but not outgroup) targets. To the extent that participants engaged these regions while learning negative information about ingroup members, they exhibited less ingroup bias in their impressions. These data are consistent with a model of 'effortless bias', under which perceivers fail to process goal-inconsistent information in order to maintain desired conclusions.

  5. Systemic alterations and their oral manifestations in pregnant women. (United States)

    Silva de Araujo Figueiredo, Camilla; Gonçalves Carvalho Rosalem, Cíntia; Costa Cantanhede, Andre Luis; Abreu Fonseca Thomaz, Érika Bárbara; Fontoura Nogueira da Cruz, Maria Carmen


    The aims of this literature review are: to depict the main oral diseases that are related to pregnancy; to clarify some of the possible systemic mechanisms that are associated with these changes; and to address issues about oral care during pregnancy. A woman's organs undergo various physiological, neurological, and hormonal changes during pregnancy. Such changes occur gradually and are essential for the development of the fetus, providing what is needed for tissue formation and establishment of reserves for uterine and fetal life. In turn, the oral cavity shows some events during this period. Among the changes most frequently cited in the literature are pyogenic granuloma, gingivitis, and periodontitis. The inflammation of the periodontal tissues due to the formation of the biofilm increases dramatically in size and severity during the course of a normal pregnancy, even without changes in the amount of biofilm present. In addition, a decrease in salivary pH is observed in pregnant women and may lead to an increased incidence of dental caries in this period.

  6. 76 FR 4446 - Privacy Act of 1974; Report of Modified or Altered System of Records (United States)


    ... locked rooms. The local fire department is located nearby. The computer room is protected by an automatic sprinkler system, automatic sensors (e.g., water, heat, smoke, etc.) are installed, and portable fire... Altered System of Records AGENCY: National Center for HIV, STD and TB Prevention (NCHSTP), Department...

  7. 76 FR 4443 - Privacy Act of 1974; Report of Modified or Altered System of Records (United States)


    ... locked rooms. The local fire department is located nearby. The computer room is protected by an automatic sprinkler system, automatic sensors (e.g., water, heat, smoke, etc.) are installed, and portable fire... Altered System of Records AGENCY: National Center for HIV, STD and TB Prevention (NCHSTP), Centers...

  8. 76 FR 4440 - Privacy Act of 1974; Report of Modified or Altered System of Records (United States)


    ... locked rooms. The local fire department is located nearby. The computer room is protected by an automatic sprinkler system, automatic sensors (e.g., water, heat, smoke, etc.) are installed, and portable fire... Altered System of Records AGENCY: Division of Tuberculosis Elimination, National Center for HIV, STD...

  9. 75 FR 57806 - Privacy Act of 1974; Report of an Altered System of Records (United States)


    ... HUMAN SERVICES Health Resources and Services Administration Privacy Act of 1974; Report of an Altered System of Records AGENCY: Department of Health and Human Services (HHS), Health Resources and Services... Health and Human Services (DHHS) may disclose information from this system of records to a...

  10. Hydrothermal alteration of Hercynian granites, its significance to the evolution of geothermal systems in granitic rocks

    Energy Technology Data Exchange (ETDEWEB)

    Marques, Jose M.; Matias, Maria J.; Basto, Maria J.; Aires-Barros, Luis A. [Instituto Superior Tecnico, Centro de Petrologia e Geoquimica, Universidade Tecnica de Lisboa, Av. Rovisco Pais, 1049-001 Lisbon (Portugal); Carreira, Paula M. [Instituto Tecnologico e Nuclear, Estrada Nacional n 10, 2686 - 953 Sacavem (Portugal); Goff, Fraser E. [Earth and Planetary Sciences Department, Univ. of New Mexico, Albuquerque, NM 87131 (United States)


    We discuss geochemical and isotopic ({sup 18}O/{sup 16}O, {sup 2}H/{sup 1}H and {sup 87}Sr/{sup 86}Sr) data recording the hydrothermal alteration of northern Portuguese Hercynian granites by Na-HCO{sub 3}-CO{sub 2}-rich mineral waters. Whole-rock samples from drill cores of Vilarelho da Raia granite have {delta}{sup 18}O values in the +11.47 to +10.10 permille range. The lower values correspond to highly fractured granite samples displaying vein and pervasive alteration. In the pervasive alteration stage, which probably results from a convective hydrothermal system set up by the intrusion of the granites, the metamorphic waters are in equilibrium with hydrous minerals. In contrast, the vein alteration of these granitic rocks was caused by water of meteoric origin. The oxygen ratios between water (W) and rock (R), the so-called W/R ratios, obtained for the open system (where the heated water is lost from the system by escape to the surface) range between 0.05 and 0.11, suggesting that the recrystallization of the veins was influenced by a small flux of meteoric water. Stable isotope analyses performed on the cores show that the vein alteration stage relates to post-emplacement tectonic stresses acting on the granite, probably of late Hercynian age. Our results are consistent with the existence of two separate alteration events (pervasive and vein) caused by hydrothermal waters of different isotopic characteristics. The studies presented in this paper should be viewed as a natural analogue that uses the alteration features observed in a fossil geothermal system at Vilarelho da Raia to assess possible water-rock reactions presently occurring at depth in granitic rocks of the nearby Chaves area. (author)

  11. A Palaeoproterozoic multi-stage hydrothermal alteration system at Nalunaq gold deposit, South Greenland (United States)

    Bell, Robin-Marie; Kolb, Jochen; Waight, Tod Earle; Bagas, Leon; Thomsen, Tonny B.


    Nalunaq is an orogenic, high gold grade deposit situated on the Nanortalik Peninsula, South Greenland. Mineralisation is hosted in shear zone-controlled quartz veins, located in fine- and medium-grained amphibolite. The deposit was the site of Greenland's only operating metalliferous mine until its closure in 2014, having produced 10.67 t of gold. This study uses a combination of field investigation, petrography and U/Pb zircon and titanite geochronology to define a multi-stage hydrothermal alteration system at Nalunaq. A clinopyroxene-plagioclase-garnet(-sulphide) alteration zone (CPGZ) developed in the Nanortalik Peninsula, close to regional peak metamorphism and prior to gold-quartz vein formation. The ca. 1783-1762-Ma gold-quartz veins are hosted in reactivated shear zones with a hydrothermal alteration halo of biotite-arsenopyrite-sericite-actinolite-pyrrhotite(-chlorite-plagioclase-löllingite-tourmaline-titanite), which is best developed in areas of exceptionally high gold grades. Aplite dykes dated to ca. 1762 Ma cross-cut the gold-quartz veins, providing a minimum age for mineralisation. A hydrothermal calcite-titanite alteration assemblage is dated to ca. 1766 Ma; however, this alteration is highly isolated, and as a result, its field relationships are poorly constrained. The hydrothermal alteration and mineralisation is cut by several generations of ca. 1745-Ma biotite granodiorite accompanied by brittle deformation. A ca. 1745-Ma lower greenschist facies hydrothermal epidote-calcite-zoisite alteration assemblage with numerous accessory minerals forms halos surrounding the late-stage fractures. The contrasting hydrothermal alteration styles at Nalunaq indicate a complex history of exhumation from amphibolite facies conditions to lower greenschist facies conditions in an orogenic belt which resembles modern Phanerozoic orogens.

  12. A Palaeoproterozoic multi-stage hydrothermal alteration system at Nalunaq gold deposit, South Greenland (United States)

    Bell, Robin-Marie; Kolb, Jochen; Waight, Tod Earle; Bagas, Leon; Thomsen, Tonny B.


    Nalunaq is an orogenic, high gold grade deposit situated on the Nanortalik Peninsula, South Greenland. Mineralisation is hosted in shear zone-controlled quartz veins, located in fine- and medium-grained amphibolite. The deposit was the site of Greenland's only operating metalliferous mine until its closure in 2014, having produced 10.67 t of gold. This study uses a combination of field investigation, petrography and U/Pb zircon and titanite geochronology to define a multi-stage hydrothermal alteration system at Nalunaq. A clinopyroxene-plagioclase-garnet(-sulphide) alteration zone (CPGZ) developed in the Nanortalik Peninsula, close to regional peak metamorphism and prior to gold-quartz vein formation. The ca. 1783-1762-Ma gold-quartz veins are hosted in reactivated shear zones with a hydrothermal alteration halo of biotite-arsenopyrite-sericite-actinolite-pyrrhotite(-chlorite-plagioclase-löllingite-tourmaline-titanite), which is best developed in areas of exceptionally high gold grades. Aplite dykes dated to ca. 1762 Ma cross-cut the gold-quartz veins, providing a minimum age for mineralisation. A hydrothermal calcite-titanite alteration assemblage is dated to ca. 1766 Ma; however, this alteration is highly isolated, and as a result, its field relationships are poorly constrained. The hydrothermal alteration and mineralisation is cut by several generations of ca. 1745-Ma biotite granodiorite accompanied by brittle deformation. A ca. 1745-Ma lower greenschist facies hydrothermal epidote-calcite-zoisite alteration assemblage with numerous accessory minerals forms halos surrounding the late-stage fractures. The contrasting hydrothermal alteration styles at Nalunaq indicate a complex history of exhumation from amphibolite facies conditions to lower greenschist facies conditions in an orogenic belt which resembles modern Phanerozoic orogens.

  13. Microbial community changes in biological phosphate-removal systems on altering sludge phosphorus content

    NARCIS (Netherlands)

    Liu, WT; Linning, KD; Nakamura, K; Mino, T; Matsuo, T; Forney, LJ

    Biomarkers (respiratory quinones and cellular fatty acids) and denaturing gradient gel electrophoresis (DGGE) of PCR-amplified 16S rRNA genes were used to characterize the microbial community structure of lab-scale enhanced biological phosphate-removal (EBPR) systems in response to altering sludge

  14. Impact of DNA mismatch repair system alterations on human fertility and related treatments. (United States)

    Hu, Min-hao; Liu, Shu-yuan; Wang, Ning; Wu, Yan; Jin, Fan


    DNA mismatch repair (MMR) is one of the biological pathways, which plays a critical role in DNA homeostasis, primarily by repairing base-pair mismatches and insertion/deletion loops that occur during DNA replication. MMR also takes part in other metabolic pathways and regulates cell cycle arrest. Defects in MMR are associated with genomic instability, predisposition to certain types of cancers and resistance to certain therapeutic drugs. Moreover, genetic and epigenetic alterations in the MMR system demonstrate a significant relationship with human fertility and related treatments, which helps us to understand the etiology and susceptibility of human infertility. Alterations in the MMR system may also influence the health of offspring conceived by assisted reproductive technology in humans. However, further studies are needed to explore the specific mechanisms by which the MMR system may affect human infertility. This review addresses the physiological mechanisms of the MMR system and associations between alterations of the MMR system and human fertility and related treatments, and potential effects on the next generation.

  15. Impaired sense of smell and altered olfactory system in RAG-1-/- immunodeficient mice

    Directory of Open Access Journals (Sweden)

    Lorenza eRattazzi


    Full Text Available Immune deficiencies are often associated with a number of physical manifestations including loss of sense of smell and an increased level of anxiety. We have previously shown that T and B cell-deficient recombinase activating gene (RAG-1-/- knockout mice have an increased level of anxiety-like behavior and altered gene expression involved in olfaction. In this study, we expanded these findings by testing the structure and functional development of the olfactory system in RAG-1-/- mice. Our results show that these mice have a reduced engagement in different types of odors and this phenotype is associated with disorganized architecture of glomerular tissue and atrophy of the main olfactory epithelium. Most intriguingly this defect manifests specifically in adult age and is not due to impairment in the patterning of the olfactory neuron staining at the embryo stage. Together these findings provide a formerly unreported biological evidence for an altered function of the olfactory system in RAG-1-/- mice.

  16. Impaired sense of smell and altered olfactory system in RAG-1(-∕-) immunodeficient mice. (United States)

    Rattazzi, Lorenza; Cariboni, Anna; Poojara, Ridhika; Shoenfeld, Yehuda; D'Acquisto, Fulvio


    Immune deficiencies are often associated with a number of physical manifestations including loss of sense of smell and an increased level of anxiety. We have previously shown that T and B cell-deficient recombinase activating gene (RAG-1)(-∕-) knockout mice have an increased level of anxiety-like behavior and altered gene expression involved in olfaction. In this study, we expanded these findings by testing the structure and functional development of the olfactory system in RAG-1 (-∕-) mice. Our results show that these mice have a reduced engagement in different types of odors and this phenotype is associated with disorganized architecture of glomerular tissue and atrophy of the main olfactory epithelium. Most intriguingly this defect manifests specifically in adult age and is not due to impairment in the patterning of the olfactory neuron staining at the embryo stage. Together these findings provide a formerly unreported biological evidence for an altered function of the olfactory system in RAG-1 (-∕-) mice.

  17. Volatiles on solar system objects: Carbon dioxide on Iapetus and aqueous alteration in CM chondrites (United States)

    Palmer, Eric Edward


    Volatiles are critical in understanding the history of the solar system. We conducted two case studies intended to further this understanding. First, we analyzed the presence of CO2 on Iapetus. Second, we evaluated aqueous alteration in CM chondrites. We studied the distribution, stability and production of CO2 on Saturn's moon Iapetus. We determined that CO2 is concentrated exclusively on Iapetus' dark material with an effective thickness of 31 nm. The total CO2 on Iapetus' surface is 2.3x108 kg. However, CO2 should not be present because it has a limited residence time on the surface of Iapetus. Our thermal calculations and modeling show that CO2 in the form of frost will not remain on Iapetus' surface beyond a few hundred years. Thus, it must be complexed with dark material. However, photodissociation will destroy the observed inventory in ˜1/2 an Earth year. The lack of thermal and radiolytic stability requires an active source. We conducted experiments showing UV radiation generates CO2 under Iapetus-like conditions. We created a simulated regolith by mixing crushed water ice with isotopically labeled carbon. We then irradiated it with UV light at low temperature and pressure, producing 1.1x1015 parts m-2 s-1. Extrapolating to Iapetus, photolysis could generate 8.4x107 kg y-1, which makes photolytic production a good candidate for the source of the CO2 detected on Iapetus. We also studied the aqueous alteration of metal-bearing assemblages in CM chondrites. We examined Murchison, Cold Bokkeveld, Nogoya, and Murray using microscopy, electron microprobe analysis and scanning electron microscopy. Alteration on CM meteorites occurred within at least three microchemical environments: S-rich water, Si-rich water and water without substantial reactive components. Kamacite alters into tochilinite, cronstedtite, or magnetite. Sulfur associated alteration can form accessory minerals: P-rich sulfides, eskolaite and schreibersite. Additionally, we determined that there

  18. Short-term sleep deprivation leads to decreased systemic redox metabolites and altered epigenetic status. (United States)

    Trivedi, Malav S; Holger, Dana; Bui, Anh Tuyet; Craddock, Travis J A; Tartar, Jaime L


    Sleep is critical for repair as well as the rejuvenation processes in the body and many of these functions are regulated via underlying cellular metabolic homeostasis. Changes in sleep pattern are reported to alter such metabolic function resulting in altered disease susceptibility or behavior. Here, we measured the extent to which overnight total sleep deprivation (SD) in young adult humans can influence systemic (plasma-derived) redox-metabolism including the major antioxidant, glutathione as well as DNA methylation levels. Nineteen participants (n = 19, μ age = 21, SD = 3.09) underwent morning testing before and after overnight total SD. Biochemical measures before and after SD revealed that glutathione, ATP, cysteine, and homocysteine levels were significantly reduced following one night of sleep deprivation (all p's sleep deprivation (maintaining wakefulness) uses up metabolic reserves, we observed that morning cortisol levels were blunted after sleep deprivation. There were no significant correlations between self-reported or actigraphy-measured sleep and the biochemical measurements, strongly indicating that prior sleep behavior did not have any direct influence on the biochemical measures taken at baseline or after sleep deprivation. Results from the current investigation supports the previous literature implicating the induction of oxidative stress and ATP depletion with sleep deprivation. Furthermore, such altered antioxidant status can also induce downstream epigenetic changes. Although we did not measure the specific genes that were altered under the influence of such sleep deprivation, such epigenetic changes could potentially contribute towards disease predisposition.

  19. 5-HT systems: emergent targets for memory formation and memory alterations. (United States)

    Meneses, Alfredo


    Drugs acting through 5-hydroxytryptamine (serotonin or 5-HT) systems modulate memory and its alterations, although the mechanisms involved are poorly understood. 5-HT drugs may present promnesic and/or antiamnesic (or even being amnesic) effects. Key questions regarding 5-HT markers include whether receptors directly or indirectly participate and/or contribute to the physiological and pharmacological basis of memory and its pathogenesis; hence, the major aim of this article was to examine recent advances in emergent targets of the 5-HT systems for memory formation and memory alterations. Recent reviews and findings are summarized, mainly in the context of the growing notion of memory deficits in brain disorders (e.g., posttraumatic stress disorder, mild cognitive impairment, consumption of drugs, poststroke cognitive dysfunctions, schizophrenia, Parkinson disease, and infection-induced memory impairments). Mainly, mammalian and (some) human data were the focus. At least agonists and antagonists for 5-HT1A/1B, 5-HT2A/2B/2C, 5-HT3, 5-HT4, 5-HT6, and 5-HT7 receptors as well as serotonin uptake inhibitors seem to have a promnesic and/or antiamnesic effect in different conditions and 5-HT markers seem to be associated to neural changes. Available evidence offers clues about the possibilities, but the exact mechanisms remain unclear. For instance, 5-HT transporter expression seems to be a reliable neural marker related to memory mechanisms and its alterations.

  20. Security Policies for Mitigating the Risk of Load Altering Attacks on Smart Grid Systems

    Energy Technology Data Exchange (ETDEWEB)

    Ryutov, Tatyana; AlMajali, Anas; Neuman, Clifford


    While demand response programs implement energy efficiency and power quality objectives, they bring potential security threats to the Smart Grid. The ability to influence load in a system enables attackers to cause system failures and impacts the quality and integrity of power delivered to customers. This paper presents a security mechanism to monitor and control load according to a set of security policies during normal system operation. The mechanism monitors, detects, and responds to load altering attacks. We examined the security requirements of Smart Grid stakeholders and constructed a set of load control policies enforced by the mechanism. We implemented a proof of concept prototype and tested it using the simulation environment. By enforcing the proposed policies in this prototype, the system is maintained in a safe state in the presence of load drop attacks.

  1. Glycans in the immune system and The Altered Glycan Theory of Autoimmunity: a critical review. (United States)

    Maverakis, Emanual; Kim, Kyoungmi; Shimoda, Michiko; Gershwin, M Eric; Patel, Forum; Wilken, Reason; Raychaudhuri, Siba; Ruhaak, L Renee; Lebrilla, Carlito B


    Herein we will review the role of glycans in the immune system. Specific topics covered include: the glycosylation sites of IgE, IgM, IgD, IgE, IgA, and IgG; how glycans can encode "self" identity by functioning as either danger associated molecular patterns (DAMPs) or self-associated molecular patterns (SAMPs); the role of glycans as markers of protein integrity and age; how the glycocalyx can dictate the migration pattern of immune cells; and how the combination of Fc N-glycans and Ig isotype dictate the effector function of immunoglobulins. We speculate that the latter may be responsible for the well-documented association between alterations of the serum glycome and autoimmunity. Due to technological limitations, the extent of these autoimmune-associated glycan alterations and their role in disease pathophysiology has not been fully elucidated. Thus, we also review the current technologies available for glycan analysis, placing an emphasis on Multiple Reaction Monitoring (MRM), a rapid high-throughput technology that has great potential for glycan biomarker research. Finally, we put forth The Altered Glycan Theory of Autoimmunity, which states that each autoimmune disease will have a unique glycan signature characterized by the site-specific relative abundances of individual glycan structures on immune cells and extracellular proteins, especially the site-specific glycosylation patterns of the different immunoglobulin(Ig) classes and subclasses.

  2. Renal Oxidative Stress Induced by Long-Term Hyperuricemia Alters Mitochondrial Function and Maintains Systemic Hypertension

    Directory of Open Access Journals (Sweden)

    Magdalena Cristóbal-García


    Full Text Available We addressed if oxidative stress in the renal cortex plays a role in the induction of hypertension and mitochondrial alterations in hyperuricemia. A second objective was to evaluate whether the long-term treatment with the antioxidant Tempol prevents renal oxidative stress, mitochondrial alterations, and systemic hypertension in this model. Long-term (11-12 weeks and short-term (3 weeks effects of oxonic acid induced hyperuricemia were studied in rats (OA, 750 mg/kg BW, OA+Allopurinol (AP, 150 mg/L drinking water, OA+Tempol (T, 15 mg/kg BW, or vehicle. Systolic blood pressure, renal blood flow, and vascular resistance were measured. Tubular damage (urine N-acetyl-β-D-glucosaminidase and oxidative stress markers (lipid and protein oxidation along with ATP levels were determined in kidney tissue. Oxygen consumption, aconitase activity, and uric acid were evaluated in isolated mitochondria from renal cortex. Short-term hyperuricemia resulted in hypertension without demonstrable renal oxidative stress or mitochondrial dysfunction. Long-term hyperuricemia induced hypertension, renal vasoconstriction, tubular damage, renal cortex oxidative stress, and mitochondrial dysfunction and decreased ATP levels. Treatments with Tempol and allopurinol prevented these alterations. Renal oxidative stress induced by hyperuricemia promoted mitochondrial functional disturbances and decreased ATP content, which represent an additional pathogenic mechanism induced by chronic hyperuricemia. Hyperuricemia-related hypertension occurs before these changes are evident.

  3. Inflammation and schizophrenia: alterations in cytokine levels and perturbation in antioxidative defense systems. (United States)

    Al-Asmari, A K; Khan, Md W


    Although several theories have been proposed including developmental/neurodegenerative processes, neurotransmitter abnormalities, viral infection, and immune dysfunction, the exact causative factor of schizophrenia is unclear. A relationship between inflammation and schizophrenia has been supported by abnormal cytokine production and altered antioxidant status. This study was aimed to examine the alterations in serum oxidative-antioxidative status and cytokine levels of schizophrenic patients. A total of 91 schizophrenic patients from Saudi Arabia and 50 age- and sex-matched healthy controls were enrolled in the present study. Fresh blood samples were collected to measure the levels of cytokines and markers of oxidative stress by spectrophotometric assays simultaneously. We observed that there was a significant increase in the levels of tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 and a decrease in the levels of interferon-γ. Lipid peroxides are elevated in serum, while total-sulfhydryl levels were decreased. Also, the activities of superoxide dismutase and glutathione peroxidase were decreased, while the activities of catalase, glutathione reductase, and myeloperoxidase were found to be elevated in serum. We conclude that inflammation resulting from dysregulation of cytokines and altered antioxidant systems may play a critical role in the etiology of schizophrenia.

  4. Chronic gastrointestinal inflammation induces anxiety-like behavior and alters central nervous system biochemistry in mice. (United States)

    Bercik, Premysl; Verdu, Elena F; Foster, Jane A; Macri, Joseph; Potter, Murray; Huang, Xiaxing; Malinowski, Paul; Jackson, Wendy; Blennerhassett, Patricia; Neufeld, Karen A; Lu, Jun; Khan, Waliul I; Corthesy-Theulaz, Irene; Cherbut, Christine; Bergonzelli, Gabriela E; Collins, Stephen M


    Clinical and preclinical studies have associated gastrointestinal inflammation and infection with altered behavior. We investigated whether chronic gut inflammation alters behavior and brain biochemistry and examined underlying mechanisms. AKR mice were infected with the noninvasive parasite Trichuris muris and given etanercept, budesonide, or specific probiotics. Subdiaphragmatic vagotomy was performed in a subgroup of mice before infection. Gastrointestinal inflammation was assessed by histology and quantification of myeloperoxidase activity. Serum proteins were measured by proteomic analysis, circulating cytokines were measured by fluorescence activated cell sorting array, and serum tryptophan and kynurenine were measured by liquid chromatography. Behavior was assessed using light/dark preference and step-down tests. In situ hybridization was used to assess brain-derived neurotrophic factor (BDNF) expression in the brain. T muris caused mild to moderate colonic inflammation and anxiety-like behavior that was associated with decreased hippocampal BDNF messenger RNA (mRNA). Circulating tumor necrosis factor-α and interferon-γ, as well as the kynurenine and kynurenine/tryptophan ratio, were increased. Proteomic analysis showed altered levels of several proteins related to inflammation and neural function. Administration of etanercept, and to a lesser degree of budesonide, normalized behavior, reduced cytokine and kynurenine levels, but did not influence BDNF expression. The probiotic Bifidobacterium longum normalized behavior and BDNF mRNA but did not affect cytokine or kynurenine levels. Anxiety-like behavior was present in infected mice after vagotomy. Chronic gastrointestinal inflammation induces anxiety-like behavior and alters central nervous system biochemistry, which can be normalized by inflammation-dependent and -independent mechanisms, neither of which requires the integrity of the vagus nerve. Copyright © 2010 AGA Institute. Published by Elsevier Inc

  5. Social isolation impairs adult neurogenesis in the limbic system and alters behaviors in female prairie voles. (United States)

    Lieberwirth, Claudia; Liu, Yan; Jia, Xixi; Wang, Zuoxin


    Disruptions in the social environment, such as social isolation, are distressing and can induce various behavioral and neural changes in the distressed animal. We conducted a series of experiments to test the hypothesis that long-term social isolation affects brain plasticity and alters behavior in the highly social prairie vole (Microtus ochrogaster). In Experiment 1, adult female prairie voles were injected with a cell division marker, 5-bromo-2'-deoxyuridine (BrdU), and then same-sex pair-housed (control) or single-housed (isolation) for 6 weeks. Social isolation reduced cell proliferation, survival, and neuronal differentiation and altered cell death in the dentate gyrus of the hippocampus and the amygdala. In addition, social isolation reduced cell proliferation in the medial preoptic area and cell survival in the ventromedial hypothalamus. These data suggest that long-term social isolation affects distinct stages of adult neurogenesis in specific limbic brain regions. In Experiment 2, isolated females displayed higher levels of anxiety-like behaviors in both the open field and elevated plus maze tests and higher levels of depression-like behavior in the forced swim test than controls. Further, isolated females showed a higher level of affiliative behavior than controls, but the two groups did not differ in social recognition memory. Together, our data suggest that social isolation not only impairs cell proliferation, survival, and neuronal differentiation in limbic brain areas, but also alters anxiety-like, depression-like, and affiliative behaviors in adult female prairie voles. These data warrant further investigation of a possible link between altered neurogenesis within the limbic system and behavioral changes.

  6. Oral Drug Delivery Systems Comprising Altered Geometric Configurations for Controlled Drug Delivery

    Directory of Open Access Journals (Sweden)

    Priya Bawa


    Full Text Available Recent pharmaceutical research has focused on controlled drug delivery having an advantage over conventional methods. Adequate controlled plasma drug levels, reduced side effects as well as improved patient compliance are some of the benefits that these systems may offer. Controlled delivery systems that can provide zero-order drug delivery have the potential for maximizing efficacy while minimizing dose frequency and toxicity. Thus, zero-order drug release is ideal in a large area of drug delivery which has therefore led to the development of various technologies with such drug release patterns. Systems such as multilayered tablets and other geometrically altered devices have been created to perform this function. One of the principles of multilayered tablets involves creating a constant surface area for release. Polymeric materials play an important role in the functioning of these systems. Technologies developed to date include among others: Geomatrix® multilayered tablets, which utilizes specific polymers that may act as barriers to control drug release; Procise®, which has a core with an aperture that can be modified to achieve various types of drug release; core-in-cup tablets, where the core matrix is coated on one surface while the circumference forms a cup around it; donut-shaped devices, which possess a centrally-placed aperture hole and Dome Matrix® as well as “release modules assemblage”, which can offer alternating drug release patterns. This review discusses the novel altered geometric system technologies that have been developed to provide controlled drug release, also focusing on polymers that have been employed in such developments.

  7. Early Antipsychotic Treatment in Juvenile Rats Elicits Long-Term Alterations to the Dopamine Neurotransmitter System. (United States)

    De Santis, Michael; Lian, Jiamei; Huang, Xu-Feng; Deng, Chao


    Prescription of antipsychotic drugs (APDs) to children has substantially increased in recent years. Whilst current investigations into potential long-term effects have uncovered some alterations to adult behaviours, further investigations into potential changes to neurotransmitter systems are required. The current study investigated potential long-term changes to the adult dopamine (DA) system following aripiprazole, olanzapine and risperidone treatment in female and male juvenile rats. Levels of tyrosine hydroxylase (TH), phosphorylated-TH (p-TH), dopamine active transporter (DAT), and D₁ and D₂ receptors were measured via Western blot and/or receptor autoradiography. Aripiprazole decreased TH and D₁ receptor levels in the ventral tegmental area (VTA) and p-TH levels in the prefrontal cortex (PFC) of females, whilst TH levels decreased in the PFC of males. Olanzapine decreased PFC p-TH levels and increased D₂ receptor expression in the PFC and nucleus accumbens (NAc) in females only. Additionally, risperidone treatment increased D₁ receptor levels in the hippocampus of females, whilst, in males, p-TH levels increased in the PFC and hippocampus, D₁ receptor expression decreased in the NAc, and DAT levels decreased in the caudate putamen (CPu), and elevated in the VTA. These results suggest that early treatment with various APDs can cause different long-term alterations in the adult brain, across both treatment groups and genders.

  8. Systemic Cytokine Profiles in Strongyloides stercoralis Infection and Alterations following Treatment. (United States)

    Anuradha, Rajamanickam; Munisankar, Saravanan; Bhootra, Yukti; Jagannathan, Jeeva; Dolla, Chandrakumar; Kumaran, Paul; Shen, Kui; Nutman, Thomas B; Babu, Subash


    Strongyloides stercoralis is a soil-transmitted helminth organism that infects ~50 to 100 million people worldwide. Despite its widespread prevalence, very little is known about the immune response that characterizes human S. stercoralis infection. To study the systemic cytokine profile characteristic of Strongyloides infection, we measured the circulating levels of a large panel of pro- and anti-inflammatory cytokines in asymptomatic, infected individuals (n = 32) and compared them to those in uninfected, controls (n = 24). Infected individuals exhibited significantly lower circulating levels of proinflammatory cytokines (gamma interferon [IFN-γ], tumor necrosis factor alpha [TNF-α], and interleukin-1β [IL-1β]) and significantly higher levels of anti-inflammatory cytokines (IL-4, IL-5, IL-9, IL-10, IL-13, IL-27, IL-37, and transforming growth factor β [TGF-β]). Moreover, treatment of Strongyloides infection resulted in a significant reversal of the cytokine profile, with increased levels of proinflammatory (IFN-γ, TNF-α, IL-2, IL-17A, IL-17F, IL-22, IL-23, and IL-1β) and decreased levels of anti-inflammatory (IL-4, IL-5, IL-9, IL-10, IL-13, IL-27, IL-37, and TGF-β) cytokines following treatment. Thus, S. stercoralis infection is characterized by alterations in the levels of systemic cytokines, reflecting major alterations in the underlying immune response to this chronic helminth infection.

  9. Morphologic alterations in rat brain following systemic and intraventricular methotrexate injection: light and electron microscopic studies. (United States)

    Gregorios, J B; Gregorios, A B; Mora, J; Marcillo, A; Fojaco, R M; Green, B


    To determine the morphological substrate of acute methotrexate (MTX) encephalopathy, light and electron microscopic studies were performed on rat brains after short-term intraperitoneal (IP) and intraventricular (IV) injections of MTX. In both models, Alzheimer type II astrocytosis was the initial and major pathologic alteration seen by light microscopy. The neurons, oligodendrocytes, myelin and endothelial cells were relatively spared. Ultrastructural studies showed pleomorphism and condensation of mitochondria, membrane-bound vacuoles, prominent stacks of sparsely granular, rough endoplasmic reticulum and progressive hydropic swelling of astrocytic perikarya and their processes. The astroglial alterations were reversible after cessation of the drug but persisted for a longer time with repeated IP administration. Gastrointestinal complications and overall mortality were also greater with higher doses and increasing frequency of IP MTX injection. White matter necrosis was noted only after IV injection of high-dose MTX. The neuropathologic changes of MTX leukoencephalopathy can be replicated in an animal model by IV injection of the drug. The reversibility of the changes that were seen following IP administration correlates with the transient neurologic deficits observed in some patients after high-dose systemic MTX therapy. The initially selective astroglial effect suggests that astrocytes might be a target for MTX toxicity, although other central nervous system components may also be adversely affected by the drug.

  10. Effects of altered auditory feedback across effector systems: production of melodies by keyboard and singing. (United States)

    Pfordresher, Peter Q; Mantell, James T


    We report an experiment that tested whether effects of altered auditory feedback (AAF) during piano performance differ from its effects during singing. These effector systems differ with respect to the mapping between motor gestures and pitch content of auditory feedback. Whereas this action-effect mapping is highly reliable during phonation in any vocal motor task (singing or speaking), mapping between finger movements and pitch occurs only in limited situations, such as piano playing. Effects of AAF in both tasks replicated results previously found for keyboard performance (Pfordresher, 2003), in that asynchronous (delayed) feedback slowed timing whereas alterations to feedback pitch increased error rates, and the effect of asynchronous feedback was similar in magnitude across tasks. However, manipulations of feedback pitch had larger effects on singing than on keyboard production, suggesting effector-specific differences in sensitivity to action-effect mapping with respect to feedback content. These results support the view that disruption from AAF is based on abstract, effector independent, response-effect associations but that the strength of associations differs across effector systems.

  11. Thermal variability alters the impact of climate warming on consumer-resource systems. (United States)

    Fey, Samuel B; Vasseur, David A


    Thermal variation through space and time are prominent features of ecosystems that influence processes at multiple levels of biological organization. Yet, it remains unclear how populations embedded within biological communities will respond to climate warming in thermally variable environments, particularly as climate change alters existing patterns of thermal spatial and temporal variability. As environmental temperatures increase above historical ranges, organisms may increasingly rely on extreme habitats to effectively thermoregulate. Such locations desirable in their thermal attributes (e.g., thermal refugia) are often suboptimal for resource acquisition (e.g., underground tunnels). Thus, via the expected increase in both mean temperatures and diel thermal variation, climate warming may heighten the trade-off for consumers between behaviors maximizing thermal performance and those maximizing resource acquisition. Here, we integrate behavioral, physiological, and trophic ecology to provide a general framework for understanding how temporal thermal variation, mediated by access to a thermal refugium, alters the response of consumer-resource systems to warming. We use this framework to predict how temporal variation and access to thermal refugia affect the persistence of consumers and resources during climate warming, how the quality of thermal refugia impact consumer-resource systems, and how consumer-resource systems with fast vs. slow ecological dynamics respond to warming. Our results show that the spatial thermal variability provided by refugia can elevate consumer biomass at warmer temperatures despite reducing the fraction of time consumers spend foraging, that temporal variability detrimentally impacts consumers at high environmental temperatures, and that consumer-resource systems with fast ecological dynamics are most vulnerable to climate warming. Thus, incorporating both estimates of thermal variability and species interactions may be necessary to

  12. Alterations in the hippocampal endocannabinoid system in diet-induced obese mice. (United States)

    Massa, Federico; Mancini, Giacomo; Schmidt, Helmut; Steindel, Frauke; Mackie, Ken; Angioni, Carlo; Oliet, Stéphane H R; Geisslinger, Gerd; Lutz, Beat


    The endocannabinoid (eCB) system plays central roles in the regulation of food intake and energy expenditure. Its alteration in activity contributes to the development and maintenance of obesity. Stimulation of the cannabinoid receptor type 1 (CB(1) receptor) increases feeding, enhances reward aspects of eating, and promotes lipogenesis, whereas its blockade decreases appetite, sustains weight loss, increases insulin sensitivity, and alleviates dysregulation of lipid metabolism. The hypothesis has been put forward that the eCB system is overactive in obesity. Hippocampal circuits are not directly involved in the neuronal control of food intake and appetite, but they play important roles in hedonic aspects of eating. We investigated the possibility whether or not diet-induced obesity (DIO) alters the functioning of the hippocampal eCB system. We found that levels of the two eCBs, 2-arachidonoyl glycerol (2-AG) and anandamide, were increased in the hippocampus from DIO mice, with a concomitant increase of the 2-AG synthesizing enzyme diacylglycerol lipase-alpha and increased CB(1) receptor immunoreactivity in CA1 and CA3 regions, whereas CB(1) receptor agonist-induced [(35)S]GTPgammaS binding was unchanged. eCB-mediated synaptic plasticity was changed in the CA1 region, as depolarization-induced suppression of inhibition and long-term depression of inhibitory synapses were enhanced. Functionality of CB(1) receptors in GABAergic neurons was furthermore revealed, as mice specifically lacking CB(1) receptors on this neuronal population were partly resistant to DIO. Our results show that DIO-induced changes in the eCB system affect not only tissues directly involved in the metabolic regulation but also brain regions mediating hedonic aspects of eating and influencing cognitive processes.

  13. Trypanosoma cruzi disrupts thymic homeostasis by altering intrathymic and systemic stress-related endocrine circuitries.

    Directory of Open Access Journals (Sweden)

    Ailin Lepletier


    Full Text Available We have previously shown that experimental infection caused by Trypanosoma cruzi is associated with changes in the hypothalamus-pituitary-adrenal axis. Increased glucocorticoid (GC levels are believed to be protective against the effects of acute stress during infection but result in depletion of CD4(+CD8(+ thymocytes by apoptosis, driving to thymic atrophy. However, very few data are available concerning prolactin (PRL, another stress-related hormone, which seems to be decreased during T. cruzi infection. Considering the immunomodulatory role of PRL upon the effects caused by GC, we investigated if intrathymic cross-talk between GC and PRL receptors (GR and PRLR, respectively might influence T. cruzi-induced thymic atrophy. Using an acute experimental model, we observed changes in GR/PRLR cross-activation related with the survival of CD4(+CD8(+ thymocytes during infection. These alterations were closely related with systemic changes, characterized by a stress hormone imbalance, with progressive GC augmentation simultaneously to PRL reduction. The intrathymic hormone circuitry exhibited an inverse modulation that seemed to counteract the GC-related systemic deleterious effects. During infection, adrenalectomy protected the thymus from the increase in apoptosis ratio without changing PRL levels, whereas an additional inhibition of circulating PRL accelerated the thymic atrophy and led to an increase in corticosterone systemic levels. These results demonstrate that the PRL impairment during infection is not caused by the increase of corticosterone levels, but the opposite seems to occur. Accordingly, metoclopramide (MET-induced enhancement of PRL secretion protected thymic atrophy in acutely infected animals as well as the abnormal export of immature and potentially autoreactive CD4(+CD8(+ thymocytes to the periphery. In conclusion, our findings clearly show that Trypanosoma cruzi subverts mouse thymus homeostasis by altering intrathymic and

  14. Alterations of the Brain Reward System in Antipsychotic Naïve Schizophrenia Patients

    DEFF Research Database (Denmark)

    Nielsen, Mette Ødegaard; Rostrup, Egill; Wulff, Sanne


    BACKGROUND: Various schizophrenic symptoms are suggested to be linked to a dysfunction of the brain reward system. Several studies have found alterations in the reward processing in patients with schizophrenia; however, most previous findings might be confounded by medication effects. METHODS......: Thirty-one antipsychotic-naïve schizophrenia patients and 31 age- and gender-matched healthy control subjects were examined with functional magnetic resonance imaging while playing a variant of the monetary incentive delay task. The task variant made it possible to separate overall salience (defined...... as arousing events) into behavioral salience (events where a predicted reward requires performance) and valence anticipation (the anticipation of a monetarily significant outcome). Furthermore, the evaluation of monetary gain and loss was assessed. RESULTS: During reward anticipation, patients had...

  15. Pathogenesis of Bone Alterations in Gaucher Disease: The Role of Immune System

    Directory of Open Access Journals (Sweden)

    Juan Marcos Mucci


    Full Text Available Gaucher, the most prevalent lysosomal disorder, is an autosomal recessive inherited disorder due to a deficiency of glucocerebrosidase. Glucocerebrosidase deficiency leads to the accumulation of glucosylceramide primarily in cells of mononuclear-macrophage lineage. Clinical alterations are visceral, hematological, and skeletal. Bone disorder in Gaucher disease produces defects on bone metabolism and structure and patients suffer from bone pain and crisis. Skeletal problems include osteopenia, osteoporosis, osteolytic lesions, and osteonecrosis. On the other hand a chronic stimulation of the immune system is a well-accepted hallmark in this disease. In this review we summarize the latest findings in the mechanisms leading to the bone pathology in Gaucher disease in relationship with the proinflammatory state.

  16. The cyclic AMP cascade is altered in the fragile X nervous system.

    Directory of Open Access Journals (Sweden)

    Daniel J Kelley

    Full Text Available Fragile X syndrome (FX, the most common heritable cause of mental retardation and autism, is a developmental disorder characterized by physical, cognitive, and behavioral deficits. FX results from a trinucleotide expansion mutation in the fmr1 gene that reduces levels of fragile X mental retardation protein (FMRP. Although research efforts have focused on FMRP's impact on mGluR signaling, how the loss of FMRP leads to the individual symptoms of FX is not known. Previous studies on human FX blood cells revealed alterations in the cyclic adenosine 3', 5'-monophosphate (cAMP cascade. We tested the hypothesis that cAMP signaling is altered in the FX nervous system using three different model systems. Induced levels of cAMP in platelets and in brains of fmr1 knockout mice are substantially reduced. Cyclic AMP induction is also significantly reduced in human FX neural cells. Furthermore, cAMP production is decreased in the heads of FX Drosophila and this defect can be rescued by reintroduction of the dfmr gene. Our results indicate that a robust defect in cAMP production in FX is conserved across species and suggest that cAMP metabolism may serve as a useful biomarker in the human disease population. Reduced cAMP induction has implications for the underlying causes of FX and autism spectrum disorders. Pharmacological agents known to modulate the cAMP cascade may be therapeutic in FX patients and can be tested in these models, thus supplementing current efforts centered on mGluR signaling.

  17. Alterations in CD200-CD200R1 System during EAE Already Manifest at Presymptomatic Stages

    Directory of Open Access Journals (Sweden)

    Tony Valente


    Full Text Available In the brain of patients with multiple sclerosis, activated microglia/macrophages appear in active lesions and in normal appearing white matter. However, whether they play a beneficial or a detrimental role in the development of the pathology remains a controversial issue. The production of pro-inflammatory molecules by chronically activated microglial cells is suggested to contribute to the progression of neurodegenerative processes in neurological disease. In the healthy brain, neurons control glial activation through several inhibitory mechanisms, such as the CD200-CD200R1 interaction. Therefore, we studied whether alterations in the CD200-CD200R1 system might underlie the neuroinflammation in an experimental autoimmune encephalomyelitis (EAE model of multiple sclerosis. We determined the time course of CD200 and CD200R1 expression in the brain and spinal cord of an EAE mouse model from presymptomatic to late symptomatic stages. We also assessed the correlation with associated glial activation, inflammatory response and EAE severity. Alterations in CD200 and CD200R1 expression were mainly observed in spinal cord regions in the EAE model, mostly a decrease in CD200 and an increase in CD200R1 expression. A decrease in the expression of the mRNA encoding a full CD200 protein was detected before the onset of clinical signs, and remained thereafter. A decrease in CD200 protein expression was observed from the onset of clinical signs. By contrast, CD200R1 expression increased at EAE onset, when a glial reaction associated with the production of pro- and anti-inflammatory markers occurred, and continued to be elevated during the pathology. Moreover, the magnitude of the alterations correlated with severity of the EAE mainly in spinal cord. These results suggest that neuronal-microglial communication through CD200-CD200R1 interaction is compromised in EAE. The early decreases in CD200 expression in EAE suggest that this downregulation might also

  18. Systemic Sclerosis Patients Present Alterations in the Expression of Molecules Involved in B-Cell Regulation. (United States)

    Soto, Lilian; Ferrier, Ashley; Aravena, Octavio; Fonseca, Elianet; Berendsen, Jorge; Biere, Andrea; Bueno, Daniel; Ramos, Verónica; Aguillón, Juan Carlos; Catalán, Diego


    The activation threshold of B cells is tightly regulated by an array of inhibitory and activator receptors in such a way that disturbances in their expression can lead to the appearance of autoimmunity. The aim of this study was to evaluate the expression of activating and inhibitory molecules involved in the modulation of B cell functions in transitional, naive, and memory B-cell subpopulations from systemic sclerosis patients. To achieve this, blood samples were drawn from 31 systemic sclerosis patients and 53 healthy individuals. Surface expression of CD86, MHC II, CD19, CD21, CD40, CD22, Siglec 10, CD35, and FcγRIIB was determined by flow cytometry. IL-10 production was evaluated by intracellular flow cytometry from isolated B cells. Soluble IL-6 and IL-10 levels were measured by ELISA from supernatants of stimulated B cells. Systemic sclerosis patients exhibit an increased frequency of transitional and naive B cells related to memory B cells compared with healthy controls. Transitional and naive B cells from patients express higher levels of CD86 and FcγRIIB than healthy donors. Also, B cells from patients show high expression of CD19 and CD40, whereas memory cells from systemic sclerosis patients show reduced expression of CD35. CD19 and CD35 expression levels associate with different autoantibody profiles. IL-10(+) B cells and secreted levels of IL-10 were markedly reduced in patients. In conclusion, systemic sclerosis patients show alterations in the expression of molecules involved in B-cell regulation. These abnormalities may be determinant in the B-cell hyperactivation observed in systemic sclerosis.

  19. Systemic sclerosis patients present alterations in the expression of molecules involved in B cell regulation

    Directory of Open Access Journals (Sweden)

    Lilian eSoto


    Full Text Available The activation threshold of B cells is tightly regulated by an array of inhibitory and activator receptors, in such a way that disturbances in their expression can lead to the appearance of autoimmunity. The aim of this study was to evaluate the expression of activating and inhibitory molecules involved in the modulation of B cell functions in transitional, naïve and memory B cell sub-populations from systemic sclerosis patients. To achieve this, blood samples were drawn from thirty one systemic sclerosis patients and fifty three healthy individuals. Surface expression of CD86, MHC II, CD19, CD21, CD40, CD22, Siglec 10, CD35, and FcgammaRIIB was determined by flow cytometry. IL-10 production was evaluated by intracellular flow cytometry from isolated B cells. Soluble IL-6 and IL-10 levels were measured by ELISA from supernatants of stimulated B cells. Systemic sclerosis patients exhibit an increased frequency of transitional and naïve B cells related to memory B cells, compared to healthy controls. Transitional and naïve B cells from patients express higher levels of CD86 and FcgammaRIIB than healthy donors. Also, B cells from patients show high expression of CD19 and CD40, while memory cells from systemic sclerosis patients show reduced expression of CD35. CD19 and CD35 expression levels associate to different autoantibody profiles. IL-10+ B cells and secreted levels of IL-10 were markedly reduced in patients. In conclusion, systemic sclerosis patients show alterations in the expression of molecules involved in B cell regulation. These abnormalities may be determinant in the B cell hyperactivation observed in systemic sclerosis.

  20. Mechanisms of alteration of the immune system by ionizing radiations: a basis for radiation protection

    Energy Technology Data Exchange (ETDEWEB)

    Bourguignon, M. [Direction Generale de la Surete Nucleaire et de la Radioprotection, 75 - Paris (France); Perez, M.; Dubner, D.; Michelin, S. [Autoridad Regulatoria Nuclear, Buenos Aires (Argentina); Carosella, E. [CEA, Service de Recherches en Hemato -Immunologie, 75 - Paris (France)


    Full text of publication follows: Alterations of the immune system appear in relationship with exposure to ionizing radiation (IR) in different situations, e.g., accidents, radiation therapy of cancer, prenatal irradiation, some human diseases with hypersensitivity to IR and aging. Thus, the comprehension of the mechanisms of the alterations of the immune system by IR is necessary to elaborate strategies of protection and to pave the way for future possible therapies. At least 9 mechanisms of alterations can be identified: 1- Apoptosis. Apoptosis is a key mechanism of the natural regulation of the immune system and plays also a key role in the response to IR: lymphocytes die rapidly by apoptosis after exposure. Different pathways of induction of apoptosis have been identified, and include p53 dependent and mitochondria mediated pathways, as well as CD95 and ROS initiation; 2- TCR mutations. The T cell antigen receptor is responsible to discriminate between self and non self. Mutations of the TCR may result from exposure to IR; 3- Modification of the Th1-Th2 balance. T helper cells may express 2 distinct secretion patterns: Th1 cytokines promote cell-mediated immunity while Th2 cytokines favor humoral immunity. Although the effects of IR on the Th1/Th2 balance remains controversial, an imbalance towards a Th2 profile is likely and patients with cancer and systemic auto-immune disease often present a switch from Th1 to Th2; 4- Bystander effects and genetic instability. Stimulatory effect or genomic instability have been observed in haematopoietic cells exposed to IR and related to a bystander mechanism. 5- Shift toward an inflammatory profile. Ionizing radiation may induce a persistent inflammatory profile as a result of dis-regulation of cytokine production; such a status of persistent inflammation has been observed in Hiroshima and Nagasaki survivors. 6- Modification of antigen presentation. Antigen presentation by dendritic cells is an essential function preceding

  1. Does Acupuncture Alter Pain-related Functional Connectivity of the Central Nervous System? A Systematic Review. (United States)

    Villarreal Santiago, María; Tumilty, Steve; Mącznik, Aleksandra; Mani, Ramakrishnan


    Acupuncture has been studied for several decades to establish evidence-based clinical practice. This systematic review aims to evaluate evidence for the effectiveness of acupuncture in influencing the functional connectivity of the central nervous system in patients with musculoskeletal pain. A systematic search of the literature was conducted to identify studies in which the central response of acupuncture in patients with musculoskeletal pain was evaluated by neuroimaging techniques. Databases searched were AMED, CINAHL, Cochrane Library, EMBASE, MEDLINE, PEDro, Pubmed, SCOPUS, SPORTDiscuss, and Web of Science. Included studies were assessed by two independent reviewers for their methodological quality by using the Downs and Black questionnaire and for their levels of completeness and transparency in reporting acupuncture interventions by using Standards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA) criteria. Seven studies met the inclusion criteria. Three studies were randomized controlled trials (RCTs) and four studies were nonrandomized controlled trials (NRCTs). The neuroimaging techniques used were functional magnetic resonance imaging (fMRI) and positron emission tomography (PET). Positive effects on the functional connectivity of the central nervous system more consistently occurred during long-term acupuncture treatment. The results were heterogeneous from a descriptive perspective; however, the key findings support acupuncture's ability to alter pain-related functional connectivity in the central nervous system in patients with musculoskeletal pain.

  2. Altering shoppers' supermarket purchases to fit nutritional guidelines: an interactive information system. (United States)

    Winett, R A; Moore, J F; Wagner, J L; Hite, L A; Leahy, M; Neubauer, T E; Walberg, J L; Walker, W B; Lombard, D; Geller, E S


    This study reports the results of one effort to help supermarket shoppers alter food purchases to make purchases (and meals) that are lower in fat and higher in fiber. A prototype interactive information system using instructional video programs, feedback on purchases with specific goals for change, weekly programs, and the ability to track user interactions and intended purchases was evaluated. The major dependent measure was users' actual food purchases as derived from participants' highly detailed supermarket receipts. After a 5- to 7-week baseline phase, participants were randomly assigned to an experimental or control condition for the 7- to 8-week intervention phase. A follow-up phase began 5 to 8 weeks after participants completed the intervention and discontinued use of the system. The results indicated that experimental participants, when compared to control participants, decreased high fat purchases and increased high fiber purchases during intervention, with evidence for some maintenance of effect in follow-up. Plans for increasing the use and impact of the system are discussed.

  3. Judicial Control over Althingi: Altered Balance of Powers in the Constitutional System

    Directory of Open Access Journals (Sweden)

    Björg Thorarensen


    Full Text Available The article focuses on how the control of the judiciary over the legislature has increased in the last decades and the reasons for altered balance of powers in the Icelandic constitutional system are explored. Earlier theories of parliamentary precedence over other branches of state power are in transition. There is a growing trend towards the balancing of powers, in which the courts monitor that legislation complies with the constitution. A comparison is made with the developments in the constitutional systems of Denmark and Norway which points at the same direction. The European Convention on Human Rights and constitutional amendments in 1995 have affected the interpretation methods of the Icelandic courts and strengthened their supervisory role. Ideas underlying constitutional democracy, rule of law and effective remedies for individuals are prevailing over the idea of preferred position of the legislative power vis-à-vis the judiciary. The courts see it as a constitutional duty to adjudicate whether a legislative act conforms with constitutional human rights. The Supreme Court of Iceland has referred to the wide discretion of the legislature in the field of fiscal powers, such as regarding taxation and the social security system. However, even where legislation aims at the implementation of important political policies, the discretion of Althingi is subject to certain limits. The effective judicial control requires that Althingi must assess carefully whether legislation which limits constitutionally protected human rights conforms with the principles of equality and proportionality.

  4. Overactivation of the endocannabinoid system alters the antilipolytic action of insulin in mouse adipose tissue. (United States)

    Muller, Tania; Demizieux, Laurent; Troy-Fioramonti, Stéphanie; Gresti, Joseph; Pais de Barros, Jean-Paul; Berger, Hélène; Vergès, Bruno; Degrace, Pascal


    Evidence has accumulated that obesity-related metabolic dysregulation is associated with overactivation of the endocannabinoid system (ECS), which involves cannabinoid receptor 1 (CB1R), in peripheral tissues, including adipose tissue (AT). The functional consequences of CB1R activation on AT metabolism remain unclear. Since excess fat mobilization is considered an important primary event contributing to the onset of insulin resistance, we combined in vivo and in vitro experiments to investigate whether activation of ECS could alter the lipolytic rate. For this purpose, the appearance of plasma glycerol was measured in wild-type and CB1R(-/-) mice after acute anandamide administration or inhibition of endocannabinoid degradation by JZL195. Additional experiments were conducted on rat AT explants to evaluate the direct consequences of ECS activation on glycerol release and signaling pathways. Treatments stimulated glycerol release in mice fasted for 6 h and injected with glucose but not in 24-h fasted mice or in CB1R(-/-), suggesting that the effect was dependent on plasma insulin levels and mediated by CB1R. We concomitantly observed that Akt cascade activity was decreased, indicating an alteration of the antilipolytic action of insulin. Similar results were obtained with tissue explants exposed to anandamide, thus identifying CB1R of AT as a major target. This study indicates the existence of a functional interaction between CB1R and lipolysis regulation in AT. Further investigation is needed to test if the elevation of ECS tone encountered in obesity is associated with excess fat mobilization contributing to ectopic fat deposition and related metabolic disorders. Copyright © 2017 the American Physiological Society.

  5. Altered time structure of neuro-endocrine-immune system function in lung cancer patients

    Directory of Open Access Journals (Sweden)

    Carughi Stefano


    TcS1 was decreased in cancer patients. The melatonin/cortisol mean nocturnal level ratio was decreased in cancer patients. Conclusion The altered secretion and loss of circadian rhythmicity of many studied factors observed in the subjects suffering from neoplastic disease may be expression of gradual alteration of the integrated function of the neuro-immune-endocrine system

  6. Reconstruction of Ancestral Hydrothermal Systems on Mount Rainier Using Hydrothermally Altered Rocks in Holocene Debris Flows and Tephras (United States)

    John, D. A.; Breit, G. N.; Sisson, T. W.; Vallance, J. W.; Rye, R. O.


    geophysical data, as well as analog fossil hydrothermal systems in volcanoes elsewhere, constrain hydrothermal alteration geometry on the pre-Osceola-collapse edifice of Mount Rainier. Relatively narrow zones of acid magmatic-hydrothermal alteration in the central core of the volcano grade to more widely distributed smectite-pyrite alteration farther out on the upper flanks, capped by steam-heated alteration with a large component of alteration resulting from condensation of fumarolic vapor above the water table. Alteration was polygenetic in zones formed episodically, and was strongly controlled by fluxes of heat and magmatic fluid and by local permeability.

  7. Systems and synthetic biology approaches to alter plant cell walls and reduce biomass recalcitrance. (United States)

    Kalluri, Udaya C; Yin, Hengfu; Yang, Xiaohan; Davison, Brian H


    Fine-tuning plant cell wall properties to render plant biomass more amenable to biofuel conversion is a colossal challenge. A deep knowledge of the biosynthesis and regulation of plant cell wall and a high-precision genome engineering toolset are the two essential pillars of efforts to alter plant cell walls and reduce biomass recalcitrance. The past decade has seen a meteoric rise in use of transcriptomics and high-resolution imaging methods resulting in fresh insights into composition, structure, formation and deconstruction of plant cell walls. Subsequent gene manipulation approaches, however, commonly include ubiquitous mis-expression of a single candidate gene in a host that carries an intact copy of the native gene. The challenges posed by pleiotropic and unintended changes resulting from such an approach are moving the field towards synthetic biology approaches. Synthetic biology builds on a systems biology knowledge base and leverages high-precision tools for high-throughput assembly of multigene constructs and pathways, precision genome editing and site-specific gene stacking, silencing and/or removal. Here, we summarize the recent breakthroughs in biosynthesis and remodelling of major secondary cell wall components, assess the impediments in obtaining a systems-level understanding and explore the potential opportunities in leveraging synthetic biology approaches to reduce biomass recalcitrance. Published 2014. This article is a U.S. Government work and is in the public domain in the USA. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

  8. Endothelial Alterations in Systemic Lupus Erythematosus and Rheumatoid Arthritis: Potential Effect of Monocyte Interaction

    Directory of Open Access Journals (Sweden)

    Laura Atehortúa


    Full Text Available Patients with systemic autoimmune diseases such as rheumatoid arthritis (RA and systemic lupus erythematosus (SLE are prone to develop atherosclerosis and cardiovascular diseases five times more often than the general population; this increase in frequency could be partially explained by an increase in the macrovasculature endothelial damage. In these autoimmune diseases, a microvascular endothelial injury has also been reported in different organs and tissues, especially in sites where ultrafiltration processes occur. Different components that are characteristic to the immunopathology of RA and SLE could be involved in the endothelial cell activation, permeability increase, functional alteration, and vascular injury. Circulating immune complexes (IC detected in SLE and RA have been proposed to participate in the endothelial injury. In the vascular environment, IC can generate different responses that could be mediated by monocytes, because these cells have patrolling and monitoring functions on the endothelium. However, with certain stimuli such as TLR ligands, the monocytes are retained in the lumen, releasing proinflammatory mediators that participate in the endothelial damage. This paper aims to review some aspects about the endothelial activation and dysfunction in the context of SLE and RA, as well as the potential role that monocytes apparently play in this process.

  9. Problematic internet use is associated with structural alterations in the brain reward system in females. (United States)

    Altbäcker, Anna; Plózer, Enikő; Darnai, Gergely; Perlaki, Gábor; Horváth, Réka; Orsi, Gergely; Nagy, Szilvia Anett; Bogner, Péter; Schwarcz, Attila; Kovács, Norbert; Komoly, Sámuel; Clemens, Zsófia; Janszky, József


    Neuroimaging findings suggest that excessive Internet use shows functional and structural brain changes similar to substance addiction. Even though it is still under debate whether there are gender differences in case of problematic use, previous studies by-passed this question by focusing on males only or by using gender matched approach without controlling for potential gender effects. We designed our study to find out whether there are structural correlates in the brain reward system of problematic Internet use in habitual Internet user females. T1-weighted Magnetic Resonance (MR) images were collected in 82 healthy habitual Internet user females. Structural brain measures were investigated using both automated MR volumetry and voxel based morphometry (VBM). Self-reported measures of problematic Internet use and hours spent online were also assessed. According to MR volumetry, problematic Internet use was associated with increased grey matter volume of bilateral putamen and right nucleus accumbens while decreased grey matter volume of orbitofrontal cortex (OFC). Similarly, VBM analysis revealed a significant negative association between the absolute amount of grey matter OFC and problematic Internet use. Our findings suggest structural brain alterations in the reward system usually related to addictions are present in problematic Internet use.

  10. Microgravity-induced alterations in signal transduction in cells of the immune system (United States)

    Paulsen, Katrin; Thiel, Cora; Timm, Johanna; Schmidt, Peter M.; Huber, Kathrin; Tauber, Svantje; Hemmersbach, Ruth; Seibt, Dieter; Kroll, Hartmut; Grote, Karl-Heinrich; Zipp, Frauke; Schneider-Stock, Regine; Cogoli, Augusto; Hilliger, Andre; Engelmann, Frank; Ullrich, Oliver


    Since decades it is known that the activity of cells of the immune system is severely dysregulated in microgravity, however, the underlying molecular aspects have not been elucidated yet. The identification of gravity-sensitive molecular mechanisms in cells of the immune system is an important and indispensable prerequisite for the development of counteractive measures to prevent or treat disturbed immune cell function of astronauts during long-term space missions. Moreover, their sensitivity to altered gravity renders immune cells an ideal model system to understand if and how gravity on Earth is required for normal mammalian cell function and signal transduction. We investigated the effect of simulated weightlessness (2D clinostat) and of real microgravity (parabolic flights) on key signal pathways in a human monocytic and a T lymphocyte cell line. We found that cellular responses to microgravity strongly depend on the cell-type and the conditions in which the cells are subjected to microgravity. In Jurkat T cells, enhanced phosphorylation of the MAP kinases ERK-1/2, MEK and p38 and inhibition of nuclear translocation of NF-kB were the predominant responses to simulated weightlessness, in either stimulated or non-stimulated cells. In contrast, non-stimulated monocytic U937 cells responded to simulated weightlessness with enhanced overall tyrosine-phosphorylation and activation of c-jun, whereas PMA-stimulated U937 cells responded the opposite way with reduced tyrosine-phosphorylation and reduced activation of c-jun, compared with PMA-stimulated 1 g controls. P53 protein was phosphorylated rapidly in microgravity. The identification of gravi-sensitive mechanisms in cells of the immune system will not only enable us to understand and prevent the negative effects of long time exposure to microgravity on Astronauts, but could also lead to novel therapeutic targets in general.

  11. Alterations in the Medullary Endocannabinoid System Contribute to Age-related Impairment of Baroreflex Sensitivity. (United States)

    Schaich, Chris L; Shaltout, Hossam A; Grabenauer, Megan; Thomas, Brian F; Gallagher, Patricia E; Howlett, Allyn C; Diz, Debra I


    As they age, Sprague-Dawley (SD) rats develop elevated systolic blood pressure associated with impaired baroreflex sensitivity (BRS) for control of heart rate. We previously demonstrated in young hypertensive (mRen2)27 rats that impaired BRS is restored by CB1 cannabinoid receptor blockade in the solitary tract nucleus (NTS), consistent with elevated content of the endocannabinoid 2-arachidonoylglycerol (2-AG) in dorsal medulla relative to normotensive SD rats. There is no effect of CB1 receptor blockade in young SD rats. We now report in older SD rats that dorsal medullary 2-AG levels are 2-fold higher at 70 versus 15 weeks of age (4.22 ± 0.61 vs. 1.93 ± 0.22 ng/mg tissue; P < 0.05). Furthermore, relative expression of CB1 receptor messenger RNA is significantly lower in aged rats, whereas CB2 receptor messenger RNA is significantly higher. In contrast to young adult SD rats, microinjection of the CB1 receptor antagonist SR141716A (36 pmole) into the NTS of older SD rats normalized BRS in animals exhibiting impaired baseline BRS (0.56 ± 0.06 baseline vs. 1.06 ± 0.05 ms/mm Hg after 60 minutes; P < 0.05). Therefore, this study provides evidence for alterations in the endocannabinoid system within the NTS of older SD rats that contribute to age-related impairment of BRS.

  12. Urine proteomes of healthy aging humans reveal extracellular matrix (ECM) alterations and immune system dysfunction. (United States)

    Bakun, M; Senatorski, G; Rubel, T; Lukasik, A; Zielenkiewicz, P; Dadlez, M; Paczek, L


    Aging is a complex physiological process that poses considerable conundrums to rapidly aging societies. For example, the risk of dying from cardiovascular diseases and/or cancer steadily declines for people after their 60s, and other causes of death predominate for seniors older than 80 years of age. Thus, physiological aging presents numerous unanswered questions, particularly with regard to changing metabolic patterns. Urine proteomics analysis is becoming a non-invasive and reproducible diagnostic method. We investigated the urine proteomes in healthy elderly people to determine which metabolic processes were weakened or strengthened in aging humans. Urine samples from 37 healthy volunteers aged 19-90 years (19 men, 18 women) were analyzed for protein expression by liquid chromatography-tandem mass spectrometry. This generated a list of 19 proteins that were differentially expressed in different age groups (young, intermediate, and old age). In particular, the oldest group showed protein changes reflective of altered extracellular matrix turnover and declining immune function, in which changes corresponded to reported changes in cardiovascular tissue remodeling and immune disorders in the elderly. Thus, urinary proteome changes in the elderly appear to reflect the physiological processes of aging and are particularly clearly represented in the circulatory and immune systems. Detailed identification of "protein trails" creates a more global picture of metabolic changes that occur in the elderly.

  13. Role of altered mitochondria functions in the pathogenesis of systemic lupus erythematosus. (United States)

    Leishangthem, B D; Sharma, A; Bhatnagar, A


    Mitochondria, main producers of reactive-oxygen species (ROS), were studied to examine their role in the pathogenesis of systemic lupus erythematosus (SLE). PBMCs and mitochondria were isolated from SLE patients and healthy volunteers for various parameters. Mitochondrial ROS, swelling, hyperpolarization and levels of cytochrome c, caspase3 in the cells were assessed by flow cytometry. ROS was significantly increased in SLE patients (SLE vs controls: 1.83 ± 1.03 vs 1.10 ± 0.35; p mitochondria was greater in patients (SLE vs controls: 7.10 ± 5.50% vs 2.5 ± 1.8%; p Mitochondria swelling was found to be significantly altered in patients (SLE vs controls: 112.65 ± 36.56 vs 60.49 ± 20.69; p mitochondria. A significant decrease in activity of Complex I (SLE vs controls: 11.79 ± 3.18 vs 15.10 ± 6.38 nmol NADH oxidized/min/mg protein, p mitochondria in the pathogenesis of lupus. © The Author(s) 2015.

  14. Water Velocity and Bioturbation Alter Sediment Resuspension and Biogeochemistry in an Experimental Freshwater Mesocosm System (United States)

    Spivak, A.; Vanni, M. J.


    Processes such as bioturbation and resuspension can affect organic matter decomposition by altering sediment redox conditions. Increased oxygen availability may, in turn, affect remineralization rates and larger scale processes such as benthic-pelagic coupling. However, relatively few studies have explicitly tested the simultaneous effects of bioturbation and water velocity on benthic biogeochemistry and sediment resuspension. Using a mesocosm system we conducted two experiments testing the effects of bioturbator identity on particulate and dissolved nutrient dynamics before and after a resuspension event (i.e. water velocity held constant at 0.12 m s-1 for 2 hr; Expt. 1) and rates of sediment resuspension with increasing water velocity (0.00 - 0.20 m s-1; Expt. 2). We manipulated bioturbator identity across four levels as sediments were undisturbed (control), manually punctured (2% of surface area), or disturbed by one of two fish species, either bluegill or catfish. For Expt. 1, the bioturbation treatments were applied for several days and measurements were made before and after the resuspension event. Initially, water column chlorophyll and total suspended sediment (TSS) concentrations were highest in the catfish treatments. Bioturbator identity did not affect the stoichiometry of TSS as strongly; C:N was unaffected by our treatments while N:P was lowest in the disturbed treatments. After the resuspension event, there was no difference in TSS concentrations or stoichiometric ratios across the bioturbation treatments. Dissolved nutrient flux rates were insensitive to the bioturbation treatments and were more strongly influenced by the resuspension event. For instance, sediment NO3- fluxes were negative (i.e. net flux into sediments) until after the resuspension event when they became positive. In Expt. 2, we gradually increased water velocity from 0.00 - 0.20 m s-1 and measured TSS concentrations only. TSS was initially highest in catfish treatments and lowest in

  15. Phenotypic Alterations Involved in CD8+ Treg Impairment in Systemic Sclerosis. (United States)

    Negrini, Simone; Fenoglio, Daniela; Parodi, Alessia; Kalli, Francesca; Battaglia, Florinda; Nasi, Giorgia; Curto, Monica; Tardito, Samuele; Ferrera, Francesca; Filaci, Gilberto


    Systemic sclerosis (SSc) is a connective tissue disease characterized by tissue fibrosis, vasculopathy, and autoimmunity. Although the exact pathogenetic mechanisms behind SSc remain to be fully elucidated, a great deal of evidence suggests the existence of an unbalanced ratio between the effector and regulatory arms of the immune system. With regard to the T regulatory (Treg) compartment, we observed that CD8+ Treg subsets display functional defects in SSc-affected patients. Since CD127 down-modulation and CD39 upregulation have been observed on Treg subsets, the phenotypic expression of these molecules was analyzed on the CD8+CD28- Treg precursors and on CD8+ Treg cells generated in vitro through interleukin-10 commitment. Immunophenotypic data from SSc patients were compared to those obtained from healthy subjects. The analyses performed on ex vivo-isolated CD8+CD28- Treg precursors did not show any significant differences in CD39 or CD127 expression as compared to values obtained from healthy donors. On the contrary, in vitro-generated CD8+ Tregs obtained from SSc patients displayed reduced expression of the CD39 molecule as compared to controls. Moreover, the percentage of CD127+ cells was significantly higher in in vitro-generated CD8+ Tregs from SSc patients compared to CD8+ Tregs obtained from healthy donors. Taken together, these findings may indicate an impairment of maturation processes affecting CD8+ Treg cells in SSc patients. This impairment of maturation involves phenotypic alterations that are mainly characterized by a deficient CD39 upregulation and a lack of down-modulation of the CD127 molecule.

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

    Directory of Open Access Journals (Sweden)

    Tanel eVisnapuu


    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.

  17. Numerical Models of Human Circulatory System under Altered Gravity: Brain Circulation (United States)

    Kim, Chang Sung; Kiris, Cetin; Kwak, Dochan; David, Tim


    A computational fluid dynamics (CFD) approach is presented to model the blood flow through the human circulatory system under altered gravity conditions. Models required for CFD simulation relevant to major hemodynamic issues are introduced such as non-Newtonian flow models governed by red blood cells, a model for arterial wall motion due to fluid-wall interactions, a vascular bed model for outflow boundary conditions, and a model for auto-regulation mechanism. The three-dimensional unsteady incompressible Navier-Stokes equations coupled with these models are solved iteratively using the pseudocompressibility method and dual time stepping. Moving wall boundary conditions from the first-order fluid-wall interaction model are used to study the influence of arterial wall distensibility on flow patterns and wall shear stresses during the heart pulse. A vascular bed modeling utilizing the analogy with electric circuits is coupled with an auto-regulation algorithm for multiple outflow boundaries. For the treatment of complex geometry, a chimera overset grid technique is adopted to obtain connectivity between arterial branches. For code validation, computed results are compared with experimental data for steady and unsteady non-Newtonian flows. Good agreement is obtained for both cases. In sin-type Gravity Benchmark Problems, gravity source terms are added to the Navier-Stokes equations to study the effect of gravitational variation on the human circulatory system. This computational approach is then applied to localized blood flows through a realistic carotid bifurcation and two Circle of Willis models, one using an idealized geometry and the other model using an anatomical data set. A three- dimensional anatomical Circle of Willis configuration is reconstructed from human-specific magnetic resonance images using an image segmentation method. The blood flow through these Circle of Willis models is simulated to provide means for studying gravitational effects on the brain

  18. Dietary protein restriction causes modification in aluminum-induced alteration in glutamate and GABA system of rat brain

    Directory of Open Access Journals (Sweden)

    Chatterjee Ajay K


    Full Text Available Abstract Background Alteration of glutamate and γ-aminobutyrate system have been reported to be associated with neurodegenerative disorders and have been postulated to be involved in aluminum-induced neurotoxicity as well. Aluminum, an well known and commonly exposed neurotoxin, was found to alter glutamate and γ-aminobutyrate levels as well as activities of associated enzymes with regional specificity. Protein malnutrition also reported to alter glutamate level and some of its metabolic enzymes. Thus the region-wise study of levels of brain glutamate and γ-aminobutyrate system in protein adequacy and inadequacy may be worthwhile to understand the mechanism of aluminum-induced neurotoxicity. Results Protein restriction does not have any significant impact on regional aluminum and γ-aminobutyrate contents of rat brain. Significant interaction of dietary protein restriction and aluminum intoxication to alter regional brain glutamate level was observed in the tested brain regions except cerebellum. Alteration in glutamate α-decarboxylase and γ-aminobutyrate transaminase activities were found to be significantly influenced by interaction of aluminum intoxication and dietary protein restriction in all the tested brain regions. In case of regional brain succinic semialdehyde content, this interaction was significant only in cerebrum and thalamic area. Conclusion The alterations of regional brain glutamate and γ-aminobutyrate levels by aluminum are region specific as well as dependent on dietary protein intake. The impact of aluminum exposure on the metabolism of these amino acid neurotransmitters are also influenced by dietary protein level. Thus, modification of dietary protein level or manipulation of the brain amino acid homeostasis by any other means may be an useful tool to find out a path to restrict amino acid neurotransmitter alterations in aluminum-associated neurodisorders.

  19. Adaptations of the vestibular system to short and long-term exposures to altered gravity (United States)

    Bruce, L.

    Long-term space flight creates unique environmental conditions to which the vestibular system must adapt for optimal survival. We are studying two aspects of this vestibular adaptation: (1) How does long-term exposure to microgravity and hypergravity affect the development of vestibular afferents? (2) How does short- term exposure to extremely rapid changes in gravity, such as those that occur during launch and landing, affect the vestibular system. During space flight the gravistatic receptors in the otolith organs are effectively unloaded. In hypergravity conditions they are overloaded. However, the angular acceleration receptors of the semicircular canals receive relatively normal stimulation in both micro- and hypergravity.Rat embryos exposed to microgravity from gestation day 10 (prior to vestibular function) until gestation day 20 (vestibular system is somewhat functional) showed that afferents from the posterior vertical canal projecting to the medial vestibular nucleus developed similarly in microgravity, hypergravity, and in controls . However, afferents from the saccule showed delayed development in microgravity as compared to development in hypergravity and in controls. Cerebellar plasticity is crucial for modification of sensory-motor control and learning. Thus we explored the possibility that strong vestibular stimuli would modify cerebellar motor control (i.e., eye movement, postural control, gut motility) by altering the morphology of cerebellar Purkinje cells. To study the effects of short-term exposures to strong vestibular stimuli we focused on structural changes in the vestibulo-cerebellum that are caused by strong vestibular stimuli. Adult mice were exposed to various combinations of constant and/or rapidly changing angular and linear accelerations for 8.5 min (the time length of shuttle launch). Our data shows that these stimuli cause intense excitation of cerebellar Purkinje cells, inducing up-regulation of clathrin-mediated endocytosis

  20. Repeated dexamphetamine treatment alters the dopaminergic system and increases the phMRI response to methylphenidate (United States)

    Schrantee, Anouk; Tremoleda, Jordi L.; Wylezinska-Arridge, Marzena; Bouet, Valentine; Hesseling, Peter; Meerhoff, Gideon F.; de Bruin, Kora M.; Koeleman, Jan; Freret, Thomas; Boulouard, Michel; Desfosses, Emilie; Galineau, Laurent; Gozzi, Alessandro; Dauphin, François; Gsell, Willy; Booij, Jan; Lucassen, Paul J.; Reneman, Liesbeth


    Dexamphetamine (AMPH) is a psychostimulant drug that is used both recreationally and as medication for attention deficit hyperactivity disorder. Preclinical studies have demonstrated that repeated exposure to AMPH can induce damage to nerve terminals of dopamine (DA) neurons. We here assessed the underlying neurobiological changes in the DA system following repeated AMPH exposure and pre-treated rats with AMPH or saline (4 times 5 mg/kg s.c., 2 hours apart), followed by a 1-week washout period. We then used pharmacological MRI (phMRI) with a methylphenidate (MPH) challenge, as a sensitive and non-invasive in-vivo measure of DAergic function. We subsequently validated the DA-ergic changes post-mortem, using a.o. high-performance liquid chromatography (HPLC) and autoradiography. In the AMPH pre-treated group, we observed a significantly larger BOLD response to the MPH challenge, particularly in DA-ergic brain areas and their downstream projections. Subsequent autoradiography studies showed that AMPH pre-treatment significantly reduced DA transporter (DAT) density in the caudate-putamen (CPu) and nucleus accumbens, whereas HPLC analysis revealed increases in the DA metabolite homovanillic acid in the CPu. Our results suggest that AMPH pre-treatment alters DAergic responsivity, a change that can be detected with phMRI in rats. These phMRI changes likely reflect increased DA release together with reduced DAT binding. The ability to assess subtle synaptic changes using phMRI is promising for both preclinical studies of drug discovery, and for clinical studies where phMRI can be a useful tool to non-invasively investigate DA abnormalities, e.g. in neuropsychiatric disorders. PMID:28241065

  1. On the sputter alteration of regoliths of outer solar system bodies (United States)

    Hapke, Bruce


    Several processes that are expected to occur when the porous regoliths of outer solar system bodies (without atmospheres) are subjected to energetic ion bombardment are discussed. The conclusions reached in much of the literature addressing sputtering are quantitatively or qualitatively incorrect because effects of soil porosity have been neglected. It is shown theoretically and experimentally that porosity reduces the effective sputtering yield of a soil by more than an order of magnitude. Between 90 and 97% of the sputtered atoms are trapped within the regolith, where they are factionated by differential desorption. Experiments indicate that more volatile species have higher desorption probabilities. This process is the most important way in which alteration of chemical and optical properties occurs when a regolith is sputtered. When a basic silicate soil is irradiated these effects lead to sputter-deposited films enriched in metallic iron, while O, Na and K are preferentially lost. The Na and K are present in the atmosphere above the sputtered silicate in quantities much greater than their abundances in the regolith. Icy regoliths of SO2 should be enriched in elemental S and/or S2O. This prediction is supported by the probable identification of S2O and polysulfur oxide bands in the IR spectra of H-sputtered SO2 reported by Moore. When porous mixtures of water, ammonia and methane frosts are sputtered, the loss of H and surface reactions of C, N and O in the deposits should produce complex hydrocarbons and carbohydrates, some of which may be quite dark. Such reactions may have played a role in the formation of the matrix material of carbonaceous chondrites prior to agglomeration.

  2. A multi-faceted approach to characterize acid-sulfate alteration processes in volcanic hydrothermal systems on Earth and Mars (United States)

    Marcucci, Emma Cordts

    Acid-sulfate alteration is a dominant weathering process in high temperature, low pH, sulfur-rich volcanic environments. Additionally, hydrothermal environments have been proposed as locations where life could have originated on Earth. Based on the extensive evidence of flowing surface water and persistent volcanism, similar locations and processes could have existed on early Mars. Globally observed alteration mineral assemblages likely represent relic Martian hydrothermal settings. Yet the limited understanding of environmental controls, limits the confidence of interpreting the paleoconditions of these hydrothermal systems and assessing their habitability to support microbial life. This thesis presents a series of laboratory experiments, geochemical models, analog fieldwork, and Martian remote sensing to characterize distinguishing features and controls of acid-sulfate alteration. The experiments and models were designed to replicate alteration is a highly acidic, sulfurous, and hot field sites. The basaltic minerals were individually reacted in both experimental and model simulations with varying initial parameters to infer the geochemical pathways of acid-sulfate alteration on Earth and Mars. It was found that for a specific starting material, secondary mineralogies were consistent. Variations in pH, temperature and duration affected the abundance, shape, and size of mineral products. Additionally evaporation played a key role in secondary deposits; therefore, both alteration and evaporitic processes need to be taken into consideration. Analog volcanic sites in Nicaragua were used to supplement this work and highlight differences between natural and simulated alteration. In situ visible near-infrared spectroscopy demonstrated that primary lithology and gas chemistry were dominant controls of alteration, with secondary effects from environmental controls, such as temperature and pH. The spectroscopic research from the field was directly related to Mars

  3. [Selective alteration of the declarative memory systems in patients treated with a high number of electroconvulsive therapy sessions]. (United States)

    Rami-González, L; Boget-Llucià, T; Bernardo, M; Marcos, T; Cañizares-Alejos, S; Penadés, R; Portella, M J; Castelví, M; Raspall, T; Salamero, M

    The reversible electrochemical effects of electroconvulsive therapy (ECT) on specific areas of the brain enable the neuroanatomical bases of some cognitive functions to be studied. In research carried out on memory systems, a selective alteration of the declarative ones has been observed after treatment with ECT. Little work has been done to explore the differential alteration of the memory subsystems in patients with a high number of ECT sessions. AIM. To study the declarative and non declarative memory system in psychiatric patients submitted to maintenance ECT treatment, with a high number of previous ECT sessions. 20 patients submitted to treatment with ECT (10 diagnosed as having depression and 10 with schizophrenia) and 20 controls, who were paired by age, sex and psychopathological diagnosis. For the evaluation of the declarative memory system, the Wechsler Memory Scale (WMS) logical memory test was used. The Hanoi Tower procedural test was employed to evaluate the non declarative system. Patients treated with ECT performed worse in the WMS logical memory test, but this was only significant in patients diagnosed as suffering from depression. No significant differences were observed in the Hanoi Tower test. A selective alteration of the declarative systems was observed in patients who had been treated with a high number of ECT sessions, while the non declarative memory systems remain unaffected.

  4. Strontium and oxygen isotopic profiles through 3 km of hydrothermally altered oceanic crust in the Reykjanes Geothermal System, Iceland (United States)

    Marks, N. E.; Zierenberg, R. A.; Schiffman, P.


    The Iceland Deep Drilling Program well of opportunity RN-17 was drilled 3 km into a section of hydrothermally altered basaltic crust in the Reykjanes geothermal system in Iceland. The system is located on the landward extension of the Mid-Atlantic Ridge, and the circulating hydrothermal fluid is modified seawater, making Reykjanes a useful analogue for mid-oceanic ridge hydrothermal systems. Whole rock oxygen isotope ratios range from -0.13 to 3.61‰, which are significantly depleted relative to fresh MORB (5.8±0.2‰). If oxygen isotope exchange between fluid and rock proceeded under equilibrium in a closed system, the bulk of the exchange must have occurred in the presence of a meteoric- as opposed to seawater-derived fluid. The concentrations of Sr in the altered basalt range from well below to well above concentrations in fresh rock, and appear to be strongly correlated with the dominant alteration mineralogy, although there is no correlation with 87Sr/86Sr isotopic ratios. Whole rock Sr isotopic ratios ranged from 0.70329 in the least altered crystalline basalt, to 0.70609 in the most altered hyaloclastite samples; there is no correlation with depth. Sr isotopic variation in epidote grains measured by laser ablation MC-ICP-MS ranged from 0.70353 to 0.70731. Three depth intervals have distinctive isotopic signatures, at 1000 m, 1350 m, and 2000 m depth, where 87Sr/86Sr ratios are elevated (mean value >0.7050) relative to background levels (mean altered basalt value ~0.7042). These areas are proximal to feed zones, and the 1350 m interval directly overlies the transition from dominantly extrusive to intrusive lithologies. Strontium and oxygen isotope data indicate that the greenschist-altered basalts were in equilibrium with modified hydrothermal fluids at a relatively high mean water/rock mass ratios (generally in the range 1-3), and require the presence of both meteoric- and seawater-derived recharge fluids at various stages in the hydrothermal history.

  5. Response of the photosynthetic system to altered protein composition and changes in environmental conditions

    NARCIS (Netherlands)

    Tóth, T.


    The photosynthetic thylakoid membrane has a hierarchically ordered structure containing pigment-protein complexes that capture solar radiation and convert it into chemical energy. Its highly dynamic structure is capable to continuously respond to the altered environmental conditions, e.g., light

  6. Response of the photosynthetic system to altered protein composition and changes in environmental conditions

    NARCIS (Netherlands)

    Tóth, T.


    The photosynthetic thylakoid membrane has a hierarchically ordered structure containing pigment-protein complexes that capture solar radiation and convert it into chemical energy. Its highly dynamic structure is capable to continuously respond to the altered environmental conditions, e.g., light qua

  7. Altered systemic bioavailability and organ distribution of azathioprine in methotrexate-induced intestinal mucositis in rats

    Directory of Open Access Journals (Sweden)

    Sadaf A Karbelkar


    Conclusion: Study outcome has thrown light on altered fate of AZA when administered to individuals with mucositis which suggests modified drug therapy. These findings can further be investigated in different drug classes which might be administered concomitantly in mucositis and study outcome can be further confirmed in mucositis patients in clinical practice also.

  8. Systemic inhibition of canonical Notch signaling results in sustained callus inflammation and alters multiple phases of fracture healing.

    Directory of Open Access Journals (Sweden)

    Michael I Dishowitz

    Full Text Available The Notch signaling pathway is an important regulator of embryological bone development, and many aspects of development are recapitulated during bone repair. We have previously reported that Notch signaling components are upregulated during bone fracture healing. However, the significance of the Notch pathway in bone regeneration has not been described. Therefore, the objective of this study was to determine the importance of Notch signaling in regulating bone fracture healing by using a temporally controlled inducible transgenic mouse model (Mx1-Cre;dnMAML(f/- to impair RBPjκ-mediated canonical Notch signaling. The Mx1 promoter was synthetically activated resulting in temporally regulated systemic dnMAML expression just prior to creation of bilateral tibial fractures. This allowed for mice to undergo unaltered embryological and post-natal skeletal development. Results showed that systemic Notch inhibition prolonged expression of inflammatory cytokines and neutrophil cell inflammation, and reduced the proportion of cartilage formation within the callus at 10 days-post-fracture (dpf Notch inhibition did not affect early bone formation at 10dpf, but significantly altered bone maturation and remodeling at 20dpf. Increased bone volume fraction in dnMAML fractures, which was due to a moderate decrease in callus size with no change in bone mass, coincided with increased trabecular thickness but decreased connectivity density, indicating that patterning of bone was altered. Notch inhibition decreased total osteogenic cell density, which was comprised of more osteocytes rather than osteoblasts. dnMAML also decreased osteoclast density, suggesting that osteoclast activity may also be important for altered fracture healing. It is likely that systemic Notch inhibition had both direct effects within cell types as well as indirect effects initiated by temporally upstream events in the fracture healing cascade. Surprisingly, Notch inhibition did not alter

  9. Magnetic effects of hydrothermal alteration in porphyry copper and iron-oxide copper-gold systems: A review (United States)

    Clark, David A.


    Magnetic anomaly patterns can be used as a tool for mapping lithology, metamorphic zones and hydrothermal alteration systems, as well as identifying structures that may control passage of magmas or hydrothermal fluids associated with mineralisation. Reliable geological interpretation of mineralised systems requires an understanding of the magmatic, metamorphic and hydrothermal processes that create, alter and destroy magnetic minerals in rocks. Predictive magnetic exploration models for porphyry copper and iron oxide copper-gold (IOCG) deposits can be derived from standard geological models by integrating magnetic petrological principles with petrophysical data, deposit descriptions, and modelling of observed magnetic signatures of these deposits. Even within a particular geological province, the magnetic signatures of similar deposits may differ substantially, due to differences in the local geological setting. Searching for “look-alike” signatures of a known deposit is likely to be unrewarding unless pertinent geological factors are taken into account. These factors include the tectonic setting and magma type, composition and disposition of host rocks, depth of emplacement and post-emplacement erosion level, depth of burial beneath younger cover, post-emplacement faulting and tilting, remanence effects contingent on ages of intrusion and alteration, and metamorphism. Because the effects of these factors on magnetic signatures are reasonably well understood, theoretical magnetic signatures appropriate for the local geological environment can qualitatively guide exploration and make semiquantitative predictions of anomaly amplitudes and patterns. The predictive models also allow detectability of deposit signatures to be assessed, for example when deposits are buried beneath a considerable thickness of nonmagnetic overburden, are covered by highly magnetic heterogeneous volcanic rocks, or there is a strong regional magnetic gradient. This paper reviews the

  10. Pathogenic LRRK2 mutations do not alter gene expression in cell model systems or human brain tissue.

    Directory of Open Access Journals (Sweden)

    Michael J Devine

    Full Text Available Point mutations in LRRK2 cause autosomal dominant Parkinson's disease. Despite extensive efforts to determine the mechanism of cell death in patients with LRRK2 mutations, the aetiology of LRRK2 PD is not well understood. To examine possible alterations in gene expression linked to the presence of LRRK2 mutations, we carried out a case versus control analysis of global gene expression in three systems: fibroblasts isolated from LRRK2 mutation carriers and healthy, non-mutation carrying controls; brain tissue from G2019S mutation carriers and controls; and HEK293 inducible LRRK2 wild type and mutant cell lines. No significant alteration in gene expression was found in these systems following correction for multiple testing. These data suggest that any alterations in basal gene expression in fibroblasts or cell lines containing mutations in LRRK2 are likely to be quantitatively small. This work suggests that LRRK2 is unlikely to play a direct role in modulation of gene expression, although it remains possible that this protein can influence mRNA expression under pathogenic cicumstances.

  11. 75 FR 5606 - Privacy Act of 1974; Report of an Altered System of Records (United States)


    ... Document Management System (DMS), HHS/ HRSA/BHPr,'' for recipients of CBB loans and scholarships, at the... RECORD NUMBER 09-15-0069 System Name: Campus Based Branch (CBB) Program Document Management System (DMS... documents for efficient access and verification. Routine uses of records maintained in the system, including...

  12. Encapsulation altered starch digestion: toward developing starch-based delivery systems. (United States)

    Janaswamy, Srinivas


    Starch is an abundant biomaterial that forms a vital energy source for humans. Altering its digestion, e.g. increasing the proportions of slowly digestible starch (SDS) and resistant starch (RS), would revolutionize starch utility in addressing a number of health issues related to glucose absorption, glycemic index and colon health. The research reported in this article is based on my hypothesis that water channels present in the B-type starch crystalline matrix, particularly in tuber starches, can embed guest molecules such as nutraceuticals, drugs, flavor compounds and vitamins leading to altered starch digestion. Toward this goal, potato starch has been chosen as the model tuber starch, and ibuprofen, benzocaine, sulfapyridine, curcumin, thymol and ascorbic acid as model guest molecules. X-ray powder diffraction and FT-IR analyses clearly suggest the incorporation of guest molecules in the water channels of potato starch. Furthermore, the in vitro digestion profiles of complexes are intriguing with major variations occurring after 60 min of starch digestion and finally at 120 min. These changes are concomitantly reflected in the SDS and RS amounts, with about 24% decrease in SDS for benzocaine complex and 6% increase in RS for ibuprofen complex, attesting the ability of guest molecule encapsulation in modulating the digestion properties of potato starch. Overall, this research provides an elegant opportunity for the design and development of novel starch-based stable carriers that not only bestow tailored glucose release rates but could also transport health promoting and disease preventing compounds.

  13. Long-lasting alterations of the immune system by ionizing radiation exposure: implications for disease development among atomic bomb survivors. (United States)

    Kusunoki, Yoichiro; Hayashi, Tomonori


    The immune systems of the atomic-bomb (A-bomb) survivors were damaged proportionately to irradiation levels at the time of the bombing over 60 years ago. Although the survivor's immune system repaired and regenerated as the hematopoietic system has recovered, significant residual injury persists, as manifested by abnormalities in lymphoid cell composition and function. This review summarizes the long-lasting alterations in immunological functions associated with atomic-bomb irradiation, and discusses the likelihood that damaging effects of radiation on the immune system may be involved partly in disease development so frequently observed in A-bomb survivors. Significant immunological alterations noted include: (i) attrition of T-cell functions, as reductions in mitogen-dependent proliferation and interleukin-2 (IL-2) production; (ii) decrease in helper T-cell populations; and (iii) increase in blood inflammatory cytokine levels. These findings suggest that A-bomb radiation exposure perturbed one or more of the primary processes responsible for T-cell homeostasis and the balance between cell renewal and survival and cell death among naive and memory T cells. Such perturbed T-cell homeostasis may result in acceleration of immunological aging. Persistent inflammation, linked in some way to the perturbation of T-cell homeostasis, is key in addressing whether such noted immunological changes observed in A-bomb survivors are in fact associated with disease development.

  14. Chronic Sleep Disruption Alters Gut Microbiota, Induces Systemic and Adipose Tissue Inflammation and Insulin Resistance in Mice (United States)

    Poroyko, Valeriy A.; Carreras, Alba; Khalyfa, Abdelnaby; Khalyfa, Ahamed A.; Leone, Vanessa; Peris, Eduard; Almendros, Isaac; Gileles-Hillel, Alex; Qiao, Zhuanhong; Hubert, Nathaniel; Farré, Ramon; Chang, Eugene B.; Gozal, David


    Chronic sleep fragmentation (SF) commonly occurs in human populations, and although it does not involve circadian shifts or sleep deprivation, it markedly alters feeding behaviors ultimately promoting obesity and insulin resistance. These symptoms are known to be related to the host gut microbiota. Mice were exposed to SF for 4 weeks and then allowed to recover for 2 weeks. Taxonomic profiles of fecal microbiota were obtained prospectively, and conventionalization experiments were performed in germ-free mice. Adipose tissue insulin sensitivity and inflammation, as well as circulating measures of inflammation, were assayed. Effect of fecal water on colonic epithelial permeability was also examined. Chronic SF-induced increased food intake and reversible gut microbiota changes characterized by the preferential growth of highly fermentative members of Lachnospiraceae and Ruminococcaceae and a decrease of Lactobacillaceae families. These lead to systemic and visceral white adipose tissue inflammation in addition to altered insulin sensitivity in mice, most likely via enhanced colonic epithelium barrier disruption. Conventionalization of germ-free mice with SF-derived microbiota confirmed these findings. Thus, SF-induced metabolic alterations may be mediated, in part, by concurrent changes in gut microbiota, thereby opening the way for gut microbiome-targeted therapeutics aimed at reducing the major end-organ morbidities of chronic SF. PMID:27739530

  15. Developmental exposure to the pesticide dieldrin alters the dopamine system and increases neurotoxicity in an animal model of Parkinson's disease. (United States)

    Richardson, Jason R; Caudle, W Michael; Wang, Minzheng; Dean, E Danielle; Pennell, Kurt D; Miller, Gary W


    Exposure to pesticides has been suggested to increase the risk of Parkinson's disease (PD), but the mechanisms responsible for this association are not clear. Here, we report that perinatal exposure of mice during gestation and lactation to low levels of dieldrin (0.3, 1, or 3 mg/kg every 3 days) alters dopaminergic neurochemistry in their offspring and exacerbates MPTP toxicity. At 12 wk of age, protein and mRNA levels of the dopamine transporter (DAT) and vesicular monoamine transporter 2 (VMAT2) were increased by perinatal dieldrin exposure in a dose-related manner. We then administered MPTP (2 x 10 mg/kg s.c) at 12 wk of age and observed a greater reduction of striatal dopamine in dieldrin-exposed offspring, which was associated with a greater DAT:VMAT2 ratio. Additionally, dieldrin exposure during development potentiated the increase in GFAP and alpha-synuclein levels induced by MPTP, indicating increased neurotoxicity. In all cases there were greater effects observed in the male offspring than the female, similar to that observed in human cases of PD. These data suggest that developmental exposure to dieldrin leads to persistent alterations of the developing dopaminergic system and that these alterations induce a "silent" state of dopamine dysfunction, thereby rendering dopamine neurons more vulnerable later in life.

  16. Altered systemic bile acid homeostasis contributes to liver disease in pediatric patients with intestinal failure (United States)

    Xiao, Yong-Tao; Cao, Yi; Zhou, Ke-Jun; Lu, Li-Na; Cai, Wei


    Intestinal failure (IF)-associated liver disease (IFALD), as a major complication, contributes to significant morbidity in pediatric IF patients. However, the pathogenesis of IFALD is still uncertain. We here investigate the roles of bile acid (BA) dysmetabolism in the unclear pathogenesis of IFALD. It found that the histological evidence of pediatric IF patients exhibited liver injury, which was characterized by liver bile duct proliferation, inflammatory infiltration, hepatocyte apoptosis and different stages of fibrosis. The BA compositions were altered in serum and liver of pediatric IF patients, as reflected by a primary BA dominant composition. In IF patients, the serum FGF19 levels decreased significantly, and were conversely correlated with ileal inflammation grades (r = −0.50, p CYP7A1) increased evidently. In conclusion, ileum inflammation decreases FXR expression corresponding to reduce serum FGF19 concentration, along with increased hepatic bile acid synthesis, leading to liver damages in IF patients. PMID:27976737

  17. Altered visual information processing systems in bipolar disorder: evidence from visual MMN and P3

    Directory of Open Access Journals (Sweden)

    Toshihiko eMaekawa


    Full Text Available Objective: Mismatch negativity (MMN and P3 are unique ERP components that provide objective indices of human cognitive functions such as short-term memory and prediction. Bipolar disorder (BD is an endogenous psychiatric disorder characterized by extreme shifts in mood, energy, and ability to function socially. BD patients usually show cognitive dysfunction, and the goal of this study was to access their altered visual information processing via visual MMN (vMMN and P3 using windmill pattern stimuli.Methods: Twenty patients with BD and 20 healthy controls matched for age, gender, and handedness participated in this study. Subjects were seated in front of a monitor and listened to a story via earphones. Two types of windmill patterns (standard and deviant and white circle (target stimuli were randomly presented on the monitor. All stimuli were presented in random order at 200-ms durations with an 800-ms inter-stimulus interval. Stimuli were presented at 80% (standard, 10% (deviant, and 10% (target probabilities. The participants were instructed to attend to the story and press a button as soon as possible when the target stimuli were presented. Event-related potentials were recorded throughout the experiment using 128-channel EEG equipment. vMMN was obtained by subtracting standard from deviant stimuli responses, and P3 was evoked from the target stimulus.Results: Mean reaction times for target stimuli in the BD group were significantly higher than those in the control group. Additionally, mean vMMN-amplitudes and peak P3-amplitudes were significantly lower in the BD group than in controls.Conclusions: Abnormal vMMN and P3 in patients indicate a deficit of visual information processing in bipolar disorder, which is consistent with their increased reaction time to visual target stimuli.Significance: Both bottom-up and top-down visual information processing are likely altered in BD.

  18. Alcohol abuse and smoking alter inflammatory mediator production by pulmonary and systemic immune cells. (United States)

    Gaydos, Jeanette; McNally, Alicia; Guo, Ruixin; Vandivier, R William; Simonian, Philip L; Burnham, Ellen L


    Alcohol use disorders (AUDs) and tobacco smoking are associated with an increased predisposition for community-acquired pneumonia and the acute respiratory distress syndrome. Mechanisms are incompletely established but may include alterations in response to pathogens by immune cells, including alveolar macrophages (AMs) and peripheral blood mononuclear cells (PBMCs). We sought to determine the relationship of AUDs and smoking to expression of IFNγ, IL-1β, IL-6, and TNFα by AMs and PBMCs from human subjects after stimulation with lipopolysaccharide (LPS) or lipoteichoic acid (LTA). AMs and PBMCs from healthy subjects with AUDs and controls, matched on smoking, were cultured with LPS (1 μg/ml) or LTA (5 μg/ml) in the presence and absence of the antioxidant precursor N-acetylcysteine (10 mM). Cytokines were measured in cell culture supernatants. Expression of IFNγ, IL-1β, IL-6, and TNFα in AMs and PBMCs was significantly increased in response to stimulation with LPS and LTA. AUDs were associated with augmented production of proinflammatory cytokines, particularly IFNγ and IL-1β, by AMs and PBMCs in response to LPS. Smoking diminished the impact of AUDs on AM cytokine expression. Expression of basal AM and PBMC Toll-like receptors-2 and -4 was not clearly related to differences in cytokine expression; however, addition of N-acetylcysteine with LPS or LTA led to diminished AM and PBMC cytokine secretion, especially among current smokers. Our findings suggest that AM and PBMC immune cell responses to LPS and LTA are influenced by AUDs and smoking through mechanisms that may include alterations in cellular oxidative stress.

  19. 6-Hydroxydopamine-induced glutathione alteration occurs via glutathione enzyme system in primary cultured astrocytes

    Institute of Scientific and Technical Information of China (English)

    Ji ZHANG; Jun HU; Jian-hua DING; Hong-hong YAO; Gang HU


    Aim: To define the role of enzymes involved in glutathione metabolism in 6-hydroxydopamine (6-OHDA)-induced glutathione alteration in primary cultured astrocytes.Methods: Total glutathione (GSx) levels were determined using the modified enzymatic microtiter plate assay.The mRNA levels ofγ-glutamylcysteine synthetase (γGCS), γ-glutamyltransferase (γGT), glutathione peroxidase (GPx), GR (glutathione reductase), and glutathione transferases (GST) were determined using RT-PCR.γGT activity was determined using γGT assay kits.Results: In primary cultured astrocytes, 6-OHDA induced a significant elevation of cellular GSx levels after treatment for 24 h.However, the GSx levels decreased after 24 h and the values were even lower than the value in the control group without 6-OHDA at 48 h.RT-PCR data showed that the mRNA levels of γGCS, the ratelimiting enzyme of γ-L-glutamyl-L-cysteinylglycine (GSH) synthesis, were increased by 6-OHDA after treatment for 24 h and 48 h; the mRNA levels of GPx, GR, and GST did not alter in 6-OHDA-treated astrocytes after treatment for 24 h and 48 h; and 6-OHDA increased the mRNA levels and the activity of γGT after treatment for 48 h,which induced a decrease in GSx levels, despite the up-regulation of γGCS after exposure to 6-OHDA for 48 h.Conclusion: The change in γGCS correlated with the increase in GSH levels induced by 6-OHDA after treatment for 24 h.GSx levels decreased because of increased γGT mRNA levels and γGT activity induced by 6-OHDA after treatment for 48 h.

  20. Altered parasympathetic nervous system regulation of the sinoatrial node in Akita diabetic mice. (United States)

    Krishnaswamy, Pooja S; Egom, Emmanuel E; Moghtadaei, Motahareh; Jansen, Hailey J; Azer, John; Bogachev, Oleg; Mackasey, Martin; Robbins, Courtney; Rose, Robert A


    Cardiovascular autonomic neuropathy (CAN) is a serious complication of diabetes mellitus that impairs autonomic regulation of heart rate (HR). This has been attributed to damage to the nerves that modulate spontaneous pacemaker activity in the sinoatrial node (SAN). Our objective was to test the hypothesis that impaired parasympathetic regulation of HR in diabetes is due to reduced responsiveness of the SAN to parasympathetic agonists. We used the Akita mouse model of type 1 diabetes to study the effects of the parasympathetic agonist carbachol (CCh) on SAN function using intracardiac programmed stimulation, high resolution optical mapping and patch-clamping of SAN myocytes. CCh decreased HR by 30% and increased corrected SAN recovery time (cSNRT) by 123% in wildtype mice. In contrast, CCh only decreased HR by 12%, and only increased cSNRT by 37% in Akita mice. These alterations were due to smaller effects of CCh on SAN electrical conduction and spontaneous action potential firing in isolated SAN myocytes. Voltage clamp experiments demonstrate that the acetylcholine-activated K(+) current (IKACh) is reduced in Akita SAN myocytes due to enhanced desensitization and faster deactivation kinetics. These IKACh alterations were normalized by treating Akita SAN myocytes with PI(3,4,5)P3 or an inhibitor of regulator of G-protein signaling 4 (RGS4). There was no difference in the effects of CCh on the hyperpolarization-activated current (If) between wildtype and Akita mice. Our study demonstrates that Akita diabetic mice demonstrate impaired parasympathetic regulation of HR and SAN function due to reduced responses of the SAN to parasympathetic agonists. Our experiments demonstrate a key role for insulin-dependent phosphoinositide 3-kinase (PI3K) signaling in the parasympathetic dysfunction seen in the SAN in diabetes.

  1. 76 FR 4458 - Privacy Act of 1974; Report of Modified or Altered System of Records (United States)


    ... automatic sprinkler system, numerous automatic sensors (e.g., water, heat, smoke, etc.) are installed, and a proper mix of portable fire extinguishers is located throughout the computer room. The system is backed... cardkey system. The hard copy records are kept in locked cabinets in locked rooms. The local...

  2. Nutritional n-3 PUFAs deficiency during perinatal periods alters brain innate immune system and neuronal plasticity-associated genes. (United States)

    Madore, Charlotte; Nadjar, Agnès; Delpech, Jean-Christophe; Sere, A; Aubert, A; Portal, Céline; Joffre, Corinne; Layé, Sophie


    Low dietary intake of the n-3 polyunsaturated fatty acids (PUFAs) is a causative factor of neurodevelopmental disorders. However the mechanisms linking n-3 PUFAs low dietary intake and neurodevelopmental disorders are poorly understood. Microglia, known mainly for their immune function in the injured or infected brain, have recently been demonstrated to play a pivotal role in regulating maturation of neuronal circuits during normal brain development. Disruption of this role during the perinatal period therefore could significantly contribute to psychopathologies with a neurodevelopmental neurodevelopmental component. N-3 PUFAs, essential lipids and key structural components of neuronal membrane phospholipids, are highly incorporated in cell membranes during the gestation and lactation phase. We previously showed that in a context of perinatal n-3 PUFAs deficiency, accretion of these latter is decreased and this is correlated to an alteration of endotoxin-induced inflammatory response. We thus postulated that dietary n-3 PUFAs imbalance alters the activity of microglia in the developing brain, leading to abnormal formation of neuronal networks. We first confirmed that mice fed with a n-3 PUFAs deficient diet displayed decreased n-3 PUFAs levels in the brain at post-natal days (PND)0 and PND21. We then demonstrated that n-3 PUFAs deficiency altered microglia phenotype and motility in the post-natal developing brain. This was paralleled by an increase in pro-inflammatory cytokines expression at PND21 and to modification of neuronal plasticity-related genes expression. Overall, our findings show for the first time that a dietary n-3 PUFAs deficiency from the first day of gestation leads to the development of a pro-inflammatory condition in the central nervous system that may contribute to neurodevelopmental alterations. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Temporal and spatial distribution of alteration, mineralization and fluid inclusions in the transitional high-sulfidation epithermal-porphyry copper system at Red Mountain, Arizona (United States)

    Lecumberri-Sanchez, Pilar; Newton, M. Claiborne; Westman, Erik C.; Kamilli, Robert J.; Canby, Vertrees M.; Bodnar, Robert J.


    Red Mountain, Arizona, is a Laramide porphyry Cu system (PCD) that has experienced only a modest level of erosion compared to most other similar deposits in the southwestern United States. As a result, the upper portion of the magmatic–hydrothermal system, which represents the transition from shallower high-sulfidation epithermal mineralization to deeper porphyry Cu mineralization, is well preserved. Within the Red Mountain system, alteration, mineralization and fluid inclusion assemblages show a systematic distribution in both time and space. Early-potassic alteration (characterized by the minerals biotite and magnetite) is paragenetically earlier than late-potassic alteration (K-feldspar–anhydrite) and both are followed by later phyllic (sericite–pyrite) alteration. Advanced argillic alteration (pyrophyllite–alunite–other clay minerals) is thought to be coeval with or postdate phyllic alteration. Minerals characteristic of advanced argillic alteration are present in the near surface. Phyllic alteration extends to greater depths compared to advanced argillic alteration. Early-potassic and late-potassic alteration are only observed in the deepest part of the system. Considerable overlap of phyllic alteration with both early-potassic and late-potassic alteration zones is observed. The hypogene mineralization contains 0.4–1.2% Cu and is spatially and temporally related to the late-potassic alteration event. Molybdenum concentration is typically In the deepest part of the system, an early generation of low-to-moderate density and salinity liquid + vapor inclusions with opaque daughter minerals is followed in time by halite-bearing inclusions that also contain opaque daughter minerals indicating that an early intermediate-density magmatic fluid evolved to a high-density, high-salinity mineralizing fluid. The increase in density and salinity of fluids with time observed in the deeper parts of the system may be the result of immiscibility (“boiling”) of

  4. Method for photo-altering a biological system to improve biological effect (United States)

    Hill, Richard A.; Doiron, Daniel R.; Crean, David H.


    Photodynamic therapy is a new adjunctive therapy for filtration surgery that does not use chemotherapy agents or radiation, but uses pharmacologically-active sensitizing compounds to produce a titratable, localized, transient, post operative avascular conjunctiva. A photosensitizing agent in a biological system is selectively activated by delivering the photosensitive agent to the biological system and laser activating only a spatially selected portion of the delivered photosensitive agent. The activated portion of the photosensitive agent reacts with the biological system to obtain a predetermined biological effect. As a result, an improved spatial disposition and effectuation of the biological effect by the photosensitive agent in the biological system is achieved.

  5. 78 FR 47322 - Privacy Act of 1974; Report of an Altered System of Records (United States)


    ... defending a claim against the Public Health Service based upon an individual's mental or physical condition... maintenance functions include but are not limited to providing continuous user availability, developing system...-know basis. All physical and logical access to the system is removed upon termination of...

  6. 76 FR 4431 - Privacy Act of 1974; Report of Modified or Altered System of Records (United States)


    ... controlled by a cardkey and security code (numeric keypad) system. The local fire department is located directly next door to the Clifton Road facility. The computer room is protected by an automatic sprinkler system, numerous automatic sensors (e.g., water, heat, smoke, etc.) are installed, and a proper mix...

  7. Alterations in the histaminergic system in Alzheimer's disease: a postmortem study. (United States)

    Shan, Ling; Bossers, Koen; Unmehopa, Unga; Bao, Ai-Min; Swaab, Dick F


    Histamine is produced by the hypothalamic tuberomamillary nucleus (TMN). We studied its involvement in Alzheimer's disease (AD) by in situ hybridization of histidine decarboxylase (HDC), the key enzyme of histamine production, in 9 AD patients and 9 controls. Additionally, messenger (m) RNA levels of the 4 histamine receptors (H(1-4)R) and of the enzyme involved in histamine metabolism, histamine methyltransferase (HMT), were determined by quantitative polymerase chain reaction (qPCR) in the prefrontal cortex (PFC) in the course of AD (n = 49). Moreover, alterations in glia markers were studied. HDC-mRNA levels in the TMN were unchanged in AD, despite of the reduced number of Nissl-stained neurons (p = 0.001). However, a decrease in HDC-mRNA was observed in its medial part (mTMN; p = 0.047). In the course of AD only females had increased prefrontal cortex expression of histamine receptor-3 (H(3)R) (p = 0.007) and histamine methyltransferase-mRNA (p = 0.011) and of the glia markers, glial fibrillary acidic protein-mRNA, vimentin-mRNA and proteolipid protein-mRNA. These findings indicate the presence of regional changes in the TMN that are at least partly gender-dependent.

  8. Altered TNF-Alpha, Glucose, Insulin and Amino Acids in Islets Langerhans Cultured in a Microgravity Model System (United States)

    Tobin, Brian W.; Leeper-Woodford, Sandra K.; Hashemi, Brian B.; Smith, Scott M.; Sams, Clarence F.


    The present studies were designed to determine effects of a microgravity model system upon lipopolysaccharide (LPS) stimulated tumor necrosis factor alpha (TNF-alpha) activity and indices of insulin and fuel homeostasis of pancreatic islets of Langerhans. Islets (1726+/-1 17,150 u IEU) from Wistar Furth rats were treated as: 1) HARV (High Aspect Ratio Vessel cell culture) , 2) HARV plus LPS, 3) static culture, 4) static culture plus LPS. TNF-alpha (L929 cytotoxicity assay) was significantly increased in LPS-induced HARV and static cultures, yet the increase was more pronounced in the static culture group (parginine in islets cultured in HARVs. While nitrogenous compound analysis indicated a ubiquitous reliance upon glutamine in all experimental groups, arginine was converted to ornithine at a two-fold greater rate in the islets cultured in the HARV microgravity model system (p<0.05). These studies demonstrate alterations in LPS induced TNF-alpha production of pancreatic islets of Langerhans, favoring a lesser TNF activity in the HARV. These alterations in fuel homeostasis may be promulgated by gravity averaged cell culture methods or by three dimensional cell assembly.

  9. Improved metabolic health alters host metabolism in parallel with changes in systemic xeno-metabolites of gut origin.

    Directory of Open Access Journals (Sweden)

    Caitlin Campbell

    Full Text Available Novel plasma metabolite patterns reflective of improved metabolic health (insulin sensitivity, fitness, reduced body weight were identified before and after a 14-17 wk weight loss and exercise intervention in sedentary, obese insulin-resistant women. To control for potential confounding effects of diet- or microbiome-derived molecules on the systemic metabolome, sampling was during a tightly-controlled feeding test week paradigm. Pairwise and multivariate analysis revealed intervention- and insulin-sensitivity associated: (1 Changes in plasma xeno-metabolites ("non-self" metabolites of dietary or gut microbial origin following an oral glucose tolerance test (e.g. higher post-OGTT propane-1,2,3-tricarboxylate [tricarballylic acid] or in the overnight-fasted state (e.g., lower γ-tocopherol; (2 Increased indices of saturated very long chain fatty acid elongation capacity; (3 Increased post-OGTT α-ketoglutaric acid (α-KG, fasting α-KG inversely correlated with Matsuda index, and altered patterns of malate, pyruvate and glutamine hypothesized to stem from improved mitochondrial efficiency and more robust oxidation of glucose. The results support a working model in which improved metabolic health modifies host metabolism in parallel with altering systemic exposure to xeno-metabolites. This highlights that interpretations regarding the origins of peripheral blood or urinary "signatures" of insulin resistance and metabolic health must consider the potentially important contribution of gut-derived metabolites toward the host's metabolome.

  10. 75 FR 30411 - Privacy Act of 1974; Report of a Modified or Altered System of Records (United States)


    ... Health Care Financing Administration systems of records. The new assigned identifying number for this.... The purpose for which the disclosure is to be made is of sufficient importance to warrant the effect...

  11. Functional and anatomic alterations in the gentamicin-damaged vestibular system in the guinea pig

    NARCIS (Netherlands)

    Oei, MLYM; Segenhout, HM; Dijk, T; Stokroos, [No Value; van der Want, TJL; Albers, FWJ


    Hypothesis: The purpose of this study was to investigate the expected functional and morphologic effect of gentamicin on the vestibular system simultaneously by measurement of vestibular evoked potentials and electron microscopic evaluation. Background: Vestibular short-latency evoked potentials to

  12. 32 CFR Appendix B to Part 323 - Criteria for New and Altered Record Systems (United States)


    ... DEFENSE (CONTINUED) PRIVACY PROGRAM DEFENSE LOGISTICS AGENCY PRIVACY PROGRAM Pt. 323, App. B Appendix B to.... The connecting of two or more formerly independent automated systems or networks together creating a...

  13. Environmental pollutants and alterations in the reproductive system in wild male mink (Neovison vison) from Sweden. (United States)

    Persson, Sara; Magnusson, Ulf


    The wild American mink, a semi-aquatic top predator, is exposed to high levels of environmental pollutants that may affect its reproductive system. In this study, the reproductive organs from 101 wild male mink collected in Sweden were examined during necropsy. Potential associations between various variables of the reproductive system and fat concentrations of polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), dichlorodiphenyldichloroethylene (p,p'-DDE) and other organochlorine pesticides and liver concentrations of perfluoroalkyl acids (PFAAs) were investigated using multiple regression models. The anogenital distance was negatively associated (penvironmental pollution affects male reproduction in both wildlife and humans. Overall, the study suggests endocrine disrupting effects in wild mink and identifies potentially important pollutants in the complex mixture of contaminants in the environment. In addition, the results suggest that the variables of the reproductive system of male mink used in this study are good candidates for use as indicators of environmental pollution affecting the mammalian reproductive system.

  14. Alterations of hydraulic soil properties influenced by land-use changes and agricultural management systems (United States)

    Weninger, Thomas; Kreiselmeier, Janis; Chandrasekhar, Parvathy; Jülich, Stefan; Schwärzel, Kai; Schwen, Andreas


    Estimation and modeling of soil water movement and the hydrologic balance of soils requires sound knowledge about hydraulic soil properties (HSP). The soil water characteristics, the hydraulic conductivity function and the pore size distribution (PSD) are commonly used instruments for the mathematical representation of HSP. Recent research highlighted the temporal variability of these functions caused by meteorological or land-use influences. State of the art modeling software for the continuous simulation of soil water movement uses a stationary approach for the HSP which means that their time dependent alterations and the subsequent effects on soil water balance is not considered. Mathematical approaches to describe the evolution of PSD are nevertheless known, but there is a lack of sound data basis for parameter estimation. Based on extensive field and laboratory measurements at 5 locations along a climatic gradient across Austria and Germany, this study will quantify short-term changes in HSP, detect driving forces and introduce a method to predict the effects of soil and land management actions on the soil water balance. Amongst several soil properties, field-saturated and unsaturated hydraulic conductivities will be determined using a hood infiltration experiments in the field as well as by evaporation and dewpoint potentiometer method in the lab. All measurements will be carried out multiple times over a span of 2 years which will allow a detailed monitoring of changes in HSP. Experimental sites where we expect significant inter-seasonal changes will be equipped with sensors for soil moisture and matric potential. The choice of experimental field sites follows the intention to involve especially the effects of tillage operations, different cultivation strategies, microclimatically effective structures and land-use changes. The international project enables the coverage of a broad range of soil types as well as climate conditions and hence will have broad

  15. Central autonomic nervous system response to autonomic challenges is altered in patients with a previous episode of Takotsubo cardiomyopathy. (United States)

    Pereira, Vitor H; Marques, Paulo; Magalhães, Ricardo; Português, João; Calvo, Lucy; Cerqueira, João J; Sousa, Nuno


    Takotsubo cardiomyopathy is an intriguing disease characterized by acute transient left ventricular dysfunction usually triggered by an episode of severe stress. The excessive levels of catecholamines and the overactivation of the sympathetic system are believed to be the main pathophysiologic mechanisms of Takotsubo cardiomyopathy, but it is unclear whether there is a structural or functional signature of the disease. In this sense, our aim was to characterize the central autonomic system response to autonomic challenges in patients with a previous episode of Takotsubo cardiomyopathy when compared with a control group of healthy volunteers. Functional magnetic resonance imaging (fMRI) was performed in four patients with a previous episode of Takotsubo cardiomyopathy (average age of 67 ± 12 years) and in eight healthy volunteers (average age of 66 ± 5 years) while being submitted to different autonomic challenges (cold exposure and Valsalva manoeuvre). The fMRI analysis revealed a significant variation of the blood oxygen level dependent signal triggered by the Valsalva manoeuvre in specific areas of the brain involved in the cortical control of the autonomic system and significant differences in the pattern of activation of the insular cortex, amygdala and the right hippocampus between patients with Takotsubo cardiomyopathy and controls, even though these regions did not present significant volumetric changes. The central autonomic response to autonomic challenges is altered in patients with Takotsubo cardiomyopathy, thus suggesting a dysregulation of the central autonomic nervous system network. Subsequent studies are needed to unveil whether these alterations are causal or predisposing factors to Takotsubo cardiomyopathy. © The European Society of Cardiology 2015.

  16. The altered gravity effect on proliferative system of two-day pea germs (United States)

    Artemenko, O. A.

    The study of clinorotation effect on proliferative system sensibility of plants is very important for understanding and future investigations of their development characteristics and for examination of cell cycle regulation molecular mechanisms. Determination of two-day pea germ mitotic activity of cells, correlation of mitosis phase and DNA content point to decrease of these parameters under clinorotation during the first 12 hours of the factor influence. Cell cycle stabilization after 12 hours of the experiment show high adaptation capacity of plant proliferative system.

  17. Physicochemical and Geotechnical Alterations to MX-80 Bentonite at the Waste Canister Interface in an Engineered Barrier System

    Directory of Open Access Journals (Sweden)

    Christopher W. Davies


    Full Text Available The study investigated the basic geomechanical and mineralogical evolution of the bentonite barrier under various experimental boundary conditions which replicated the near-field Thermo-Hydro-Chemico (THC conditions in a repository. The relationships between the physicochemical alterations and changes in the geotechnical properties have seldom been studied, especially on a consistent dataset. This paper attempts to link the physicochemical properties of Na-bentonite (MX-80 to the macro-scale engineering functionality of the bentonite post THC exposure. Experiments investigated the impact of THC variables on the engineering and physicochemical functionality of the bentonite with respect to its application within a High-Level Waste (HLW engineered barrier system. Intrinsic alterations to the MX-80 bentonite under relatively short-term exposure to hydrothermal and chemical conditions were measured. Additionally, two long-term tests were conducted under ambient conditions to consider the impact of exposure duration. The intrinsic measurements were then related to the overall performance of the bentonite as a candidate barrier material for application in a UK geological disposal facility. Findings indicate that exposure to thermo-saline-corrosion conditions (i.e., corrosion products derived from structural grade 275 carbon steel inhibits the free swell capacity and plasticity of the bentonite. However, the measured values remained above the design limits set out for the Swedish multi-barrier concept, from which the UK concept may take a lead. Corrosion alone does not appear to significantly affect the geotechnical measurements compared with the influence of thermal loading and high saline pore water after relatively short-term exposure. Thermal and corrosion exposure displayed no impact on the intrinsic swelling of the smectite component, indicating that no significant structural alteration had occurred. However, when exploring more complex saline

  18. Cocaine Self-Administration Alters the Relative Effectiveness of Multiple Memory Systems during Extinction (United States)

    Gabriele, Amanda; Setlow, Barry; Packard, Mark G.


    Rats were trained to run a straight-alley maze for an oral cocaine or sucrose vehicle solution reward, followed by either response or latent extinction training procedures that engage neuroanatomically dissociable "habit" and "cognitive" memory systems, respectively. In the response extinction condition, rats performed a runway approach response…

  19. 75 FR 19652 - Privacy Act of 1974; Report of an Altered System of Records (United States)


    ... Percent--Sliding Fee Scale. Patient Percent--Language Barrier Present. Patient Percent--Migrant/Seasonal... reviewing and processing assistance from contractors and the breach notification language. This system of... specific language to appropriate Federal agencies and Department contractors that have a need to know the...

  20. 77 FR 19295 - Privacy Act of 1974; Report of an Altered System of Records (United States)


    ... against the Public Health Service based upon an individual's mental or physical condition and alleged to... Health Professions, Health Resources and Services Administration. SRA's physical address is 4350 Fair... but are not limited to providing continuous user availability, develop system enhancements, upgrade...


    NARCIS (Netherlands)



    Psychosocial factors are implicated in the development, in the course of, and in the recovery from disease. The immune system may be a mediator of the disease. Studies with animal models using social interactions in rodents suggest that short- and long-term social stress does not invariably suppress

  2. 76 FR 4438 - Privacy Act of 1974; Report of Modified or Altered System of Records (United States)


    ... Treatment of Tuberculosis and other Mycobacterioses HHS/CDC/NCHSTP.'' HHS is proposing to add the following... of Treatment of Tuberculosis and other Mycobacterioses. HHS/CDC/NCHSTP.'' This System of Records will... for whom routine tuberculosis treatment is ineffective. Also included are contacts to tuberculosis...

  3. 77 FR 4004 - Privacy Act of 1974; Altered System of Records (United States)


    ...; Economic information--housing characteristics, income, occupation, employment and unemployment information... name of the system of records to ``Economic Survey Collection;'' would amend certain provisions... to include all economic programs, as well as surveys, such as the Survey of Business Owners...

  4. 76 FR 4483 - Privacy Act of 1974; Report of Modified or Altered System of Records (United States)


    ... Agent Transfer and Entity Registration Information System (SATERIS), HHS/CDC/COTPER''. HHS is proposing... confirmed breach of the security or confidentiality of information disclosed is relevant and necessary for.... 09-20-0170, ``National Select Agent Registry (NSAR)/Select Agent Transfer and Entity Registration...

  5. Altered autonomic nervous system activity in women with unexplained recurrent pregnancy loss. (United States)

    Kataoka, Kumie; Tomiya, Yumi; Sakamoto, Ai; Kamada, Yasuhiko; Hiramatsu, Yuji; Nakatsuka, Mikiya


    Autonomic nervous system activity was studied to evaluate the physical and mental state of women with unexplained recurrent pregnancy loss (RPL). Heart rate variability (HRV) is a measure of beat-to-beat temporal changes in heart rate and provides indirect insight into autonomic nervous system tone and can be used to assess sympathetic and parasympathetic tone. We studied autonomic nervous system activity by measuring HRV in 100 women with unexplained RPL and 61 healthy female volunteers as controls. The degree of mental distress was assessed using the Kessler 6 (K6) scale. The K6 score in women with unexplained RPL was significantly higher than in control women. HRV evaluated on standard deviation of the normal-to-normal interval (SDNN) and total power was significantly lower in women with unexplained RPL compared with control women. These indices were further lower in women with unexplained RPL ≥4. On spectral analysis, high-frequency (HF) power, an index of parasympathetic nervous system activity, was significantly lower in women with unexplained RPL compared with control women, but there was no significant difference in the ratio of low-frequency (LF) power to HF power (LF/HF), an index of sympathetic nervous system activity, between the groups. The physical and mental state of women with unexplained RPL should be evaluated using HRV to offer mental support. Furthermore, study of HRV may elucidate the risk of cardiovascular diseases and the mechanisms underlying unexplained RPL. © 2014 The Authors. Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology.

  6. Coarse muscovite veins and alteration deep in the Yerington batholith, Nevada: insights into fluid exsolution in the roots of porphyry copper systems (United States)

    Runyon, Simone E.; Steele-MacInnis, Matthew; Seedorff, Eric; Lecumberri-Sanchez, Pilar; Mazdab, Frank K.


    Veins and pervasive wall-rock alteration composed of coarse muscovite±quartz±pyrite are documented for the first time in a porphyritic granite at Luhr Hill in the Yerington District, Nevada. Coarse muscovite at Luhr Hill occurs at paleodepths of 6-7 km in the roots of a porphyry copper system and crops out on the scale of tens to hundreds of meters, surrounded by rock that is unaltered or variably altered to sodic-calcic assemblages. Coarse muscovite veins exhibit a consistent orientation, subvertical and N-S striking, which structurally restores to subhorizontal at the time of formation. Along strike, coarse muscovite veins swell from distal, millimeter-thick muscovite-only veinlets to proximal, centimeter-thick quartz-sulfide-bearing muscovite veins. Crosscutting relationships between coarse muscovite veins, pegmatite dikes, and sodic-calcic veins indicate that muscovite veins are late-stage magmatic-hydrothermal features predating final solidification of the Luhr Hill porphyritic granite. Fluid inclusions in the muscovite-quartz veins are high-density aqueous inclusions of 3-9 wt% NaCl eq. and alteration differs in texture, composition, and process of formation from sericite at shallower levels of the hydrothermal system. Although the definition of greisen is controversial, we suggest that coarse muscovite alteration is more similar to alteration in greisen-type Sn-W-Mo districts worldwide than to sericitic alteration at higher levels of porphyry copper systems. The fluids that form coarse muscovite veins and alteration in the roots of porphyry copper systems are distinct from fluids that formed copper ore or widespread, shallower, acidic alteration. We propose that this style of veins and alteration at Luhr Hill represents degassing of moderate volumes of overpressured hydrothermal fluid during late crystallization of deep levels of the Yerington batholith.

  7. Pervasive, high temperature hydrothermal alteration in the RN-17B drill core, Reykjanes Geothermal System-Iceland Deep Drilling Project (United States)

    Zierenberg, R. A.; Schiffman, P.; Marks, N. E.; Reed, M. H.; Elders, W. A.; Fridleifsson, G. O.


    burial at T<300 is replaced by more calcic plagioclase at higher temperature. Texturally, hydrothermal anorthite (An90-98) and pargasite (up to 13.5 wt % Al2O3) appear to have grown at the expense of earlier formed epidote + chlorite + actinolite. Measured downhole temperature at 2800m in RN-17B following reequilibration was 320°C, although amphibole-plagioclase geothermometry imply that anorthite + pargasite, if in equilibrium, should have formed at much higher temperatures. The differences in extent and intensity of alteration inferred from examination of cuttings compared to drill core indicate that selective recovery and mixing of cuttings from multiple depths may be a larger problem than presently appreciated. Previous work has shown that the Reykjanes geothermal system has evolved from a meteoric water-dominated system to higher salinity system dominated by seawater-recharge. The paragenetic relationships that are discernible in the core hopefully will allow us to quantify the alteration processes related to the change in salinity.

  8. Maternal obesity alters the apelinergic system at the feto-maternal interface. (United States)

    Hanssens, Sandy; Marx-Deseure, Aurore; Lecoutre, Simon; Butruille, Laura; Fournel, Audren; Knauf, Claude; Besengez, Capucine; Breton, Christophe; Storme, Laurent; Deruelle, Philippe; Lesage, Jean


    Apelin and its receptor APJ have been implicated in pathologies including cardiovascular disease, diabetes and obesity. Little is known about the function of the apelinergic system during gestation. We evaluated in mice this system at the feto-maternal interface in insulin-resistant obese female (HF) mice. Maternal apelinemia was decreased at term and fetal apelinemia was sixfold higher than maternal level. Ex-vivo, the placenta releases apelin at E12.5 and E18.5. In HF pregnant mice at term, apelinemia as well as placental apelin and APJ mRNA levels were increased whereas placental release of apelin was drastically reduced compared to controls. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Cocaine self-administration alters the relative effectiveness of multiple memory systems during extinction


    Gabriele, Amanda; Setlow, Barry; Packard, Mark G.


    Rats were trained to run a straight-alley maze for an oral cocaine or sucrose vehicle solution reward, followed by either response or latent extinction training procedures that engage neuroanatomically dissociable “habit” and “cognitive” memory systems, respectively. In the response extinction condition, rats performed a runway approach response to an empty fluid well. In the latent extinction condition, rats were placed at the empty fluid well without performing a runway approach response. R...

  10. Brexpiprazole Alters Monoaminergic Systems following Repeated Administration: an in Vivo Electrophysiological Study


    Oosterhof, Chris A.; Mansari, Mostafa El; Bundgaard, Christoffer; Blier, Pierre


    Background: Brexpiprazole was recently approved as adjunctive therapy for depression and treatment of schizophrenia in adults. To complement results from a previous study in which its acute effects were characterized, the present study assessed the effect of repeated brexpiprazole administration on monoaminergic systems. Methods: Brexpiprazole (1mg/kg, subcutaneous) or vehicle was administered once daily for 2 and 14 days. Single-unit electrophysiological recordings from noradrenaline neurons...

  11. Life History Responses and Feeding Behavior of Microcrustacea in Altered Gravity - Applicability in Bioregenerative Life Support Systems (BLSS) (United States)

    Fischer, Jessica; Schoppmann, Kathrin; Laforsch, Christian


    Manned space missions, as for example to the planet Mars, are a current objective in space exploration. During such long-lasting missions, aquatic bioregenerative life support systems (BLSS) could facilitate independence of resupply from Earth by regenerating the atmosphere, purifying water, producing food and processing waste. In such BLSS, microcrustaceans could, according to their natural role in aquatic ecosystems, link oxygen liberating, autotrophic algae and higher trophic levels, such as fish. However, organisms employed in BLSS will be exposed to high acceleration (hyper- g) during launch of spacecrafts as well as to microgravity (μ g) during space travel. It is thus essential that these organisms survive, perform and reproduce under altered gravity conditions. In this study we present the first data in this regard for the microcrustaceas Daphnia magna and Heterocypris incongruens. We found that after hyper- g exposure (centrifugation) approximately one third of the D. magna population died within one week (generally indicating that possible belated effects have to be considered when conducting and interpreting experiments during which hyper- g occurs). However, suchlike and even higher losses could be countervailed by the surviving daphnids' unaltered high reproductive capacity. Furthermore, we can show that foraging and feeding behavior of D. magna (drop tower) and H. incongruens (parabolic flights) are rarely altered in μ g. Our results thus indicate that both species are suitable candidates for BLSS utilized in space.

  12. Systems Biology of cancer: Moving toward the Integrative Study of the metabolic alterations in cancer cells.

    Directory of Open Access Journals (Sweden)

    Claudia Erika Hernández Patiño


    Full Text Available One of the main objectives in systems biology is to understand the biological mechanisms that give rise to the phenotype of a microorganism by using high-throughput technologies and genome-scale mathematical modeling. The computational modeling of genome-scale metabolic reconstructions is one systemic and quantitative strategy for characterizing the metabolic phenotype associated with human diseases and potentially for designing drugs with optimal clinical effects. The purpose of this short review is to describe how computational modeling, including the specific case of constraint-based modeling, can be used to explore, characterize and predict the metabolic capacities that distinguish the metabolic phenotype of cancer cell lines. As we show herein, this computational framework is far from a pure theoretical description, and to ensure proper biological interpretation, it is necessary to integrate high-throughput data and generate predictions for later experimental assessment. Hence, genome-scale modeling serves as a platform for the following: 1 the integration of data from high-throughput technologies, 2 the assessment of how metabolic activity is related to phenotype in cancer cell lines and 3 the design of new experiments to evaluate the outcomes of the in silico analysis. By combining the functions described above, we show that computational modeling is a useful methodology to construct an integrative, systemic and quantitative scheme for understanding the metabolic profiles of cancer cell lines, a first step to determine the metabolic mechanism by which cancer cells maintain and support their malignant phenotype in human tissues.

  13. Systems biology of cancer: moving toward the integrative study of the metabolic alterations in cancer cells. (United States)

    Hernández Patiño, Claudia E; Jaime-Muñoz, Gustavo; Resendis-Antonio, Osbaldo


    One of the main objectives in systems biology is to understand the biological mechanisms that give rise to the phenotype of a microorganism by using high-throughput technologies (HTs) and genome-scale mathematical modeling. The computational modeling of genome-scale metabolic reconstructions is one systemic and quantitative strategy for characterizing the metabolic phenotype associated with human diseases and potentially for designing drugs with optimal clinical effects. The purpose of this short review is to describe how computational modeling, including the specific case of constraint-based modeling, can be used to explore, characterize, and predict the metabolic capacities that distinguish the metabolic phenotype of cancer cell lines. As we show herein, this computational framework is far from a pure theoretical description, and to ensure proper biological interpretation, it is necessary to integrate high-throughput data and generate predictions for later experimental assessment. Hence, genome-scale modeling serves as a platform for the following: (1) the integration of data from HTs, (2) the assessment of how metabolic activity is related to phenotype in cancer cell lines, and (3) the design of new experiments to evaluate the outcomes of the in silico analysis. By combining the functions described above, we show that computational modeling is a useful methodology to construct an integrative, systemic, and quantitative scheme for understanding the metabolic profiles of cancer cell lines, a first step to determine the metabolic mechanism by which cancer cells maintain and support their malignant phenotype in human tissues.

  14. Altered Dynamics Between Neural Systems Sub-serving Decisions for Unhealthy Food

    Directory of Open Access Journals (Sweden)

    Qinghua eHe


    Full Text Available Using BOLD functional magnetic resonance imaging (fMRI techniques, we examined the relationships between activities in the neural systems elicited by the decision stage of the Iowa Gambling Task (IGT, and food choices of either vegetables or snacks high in fat and sugar. Twenty-three healthy normal weight adolescents and young adults, ranging in age from 14-21, were studied. Neural systems implicated in decision-making and inhibitory control were engaged by having participants perform the IGT during fMRI scanning. The Youth/Adolescent Questionnaire, a food frequency questionnaire, was used to obtain daily food choices. Higher consumption of vegetables correlated with higher activity in prefrontal cortical regions, namely the left superior frontal gyrus (SFG, and lower activity in sub-cortical regions, namely the right insular cortex. In contrast, higher consumption of fatty and sugary snacks correlated with lower activity in the prefrontal regions, combined with higher activity in the sub-cortical, insular cortex.These results provide preliminary support for our hypotheses that unhealthy food choices in real life are reflected by neuronal changes in key neural systems involved in habits, decision-making and self-control processes. These findings have implications for the creation of decision-making based intervention strategies that promote healthier eating.

  15. Altered dynamics between neural systems sub-serving decisions for unhealthy food. (United States)

    He, Qinghua; Xiao, Lin; Xue, Gui; Wong, Savio; Ames, Susan L; Xie, Bin; Bechara, Antoine


    Using BOLD functional magnetic resonance imaging (fMRI) techniques, we examined the relationships between activities in the neural systems elicited by the decision stage of the Iowa Gambling Task (IGT), and food choices of either vegetables or snacks high in fat and sugar. Twenty-three healthy normal weight adolescents and young adults, ranging in age from 14 to 21, were studied. Neural systems implicated in decision-making and inhibitory control were engaged by having participants perform the IGT during fMRI scanning. The Youth/Adolescent Questionnaire, a food frequency questionnaire, was used to obtain daily food choices. Higher consumption of vegetables correlated with higher activity in prefrontal cortical regions, namely the left superior frontal gyrus (SFG), and lower activity in sub-cortical regions, namely the right insular cortex. In contrast, higher consumption of fatty and sugary snacks correlated with lower activity in the prefrontal regions, combined with higher activity in the sub-cortical, insular cortex. These results provide preliminary support for our hypotheses that unhealthy food choices in real life are reflected by neuronal changes in key neural systems involved in habits, decision-making and self-control processes. These findings have implications for the creation of decision-making based intervention strategies that promote healthier eating.

  16. Alterations in the cholinergic system of brain stem neurons in a mouse model of Rett syndrome. (United States)

    Oginsky, Max F; Cui, Ningren; Zhong, Weiwei; Johnson, Christopher M; Jiang, Chun


    Rett syndrome is an autism-spectrum disorder resulting from mutations to the X-linked gene, methyl-CpG binding protein 2 (MeCP2), which causes abnormalities in many systems. It is possible that the body may develop certain compensatory mechanisms to alleviate the abnormalities. The norepinephrine system originating mainly in the locus coeruleus (LC) is defective in Rett syndrome and Mecp2-null mice. LC neurons are subject to modulation by GABA, glutamate, and acetylcholine (ACh), providing an ideal system to test the compensatory hypothesis. Here we show evidence for potential compensatory modulation of LC neurons by post- and presynaptic ACh inputs. We found that the postsynaptic currents of nicotinic ACh receptors (nAChR) were smaller in amplitude and longer in decay time in the Mecp2-null mice than in the wild type. Single-cell PCR analysis showed a decrease in the expression of α3-, α4-, α7-, and β3-subunits and an increase in the α5- and α6-subunits in the mutant mice. The α5-subunit was present in many of the LC neurons with slow-decay nAChR currents. The nicotinic modulation of spontaneous GABAA-ergic inhibitory postsynaptic currents in LC neurons was enhanced in Mecp2-null mice. In contrast, the nAChR manipulation of glutamatergic input to LC neurons was unaffected in both groups of mice. Our current-clamp studies showed that the modulation of LC neurons by ACh input was reduced moderately in Mecp2-null mice, despite the major decrease in nAChR currents, suggesting possible compensatory processes may take place, thus reducing the defects to a lesser extent in LC neurons.

  17. Altered α-synuclein, parkin, and synphilin isoform levels in multiple system atrophy brains

    DEFF Research Database (Denmark)

    Brudek, Tomasz; Winge, Kristian; Rasmussen, Nadja Bredo


    Together with Parkinson's disease (PD) and dementia with Lewy bodies, multiple system atrophy (MSA) is a member of a diverse group of neurodegenerative disorders termed α-synucleinopathies. Previously, it has been shown that α-synuclein, parkin, and synphilin-1 display disease-specific transcript......Together with Parkinson's disease (PD) and dementia with Lewy bodies, multiple system atrophy (MSA) is a member of a diverse group of neurodegenerative disorders termed α-synucleinopathies. Previously, it has been shown that α-synuclein, parkin, and synphilin-1 display disease......-specific transcription patterns in frontal cortex in PD, dementia with Lewy bodies, and MSA, and thus may mediate the development of α-synucleinopathies. In this study, the differential expression of α-synuclein isoforms on transcriptional and translational levels was ascertained in MSA patients in comparison with PD...... for parkin and synphilin-1 isoforms. In MSA brains, α-synuclein140 and α-synuclein 112 isoform levels were significantly increased, whereas levels of the α-synuclein 126 isoform were decreased in the substantia nigra, striatum, cerebellar cortex, and nucleus dentatus versus controls. Moreover, in MSA cases...

  18. LDA merging and splitting with applications to multiagent cooperative learning and system alteration. (United States)

    Pang, Shaoning; Ban, Tao; Kadobayashi, Youki; Kasabov, Nikola K


    To adapt linear discriminant analysis (LDA) to real-world applications, there is a pressing need to equip it with an incremental learning ability to integrate knowledge presented by one-pass data streams, a functionality to join multiple LDA models to make the knowledge sharing between independent learning agents more efficient, and a forgetting functionality to avoid reconstruction of the overall discriminant eigenspace caused by some irregular changes. To this end, we introduce two adaptive LDA learning methods: LDA merging and LDA splitting. These provide the benefits of ability of online learning with one-pass data streams, retained class separability identical to the batch learning method, high efficiency for knowledge sharing due to condensed knowledge representation by the eigenspace model, and more preferable time and storage costs than traditional approaches under common application conditions. These properties are validated by experiments on a benchmark face image data set. By a case study on the application of the proposed method to multiagent cooperative learning and system alternation of a face recognition system, we further clarified the adaptability of the proposed methods to complex dynamic learning tasks.

  19. Progressive alterations of central nervous system structure and function are caused by charged particle radiation (United States)

    Nelson, G. A.; Cns Nscor Team

    A new NASA-sponsored program project (NSCOR) has been organized to conduct the first comprehensive investigation of the response of a mammalian brain structure (mouse hippocampus) to charged-particle radiation. The NSCOR collaboration has three main goals. The first goal is to quantify the time- and dose-dependent changes in cellular composition and architecture. By using stereology on preserved brains, subsets of cells (neurons, glia, endothelia and stem cells) will be quantified out to 2 years after irradiation with accelerated protons and iron ions. To further characterize changes in vasculature architecture a polymer infusion technique will be used to produce a three-dimensional vasculature cast that then will be mapped by x-ray tomography to determine topological changes, and microscopic infarcts associated with amyloid protein deposits. The 2nd goal is to quantify hippocampal function(s). The primary measurement of function will be extracellular electrical recordings from hippocampal ``brain slices'' that reflect underlying functions such as connectivity, action potential generation & conduction, and neurotransmitter formation, secretion, and uptake. Individual nerve membrane properties will be assessed by ``patch clamp'' recordings. Two non-invasive methods will evaluate brain function and the evolution of changes with time. Electroencephalograms will map macroscopic spontaneous electrical activity while two state-of-the-art MRI magnetization sequences will visualize and quantify local oxygen utilization and white matter fiber tracts structural integrity. To quantify the brains' overall performance under stress, animals will receive a systemic shock mediated by the immune system in the form of a reaction to lipopolysaccharide. A second strategy will employ the APP23 transgenic mouse that develops the pathological changes associated with Alzheimer's disease. Measurements of irradiated mice will determine whether radiation exposure affects the latency and

  20. Perspectivism, Animism and Quimeras: A reflection on Amerindian design systems as techniques for altering perception

    Directory of Open Access Journals (Sweden)

    Els Lagrou


    Full Text Available 72 This article explores how different formal techniques used by the Cashinahua and other “people with design” can be considered as “perspectival techniques”, meaning techniques enabling the onlooker to change point of view. I also consider the possibility of baptizing these design systems as “abstract chimeras”. I use chimera in the sense given to the term by Severi, calling attention to the tension between what is shown and what is hidden in an image. I argue that in the case of Amerindian design systems we are dealing with extremely minimalistic images, which suppose a real engagement of the act of seeing with the image. I show how different formal characteristics of the composition of the images constitute techniques for the focalization of the gaze, whose kinesthetic effect consists in projecting the onlooker into the graphic space, causing the opacity of the surface to disappear and producing movement and profundity in the perceptive space. The line produces the suggestion of transparency of the skin, produces pathways and opens towards the perception of figuration inside the frame of the patterned surface. Normal 0 21 false false false ES-CO X-NONE X-NONE /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Tabla normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:10.0pt; font-family:"Calibri","sans-serif"; mso-bidi-font-family:"Times New Roman";}

  1. Immunological alterations in patients with primary tumors in central nervous system

    Directory of Open Access Journals (Sweden)



    Full Text Available Natural killer (NK cells play an important role in immune surveillance against tumors. The present work aimed to study the cytotoxic activity of NK cells and T cell subsets in peripheral blood of 13 patients with primary tumors in central nervous system (CNS. As controls 29 healthy subjects with the age range equivalent to the patients were studied. The methods employed were: a determination of cytotoxic activity of NK cells towards K562 target cells, evaluated by single cell-assay; b enumeration of CD3+ lymphocytes and their CD4+ and CD8+ subsets defined by monoclonal antibodies; c the identification of tumors were done by histologic and immunochemistry studies. The results indicated that adults and children with tumor in CNS display reduced percentage of total T cells, helper/inducer subset and low helper/suppressor ratio. The cytotoxic activity of NK cells was decreased in patients with CNS tumors due mainly to a decrease in the proportion of target-binding lymphocytes. These results suggest that cytotoxic activity of NK cells may be affected by the immunoregulatory disturbances observed in patients with primary tumors in CNS.

  2. Alterations in dopamine system function across the estrous cycle of the MAM rodent model of schizophrenia. (United States)

    Perez, Stephanie M; Chen, Li; Lodge, Daniel J


    Clinical studies have reported differences in the incidence and severity of schizophrenia symptoms between male and female schizophrenia patients. Unfortunately, the cause of these differences is not currently known due, in part, to the fact that preclinical studies largely focus on male subjects. Dopamine neuron activity has been previously demonstrated to change across the estrous cycle, and may therefore be of relevance, as aberrant dopamine signaling is thought to underlie the positive symptoms of schizophrenia. Here we examine dopamine neuron activity across the estrous cycle in the MAM rodent model of schizophrenia. We demonstrate that the elevation in dopamine neuron activity, consistently observed in male MAM-treated rats, is most prominent during estrus and attenuated in met-estrus. Furthermore, this appears to be mediated, in part, by progesterone in the ventral hippocampus, as increases in dopamine neuron population activity (observed in estrus) were normalized by the intra-hippocampal administration of the progesterone receptor antagonist, mifepristone (but not the estrogen receptor antagonists, fulvestrant). Taken together, these data suggest that changes in dopamine system function occur across the estrous cycle in MAM-treated rats and may contribute to the differences in symptomatology between male and female schizophrenia patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Serum insulin-like system alterations in patients with spinocerebellar ataxia type 3. (United States)

    Saute, Jonas Alex Morales; da Silva, Andrew Chaves Feitosa; Muller, Alexandre Pastoris; Hansel, Gisele; de Mello, Alexandre Silva; Maeda, Fábio; Vedolin, Leonardo; Saraiva-Pereira, Maria Luiza; Souza, Diogo Onofre; Arpa, Javier; Torres-Aleman, Ignacio; Portela, Luis Valmor Cruz; Jardim, Laura Bannach


    Spinocerebellar ataxias (SCAs) constitute a group of autosomal dominant neurodegenerative disorders with no current treatment. The insulin/insulin-like growth factor 1 (IGF-1) system (IIS) has been shown to play a role in the neurological dysfunction of SCAs and other polyglutamine disorders. We aimed to study the biomarker profile of serum IIS components in SCA3. We performed a case-control study with 46 SCA3 patients and 42 healthy individuals evaluating the peripheral IIS profile (insulin, IGF-1, IGFBP1 and 3) and the correlation with clinical, molecular, and neuroimaging findings. SCA3 patients presented lower insulin and IGFBP3 levels and higher insulin sensitivity (HOMA2), free IGF-I, and IGFBP1 levels when compared with controls. IGFBP-1 levels were directly associated with CAG expanded repeat length; IGF-1 was associated with the volumetries of specific brainstem regions on magnetic resonance imaging (MRI). Insulin levels and sensitivity were related to age at onset of symptoms. Our findings indicate an involvement of IIS components in SCA3 neurobiology and IGFBP-1 as a potential biomarker of the disease. Copyright © 2010 Movement Disorder Society.

  4. Deletion of mouse FXR gene disturbs multiple neurotransmitter systems and alters neurobehavior. (United States)

    Huang, Fei; Wang, Tingting; Lan, Yunyi; Yang, Li; Pan, Weihong; Zhu, Yonghui; Lv, Boyang; Wei, Yuting; Shi, Hailian; Wu, Hui; Zhang, Beibei; Wang, Jie; Duan, Xiaofeng; Hu, Zhibi; Wu, Xiaojun


    Farnesoid X receptor (FXR) is a nuclear hormone receptor involved in bile acid synthesis and homeostasis. Dysfunction of FXR is involved in cholestasis and atherosclerosis. FXR is prevalent in liver, gallbladder, and intestine, but it is not yet clear whether it modulates neurobehavior. In the current study, we tested the hypothesis that mouse FXR deficiency affects a specific subset of neurotransmitters and results in an unique behavioral phenotype. The FXR knockout mice showed less depressive-like and anxiety-related behavior, but increased motor activity. They had impaired memory and reduced motor coordination. There were changes of glutamatergic, GABAergic, serotoninergic, and norepinephrinergic neurotransmission in either hippocampus or cerebellum. FXR deletion decreased the amount of the GABA synthesis enzyme GAD65 in hippocampus but increased GABA transporter GAT1 in cerebral cortex. FXR deletion increased serum concentrations of many bile acids, including taurodehydrocholic acid, taurocholic acid, deoxycholic acid (DCA), glycocholic acid (GCA), tauro-α-muricholic acid, tauro-ω-muricholic acid, and hyodeoxycholic acid (HDCA). There were also changes in brain concentrations of taurocholic acid, taurodehydrocholic acid, tauro-ω-muricholic acid, tauro-β-muricholic acid, deoxycholic acid, and lithocholic acid (LCA). Taken together, the results from studies with FXR knockout mice suggest that FXR contributes to the homeostasis of multiple neurotransmitter systems in different brain regions and modulates neurobehavior. The effect appears to be at least partially mediated by bile acids that are known to cross the blood-brain barrier (BBB) inducing potential neurotoxicity.

  5. Altered Striatocerebellar Metabolism and Systemic Inflammation in Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    Chiun-Chieh Yu


    Full Text Available Parkinson’s disease (PD is the most second common neurodegenerative movement disorder. Neuroinflammation due to systemic inflammation and elevated oxidative stress is considered a major factor promoting the pathogenesis of PD, but the relationship of structural brain imaging parameters to clinical inflammatory markers has not been well studied. Our aim was to evaluate the association of magnetic resonance spectroscopy (MRS measures with inflammatory markers. Blood samples were collected from 33 patients with newly diagnosed PD and 30 healthy volunteers. MRS data including levels of N-acetylaspartate (NAA, creatine (Cre, and choline (Cho were measured in the bilateral basal ganglia and cerebellum. Inflammatory markers included plasma nuclear DNA, plasma mitochondrial DNA, and apoptotic leukocyte levels. The Cho/Cre ratio in the dominant basal ganglion, the dominant basal ganglia to cerebellum ratios of two MRS parameters NAA/Cre and Cho/Cre, and levels of nuclear DNA, mitochondrial DNA, and apoptotic leukocytes were significantly different between PD patients and normal healthy volunteers. Significant positive correlations were noted between MRS measures and inflammatory marker levels. In conclusion, patients with PD seem to have abnormal levels of inflammatory markers in the peripheral circulation and deficits in MRS measures in the dominant basal ganglion and cerebellum.

  6. Alteration of the systemic and microcirculation by a single oral dose of flavan-3-ols.

    Directory of Open Access Journals (Sweden)

    Kodai Ingawa

    Full Text Available Several systematic reviews have reported that flow mediated dilatation (FMD was significantly increased in subjects after ingestion of chocolate that contains flavan-3-ols; however, the mechanisms responsible for this effect are not clear. In this study, we evaluated the effects of a single oral dose of flavan-3-ols on the systemic circulation and microcirculation in the cremaster muscle using intravital video microscopy in vivo. The cremaster muscle in rats was spread over a plastic chamber and a gastric tube was placed into the stomach. Blood flow in the cremasteric artery was determined using a laser Doppler flowmeter, while blood pressure and heart rate were measured by the tail-cuff method. Red blood cell velocity in arterioles and blood flow in the artery were significantly increased 5 min after the administration of 10 mg/kg flavan-3-ols compared with distilled water treatment. The number of capillaries recruited in the cremaster muscle was also significantly increased 15 min after treatment. Microscopic observation confirmed that increased shear stress on endothelial cells was maintained during the measurement period. The mean arterial blood pressure and heart rate were also significantly elevated soon after administration and returned to baseline before the end of the observation period. Plasma nitrate and nitrite levels, and NO phosphorylation of aortic tissue were significantly increased at 60 min after administration of flavan-3-ols. According to these results, a single oral dose of flavan-3-ols elevates blood pressure and flow transiently, and these effects induce NO production through increased shear stress on endothelial cells.

  7. In vitro and in vivo models of Huntington's disease show alterations in the endocannabinoid system. (United States)

    Bari, Monica; Battista, Natalia; Valenza, Marta; Mastrangelo, Nicolina; Malaponti, Marinella; Catanzaro, Giuseppina; Centonze, Diego; Finazzi-Agrò, Alessandro; Cattaneo, Elena; Maccarrone, Mauro


    In this study, we analyzed the components of the endocannabinoid system (ECS) in R6/2 mice, a widely used model of Huntington's disease (HD). We measured the endogenous content of N-arachidonoylethanolamine and 2-arachidonoylglycerol and the activity of their biosynthetic enzymes (N-acyl-phosphatidylethanolamine-hydrolyzing phospholipase D and diacylglycerol lipase, respectively) and hydrolytic enzymes [fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase, respectively] and of their target receptors (type 1 cannabinoid receptor, type 2 cannabinoid receptor, and transient receptor potential vanilloid-1) in the brains of wild-type and R6/2 mice of different ages, as well as in the striatum and cortex of 12-week-old animals. In addition, we measured FAAH activity in lymphocytes of R6/2 mice. In the whole brains of 12-week-old R6/2 mice, we found reductions in N-acyl-phosphatidylethanolamine-hydrolyzing phospholipase D activity, diacylglycerol lipase activity and cannabinoid receptor binding, mostly associated with changes in the striatum but not in the cortex, as well as an increase in 2-arachidonoylglycerol content as compared with wild-type littermates, without any other change in ECS elements. Then, our analysis was extended to HD43 cells, an inducible cellular model of HD derived from rat ST14A cells. In both induced and noninduced conditions, we demonstrated a fully functional ECS. Overall, our data suggest that the ECS is differently affected in mouse and human HD, and that HD43 cells are suitable for high-throughput screening of FAAH-oriented drugs affecting HD progression.

  8. Irradiation Alters MMP-2/TIMP-2 System and Collagen Type IV Degradation in Brain

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Won Hee [School of Biomedical Engineering and Sciences, Virginia Polytechnic Institute and State University, Blacksburg, Virginia (United States); Warrington, Junie P.; Sonntag, William E. [Reynolds Oklahoma Center on Aging, Department of Geriatric Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma (United States); Lee, Yong Woo, E-mail: [School of Biomedical Engineering and Sciences, Virginia Polytechnic Institute and State University, Blacksburg, Virginia (United States); Department of Biomedical Sciences and Pathobiology, Virginia Polytechnic Institute and State University, Blacksburg, Virginia (United States)


    Purpose: Blood-brain barrier (BBB) disruption is one of the major consequences of radiation-induced normal tissue injury in the central nervous system. We examined the effects of whole-brain irradiation on matrix metalloproteinases (MMPs)/tissue inhibitors of metalloproteinases (TIMPs) and extracellular matrix (ECM) degradation in the brain. Methods and Materials: Animals received either whole-brain irradiation (a single dose of 10 Gy {gamma}-rays or a fractionated dose of 40 Gy {gamma}-rays, total) or sham-irradiation and were maintained for 4, 8, and 24 h following irradiation. mRNA expression levels of MMPs and TIMPs in the brain were analyzed by real-time reverse transcriptase-polymerase chain reaction (PCR). The functional activity of MMPs was measured by in situ zymography, and degradation of ECM was visualized by collagen type IV immunofluorescent staining. Results: A significant increase in mRNA expression levels of MMP-2, MMP-9, and TIMP-1 was observed in irradiated brains compared to that in sham-irradiated controls. In situ zymography revealed a strong gelatinolytic activity in the brain 24 h postirradiation, and the enhanced gelatinolytic activity mediated by irradiation was significantly attenuated in the presence of anti-MMP-2 antibody. A significant reduction in collagen type IV immunoreactivity was also detected in the brain at 24 h after irradiation. In contrast, the levels of collagen type IV were not significantly changed at 4 and 8 h after irradiation compared with the sham-irradiated controls. Conclusions: The present study demonstrates for the first time that radiation induces an imbalance between MMP-2 and TIMP-2 levels and suggests that degradation of collagen type IV, a major ECM component of BBB basement membrane, may have a role in the pathogenesis of brain injury.

  9. Altered cortical beta‐band oscillations reflect motor system degeneration in amyotrophic lateral sclerosis (United States)

    Proudfoot, Malcolm; Rohenkohl, Gustavo; Quinn, Andrew; Colclough, Giles L.; Wuu, Joanne; Talbot, Kevin; Woolrich, Mark W.; Benatar, Michael


    Abstract Continuous rhythmic neuronal oscillations underpin local and regional cortical communication. The impact of the motor system neurodegenerative syndrome amyotrophic lateral sclerosis (ALS) on the neuronal oscillations subserving movement might therefore serve as a sensitive marker of disease activity. Movement preparation and execution are consistently associated with modulations to neuronal oscillation beta (15–30 Hz) power. Cortical beta‐band oscillations were measured using magnetoencephalography (MEG) during preparation for, execution, and completion of a visually cued, lateralized motor task that included movement inhibition trials. Eleven “classical” ALS patients, 9 with the primary lateral sclerosis (PLS) phenotype, and 12 asymptomatic carriers of ALS‐associated gene mutations were compared with age‐similar healthy control groups. Augmented beta desynchronization was observed in both contra‐ and ipsilateral motor cortices of ALS patients during motor preparation. Movement execution coincided with excess beta desynchronization in asymptomatic mutation carriers. Movement completion was followed by a slowed rebound of beta power in all symptomatic patients, further reflected in delayed hemispheric lateralization for beta rebound in the PLS group. This may correspond to the particular involvement of interhemispheric fibers of the corpus callosum previously demonstrated in diffusion tensor imaging studies. We conclude that the ALS spectrum is characterized by intensified cortical beta desynchronization followed by delayed rebound, concordant with a broader concept of cortical hyperexcitability, possibly through loss of inhibitory interneuronal influences. MEG may potentially detect cortical dysfunction prior to the development of overt symptoms, and thus be able to contribute to the assessment of future neuroprotective strategies. Hum Brain Mapp 38:237–254, 2017. © 2016 Wiley Periodicals, Inc. PMID:27623516

  10. Early weaning PCB 95 exposure alters the neonatal endocrine system: thyroid adipokine dysfunction. (United States)

    Ahmed, R G


    Polychlorinated biphenyls (PCBs) are persistent environmental pollutants that can severely disrupt the endocrine system. In the present study, early-weaned male rats were administered a single dose of 2,3,6-2',5'-pentachlorinated biphenyl (PCB 95; 32 mg/kg per day, by i.p. injection) for two consecutive days (postnatal days (PNDs) 15 and 16) and killed 24 and 48 h after the administration of the last dose. Compared with the control group, administration of PCB 95 induced a reduction (P<0.01) in serum concentrations of thyroxine, triiodothyronine, and GH and an increase (P<0.01) in the serum concentration of TSH at PNDs 17 and 18. These conspicuous perturbations led to some histopathological deterioration in the thyroid gland characterized by follicular degeneration, edema, fibrosis, hemorrhage, luminal obliteration, and hypertrophy with reduced colloidal contents at PND 18. The dyshormonogenesis and thyroid dysgenesis may be attributed to the elevation of DNA fragmentation at PNDs 17 and 18. Furthermore, this hypothyroid state revealed higher (P<0.01) serum concentrations of leptin, adiponectin, and tumor necrosis factor and lower (P<0.01) serum concentrations of IGF1 and insulin at both PNDs compared with the control group. Interestingly, the body weight of the neonates in the PCB 95 group exhibited severe decreases throughout the experimental period in relation to that of the control group. These results imply that PCB 95 may act as a disruptor of the developmental hypothalamic-pituitary-thyroid axis. Hypothyroidism caused by PCB 95 may impair the adipokine axis, fat metabolism, and in general postnatal development. Thus, further studies need to be carried out to understand this concept.

  11. Mild systemic inflammation and moderate hypoxia transiently alter neuronal excitability in mouse somatosensory cortex. (United States)

    Mordel, Jérôme; Sheikh, Aminah; Tsohataridis, Simeon; Kanold, Patrick O; Zehendner, Christoph M; Luhmann, Heiko J


    During the perinatal period, the brain is highly vulnerable to hypoxia and inflammation, which often cause white matter injury and long-term neuronal dysfunction such as motor and cognitive deficits or epileptic seizures. We studied the effects of moderate hypoxia (HYPO), mild systemic inflammation (INFL), or the combination of both (HYPO+INFL) in mouse somatosensory cortex induced during the first postnatal week on network activity and compared it to activity in SHAM control animals. By performing in vitro electrophysiological recordings with multi-electrode arrays from slices prepared directly after injury (P8-10), one week after injury (P13-16), or in young adults (P28-30), we investigated how the neocortical network developed following these insults. No significant difference was observed between the four groups in an extracellular solution close to physiological conditions. In extracellular 8mM potassium solution, slices from the HYPO, INFL, and HYPO+INFL group were more excitable than SHAM at P8-10 and P13-16. In these two age groups, the number and frequency of spontaneous epileptiform events were significantly increased compared to SHAM. The frequency of epileptiform events was significantly reduced by the NMDA antagonist D-APV in HYPO, INFL, and HYPO+INFL, but not in SHAM, indicating a contribution of NMDA receptors to this pathophysiological activity. In addition, the AMPA/kainate receptor antagonist CNQX suppressed the remaining epileptiform activity. Electrical stimulation evoked prominent epileptiform activity in slices from HYPO, INFL and HYPO+INFL animals. Stimulation threshold to elicit epileptiform events was lower in these groups than in SHAM. Evoked events spread over larger areas and lasted longer in treated animals than in SHAM. In addition, the evoked epileptiform activity was reduced in the older (P28-30) group indicating that cortical dysfunction induced by hypoxia and inflammation was transient and compensated during early development.

  12. Silver and titanium dioxide nanoparticles alter oxidative/inflammatory response and renin-angiotensin system in brain. (United States)

    Krawczyńska, Agata; Dziendzikowska, Katarzyna; Gromadzka-Ostrowska, Joanna; Lankoff, Anna; Herman, Andrzej Przemysław; Oczkowski, Michał; Królikowski, Tomasz; Wilczak, Jacek; Wojewódzka, Maria; Kruszewski, Marcin


    The study was designed to examine the effects of silver AgNPs, 20 nm) and titanium dioxide (Aeroxide(®) P25 TiO2NPs, 21 nm) nanoparticles on brain oxidative stress parameters, its antioxidant potential and brain renin-angiotensin system (RAS) in vivo. The analysis was performed 28 days after single dose injection of TiO2NPs and AgNPs (10 or 5 mg/kg body weight, respectively). The AgNPs, but not TiO2NPs, administration resulted in decreased lipid and cholesterol peroxidation. Antioxidant enzymes gene expression and/or activity were changed differently for TiO2NPs and AgNPs group. The TiO2NPs decreased aromatase gene expression, and glutathione peroxidase and reductase activities. In AgNPs group the sodium dismutase 1 and glutathione reductase mRNA levels were decreased as opposed to their activities. Both NPs altered the expression of brain RAS genes (angiotensinogen, renin, angiotensin I converting enzyme 1 and 2), but only TiO2NPs caused similar changes on protein level. The expression of amyloid beta precursor protein gene was not altered by any kind of injected NPs. The TiO2NPs were more potent modulator of gene expression in the brain than AgNPs, despite the two times lower dosage. These results suggest that AgNPs and TiO2NPs exposure may modulate the brain function, but with different strength.

  13. Short-term exposure of arsenite disrupted thyroid endocrine system and altered gene transcription in the HPT axis in zebrafish. (United States)

    Sun, Hong-Jie; Li, Hong-Bo; Xiang, Ping; Zhang, Xiaowei; Ma, Lena Q


    Arsenic (As) pollution in aquatic environment may adversely impact fish health by disrupting their thyroid hormone homeostasis. In this study, we explored the effect of short-term exposure of arsenite (AsIII) on thyroid endocrine system in zebrafish. We measured As concentrations, As speciation, and thyroid hormone thyroxine levels in whole zebrafish, oxidative stress (H2O2) and damage (MDA) in the liver, and gene transcription in hypothalamic-pituitary-thyroid (HPT) axis in the brain and liver tissues of zebrafish after exposing to different AsIII concentrations for 48 h. Result indicated that exposure to AsIII increased inorganic As in zebrafish to 0.46-0.72 mg kg(-1), induced oxidative stress with H2O2 being increased by 1.4-2.5 times and caused oxidative damage with MDA being augmented by 1.6 times. AsIII exposure increased thyroxine levels by 1.3-1.4 times and modulated gene transcription in HPT axis. Our study showed AsIII caused oxidative damage, affected thyroid endocrine system and altered gene transcription in HPT axis in zebrafish.

  14. Serological and Genetic Evidence for Altered Complement System Functionality in Systemic Lupus Erythematosus: Findings of the GAPAID Consortium. (United States)

    Prechl, József; Papp, Krisztián; Hérincs, Zoltán; Péterfy, Hajna; Lóránd, Veronika; Szittner, Zoltán; Estonba, Andone; Rovero, Paolo; Paolini, Ilaria; Del Amo, Jokin; Uribarri, Maria; Alcaro, Maria Claudia; Ruiz-Larrañaga, Otsanda; Migliorini, Paola; Czirják, László


    Systemic lupus erythematosus is a chronic autoimmune disease with multifactorial ethiopathogenesis. The complement system is involved in both the early and late stages of disease development and organ damage. To better understand autoantibody mediated complement consumption we examined ex vivo immune complex formation on autoantigen arrays. We recruited patients with SLE (n = 211), with other systemic autoimmune diseases (n = 65) and non-autoimmune control subjects (n = 149). Standard clinical and laboratory data were collected and serum complement levels were determined. The genotype of SNP rs1143679 in the ITGAM gene was also determined. Ex vivo formation of immune complexes, with respect to IgM, IgG, complement C4 and C3 binding, was examined using a functional immunoassay on autoantigen microarray comprising nucleic acids, proteins and lipids. Complement consumption of nucleic acids increased upon binding of IgM and IgG even when serum complement levels were decreased due to consumption in SLE patients. A negative correlation between serum complement levels and ex vivo complement deposition on nucleic acid autoantigens is demonstrated. On the contrary, complement deposition on tested protein and lipid autoantigens showed positive correlation with C4 levels. Genetic analysis revealed that the non-synonymous variant rs1143679 in complement receptor type 3 is associated with an increased production of anti-dsDNA IgG antibodies. Notwithstanding, homozygous carriers of the previously reported susceptible allele (AA) had lower levels of dsDNA specific IgM among SLE patients. Both the non-synonymous variant rs1143679 and the high ratio of nucleic acid specific IgG/IgM were associated with multiple organ involvement. In summary, secondary complement deficiency in SLE does not impair opsonization of nucleic-acid-containing autoantigens but does affect other antigens and potentially other complement dependent processes. Dysfunction of the receptor recognizing complement

  15. C5a alters blood-brain barrier integrity in a human in vitro model of systemic lupus erythematosus. (United States)

    Mahajan, Supriya D; Parikh, Neil U; Woodruff, Trent M; Jarvis, James N; Lopez, Molly; Hennon, Teresa; Cunningham, Patrick; Quigg, Richard J; Schwartz, Stanley A; Alexander, Jessy J


    The blood-brain barrier (BBB) plays a crucial role in brain homeostasis, thereby maintaining the brain environment precise for optimal neuronal function. Its dysfunction is an intriguing complication of systemic lupus erythematosus (SLE). SLE is a systemic autoimmune disorder where neurological complications occur in 5-50% of cases and is associated with impaired BBB integrity. Complement activation occurs in SLE and is an important part of the clinical profile. Our earlier studies demonstrated that C5a generated by complement activation caused the loss of brain endothelial layer integrity in rodents. The goal of the current study was to determine the translational potential of these studies to a human system. To assess this, we used a two dimensional in vitro BBB model constructed using primary human brain microvascular endothelial cells and astroglial cells, which closely emulates the in vivo BBB allowing the assessment of BBB integrity. Increased permeability monitored by changes in transendothelial electrical resistance and cytoskeletal remodelling caused by actin fiber rearrangement were observed when the cells were exposed to lupus serum and C5a, similar to the observations in mice. In addition, our data show that C5a/C5aR1 signalling alters nuclear factor-κB translocation into nucleus and regulates the expression of the tight junction proteins, claudin-5 and zonula occludens 1 in this setting. Our results demonstrate for the first time that C5a regulates BBB integrity in a neuroinflammatory setting where it affects both endothelial and astroglial cells. In addition, we also demonstrate that our previous findings in a mouse model, were emulated in human cells in vitro, bringing the studies one step closer to understanding the translational potential of C5a/C5aR1 blockade as a promising therapeutic strategy in SLE and other neurodegenerative diseases. © 2015 John Wiley & Sons Ltd.

  16. Alcohol exposure in utero leads to enhanced prepubertal mammary development and alterations in mammary IGF and estradiol systems. (United States)

    Polanco, Tiffany A; Crismale-Gann, Catina; Cohick, Wendie S


    Exposure to alcohol during fetal development increases susceptibility to mammary cancer in adult rats. This study determined if early changes in mammary morphology and the insulin-like growth factor (IGF)/estradiol axis are involved in the mechanisms that underlie this increased susceptibility. Pregnant Sprague-Dawley rats were fed a liquid diet containing 6.7% ethanol (alcohol), an isocaloric liquid diet (pair-fed), or rat chow ad libitum from days 11 to 21 of gestation. At birth, female pups were cross-fostered to ad libitum-fed control dams. Offspring were euthanized at postnatal days (PND) 20, 40, or 80. Animals were injected with BrdU before euthanasia, then mammary glands, serum, and livers were collected. Mammary glands from animals exposed to alcohol in utero displayed increased epithelial cell proliferation and aromatase expression at PND 20 and 40. Mammary IGF-I mRNA was higher in alcohol-exposed animals relative to controls at PND 20, while mammary IGFBP-5 mRNA was lower in this group at PND 40. Hepatic IGF-I mRNA expression was increased at all time points in alcohol-exposed animals, however, circulating IGF-I levels were not altered. These data indicate that alcohol exposure in utero may advance mammary development via the IGF and estradiol systems, which could contribute to increased susceptibility to mammary cancer later in life.

  17. Apparent partial resetting of U-Th-Pb systems in experimentally altered monazite resulting from nano-mixtures due to incomplete replacement. (United States)

    Grand'homme, Alexis; Janots, Emilie; Seydoux-Guillaume, Anne-Magali; Guillaume, Damien; Bosse, Valérie; Magnin, Valérie


    Hydrothermal alteration experiments of natural monazite crystals (Manangotry, Madagascar; 555 Ma) under alkali conditions (NaOH 1M in 18O doped solution) at low temperature conditions (300, 400, 500 and 600°C), 200 MPa, were conducted to clarify the origin of unsupported Pb (radiogenic or not) in altered monazite (Seydoux-Guillaume et al., 2012). At 300°C, no evidence of monazite replacement was observed. From 400 to 600°C, experimental products show a replacement texture with pristine monazite (Mnz1) surrounded by an alteration rim with a different composition (SEM and EPMA). In the altered domains, in-situ isotopic and chemical U-Th-Pb dating yields intermediate ages between original monazite (555 Ma) and complete experimental resetting (0 Ma). Incomplete resetting is due to the systematic presence of Pb in altered domains, whose concentration decreases with increasing temperature. Transmission Electron Microscope (TEM) observations reveal an incomplete replacement of Mnz1 by a secondary monazite (Mnz2), free of Pb, within the altered domain. The latter domain, apparently homogeneous in BSE images, is in fact constituted by closely associated nano-mixtures of Mnz1 and Mnz2. Furthermore, the volume of Mnz2 within the altered domain, i.e. the efficiency of replacement, increases with increasing temperature. Apparent partial resetting of U-Th-Pb systems results from the unavoidable nano-mixture of different proportion of Mnz1 and Mnz2 within the analytical microvolume (EPMA, LA-ICP-MS). This study therefore indicates that the micrometric resolution (even the 5 μm3 for EPMA) of in-situ dating techniques may be not sufficient to solve such nano-replacement domains, especially when alteration occurs at low-temperature. Ref: Seydoux-Guillaume, A.-M., Montel, J.-M., Bingen, B., Bosse, V., de Parseval, P., Paquette, J.-L., Janots, E., and Wirth, R., (2012). Chemical Geology, v. 330-331, p. 140-158.

  18. Evaluation of the systemic innate immune response and metabolic alterations of nonlactating cows with diet-induced subacute ruminal acidosis. (United States)

    Rodríguez-Lecompte, J C; Kroeker, A D; Ceballos-Márquez, A; Li, S; Plaizier, J C; Gomez, D E


    Subacute ruminal acidosis (SARA) increases lipopolysaccharide endotoxin in the rumen, which might translocate into the systemic circulation, triggering a cascade of clinical and immunological alterations. The objective of this study was to characterize the clinical immune and metabolic responses to ruminal-derived lipopolysaccharide in nonlactating cows induced with SARA using 2 challenges, a grain-based SARA challenge (GBSC) or an alfalfa-pellet SARA challenge (APSC). Six dry, nonlactating Holstein cows were used in a 3 × 3 Latin square arrangement of treatments with 4-wk experimental cycles. All cows received the control diet containing 70% forage and 30% mixed concentrates (dry matter basis) for 3 wk. In wk 4, cows received a control diet, GBSC (38% wheat-barley pellets, 32% other mixed concentrate, and 30% forages), or APSC (45% mixed concentrate, 32% alfalfa pellets, and 23% other forages). Total plasma proteins and immunology-related proteins, acute phase proteins, blood cells, serum chemistry, mRNA gene expression of peripheral blood cell surface markers, and selected proinflammatory cytokines were evaluated. Ruminal pH was lower in both groups with induced SARA compared with a control group. Ruminal endotoxins were higher in GBSC; however, plasma endotoxin was not detected in any study group. No significant differences in feed intake, rectal temperature, white blood cell counts, or differentials were found between control and SARA challenge groups; changes in glucose, urea, Ca, and Mg were observed in SARA groups. Total plasma proteins were lower in both SARA groups, and acute phase proteins were higher in GBSC. The expression of CD14, MD2, and TLR4 mRNA in peripheral blood leukocytes was not affected by SARA induction. The induction of SARA as a result of GBSC or APSC challenge was successful; however, LPS was not detected in plasma. Changes in clinical, metabolic, and inflammatory responses were not observed in the SARA-challenged cows, suggesting that

  19. Qualitative alteration of peripheral motor system begins prior to appearance of typical sarcopenia syndrome in middle-aged rats. (United States)

    Tamaki, Tetsuro; Hirata, Maki; Uchiyama, Yoshiyasu


    Qualitative changes in the peripheral motor system were examined using young, adult, middle-aged, and old-aged rats in order to assess before and after the appearance of sarcopenia symptoms. Significant loss of muscle mass and strength, and slow-type fiber grouping with a loss of innervated nerve fibers were used as typical markers of sarcopenia. Dynamic twitch and tetanus tension and evoked electromyogram (EEMG) were measured via electrical stimulation through the sciatic nerve under anesthesia using our force-distance transducer system before and after sciatectomy. Digital and analog data sampling was performed and shortening and relaxing velocity of serial twitches was calculated with tension force. Muscle tenderness in passive stretching was also measured as stretch absorption ability, associated with histological quantitation of muscle connective tissues. The results indicated the validity of the present model, in which old-aged rats clearly showed the typical signs of sarcopenia, specifically in the fast-type plantaris muscles, while the slow-type soleus showed relatively mild syndromes. These observations suggest the following qualitative alterations as the pathophysiological mechanism of sarcopenia: (1) reduction of shortening and relaxing velocity of twitch; (2) decline of muscle tenderness following an increase in the connective tissue component; (3) impaired recruitment of motor units (MUs) (sudden depression of tetanic force and EEMG) in higher stimulation frequencies over 50-60 Hz; and (4) easy fatigability in the neuromuscular junctions. These findings are likely to be closely related to significant losses in fast-type MUs, muscle strength and contraction velocity, which could be a causative factor in falls in the elderly. Importantly, some of these symptoms began in middle-aged rats that showed no other signs of sarcopenia. Thus, prevention should be started in middle age that could be retained relatively higher movement ability.

  20. Maternal Dexamethasone Treatment Alters Tissue and Circulating Components of the Renin-Angiotensin System in the Pregnant Ewe and Fetus. (United States)

    Forhead, Alison J; Jellyman, Juanita K; De Blasio, Miles J; Johnson, Emma; Giussani, Dino A; Broughton Pipkin, Fiona; Fowden, Abigail L


    Antenatal synthetic glucocorticoids promote fetal maturation in pregnant women at risk of preterm delivery and their mechanism of action may involve other endocrine systems. This study investigated the effect of maternal dexamethasone treatment, at clinically relevant doses, on components of the renin-angiotensin system (RAS) in the pregnant ewe and fetus. From 125 days of gestation (term, 145 ± 2 d), 10 ewes carrying single fetuses of mixed sex (3 female, 7 male) were injected twice im, at 10-11 pm, with dexamethasone (2 × 12 mg, n = 5) or saline (n = 5) at 24-hour intervals. At 10 hours after the second injection, maternal dexamethasone treatment increased angiotensin-converting enzyme (ACE) mRNA levels in the fetal lungs, kidneys, and heart and ACE concentration in the circulation and lungs, but not kidneys, of the fetuses. Fetal cardiac mRNA abundance of angiotensin II (AII) type 2 receptor decreased after maternal dexamethasone treatment. Between the two groups of fetuses, there were no significant differences in plasma angiotensinogen or renin concentrations; in transcript levels of renal renin, or AII type 1 or 2 receptors in the lungs and kidneys; or in pulmonary, renal or cardiac protein content of the AII receptors. In the pregnant ewes, dexamethasone administration increased pulmonary ACE and plasma angiotensinogen, and decreased plasma renin, concentrations. Some of the effects of dexamethasone treatment on the maternal and fetal RAS were associated with altered insulin and thyroid hormone activity. Changes in the local and circulating RAS induced by dexamethasone exposure in utero may contribute to the maturational and tissue-specific actions of antenatal glucocorticoid treatment.

  1. Qualitative alteration of peripheral motor system begins prior to appearance of typical sarcopenia syndrome in middle-aged rats

    Directory of Open Access Journals (Sweden)

    Tetsuro eTamaki


    Full Text Available Qualitative changes in the peripheral motor system were examined using Young, Adult, Middle-aged and Old-aged rats in order to assess before and after the appearance of sarcopenia symptoms. Significant loss of muscle mass and strength, and slow-type fiber grouping with a loss of innervated nerve fibers were used as typical markers of sarcopenia. Dynamic twitch and tetanus tension and evoked electromyogram (EEMG were measured via electrical stimulation through the sciatic nerve under anesthesia using our force-distance transducer system before and after sciatectomy. Digital and analogue data sampling was performed and shortening and relaxing velocity of serial twitches was calculated with tension force. Muscle tenderness in passive stretching was also measured as stretch absorption ability, associated with histological quantitation of muscle connective tissues. The results indicated the validity of the present model, in which Old-aged rats clearly showed the typical signs of sarcopenia, specifically in the fast-type plantaris muscles, while the slow-type soleus showed relatively mild syndromes. These observations suggest the following qualitative alterations as the pathophysiological mechanism of sarcopenia: 1 reduction of shortening and relaxing velocity of twitch; 2 decline of muscle tenderness following an increase in the connective tissue component; 3 impaired recruitment of motor units (sudden depression of tetanic force and EEMG in higher stimulation frequencies over 50-60 Hz; and 4 easy fatigability in the neuromuscular junctions. These findings are likely to be closely related to significant losses in fast-type motor units, muscle strength and contraction velocity, which could be a causative factor in falls in the elderly. Importantly, some of these symptoms began in Middle-aged rats that showed no other signs of sarcopenia. Thus, prevention should be started in middle age that could be retained relatively higher movement ability.

  2. Acetaminophen-Induced Liver Injury Alters the Acyl Ethanolamine-Based Anti-Inflammatory Signaling System in Liver

    Directory of Open Access Journals (Sweden)

    Patricia Rivera


    Full Text Available Protective mechanisms against drug-induced liver injury are actively being searched to identify new therapeutic targets. Among them, the anti-inflammatory N-acyl ethanolamide (NAE-peroxisome proliferators activated receptor alpha (PPARα system has gained much interest after the identification of its protective role in steatohepatitis and liver fibrosis. An overdose of paracetamol (APAP, a commonly used analgesic/antipyretic drug, causes hepatotoxicity, and it is being used as a liver model. In the present study, we have analyzed the impact of APAP on the liver NAE-PPARα system. A dose-response (0.5–5–10–20 mM and time-course (2–6–24 h study in human HepG2 cells showed a biphasic response, with a decreased PPARα expression after 6-h APAP incubation followed by a generalized increase of NAE-PPARα system-related components (PPARα, NAPE-PLD, and FAAH, including the NAEs oleoyl ethanolamide (OEA and docosahexaenoyl ethanolamide, after a 24-h exposure to APAP. These results were partially confirmed in a time-course study of mice exposed to an acute dose of APAP (750 mg/kg. The gene expression levels of Pparα and Faah were decreased after 6 h of treatment and, after 24 h, the gene expression levels of Nape-pld and Faah, as well as the liver levels of OEA and palmitoyl ethanolamide, were increased. Repeated APAP administration (750 mg/kg/day up to 4 days also decreased the expression levels of PPARα and FAAH, and increased the liver levels of NAEs. A resting period of 15 days completely restored these impairments. Liver immunohistochemistry in a well-characterized human case of APAP hepatotoxicity confirmed PPARα and FAAH decrements. Histopathological and hepatic damage (Cyp2e1, Caspase3, αSma, Tnfα, and Mcp1-related alterations observed after repeated APAP administration were aggravated in the liver of Pparα-deficient mice. Our results demonstrate that the anti-inflammatory NAE-PPARα signaling system is implicated in liver

  3. R7T7 glass alteration mechanism in an aqueous closed system: understanding and modelling the long term alteration kinetic; Etude des mecanismes d'alteration par l'eau du verre R7T7 en milieu confine: comprehension et modelisation de la cinetique residuelle

    Energy Technology Data Exchange (ETDEWEB)

    Chave, T


    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)

  4. Intrarenal alterations of the angiotensin-converting enzyme type 2/angiotensin 1-7 complex of the renin-angiotensin system do not alter the course of malignant hypertension in Cyp1a1-Ren-2 transgenic rats. (United States)

    Husková, Zuzana; Kopkan, Libor; Červenková, Lenka; Doleželová, Šárka; Vaňourková, Zdeňka; Škaroupková, Petra; Nishiyama, Akira; Kompanowska-Jezierska, Elzbieta; Sadowski, Janusz; Kramer, Herbert J; Červenka, Luděk


    The role of the intrarenal renin-angiotensin system (RAS) in the pathophysiology of malignant hypertension is not fully understood. Accumulating evidence indicates that the recently discovered vasodilator axis of the RAS, angiotensin-converting enzyme (ACE) type 2 (ACE2)/angiotensin 1-7 (ANG 1-7), constitutes an endogenous system counterbalancing the hypertensiogenic axis, ACE/angiotensin II (ANG II)/AT1 receptor. This study aimed to evaluate the role of the intrarenal vasodilator RAS axis in the pathophysiology of ANG II-dependent malignant hypertension in Cyp1a1-Ren-2 transgenic rats. ANG II-dependent malignant hypertension was induced by 13 days' dietary administration of indole-3-carbinol (I3C), a natural xenobiotic that activates the mouse renin gene in Cyp1a1-Ren-2 transgenic rats. It was hypothesized that pharmacologically-induced inhibition of the ACE2/ANG 1-7 complex should aggravate, and activation of this axis should attenuate, the course of ANG II-dependent malignant hypertension. Blood pressure (BP) was monitored by radiotelemetry. ACE2 inhibitor (DX 600, 0.2 μg/day) and ACE2 activator (DIZE, 1 mg/day) were administrated via osmotic minipumps. Even though ACE2 inhibitor significantly decreased and ACE2 activator increased intrarenal ANG 1-7 concentrations, the course of BP, as well as of albuminuria, cardiac hypertrophy and renal glomerular damage, were not altered. It was shown that intrarenal alterations in the ACE2/ANG 1-7 complex did not significantly modify the course of malignant hypertension in I3C-induced Cyp1a1-Ren-2 transgenic rats. Thus, in our experimental setting alterations of this intrarenal vasodilator complex of the RAS do not significantly modify the form of malignant hypertension that clearly depends on the inappropriately increased activity of the ACE/ANG II/AT1 receptor axis.

  5. Alterations in HPA-axis and autonomic nervous system functioning in childhood anxiety disorders point to a chronic stress hypothesis. (United States)

    Dieleman, Gwendolyn C; Huizink, Anja C; Tulen, Joke H M; Utens, Elisabeth M W J; Creemers, Hanneke E; van der Ende, Jan; Verhulst, Frank C


    It is of debate whether or not childhood anxiety disorders (AD) can be captured by one taxonomic construct. This study examined whether perceived arousal (PA), autonomic nervous system (ANS) and hypothalamic-pituitary-adrenal (HPA) axis measures can distinguish children with different primary diagnoses of clinical anxiety disorders (AD) from each other, and from a general population reference group (GP). The study sample consisted of 152 AD children (comparing separation anxiety disorder, generalized anxiety disorder, social phobia and specific phobia), aged 8- to 12-years, and 200 same-aged reference children. HPA-axis functioning was measured by a diurnal cortisol profile. ANS functioning was measured by continuous measures of skin conductance level in rest and during a mental arithmetic task and high frequency heart rate variability in rest. PA was assessed by a questionnaire. The AD sample showed lower high frequency heart rate variability during rest, heightened anticipatory PA, higher basal and reactive skin conductance levels and lower basal HPA-axis functioning compared to the GP sample. The existence of three or more clinical disorders, i.e. a high clinical 'load', was associated with lower basal HPA-axis functioning, higher skin conductance level and lower posttest PA. Specific phobia could be discerned from social phobia and separation anxiety disorder on higher skin conductance level. Our findings indicated that children with AD have specific psychophysiological characteristics, which resemble the psychophysiological characteristics of chronic stress. A high clinical 'load' is associated with an altered ANS and HPA-axis functioning. Overall, ANS and HPA-axis functioning relate to AD in general, accept for specific phobia. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Adipose Tissue Dysfunction and Altered Systemic Amino Acid Metabolism Are Associated with Non-Alcoholic Fatty Liver Disease.

    Directory of Open Access Journals (Sweden)

    Sulin Cheng

    Full Text Available Fatty liver is a major cause of obesity-related morbidity and mortality. The aim of this study was to identify early metabolic alterations associated with liver fat accumulation in 50- to 55-year-old men (n = 49 and women (n = 52 with and without NAFLD.Hepatic fat content was measured using proton magnetic resonance spectroscopy (1H MRS. Serum samples were analyzed using a nuclear magnetic resonance (NMR metabolomics platform. Global gene expression profiles of adipose tissues and skeletal muscle were analyzed using Affymetrix microarrays and quantitative PCR. Muscle protein expression was analyzed by Western blot.Increased branched-chain amino acid (BCAA, aromatic amino acid (AAA and orosomucoid were associated with liver fat accumulation already in its early stage, independent of sex, obesity or insulin resistance (p<0.05 for all. Significant down-regulation of BCAA catabolism and fatty acid and energy metabolism was observed in the adipose tissue of the NAFLD group (p<0.001for all, whereas no aberrant gene expression in the skeletal muscle was found. Reduced BCAA catabolic activity was inversely associated with serum BCAA and liver fat content (p<0.05 for all.Liver fat accumulation, already in its early stage, is associated with increased serum branched-chain and aromatic amino acids. The observed associations of decreased BCAA catabolism activity, mitochondrial energy metabolism and serum BCAA concentration with liver fat content suggest that adipose tissue dysfunction may have a key role in the systemic nature of NAFLD pathogenesis.

  7. Growth Hormone Alters the Glutathione S-Transferase and Mitochondrial Thioredoxin Systems in Long-Living Ames Dwarf Mice (United States)

    Rojanathammanee, Lalida; Rakoczy, Sharlene


    Ames dwarf mice are deficient in growth hormone (GH), prolactin, and thyroid-stimulating hormone and live significantly longer than their wild-type (WT) siblings. The lack of GH is associated with stress resistance and increased longevity. However, the mechanism underlying GH’s actions on cellular stress defense have yet to be elucidated. In this study, WT or Ames dwarf mice were treated with saline or GH (WT saline, Dwarf saline, and Dwarf GH) two times daily for 7 days. The body and liver weights of Ames dwarf mice were significantly increased after 7 days of GH administration. Mitochondrial protein levels of the glutathione S-transferase (GST) isozymes, K1 and M4 (GSTK1 and GSTM4), were significantly higher in dwarf mice (Dwarf saline) when compared with WT mice (WT saline). GH administration downregulated the expression of GSTK1 proteins in dwarf mice. We further investigated GST activity from liver lysates using different substrates. Substrate-specific GST activity (bromosulfophthalein, dichloronitrobenzene, and 4-hydrox-ynonenal) was significantly reduced in GH-treated dwarf mice. In addition, GH treatment attenuated the activity of thioredoxin and glutaredoxin in liver mitochondria of Ames mice. Importantly, GH treatment suppressed Trx2 and TrxR2 mRNA expression. These data indicate that GH has a role in stress resistance by altering the functional capacity of the GST system through the regulation of specific GST family members in long-living Ames dwarf mice. It also affects the regulation of thioredoxin and glutaredoxin, factors that regulate posttranslational modification of proteins and redox balance, thereby further influencing stress resistance. PMID:24285747

  8. Functional alterations of the ubiquitin-proteasome system in motor neurons of a mouse model of familial amyotrophic lateral sclerosis. (United States)

    Cheroni, Cristina; Marino, Marianna; Tortarolo, Massimo; Veglianese, Pietro; De Biasi, Silvia; Fontana, Elena; Zuccarello, Laura Vitellaro; Maynard, Christa J; Dantuma, Nico P; Bendotti, Caterina


    In familial and sporadic amyotrophic lateral sclerosis (ALS) and in rodent models of the disease, alterations in the ubiquitin-proteasome system (UPS) may be responsible for the accumulation of potentially harmful ubiquitinated proteins, leading to motor neuron death. In the spinal cord of transgenic mice expressing the familial ALS superoxide dismutase 1 (SOD1) gene mutation G93A (SOD1G93A), we found a decrease in constitutive proteasome subunits during disease progression, as assessed by real-time PCR and immunohistochemistry. In parallel, an increased immunoproteasome expression was observed, which correlated with a local inflammatory response due to glial activation. These findings support the existence of proteasome modifications in ALS vulnerable tissues. To functionally investigate the UPS in ALS motor neurons in vivo, we crossed SOD1G93A mice with transgenic mice that express a fluorescently tagged reporter substrate of the UPS. In double-transgenic Ub(G76V)-GFP /SOD1G93A mice an increase in Ub(G76V)-GFP reporter, indicative of UPS impairment, was detectable in a few spinal motor neurons and not in reactive astrocytes or microglia, at symptomatic stage but not before symptoms onset. The levels of reporter transcript were unaltered, suggesting that the accumulation of Ub(G76V)-GFP was due to deficient reporter degradation. In some motor neurons the increase of Ub(G76V)-GFP was accompanied by the accumulation of ubiquitin and phosphorylated neurofilaments, both markers of ALS pathology. These data suggest that UPS impairment occurs in motor neurons of mutant SOD1-linked ALS mice and may play a role in the disease progression.

  9. Interacting effects of discharge and channel morphology on transport of semibuoyant fish eggs in large, altered river systems.

    Directory of Open Access Journals (Sweden)

    Thomas A Worthington

    Full Text Available Habitat fragmentation and flow regulation are significant factors related to the decline and extinction of freshwater biota. Pelagic-broadcast spawning cyprinids require moving water and some length of unfragmented stream to complete their life cycle. However, it is unknown how discharge and habitat features interact at multiple spatial scales to alter the transport of semi-buoyant fish eggs. Our objective was to assess the relationship between downstream drift of semi-buoyant egg surrogates (gellan beads and discharge and habitat complexity. We quantified transport time of a known quantity of beads using 2-3 sampling devices at each of seven locations on the North Canadian and Canadian rivers. Transport time was assessed based on median capture time (time at which 50% of beads were captured and sampling period (time period when 2.5% and 97.5% of beads were captured. Habitat complexity was assessed by calculating width∶depth ratios at each site, and several habitat metrics determined using analyses of aerial photographs. Median time of egg capture was negatively correlated to site discharge. The temporal extent of the sampling period at each site was negatively correlated to both site discharge and habitat-patch dispersion. Our results highlight the role of discharge in driving transport times, but also indicate that higher dispersion of habitat patches relates to increased retention of beads within the river. These results could be used to target restoration activities or prioritize water use to create and maintain habitat complexity within large, fragmented river systems.

  10. Medullary Endocannabinoids Contribute to the Differential Resting Baroreflex Sensitivity in Rats with Altered Brain Renin-Angiotensin System Expression. (United States)

    Schaich, Chris L; Grabenauer, Megan; Thomas, Brian F; Shaltout, Hossam A; Gallagher, Patricia E; Howlett, Allyn C; Diz, Debra I


    CB1 cannabinoid receptors are expressed on vagal afferent fibers and neurons within the solitary tract nucleus (NTS), providing anatomical evidence for their role in arterial baroreflex modulation. To better understand the relationship between the brain renin-angiotensin system (RAS) and endocannabinoid expression within the NTS, we measured dorsal medullary endocannabinoid tissue content and the effects of CB1 receptor blockade at this brain site on cardiac baroreflex sensitivity (BRS) in ASrAOGEN rats with low glial angiotensinogen, normal Sprague-Dawley rats and (mRen2)27 rats with upregulated brain RAS expression. Mass spectrometry revealed higher levels of the endocannabinoid 2-arachidonoylglycerol in (mRen2)27 compared to ASrAOGEN rats (2.70 ± 0.28 vs. 1.17 ± 0.09 ng/mg tissue; P < 0.01), while Sprague-Dawley rats had intermediate content (1.85 ± 0.27 ng/mg tissue). Microinjection of the CB1receptor antagonist SR141716A (36 pmol) into the NTS did not change cardiac BRS in anesthetized Sprague-Dawley rats (1.04 ± 0.05 ms/mmHg baseline vs. 1.17 ± 0.11 ms/mmHg after 10 min). However, SR141716A in (mRen2)27 rats dose-dependently improved BRS in this strain: 0.36 pmol of SR141716A increased BRS from 0.43 ± 0.03 to 0.71 ± 0.04 ms/mmHg (P < 0.001), and 36 pmol of SR141716A increased BRS from 0.47 ± 0.02 to 0.94 ± 0.10 ms/mmHg (P < 0.01). In contrast, 0.36 pmol (1.50 ± 0.12 vs. 0.86 ± 0.08 ms/mmHg; P < 0.05) and 36 pmol (1.38 ± 0.16 vs. 0.46 ± 0.003 ms/mmHg; P < 0.01) of SR141716A significantly reduced BRS in ASrAOGEN rats. These observations reveal differential dose-related effects of the brain endocannabinoid system that influence cardiovagal BRS in animals with genetic alterations in the brain RAS.

  11. Iceland Deep Drilling Project: (V) Isotopic Evidence of Hydrothermal Exchange and Seawater Ingress from Alteration Minerals in the Reykjanes Geothermal System (United States)

    Marks, N. E.; Zierenberg, R. A.; Schiffman, P.


    The Reykjanes geothermal system is a seawater recharged hydrothermal system located on the landward extension of the Mid-Atlantic Ridge in Iceland. Fluid compositions in the system have evolved through time as a result of changing proportions of meteoric water as well as differing pressure and temperature conditions imposed by glaciation (Sveinbjornsdottir, 1986; Fridleifsson et al., 2005; Marks et al., 2009). Samples from the deepest part of Reykjanes well RN-17 include greenschist to pyroxene hornfels facies assemblages, suggesting seawater penetration into a part of the system that is close to the high temperature reaction zone. Electron microprobe studies of drill cuttings reveal intense alteration of hyaloclastites with calc-silicate alteration assemblages comprising calcic hydrothermal plagioclase, grandite garnet, prehnite, epidote, hydrothermal clinopyroxene, and titanite. In contrast, crystalline basalts and intrusive rocks display a wide range in alteration intensity from essentially unaltered to pervasive and nearly complete replacement of feldspar and pyroxene. Epidote is widely distributed throughout the RN-17 samples and fills veins and vugs, replaces glass in hyaloclastites and the interstitial matrix of basalt samples, and is also an alteration product of primary plagioclase. 87Sr/86Sr values of individual epidote grains measured by LA-ICPMS were typically 0.7045-0.7050, but ranged as high as 0.7073 in individual grains. Anhydrite is widespread in shallow portions of the Reykjanes system to about 1500 m. 87Sr/86Sr values of anhydrite from the Reykjanes geothermal system range from 0.7044-0.7053, and gypsum values range from 0.7093 to 0.7094. The Sr isotopic ratios of alteration minerals are shifted from basaltic values (0.7030-0.7034; O’Nions and Grönvold, 1973; Sun and Jahn, 1975) toward seawater values (0.70916; Palmer and Edmond, 1989). This suggests that seawater Sr is able to penetrate deep within the geothermal system, and that seawater Sr

  12. Airborne Magnetic and Electromagnetic Data map Rock Alteration and Water Content at Mount Adams, Mount Baker and Mount Rainier, Washington: Implications for Lahar Hazards and Hydrothermal Systems (United States)

    Finn, C. A.; Deszcz-Pan, M.; Horton, R.; Breit, G.; John, D.


    High resolution helicopter-borne magnetic and electromagnetic (EM) data flown over the rugged, ice-covered, highly magnetic and mostly resistive volcanoes of Mount Rainier, Mount Adams and Mount Baker, along with rock property measurements, reveal the distribution of alteration, water and hydrothermal fluids that are essential to evaluating volcanic landslide hazards and understanding hydrothermal systems. Hydrothermally altered rocks, particularly if water saturated, can weaken stratovolcanoes, thereby increasing the potential for catastrophic sector collapses that can lead to far-traveled, destructive debris flows. Intense hydrothermal alteration significantly reduces the magnetization and resistivity of volcanic rock resulting in clear recognition of altered rock by helicopter magnetic and EM measurements. Magnetic and EM data, combined with geological mapping and rock property measurements, indicate the presence of appreciable thicknesses of hydrothermally altered rock west of the modern summit of Mount Rainier in the Sunset Amphitheater region, in the central core of Mount Adams north of the summit, and in much of the central cone of Mount Baker. We identify the Sunset Amphitheater region and steep cliffs at the western edge of the central altered zone at Mount Adams as likely sources for future debris flows. In addition, the EM data identified water-saturated rocks in the upper 100-200 m of the three volcanoes. The water-saturated zone could extend deeper, but is beyond the detection limits of the EM data. Water in hydrothermal fluids reacts with the volcanic rock to produce clay minerals. The formation of clay minerals and presence of free water reduces the effective stress, thereby increasing the potential for slope failure, and acts, with entrained melting ice, as a lubricant to transform debris avalanches into lahars. Therefore, knowing the distribution of water is also important for hazard assessments. Finally, modeling requires extremely low

  13. Leukocyte Mitochondrial DNA Alteration in Systemic Lupus Erythematosus and Its Relevance to the Susceptibility to Lupus Nephritis

    Directory of Open Access Journals (Sweden)

    Yau-Huei Wei


    Full Text Available The role of mitochondrial DNA (mtDNA alterations in the pathophysiology of systemic lupus erythematosus (SLE remains unclear. We investigated sequence variations in the D310 region and copy number change of mtDNA in 85 SLE patients and 45 normal subjects. Leukocyte DNA and RNA were extracted from leukocytes of the peripheral venous blood. The D310 sequence variations and copy number of mtDNA, and mRNA expression levels of mtDNA-encoded genes in leukocytes were determined by quantitative real-time polymerase chain reaction (Q-PCR and PCR-based direct sequencing, respectively. We found that leukocyte mtDNA in SLE patients exhibited higher frequency of D310 heteroplasmy (69.4% vs. 48.9%, p = 0.022 and more D310 variants (2.2 vs. 1.7, p = 0.014 than those found in controls. Among normal controls and patients with low, medium or high SLE disease activity index (SLEDAI, an ever-increasing frequency of D310 heteroplasmy was observed (p = 0.021. Leukocyte mtDNA copy number tended to be low in patients of high SLEDAI group (p = 0.068, especially in those harboring mtDNA with D310 heteroplasmy (p = 0.020. Moreover, the mtDNA copy number was positively correlated with the mRNA level of mtDNA-encoded ND1 (NADH dehydrogenase subunit 1 (p = 0.041 and ATPase 6 (ATP synthase subunit 6 (p = 0.030 genes. Patients with more D310 variants were more susceptible to lupus nephritis (p = 0.035. Taken together, our findings suggest that decrease in the mtDNA copy number and increase in D310 heteroplasmy of mtDNA are related to the development and progression of SLE, and that the patients harboring more D310 variants of mtDNA are more susceptible to lupus nephritis.

  14. Combined use of stable isotopes and hydrologic modeling to better understand nutrient sources and cycling in highly altered systems (Invited) (United States)

    Young, M. B.; Kendall, C.; Guerin, M.; Stringfellow, W. T.; Silva, S. R.; Harter, T.; Parker, A.


    The Sacramento and San Joaquin Rivers provide the majority of freshwater for the San Francisco Bay Delta. Both rivers are important sources of drinking and irrigation water for California, and play critical roles in the health of California fisheries. Understanding the factors controlling water quality and primary productivity in these rivers and the Delta is essential for making sound economic and environmental water management decisions. However, these highly altered surface water systems present many challenges for water quality monitoring studies due to factors such as multiple potential nutrient and contaminant inputs, dynamic source water inputs, and changing flow regimes controlled by both natural and engineered conditions. The watersheds for both rivers contain areas of intensive agriculture along with many other land uses, and the Sacramento River receives significant amounts of treated wastewater from the large population around the City of Sacramento. We have used a multi-isotope approach combined with mass balance and hydrodynamic modeling in order to better understand the dominant nutrient sources for each of these rivers, and to track nutrient sources and cycling within the complex Delta region around the confluence of the rivers. High nitrate concentrations within the San Joaquin River fuel summer algal blooms, contributing to low dissolved oxygen conditions. High δ15N-NO3 values combined with the high nitrate concentrations suggest that animal manure is a significant source of nitrate to the San Joaquin River. In contrast, the Sacramento River has lower nitrate concentrations but elevated ammonium concentrations from wastewater discharge. Downstream nitrification of the ammonium can be clearly traced using δ15N-NH4. Flow conditions for these rivers and the Delta have strong seasonal and inter-annual variations, resulting in significant changes in nutrient delivery and cycling. Isotopic measurements and estimates of source water contributions

  15. Biological soil crust as a bio-mediator alters hydrological processes in stabilized dune system of the Tengger Desert, China (United States)

    Li, Xinrong


    Biological soil crust (BSC) is a vital component in the stabilized sand dunes with a living cover up to more than 70% of the total, which has been considered as a bio-mediator that directly influences and regulates the sand dune ecosystem processes. However, its influences on soil hydrological processes have been long neglected in Chinese deserts. In this study, BSCs of different successional stages were chose to test their influence on the hydrological processes of stabilized dune, where the groundwater deep exceeds 30m, further to explore why occur the sand-binding vegetation replacement between shrubs and herbs. Our long-term observation (60 years) shows that cyanobacteria crust has been colonized and developed after 3 years since the sand-binding vegetation has been established and dune fixation using planted xerophytic shrubs and made sand barrier (straw-checkerboard) on shifting dune surface, lichen and moss crust occurred after 20 years, and the cover of moss dominated crust could reach 70 % after 50 years. The colonization and development of BSC altered the initial soil water balance of revegetated areas by influencing rainfall infiltration, soil evaporation and dew water entrapment. The results show that BSC obviously reduced the infiltration that occurred during most rainfall events (80%), when rainfall was greater than 5 mm or less than 20 mm. The presence of BSC reduced evaporation of topsoil after small rainfall (BSC. Moreover, the effect of the later successional BSC to dew entrapment, rainfall infiltration and evaporation was more obvious than the early successional BSC on stabilized dunes. In general, BSC reduced the amount of rainfall water that reached deeper soil (0.4-3m), which is where the roots of shrubs are primarily distributed. These changes in the soil moisture pattern induced shifting of sand-binding vegetation from initial planted xerophytic shrub communities with higher coverage (35%) to complex communities dominated by shallow

  16. Molecular multiproxy analysis of ancient root systems suggests strong alteration of deep subsoil organic matter by rhizomicrobial activity (United States)

    Gocke, Martina; Huguet, Arnaud; Derenne, Sylvie; Kolb, Steffen; Wiesenberg, Guido L. B.


    decreasing contents of archeal GDGTs from rhizolith via rhizosphere towards root-free loess. Furthermore, the bacterial fingerprint revealed - similar to modern root systems - higher taxonomic diversity in rhizosphere compared to rhizoliths and reference loess. This argues for microorganisms benefiting from root deposits and exudates. Highest concentrations of branched GDGTs in rhizoliths suggest that their source organisms feed on root remains. Incorporation of rhizomicrobial remains as represented by RNA and GDGTs usually affected the sediment at maximum to a distance of 2-3 cm from the former root. FA contents in rhizosphere showed strong scatter and were in part depleted compared to reference loess or, especially in deeper transects, enriched. This indicates the presence of degradation products originating from former rhizosphere processes. Especially at larger depth not affected by modern pedogenic processes, portions of mainly microbial derived C16 homologues were higher in rhizosphere loess up to distances of 10 cm, revealing that the possible extension of the rhizosphere was underestimated so far. In Corg poor subsoil, the occurence of diverse rhizosphere microorganisms and degradation processes even in several centimeters distant from roots point to a strong alteration of OM, possibly contributing to carbon mineralisation.

  17. Quantitative impact of hydrothermal alteration on electrical resistivity in geothermal systems from a joint analysis of laboratory measurements and borehole data in Krafla area, N-E Iceland (United States)

    Lévy, Léa; Páll Hersir, Gylfi; Flóvenz, Ólafur; Gibert, Benoit; Pézard, Philippe; Sigmundsson, Freysteinn; Briole, Pierre


    Rock permeability and fluid temperature are the two most decisive factors for a successful geothermal drilling. While those parameters are only measured from drilling, they might be estimated on the basis of their impact on electrical resistivity that might be imaged from surface soundings, for example through TEM (Transient Electro Magnetic) down to one km depth. The electrical conductivity of reservoir rocks is the sum of a volume term depending on fluid parameters and a surface term related to rock alteration. Understanding the link between electrical resistivity and geothermal key parameters requires the knowledge of hydrothermal alteration and its petrophysical signature with the Cation Exchange Capacity (CEC). Fluid-rock interactions related to hydrothermal circulation trigger the precipitation of alteration minerals, which are both witnesses of the temperature at the time of reaction and new paths for the electrical current. Alteration minerals include zeolites, smectites, chlorites, epidotes and amphiboles among which low temperatures parageneses are often the most conductive. The CEC of these mineral phases contributes to account for surface conductivity occuring at the water-rock interface. In cooling geothermal systems, these minerals constitute in petrophysical terms and from surface electrical conduction a memory of the equilibrium phase revealed from electrical probing at all scales. The qualitative impact of alteration minerals on resistivity structure has been studied over the years in the Icelandic geothermal context. In this work, the CEC impact on pore surfaces electrical conductivity is studied quantitatively at the borehole scale, where several types of volcanic rocks are mixed together, with various degrees of alteration and porosity. Five boreholes located within a few km at the Krafla volcano, Northeast Iceland, constitute the basis for this study. The deepest and reference hole, KJ-18, provides cuttings of rock and logging data down to 2215

  18. The Associations between Various Ectopic Visceral Adiposity and Body Surface Electrocardiographic Alterations: Potential Differences between Local and Remote Systemic Effects.

    Directory of Open Access Journals (Sweden)

    Po-Ching Chi

    Full Text Available The associations between pericardial adiposity and altered atrial conduction had been demonstrated. However, data comparing differential effects of various body sites visceral adiposity on atrial and ventricular electrocardiographic alterations remains largely unknown.We assessed both peri-cardial fat (PCF and peri-aortic visceral adiposity (TAT using dedicated computed tomography (CT software (Aquarius 3D Workstation, TeraRecon, San Mateo, CA, USA, with anthropometrics including body mass index (BMI and biochemical data obtained. We further related PCF and TAT data to standardized 12-leads electrocardiogram (ECG, including P and QRS wave morphologies. Among 3,087 study subjects (mean age, 49.6 years; 28% women, we observed a linear association among greater visceral adiposity burden, leftward deviation of P and QRS axes, longer PR interval and widened QRS duration (all p200ms, likelihood-ratio: 33.17 to 41.4 & 39.03 for PCF and TAT and widened QRS duration (>100ms, likelihood-ratio: 55.67 to 65.4 & 61.94 for PCF and TAT, all X2 p<0.05 when superimposed on age and BMI.We show in our data greater visceral fat burden may have differential associations on several body surface electrocardiographic parameters. Compared to remote adiposity, those surrounding the heart tissue demonstrated greater influences on altered cardiac activation or conduction, indicating a possible local biological effect.

  19. Wettability alteration: A comprehensive review of materials/methods and testing the selected ones on heavy-oil containing oil-wet systems. (United States)

    Mohammed, Mohammedalmojtaba; Babadagli, Tayfun


    Changing the wetting state of materials is a growing field of research in many areas of engineering and science. In the oil industry, the term wettability alteration usually refers to the process of making the reservoir rock more water-wet. This is of particular importance in naturally hydrophobic carbonates, fractured formations, and heavy-oil systems. This shift in wettability enhances oil recovery in oil-wet and weakly water-wet reservoirs and eventually increases the ultimate oil recovery. For wettability alteration, two methods have been traditionally used: Thermal and chemical. Although many attempts have been made on reviewing the advancement of research in certain aspects of wettability, a comprehensive review of these techniques, especially in terms of the classification of the chemicals used, has been ignored. In this paper, we begin with this review and provide the past experience of wettability alteration in sandstone and carbonate reservoirs. More than 100 papers were reviewed extensively with an in-depth analysis of different methods suggested in literature. The areas of controversy and contradicted observations are discussed. The limitations and the applicability of each method were analyzed. Concerns on up-scaling laboratory findings to field scale are also addressed. The most promising potential methods are identified and their critical conditions highlighted. At the end, a selection of reviewed methods is validated experimentally for one of the most challenging cases: Extra heavy-oil and bitumen recovery from fractured-strongly-oil-wet carbonates. Berea sandstone (aged to be oil-wet) and Indiana limestone samples were saturated with heavy oil (3600cp). Next, the process was initiated by soaking the cores into solvent (heptane or diluent oil) and the oil recovery was estimated using refractive index measurements. Note that solvent was selected to dilute the oil and recover a considerable amount of oil as any chemical or thermal methods yielded

  20. Risk of Impaired Control of Spacecraft/Associated Systems and Decreased Mobility Due to Vestibular/Sensorimotor Alterations Associated with Space flight (United States)

    Bloomberg, Jacob J.; Reschke, Millard F.; Clement, Gilles R.; Mulavara, Ajitkumar P.; Taylor, Laura C..


    Control of vehicles and other complex systems is a high-level integrative function of the central nervous system (CNS). It requires well-functioning subsystem performance, including good visual acuity, eye-hand coordination, spatial and geographic orientation perception, and cognitive function. Evidence from space flight research demonstrates that the function of each of these subsystems is altered by removing gravity, a fundamental orientation reference, which is sensed by vestibular, proprioceptive, and haptic receptors and used by the CNS for spatial orientation, posture, navigation, and coordination of movements. The available evidence also shows that the degree of alteration of each subsystem depends on a number of crew- and mission-related factors. There is only limited operational evidence that these alterations cause functional impacts on mission-critical vehicle (or complex system) control capabilities. Furthermore, while much of the operational performance data collected during space flight has not been available for independent analysis, those that have been reviewed are somewhat equivocal owing to uncontrolled (and/or unmeasured) environmental and/or engineering factors. Whether this can be improved by further analysis of previously inaccessible operational data or by development of new operational research protocols remains to be seen. The true operational risks will be estimable only after we have filled the knowledge gaps and when we can accurately assess integrated performance in off-nominal operational settings (Paloski et al. 2008). Thus, our current understanding of the Risk of Impaired Control of Spacecraft/Associated Systems and Decreased Mobility Due to Vestibular/Sensorimotor Alterations Associated with Space flight is limited primarily to extrapolation of scientific research findings, and, since there are limited ground-based analogs of the sensorimotor and vestibular changes associated with space flight, observation of their functional

  1. Alterations in vasomotor systems and mechanics of resistance-sized mesenteric arteries from SHR and WKY male rats following in vivo testosterone manipulation

    Directory of Open Access Journals (Sweden)

    Toot Jonathan D


    Full Text Available Abstract Background Testosterone (T and the sympathetic nervous system each contribute to the pathology of hypertension. Altered blood vessel reactivity is also associated with the pathology of high blood pressure. The purpose of this study was to examine the effects of T manipulation in the regulation of resistance-sized blood vessel reactivity. Methods Adult spontaneously hypertensive (SHR and Wistar Kyoto (WKY male rats at 8 weeks of age were used. The rats were divided into groups consisting of gonadally intact controls (CONT, castrate with sham implant (CAST and castrate with T implant (CAST + T (n = 6 to 12 per group. Following a short-term period of T treatment (approximately 4 weeks, plasma norepinephrine (NE and plasma T were assessed by performing high-performance liquid chromatography and RIA, respectively. Resistance-sized mesenteric artery reactivity was assessed on a pressurized arteriograph for myogenic reactivity (MYO, phenylephrine (PE responsiveness and passive structural mechanics. Results SHR and WKY males exhibited similar physiological trends in T manipulation, with castration significantly lowering plasma T and NE and T replacement significantly increasing plasma T and NE. T manipulation in general resulted in significant alterations in MYO of second-order mesenteric arteries, with T replacement decreasing MYO in SHR (P P P Conclusions These data suggest that T and NE are involved in a complex interaction with both myogenic reactivity and structural alterations of resistance-sized blood vessels and that these factors likely contribute to the development and maintenance of hypertension.

  2. Risk of prenatal depression and stress treatment: alteration on serotonin system of offspring through exposure to Fluoxetine (United States)

    Pei, Siran; Liu, Li; Zhong, Zhaomin; Wang, Han; Lin, Shuo; Shang, Jing


    Fluoxetine is widely used to treat depression, including depression in pregnant and postpartum women. Studies suggest that fluoxetine may have adverse effects on offspring, presumably through its action on various serotonin receptors (HTRs). However, definitive evidence and the underlying mechanisms are largely unavailable. As initial steps towards establishing a human cellular and animal model, we analyzed the expression patterns of several HTRs through the differentiation of human induced pluripotent stem (hiPS) cells into neuronal cells, and analyzed expression pattern in zebrafish embryos. Treatment of zebrafish embryos with fluoxetine significantly blocked the expression of multiple HTRs. Furthermore, fluoxetine gave rise to a change in neuropsychology. Embryos treated with fluoxetine continued to exhibit abnormal behavior upto 12 days post fertilization due to changes in HTRs. These findings support a possible long-term risk of serotonin pathway alteration, possibly resulting from the “placental drug transfer”. PMID:27703173

  3. Transcriptome Alterations Following Developmental Atrazine Exposure in Zebrafish Are Associated with Disruption of Neuroendocrine and Reproductive System Function, Cell Cycle, and Carcinogenesis (United States)

    Freeman, Jennifer L.


    Atrazine, a herbicide commonly applied to agricultural areas and a common contaminant of potable water supplies, is implicated as an endocrine-disrupting chemical (EDC) and potential carcinogen. Studies show that EDCs can cause irreversible changes in tissue formation, decreased reproductive potential, obesity, and cancer. The U.S. Environmental Protection Agency considers an atrazine concentration of ≤ 3 ppb in drinking water safe for consumption. The specific adverse human health effects associated with a developmental atrazine exposure and the underlying genetic mechanisms of these effects are not well defined. In this study, zebrafish embryos were exposed to a range of atrazine concentrations to establish toxicity. Morphological, transcriptomic, and protein alterations were then assessed at 72h postfertilization following developmental atrazine exposure at 0, 0.3, 3, or 30 ppb. A significant increase in head length was observed in all three atrazine treatments. Transcriptomic profiles revealed 21, 62, and 64 genes with altered expression in the 0.3, 3, and 30 ppb atrazine treatments, respectively. Altered genes were associated with neuroendocrine and reproductive system development, function, and disease; cell cycle control; and carcinogenesis. There was a significant overlap (42 genes) between the 3 and 30 ppb differentially expressed gene lists, with two of these genes (CYP17A1 and SAMHD1) present in all three atrazine treatments. Increased transcript levels were translated to significant upregulation in protein expression. Overall, this study identifies genetic and molecular targets altered in response to a developmental atrazine exposure to further define the biological pathways and mechanisms of toxicity. PMID:23358194

  4. Gene expression profiling in circulating endothelial cells from systemic sclerosis patients shows an altered control of apoptosis and angiogenesis that is modified by iloprost infusion (United States)


    Introduction Circulating endothelial cells are increased in patients affected by systemic sclerosis (SSc) and their number strongly correlates with vascular damage. The effects of iloprost in systemic sclerosis are only partially known. We aimed at studying the gene expression profile of circulating endothelial cells and the effects of iloprost infusion and gene expression in patients with systemic sclerosis. Methods We enrolled 50 patients affected by systemic sclerosis, 37 patients without and 13 patients with digital ulcers. Blood samples were collected from all patients before and 72 hours after either a single day or five days eight hours iloprost infusion. Blood samples were also collected from 50 sex- and age-matched healthy controls. Circulating endothelial cells and endothelial progenitors cells were detected in the peripheral blood of patients with systemic sclerosis by flow cytometry with a four-colour panel of antibodies. Statistical analysis was performed with the SPSS 16 statistical package.Circulating endothelial cells were then isolated from peripheral blood by immunomagnetic CD45 negative selection for the gene array study. Results The number of both circulating endothelial cells and progenitors was significantly higher in patients affected by systemic sclerosis than in controls and among patients in those with digital ulcers than in patients without them. Circulating endothelial cells and progenitors number increased after iloprost infusion. Gene array analysis of endothelial cells showed a different transcriptional profile in patients compared to controls. Indeed, patients displayed an altered expression of genes involved in the control of apoptosis and angiogenesis. Iloprost infusion had a profound impact on endothelial cells gene expression since the treatment was able to modulate a very high number of transcripts. Conclusions We report here that circulating endothelial cells in patients with systemic sclerosis show an altered expression of

  5. Risperidone reverses the spatial object recognition impairment and hippocampal BDNF-TrkB signalling system alterations induced by acute MK-801 treatment. (United States)

    Chen, Guangdong; Lin, Xiaodong; Li, Gongying; Jiang, Diego; Lib, Zhiruo; Jiang, Ronghuan; Zhuo, Chuanjun


    The aim of the present study was to investigate the effects of a commonly-used atypical antipsychotic, risperidone, on alterations in spatial learning and in the hippocampal brain-derived neurotrophic factor (BDNF)-tyrosine receptor kinase B (TrkB) signalling system caused by acute dizocilpine maleate (MK-801) treatment. In experiment 1, adult male Sprague-Dawley rats subjected to acute treatment of either low-dose MK801 (0.1 mg/kg) or normal saline (vehicle) were tested for spatial object recognition and hippocampal expression levels of BDNF, TrkB and the phophorylation of TrkB (p-TrkB). We found that compared to the vehicle, MK-801 treatment impaired spatial object recognition of animals and downregulated the expression levels of p-TrkB. In experiment 2, MK-801- or vehicle-treated animals were further injected with risperidone (0.1 mg/kg) or vehicle before behavioural testing and sacrifice. Of note, we found that risperidone successfully reversed the deleterious effects of MK-801 on spatial object recognition and upregulated the hippocampal BDNF-TrkB signalling system. Collectively, the findings suggest that cognitive deficits from acute N-methyl-D-aspartate receptor blockade may be associated with the hypofunction of hippocampal BDNF-TrkB signalling system and that risperidone was able to reverse these alterations.

  6. Basal regulation of HPA and dopamine systems is altered differentially in males and females by prenatal alcohol exposure and chronic variable stress. (United States)

    Uban, Kristina A; Comeau, Wendy L; Ellis, Linda A; Galea, Liisa A M; Weinberg, Joanne


    Effects of prenatal alcohol exposure (PAE) on central nervous system function include an increased prevalence of mental health problems, including substance use disorders (SUD). The hypothalamic-pituitary-adrenal (HPA) and dopamine (DA) systems have overlapping neurocircuitries and are both implicated in SUD. PAE alters both HPA and dopaminergic activity and regulation, resulting in increased HPA tone and an overall reduction in tonic DA activity. However, effects of PAE on the interaction between HPA and DA systems have not been investigated. The present study examined PAE effects on basal regulation of central stress and DA systems in key brain regions where these systems intersect. Adult Sprague-Dawley male and female offspring from prenatal alcohol-exposed (PAE), pairfed (PF), and ad libitum-fed control (C) groups were subjected to chronic variable stress (CVS) or remained as a no stress (non-CVS) control group. Corticotropin releasing hormone (CRH) mRNA, as well as glucocorticoid and DA receptor (DA-R) expression were measured under basal conditions 24h following the end of CVS. We show, for the first time, that regulation of basal HPA and DA systems, and likely, HPA-DA interactions, are altered differentially in males and females by PAE and CVS. PAE augmented the typical attenuation in weight gain during CVS in males and caused increased weight loss in females. Increased basal corticosterone levels in control, but not PAE, females suggest that PAE alters the profile of basal hormone secretion throughout CVS. CVS downregulated basal CRH mRNA in the prefrontal cortex and throughout the bed nucleus of the stria terminalis (BNST) in PAE females but only in the posterior BNST of control females. PAE males and females exposed to CVS exhibited more widespread upregulation of basal mineralocorticoid receptor mRNA throughout the hippocampus, and an attenuated decrease in DA-R expression throughout the nucleus accumbens and striatum compared to CVS-exposed control

  7. Normal Faulting, Fluid Upflow Pathways, and Alteration in the Subsurface of a Seafloor Ultramafic-Hosted Hydrothermal System, northern Apennines, Italy (United States)

    Alt, J.; Levine, D.; Crispini, L.; Gaggero, L.; Shanks, W. C., III; Gulbransen, C.


    We document the mineralogy and geochemistry of a fault that acted as a hydrothermal upflow zone in the subsurface of a seafloor ultramafic-hosted hydrothermal system in the northern Apennines, Italy. The objectives are to understand fluid flow pathways, and the relative roles of upwelling hydrothermal fluids versus cold seawater and biological effects in such systems on the modern seafloor, which is much more difficult to access and study. Peridotites were exposed on the seafloor by detachment faulting, intruded by MORB gabbros, and are overlain by MORB lavas and pelagic sediments. North of the village of Reppia are two 1-2 m wide fault shear zones in serpentinite, oriented at a high angle to the detachment surface and extending hundreds of meters below the detachment. The host peridotite is 90-100% serpentinized, and serpentinite is highly replaced by talc plus tremolite and sulfide in the shear zones. At the paleo-seafloor, the fault offsets carbonate-cemented serpentinite breccia, talc-altered serpentinite, and serpentinite in the footwall to the west, from pillow basalts of the hanging wall on the east. Here the fault rocks consist of 90% Fe-dolomite with a few percent each of calcite, quartz, serpentine, talc, sulfides, chlorite, and trace relict Cr-spinel. The fault ends upward in massive sulfide overlain by pillow basalts and pelagic sediment. Three main alteration stages are identified. 1. Background serpentinites exhibit slight LREE enrichments and elevated d34S values (+3.9 to +5.2‰) consistent with serpentinization by upwelling hot hydrothermal fluids. 2. Talc alteration of serpentinite leads to strong LREE enrichments, negative Eu anomalies, silica metasomatism, and elevated Cu during the main hydrothermal upflow stage. 3. Carbonate alteration varies from slight veining of serpentinite to near-total replacement in the shallow fault rocks, with variable enrichments of LREE, Ca, Si, and metals. Carbonate oxygen isotope temperatures of 15-150°C and d13C

  8. Alterations in pharmacological sensitivity of GABAergic but not dopaminergic and glutamatergic systems during ontogenesis in dystonic mutant hamsters. (United States)

    Richter, A; Löscher, W


    Attacks of sustained dystonia of the limbs and trunk can be initiated by handling or mild environmental stimuli (e.g. new cage) in mutant (gene symbol dtsz) Syrian golden hamsters. The severity of the dystonic syndrome in these mutant hamsters is age-dependent, with a peak at weaning (21 days of age) and a second peak at about 30-40 days of age. Spontaneous remission occurs at an age of about 70 days. The syndrome in hamsters is thus similar to transient paroxysmal dystonia in children. In the present experiments, it was examined whether dystonic hamsters exhibit age-dependent differences in susceptibility to drugs which affect GABA (gamma-aminobutyrate)ergic, glutamatergic or dopaminergic functions. After acute administration, the GABA-elevating drug aminooxyacetic acid was significantly less potent in attenuating the severity of dystonic attacks at 21 days than at 31 days of age. Similar but less marked age-dependent differences in antidystonic activity were found for phenobarbital and diazepam. In contrast to these GABAmimetic drugs, the NMDA receptor antagonist CGP 37849 (DL-[E]-2-amino-4-methyl-5-phosphono-3-pentenoic acid) or the dopamine receptor antagonist haloperidol had about the same antidystonic potency at both 21 and 31 days of age. Chronic treatment of dystonic hamsters with aminooxyacetic acid, starting at 21 days of age, did not alter the time course or the severity of dystonia.(ABSTRACT TRUNCATED AT 250 WORDS)

  9. Sodium arsenite mediated immuno-disruption through alteration of transcription profile of cytokines in chicken splenocytes under in vitro system. (United States)

    Das, Subhashree; Pan, Diganta; Bera, Asit Kumar; Rana, Tanmoy; Bhattacharya, Debasis; Bandyapadyay, Subhasis; De, Sumanta; Sreevatsava, V; Bhattacharya, Somnath; Das, Subrata Kumar; Bandyopadhayay, Sandip


    Arsenic is a ubiquitously found metalloid that commonly contaminates drinking water and agricultural food. To understand the ecotoxicological effects of arsenic in environment, it is essential to ameliorate the deleterious effects on human and animal health, particularly on the immune response. We investigated the effects of inorganic arsenic (iAs) on the immune response of chicken splenocytes. Both 1 and 10 mM concentrations of sodium arsenite treatment significantly reduced (Ptreatment also revealed time dependent differences. Relative quantification of expression of IFNγ and IL2 revealed that both genes were significantly down regulated (P<0.001) at both concentrations at each time point. iNOS gene was rapidly down regulated in splenocytes at 24 h at the high doses of As treated splenocyte, a gradual decreasing trend at low doses. Down regulation of IL-2 gene expression in response to As was further evidenced by a significant reduction (P<0.001) in the release of IL-2 into the splenocyte culture medium. We suggest that arsenic, a potent immunotoxic agent, modulates non-specific immune responses and alters the expression of cytokines in a dose and time dependent manner.

  10. Alterations in the renal elastin-elastase system in type 1 diabetic nephropathy identified by proteomic analysis. (United States)

    Thongboonkerd, Visith; Barati, Michelle T; McLeish, Kenneth R; Benarafa, Charaf; Remold-O'Donnell, Eileen; Zheng, Shirong; Rovin, Brad H; Pierce, William M; Epstein, Paul N; Klein, Jon B


    Diabetes now accounts for >40% of patients with ESRD. Despite significant progress in understanding diabetic nephropathy, the cellular mechanisms that lead to diabetes-induced renal damage are incompletely defined. For defining changes in protein expression that accompany diabetic nephropathy, the renal proteome of 120-d-old OVE26 transgenic mice with hypoinsulinemia, hyperglycemia, hyperlipidemia, and proteinuria were compared with those of background FVB nondiabetic mice (n = 5). Proteins derived from whole-kidney lysate were separated by two-dimensional PAGE and identified by matrix-assisted laser desorption ionization-time-of-flight (MALDI-TOF) mass spectrometry. Forty-one proteins from 300 visualized protein spots were differentially expressed in diabetic kidneys. Among these altered proteins, expression of monocyte/neutrophil elastase inhibitor was increased, whereas elastase IIIB was decreased, leading to the hypothesis that elastin expression would be increased in diabetic kidneys. Renal immunohistochemistry for elastin of 325-d-old FVB and OVE26 mice demonstrated marked accumulation of elastin in the macula densa, collecting ducts, and pelvicalyceal epithelia of diabetic kidneys. Elastin immunohistochemistry of human renal biopsies from patients with type 1 diabetes (n = 3) showed increased elastin expression in renal tubular cells and the interstitium but not glomeruli. These results suggest that coordinated changes in elastase inhibitor and elastase expression result in increased tubulointerstitial deposition of elastin in diabetic nephropathy. The identification of these coordinated changes in protein expression in diabetic nephropathy indicates the potential value of proteomic analysis in defining pathophysiology.

  11. Garlic attenuates chrysotile-mediated pulmonary toxicity in rats by altering the phase I and phase II drug metabolizing enzyme system. (United States)

    Ameen, Mohamed; Musthapa, M Syed; Abidi, Parveen; Ahmad, Iqbal; Rahman, Qamar


    Asbestos and its carcinogenic properties have been extensively documented. Asbestos exposure induces diverse cellular events associated with lung injury. Previously, we have shown that treatment with chrysotile shows significant alteration in phase I and phase II drug metabolizing enzyme system. In this study we have examined some potential mechanisms by which garlic treatment attenuates chrysotile-mediated pulmonary toxicity in rat. Female Wistar rats received an intratracheal instillation of 5 mg chrysotile (0.5 mL saline) as well as intragastric garlic treatment (1% body weight (v/w); 6 days per week). Effect of garlic treatment was evaluated after 1, 15, 30, 90, and 180 days by assaying aryl hydrocarbon hydroxylase (AHH), glutathione (GSH), glutathione S-transferase (GST), and production of thiobarbituric acid reactive substances (TBARS) in rat lung microsome. The results showed that AHH and TBARS formation were significantly reduced at day 90 and day 180 in chrysotile treated garlic cofed rats; GSH recovered 15 days later to the near normal level and GST elevated significantly after treatment of garlic as compared to chrysotile alone treated rat lung microsome. The data obtained shows that inhibition of AHH activity and induction of GST activity could be contributing factor in chrysotile-mediated pulmonary toxicity in garlic cofed rats. However, recovery of GSH and inhibition of TBARS formation by garlic and its constituent(s) showed that garlic may give protection by altering the drug metabolizing enzyme system.

  12. Disturbed T Cell Signaling and Altered Th17 and Regulatory T Cell Subsets in the Pathogenesis of Systemic Lupus Erythematosus

    NARCIS (Netherlands)

    Rother, N; Vlag, J. van der


    Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the presence of autoantibodies against nuclear components. Circulating immune complexes of chromatin and autoantibodies deposit in various tissues leading to inflammation and tissue damage. It has been well documented that

  13. Qualitative alteration of peripheral motor system begins prior to appearance of typical sarcopenia syndrome in middle-aged rats

    National Research Council Canada - National Science Library

    Tamaki, Tetsuro; Hirata, Maki; Uchiyama, Yoshiyasu


    .... Dynamic twitch and tetanus tension and evoked electromyogram (EEMG) were measured via electrical stimulation through the sciatic nerve under anesthesia using our force-distance transducer system before and after sciatectomy...

  14. Alterações nucleolares em algumas neuroviroses humanas Nucleolar alterations in some human viral infections of the nervous system

    Directory of Open Access Journals (Sweden)

    Alexandre Alberto de Alencar


    Full Text Available Neste trabalho estudamos alguns conceitos básicos sobre o nucléolo. Em seguida à apresentação do material de estudo, constante de casos de neuroviroses humanas, é feita um adescrição pormenorizada das alterações nucleares e nucleolares encontradas nas seguintes entidades mórbidas: polioencefalite subaguda com inclusões de DAWSON, leuco-encefalite subaguda esclerosante de VAN BOAGAERT, panencefalite nodular de PETTEDORING, poliomielite anterior aguda e raiva. As alterações nucleolares encontradas constam de hipertrofia inicial, a que se seguem profundas alterações em sua estrutura interna, sob a forma de vacuolizações e condensações granulares (os chamados nucleolinos de número e tamanhos variados. Alguns destes corpúsculos granulares, fortemente basófilos e que apresentam as mesmas características citoquímicas dos nucléolos, são lançados no carioplasma sob a forma de volumosos corpúsculos basófilos esferoidais. São feitos comentários sobre a natureza do fenômeno, concluindo-se que, tratando-se de uma ocorrência somente encontrada nas viroses, em certas formas de intoxicações e em determinados distúrbios genéticos, o seu aparecimento em um quadro histopatológico encefalítico ou mielítico permite, com segurança atribuir sua etiologia a um vírus. De todos os processos estudados, o que apresentou tais alterações nucleolares com maior exuberância foi a panencefalite nodular de PETTE-DORING.In this paper we studied the classic and modern concepts concerning the structure, composition, origen and function of the nucleole particularly in relation to the neuronal cells. The materal of study consisted of a number of cases of human neuroviroses. A detailed description of the nuclear and nucleolar alterations verfied in the following diseases was made: Dawson's Subacute Polioencephalitis, van Bogaert´s Sclerosing Subacute Leucoencephalitis, Pette Döring's Subacute Panencephalitis, Acute Anterior Poliomyelitis

  15. Sulpiride-Induced Hyperprolactinemia in Mature Female Rats: Evidence for Alterations in The Reproductive System, Pituitary and Ovarian Hormones

    Directory of Open Access Journals (Sweden)

    Sara Mostafapour


    Full Text Available Background: The prevalence of hyperprolactinemia following administration of conventional antipsychotic drugs requires further investigation. The current study is designed to evaluate the effect of sulpiride (SPD-induced hyperprolactinemia on alterations to ovarian follicular growth, gonadotropins, and ovarian hormones and to analyze the extent of potential problems in mammary glands. Materials and Methods: A total of 40 albino Wistar rats were divided into four groups: control (no treatment, control-sham (0.3 ml olive oil, low dose SPD (20 mg/kg and high dose SPD (40 mg/kg. All compounds were intraperitoneally (IP administered for a period of 28 days. Results: After 28 days, we dissected the rats’ ovarian tissues, uterine horns and mammary glands which were sent for histological analyses. We counted the numbers of normal, atretic follicles and corpora lutea (CL. Serum levels of prolactin (PRL, estradiol, progesterone, follicle stimulating hormone (FSH and luteinizing hormone (LH were evaluated. SPD-administered animals showed sporadic follicular atresia in different sizes associated with higher numbers of CL on the ovaries. The mammary glands exhibited features of galactorrhea. There was remarkable (p<0.05 elevation in SPD-administered animals’ uterine horn endometrium, myometrium and perimetrium thicknesses. The serum levels of PRL and progesterone significantly (p<0.05 increased, while the serum concentration of estradiol, LH and FSH notably (p<0.05 decreased according to the SPD administered dose. No histological and biological changes occurred in control-sham animals. SPD-induced animals had unsuccessful attempts at mating and decreased pregnancy rates. Conclusion: The present findings suggest that SPD-induced disturbances depend on PRL level. In addition, an increased PRL level is largely dependent on the administered doses of SPD.

  16. Inhibition of fried meat-induced colorectal DNA damage and altered systemic genotoxicity in humans by crucifera, chlorophyllin, and yogurt.

    Directory of Open Access Journals (Sweden)

    Daniel T Shaughnessy

    Full Text Available Dietary exposures implicated as reducing or causing risk for colorectal cancer may reduce or cause DNA damage in colon tissue; however, no one has assessed this hypothesis directly in humans. Thus, we enrolled 16 healthy volunteers in a 4-week controlled feeding study where 8 subjects were randomly assigned to dietary regimens containing meat cooked at either low (100°C or high temperature (250°C, each for 2 weeks in a crossover design. The other 8 subjects were randomly assigned to dietary regimens containing the high-temperature meat diet alone or in combination with 3 putative mutagen inhibitors: cruciferous vegetables, yogurt, and chlorophyllin tablets, also in a crossover design. Subjects were nonsmokers, at least 18 years old, and not currently taking prescription drugs or antibiotics. We used the Salmonella assay to analyze the meat, urine, and feces for mutagenicity, and the comet assay to analyze rectal biopsies and peripheral blood lymphocytes for DNA damage. Low-temperature meat had undetectable levels of heterocyclic amines (HCAs and was not mutagenic, whereas high-temperature meat had high HCA levels and was highly mutagenic. The high-temperature meat diet increased the mutagenicity of hydrolyzed urine and feces compared to the low-temperature meat diet. The mutagenicity of hydrolyzed urine was increased nearly twofold by the inhibitor diet, indicating that the inhibitors enhanced conjugation. Inhibitors decreased significantly the mutagenicity of un-hydrolyzed and hydrolyzed feces. The diets did not alter the levels of DNA damage in non-target white blood cells, but the inhibitor diet decreased nearly twofold the DNA damage in target colorectal cells. To our knowledge, this is the first demonstration that dietary factors can reduce DNA damage in the target tissue of fried-meat associated NCT00340743.

  17. Protection against 1,2-di-methylhydrazine-induced systemic oxidative stress and altered brain neurotransmitter status by probiotic Escherichia coli CFR 16 secreting pyrroloquinoline quinone. (United States)

    Pandey, Sumeet; Singh, Ashish; Chaudhari, Nirja; Nampoothiri, Laxmipriya P; Kumar, G Naresh


    Exposure to environmental pollutant 1,2-dimethylhydrazine (DMH) is attributed to systemic oxidative stress and is known to cause neurotropic effect by altering brain neurotransmitter status. Probiotics are opted as natural therapeutic against oxidative stress and also have the ability to modulate gut-brain axis. Pyrroloquinoline quinone (PQQ) is water-soluble, heat-stable antioxidant molecule. Aim of the present study was to evaluate the antioxidant efficacy of PQQ-producing probiotic E. coli CFR 16 on DMH-induced systemic oxidative damage and altered neurotransmitter status in rat brain. Adult virgin Charles Forster rats (200-250 g) were given DMH dose (25 mg/kg body weight, s.c.) for 8 weeks. Blood lipid peroxidation levels exhibited a marked increase while antioxidant enzyme activities of superoxide dismutase, catalase, glucose-6-phosphate dehydrogenase and glutathione peroxidase were found to be reduced in DMH-treated rats. Likewise, brain serotonin and norepinephrine levels displayed a significant decrease, whereas epinephrine levels demonstrated a marked increase in brain of these rats. PQQ-producing E. coli CFR 16 supplementation reduced systemic oxidative stress and also restored brain neurotransmitter status. However, E. coli CFR 16 did not show any effect on these parameters. In contrast, E. coli CFR 16:: vgb-gfp and E. coli CFR 16:: vgb-gfp vector exhibited some degree of protection again oxidative stress but they were not able to modulate neurotransmitter levels. In conclusion, continuous and sustained release of PQQ by probiotic E. coli in rat intestine ameliorates systemic oxidative stress and restored brain neurotransmitter levels.

  18. The MazEF Toxin-Antitoxin System Alters the β-Lactam Susceptibility of Staphylococcus aureus.

    Directory of Open Access Journals (Sweden)

    Christopher F Schuster

    Full Text Available Toxin-antitoxin (TA systems are genetic elements of prokaryotes which encode a stable toxin and an unstable antitoxin that can counteract toxicity. TA systems residing on plasmids are often involved in episomal maintenance whereas those on chromosomes can have multiple functions. The opportunistic pathogen Staphylococcus aureus possesses at least four different families of TA systems but their physiological roles are elusive. The chromosomal mazEF system encodes the RNase toxin MazF and the antitoxin MazE. In the light of ambiguity regarding the cleavage activity, we here verify that MazF specifically targets UACAU sequences in S. aureus in vivo. In a native strain background and under non-stress conditions, cleavage was observed in the absence or presence of mazE. Transcripts of spa (staphylococcal protein A and rsbW (anti-σB factor were cut, but translational reporter fusions indicated that protein levels of the encoded products were unaffected. Despite a comparable growth rate as the wild-type, an S. aureus mazEF deletion mutant was more susceptible to β-lactam antibiotics, which suggests that further genes, putatively involved in the antibiotic stress response or cell wall synthesis or turnover, are controlled by this TA system.

  19. The MazEF Toxin-Antitoxin System Alters the β-Lactam Susceptibility of Staphylococcus aureus. (United States)

    Schuster, Christopher F; Mechler, Lukas; Nolle, Nicoletta; Krismer, Bernhard; Zelder, Marc-Eric; Götz, Friedrich; Bertram, Ralph


    Toxin-antitoxin (TA) systems are genetic elements of prokaryotes which encode a stable toxin and an unstable antitoxin that can counteract toxicity. TA systems residing on plasmids are often involved in episomal maintenance whereas those on chromosomes can have multiple functions. The opportunistic pathogen Staphylococcus aureus possesses at least four different families of TA systems but their physiological roles are elusive. The chromosomal mazEF system encodes the RNase toxin MazF and the antitoxin MazE. In the light of ambiguity regarding the cleavage activity, we here verify that MazF specifically targets UACAU sequences in S. aureus in vivo. In a native strain background and under non-stress conditions, cleavage was observed in the absence or presence of mazE. Transcripts of spa (staphylococcal protein A) and rsbW (anti-σB factor) were cut, but translational reporter fusions indicated that protein levels of the encoded products were unaffected. Despite a comparable growth rate as the wild-type, an S. aureus mazEF deletion mutant was more susceptible to β-lactam antibiotics, which suggests that further genes, putatively involved in the antibiotic stress response or cell wall synthesis or turnover, are controlled by this TA system.

  20. Perlecan/Hspg2 deficiency alters the pericellular space of the lacunocanalicular system surrounding osteocytic processes in cortical bone. (United States)

    Thompson, William R; Modla, Shannon; Grindel, Brian J; Czymmek, Kirk J; Kirn-Safran, Catherine B; Wang, Liyun; Duncan, Randall L; Farach-Carson, Mary C


    Osteocytes project long, slender processes throughout the mineralized matrix of bone, where they connect and communicate with effector cells. The interconnected cellular projections form the functional lacunocanalicular system, allowing fluid to pass for cell-to-cell communication and nutrient and waste exchange. Prevention of mineralization in the pericellular space of the lacunocanalicular pericellular space is crucial for uninhibited interstitial fluid movement. Factors contributing to the ability of the pericellular space of the lacunocanalicular system to remain open and unmineralized are unclear. Immunofluorescence and immunogold localization by transmission electron microscopy demonstrated perlecan/Hspg2 signal localized to the osteocyte lacunocanalicular system of cortical bone, and this proteoglycan was found in the pericellular space of the lacunocanalicular system. In this study we examined osteocyte lacunocanalicular morphology in mice deficient in the large heparan sulfate proteoglycan perlecan/Hspg2 in this tissue. Ultrastructural measurements with electron microscopy of perlecan/Hspg2-deficient mice demonstrated diminished osteocyte canalicular pericellular area, resulting from a reduction in the total canalicular area. Additionally, perlecan/Hspg2-deficient mice showed decreased canalicular density and a reduced number of transverse tethering elements per canaliculus. These data indicated that perlecan/Hspg2 contributed to the integrity of the osteocyte lacunocanalicular system by maintaining the size of the pericellular space, an essential task to promote uninhibited interstitial fluid movement in this mechanosensitive environment. This work thus identified a new barrier function for perlecan/Hspg2 in murine cortical bone.

  1. 78 FR 77255 - Privacy Act of 1974; Notice of Republication and Alteration of Systems of Records Notices (SORNs) (United States)


    ...: Individuals covered by this system include people who apply to use archival materials for research in NARA...: Register people who apply to use archival materials for research at a NARA facility; register people for wireless internet access; record initial research interests of researchers; determine which archival...

  2. 32 CFR Appendix E to Part 310 - Sample of New or Altered System of Records Notice in Federal Register Format (United States)


    ... official duties. Paper records are maintained in buildings with controlled or monitored access. During non-duty hours, records are secured in locked or guarded buildings, locked offices, or guarded cabinets. The electronic records systems employ user identification and password or smart card...

  3. 76 FR 24557 - Privacy Act of 1974; as Amended; Proposed Alteration to an Existing Privacy Act System of Records... (United States)


    ... Scheduling Information of Vocational Experts, Medical Experts, and Other Health Care Professional and/or Non...: This system covers vocational experts, medical experts, other health care professional and/or non... information and contact information for all vocational experts, medical experts, other health...

  4. Alterations in Gene Expression of Components of the Renin-Angiotensin System and Its Related Enzymes in Lung Cancer

    Directory of Open Access Journals (Sweden)

    Benjamin Goldstein


    Full Text Available Objectives. The study assessed the existence and significance of associations between the expression of fifteen renin-angiotensin system component genes and lung adenocarcinoma. Materials and Methods. NCBI’s built-in statistical tool, GEO2R, was used to calculate Student’s t-tests for the associations found in a DNA expression study of adenocarcinoma and matched healthy lung tissue samples. The raw data was processed with GeneSpring™ and then used to generate figures with and without Sidak’s multiple comparison correction. Results. Ten genes were found to be significantly associated with adenocarcinoma. Seven of these associations remained statistically significant after correction for multiple comparisons. Notably, AGTR2, which encodes the AT2 angiotensin II receptor subtype, was significantly underexpressed in adenocarcinoma tissue (p<0.01. AGTR1, ACE, ENPEP, MME, and PRCP, which encode the AT1 angiotensin II receptor, angiotensin-converting enzyme, aminopeptidase N, neprilysin, and prolylcarboxypeptidase, respectively, were also underexpressed. AGT, which encodes angiotensinogen, the angiotensin peptide precursor, was overexpressed in adenocarcinoma tissue. Conclusion. The results suggest an association between the expression of the genes for renin-angiotensin system-related proteins and adenocarcinoma. While further research is necessary to conclusively demonstrate a link between the renin-angiotensin system and lung cancers, the results suggest that the renin-angiotensin system plays a role in the pathology of adenocarcinoma.

  5. Object visibility alters the relative contribution of ventral visual stream and mirror neuron system to goal anticipation during action observation

    NARCIS (Netherlands)

    Thioux, Marc; Keysers, Christian


    We used fMRI to study the effect of hiding the target of a grasping action on the cerebral activity of an observer whose task was to anticipate the size of the object being grasped. Activity in the putative mirror neuron system (pMNS) was higher when the target was concealed from the view of the

  6. Altered glycosylation of complexed native IgG molecules is associated with disease activity of systemic lupus erythematosus. (United States)

    Sjöwall, C; Zapf, J; von Löhneysen, S; Magorivska, I; Biermann, M; Janko, C; Winkler, S; Bilyy, R; Schett, G; Herrmann, M; Muñoz, L E


    In addition to the redundancy of the receptors for the Fc portion of immunoglobulins, glycans result in potential ligands for a plethora of lectin receptors found in immune effector cells. Here we analysed the exposure of glycans containing fucosyl residues and the fucosylated tri-mannose N-type core by complexed native IgG in longitudinal serum samples of well-characterized patients with systemic lupus erythematosus. Consecutive serum samples of a cohort of 15 patients with systemic lupus erythematosus during periods of increased disease activity and remission were analysed. All patients fulfilled the 1982 American College of Rheumatology classification criteria. Sera of 15 sex- and age-matched normal healthy blood donors served as controls. The levels and type of glycosylation of complexed random IgG was measured with lectin enzyme-immunosorbent assays. After specifically gathering IgG complexes from sera, biotinylated lectins Aleuria aurantia lectin and Lens culinaris agglutinin were employed to detect IgG-associated fucosyl residues and the fucosylated tri-mannose N-glycan core, respectively. In sandwich-ELISAs, IgG-associated IgM, IgA, C1q, C3c and C-reactive protein (CRP) were detected as candidates for IgG immune complex constituents. We studied associations of the glycan of complexed IgG and disease activity according to the physician's global assessment of disease activity and the systemic lupus erythematosus disease activity index 2000 documented at the moment of blood taking. Our results showed significantly higher levels of Aleuria aurantia lectin and Lens culinaris agglutinin binding sites exposed on IgG complexes of patients with systemic lupus erythematosus than on those of normal healthy blood donors. Disease activity in systemic lupus erythematosus correlated with higher exposure of Aleuria aurantia lectin-reactive fucosyl residues by immobilized IgG complexes. Top levels of Aleuria aurantia lectin-reactivity were found in samples taken during the

  7. Alterations in the neuropeptide galanin system in major depressive disorder involve levels of transcripts, methylation, and peptide


    Barde, Swapnali; Rüegg, Joelle; Prud'homme, Josée; EKSTRÖM, TOMAS J.; Palkovits, Miklos; Turecki, Gustavo; Bagdy, Gyorgy; Ihnatko, Robert; Theodorsson, Elvar; Juhasz, Gabriella; Diaz-Heijtz, Rochellys; Mechawar, Naguib; Hökfelt, Tomas G. M.


    Major depressive disorder (MDD) is a substantial burden to patients, families, and society, but many patients cannot be treated adequately. Rodent experiments suggest that the neuropeptide galanin (GAL) and its three G protein-coupled receptors, GAL(1-3), are involved in mood regulation. To explore the translational potential of these results, we assessed the transcript levels (by quantitative PCR), DNA methylation status (by bisulfite pyrosequencing), and GAL peptide by RIA of the GAL system...

  8. Clinical and biochemical profiles suggest fibromuscular dysplasia is a systemic disease with altered TGF-β expression and connective tissue features. (United States)

    Ganesh, Santhi K; Morissette, Rachel; Xu, Zhi; Schoenhoff, Florian; Griswold, Benjamin F; Yang, Jiandong; Tong, Lan; Yang, Min-Lee; Hunker, Kristina; Sloper, Leslie; Kuo, Shinie; Raza, Rafi; Milewicz, Dianna M; Francomano, Clair A; Dietz, Harry C; Van Eyk, Jennifer; McDonnell, Nazli B


    Fibromuscular dysplasia (FMD) is a rare, nonatherosclerotic arterial disease for which the molecular basis is unknown. We comprehensively studied 47 subjects with FMD, including physical examination, spine magnetic resonance imaging, bone densitometry, and brain magnetic resonance angiography. Inflammatory biomarkers in plasma and transforming growth factor β (TGF-β) cytokines in patient-derived dermal fibroblasts were measured by ELISA. Arterial pathology other than medial fibrodysplasia with multifocal stenosis included cerebral aneurysm, found in 12.8% of subjects. Extra-arterial pathology included low bone density (P<0.001); early onset degenerative spine disease (95.7%); increased incidence of Chiari I malformation (6.4%) and dural ectasia (42.6%); and physical examination findings of a mild connective tissue dysplasia (95.7%). Screening for mutations causing known genetically mediated arteriopathies was unrevealing. We found elevated plasma TGF-β1 (P=0.009), TGF-β2 (P=0.004) and additional inflammatory markers, and increased TGF-β1 (P=0.0009) and TGF-β2 (P=0.0001) secretion in dermal fibroblast cell lines from subjects with FMD compared to age- and gender-matched controls. Detailed phenotyping of patients with FMD allowed us to demonstrate that FMD is a systemic disease with alterations in common with the spectrum of genetic syndromes that involve altered TGF-β signaling and offers TGF-β as a marker of FMD.

  9. Sinorhizobium meliloti mutants lacking phosphotransferase system enzyme HPr or EIIA are altered in diverse processes, including carbon metabolism, cobalt requirements, and succinoglycan production. (United States)

    Pinedo, Catalina Arango; Bringhurst, Ryan M; Gage, Daniel J


    Sinorhizobium meliloti is a member of the Alphaproteobacteria that fixes nitrogen when it is in a symbiotic relationship. Genes for an incomplete phosphotransferase system (PTS) have been found in the genome of S. meliloti. The genes present code for Hpr and ManX (an EIIA(Man)-type enzyme). HPr and EIIA regulate carbon utilization in other bacteria. hpr and manX in-frame deletion mutants exhibited altered carbon metabolism and other phenotypes. Loss of HPr resulted in partial relief of succinate-mediated catabolite repression, extreme sensitivity to cobalt limitation, rapid die-off during stationary phase, and altered succinoglycan production. Loss of ManX decreased expression of melA-agp and lac, the operons needed for utilization of alpha- and beta-galactosides, slowed growth on diverse carbon sources, and enhanced accumulation of high-molecular-weight succinoglycan. A strain with both hpr and manX deletions exhibited phenotypes similar to those of the strain with a single hpr deletion. Despite these strong phenotypes, deletion mutants exhibited wild-type nodulation and nitrogen fixation when they were inoculated onto Medicago sativa. The results show that HPr and ManX (EIIA(Man)) are involved in more than carbon regulation in S. meliloti and suggest that the phenotypes observed occur due to activity of HPr or one of its phosphorylated forms.

  10. Altered Resting-State Functional Connectivity of the Frontal-Striatal Reward System in Social Anxiety Disorder (United States)

    Manning, Joshua; Reynolds, Gretchen; Saygin, Zeynep M.; Hofmann, Stefan G.; Pollack, Mark; Gabrieli, John D. E.; Whitfield-Gabrieli, Susan


    We investigated differences in the intrinsic functional brain organization (functional connectivity) of the human reward system between healthy control participants and patients with social anxiety disorder. Functional connectivity was measured in the resting-state via functional magnetic resonance imaging (fMRI). 53 patients with social anxiety disorder and 33 healthy control participants underwent a 6-minute resting-state fMRI scan. Functional connectivity of the reward system was analyzed by calculating whole-brain temporal correlations with a bilateral nucleus accumbens seed and a ventromedial prefrontal cortex seed. Patients with social anxiety disorder, relative to the control group, had (1) decreased functional connectivity between the nucleus accumbens seed and other regions associated with reward, including ventromedial prefrontal cortex; (2) decreased functional connectivity between the ventromedial prefrontal cortex seed and lateral prefrontal regions, including the anterior and dorsolateral prefrontal cortices; and (3) increased functional connectivity between both the nucleus accumbens seed and the ventromedial prefrontal cortex seed with more posterior brain regions, including anterior cingulate cortex. Social anxiety disorder appears to be associated with widespread differences in the functional connectivity of the reward system, including markedly decreased functional connectivity between reward regions and between reward regions and lateral prefrontal cortices, and markedly increased functional connectivity between reward regions and posterior brain regions. PMID:25928647

  11. Altered resting-state functional connectivity of the frontal-striatal reward system in social anxiety disorder.

    Directory of Open Access Journals (Sweden)

    Joshua Manning

    Full Text Available We investigated differences in the intrinsic functional brain organization (functional connectivity of the human reward system between healthy control participants and patients with social anxiety disorder. Functional connectivity was measured in the resting-state via functional magnetic resonance imaging (fMRI. 53 patients with social anxiety disorder and 33 healthy control participants underwent a 6-minute resting-state fMRI scan. Functional connectivity of the reward system was analyzed by calculating whole-brain temporal correlations with a bilateral nucleus accumbens seed and a ventromedial prefrontal cortex seed. Patients with social anxiety disorder, relative to the control group, had (1 decreased functional connectivity between the nucleus accumbens seed and other regions associated with reward, including ventromedial prefrontal cortex; (2 decreased functional connectivity between the ventromedial prefrontal cortex seed and lateral prefrontal regions, including the anterior and dorsolateral prefrontal cortices; and (3 increased functional connectivity between both the nucleus accumbens seed and the ventromedial prefrontal cortex seed with more posterior brain regions, including anterior cingulate cortex. Social anxiety disorder appears to be associated with widespread differences in the functional connectivity of the reward system, including markedly decreased functional connectivity between reward regions and between reward regions and lateral prefrontal cortices, and markedly increased functional connectivity between reward regions and posterior brain regions.

  12. Systemic short-chain fatty acids rapidly alter gastrointestinal structure, function, and expression of early response genes. (United States)

    Tappenden, K A; McBurney, M I


    Luminal and systemic short chain fatty acids (SCFA) stimulate mucosal proliferation but the mechanism(s) is unclear. This study examined acute effects of systemic SCFAs on gastrointestinal structure and function and signals potentially mediating SCFA-induced mucosal proliferation. Male Sprague-Dawley rats (246+/-2 g) received nutrients as either standard total parenteral nutrition (TPN) or an isoenergetic, isonitrogenous formulation containing SCFAs (TPN + SCFA). Animals were randomized to one of five treatments: standard TPN for 72 hr, TPN + SCFA for 72 hr, or standard TPN followed by TPN + SCFA for the final 6, 12, and 24 hr. SCFAs reduced (P SCFA groups and ileal GLUT2 protein in the 6-, 12-, and 24-hr SCFA groups (P < 0.05). SCFAs increased (P < 0.003) ileal proglucagon abundance following 6, 12, and 24 hr, and plasma GLP-2 concentration following 12 hr (P < 0.03). Jejunal c-myc expression was increased (P < 0.001) following 6, 12, and 24 hr of SCFAs. SCFAs increased ileal c-myc, c-jun, and c-fos expression following 24 hr (P < 0.02), 12 hr (P < 0.05) and 6, 12, and 24 hr (P=0.0001), respectively. In conclusion, systemic SCFAs increase plasma GLP-2 and ileal proglucagon mRNA, GLUT2 expression and protein, and c-myc, c-jun, and c-fos expression.

  13. Sm-Nd age of the fazenda brasileiro gabbro, Bahia, Brazil: example of robust behavior of the Sm-Nd isotopic system under extreme hydrothermal alteration

    Directory of Open Access Journals (Sweden)

    Márcio M. Pimentel


    Full Text Available The Fazenda Brasileiro gold mineralization is hosted by a gabbroic sill, intrusive into metavolcanicmetasedimentary rocks of the Rio Itapicuru Greenstone Belt, São Francisco Craton. The 2.05 Ga old mineralization is associated with intense shearing and hydrothermal alteration, and the host gabbro is altered to a series of rocks rich in sericite, chlorite, actinolite, carbonate and quartz. Twelve whole-rock samples of the gold mineralization, representing varied degrees of alteration, from rocks with preserved igneous textures to the ore (quartz-carbonate-sulfide-chlorite, were studied by the Sm-Nd method. All analytical points resulted in an isochron (MSWD = 1.9 indicating the age of 2142 +/- 47 Ma (1s and Epsilon Nd (T of +1.2. Chlorite-sericite-carbonate rich hydrothermal rocks indicate the age of 2148 +/- 57 Ma and Epsilon Nd (T of +1.1. The positive Epsilon Nd (T suggest limited or no contamination with older continental crust, compatible with an oceanic setting for the tholeiites. Combined withREEdata, the Sm-Nd isotopic results reveal that the hydrothermal alteration, although intense, was unable to alter significantly the Sm/Nd ratios of the original igneous rocks and did not cause important scatter of the analytical points, providing a rare example of robust behavior of the isotopic system, even under intense hydrothermal alteration.A mineralização de ouro de Fazenda Brasileiro é hospedada por um sill gabróico intrusivo em rochas metavulcânicas/metassedimentares do Greenstone Belt do Rio Itapicuru, Craton do São Francisco. A mineralização, com idade de ca. 2.05 Ga, está associada com forte cizalhamento e alteração hidrotermal, e o gabro hospedeiro está alterado para rochas ricas em clorita, actinolita, carbonato e quartzo. Doze amostras de rocha total representando graus variados de alteração hidrotermal, desde rochas com texturas ígneas reliquiares até o minério (quartzo-carbonato-sulfeto-clorita, foram estudadas pelo

  14. Laramide alteration of proterozoic diabase: A likely contributor of copper to porphyry systems in the dripping spring mountains area, Southeastern Arizona (United States)

    Force, E.R.


    Proterozoic diabase of the Dripping Spring range occurs as sills in the Proterozoic Apache Group and the Troy Quartzite and as intrusive sheets in basement rocks. The aggregate thickness of the diabase sills and intrusive sheets averages about 450 m in the part of the range showing little mid-Tertiary extension. Laramide alteration is of two types, dominated by chlorite and actinolite, respectively, and formed mostly from clinopyroxene. Actinolite-dominated assemblages are higher in Na and Ca. Hydrothermal biotite is common in the central areas of both alteration types. Laramide alteration forms two distribution patterns: a subequant pattern centered on Laramide intrusions and small porphyry deposits, characterized by actinolitic alteration, and a more extensive branching linear pattern that follows Laramide structures, centered on the larger Ray porphyry deposit, extending toward other Laramide districts and showing both alteration types. Alteration has apparently mobilized copper and other metals from diabase. The freshest diabase samples average about 120 ppm copper with little variation. In chloritic alteration, about 100 ppm of this copper is expelled in the most completely altered rocks. In actinolitic alteration, diabase may either gain or lose copper during alteration. Chloritic alteration constitutes roughly 70 percent of the diabase alteration in the study area, where alteration averages 41 percent complete. This implies liberation of about 9 ?? 106 tons (t) copper from diabase alteration, significantly less than the 16 ?? 106 t copper in Laramide mineral deposits of the superdistrict (Ray, Superior, Chilito, Christmas). However, diabase alteration may have been a significant component of the supply of copper to the Laramide mineral districts of the area. Synmineral magmatic sources of copper are not documented in this area. The distribution of Proterozoic diabase coincides with the central part of the southeastern Arizona copper province, which may thus

  15. Alterations in Gene Expression of Components of the Renin-Angiotensin System and Its Related Enzymes in Lung Cancer


    Benjamin Goldstein; Malav Trivedi; Speth, Robert C.


    Objectives. The study assessed the existence and significance of associations between the expression of fifteen renin-angiotensin system component genes and lung adenocarcinoma. Materials and Methods. NCBI’s built-in statistical tool, GEO2R, was used to calculate Student’s t-tests for the associations found in a DNA expression study of adenocarcinoma and matched healthy lung tissue samples. The raw data was processed with GeneSpring™ and then used to generate figures with and without Sidak’s ...

  16. Alterations in the histaminergic system in the substantia nigra and striatum of Parkinson's patients: a postmortem study. (United States)

    Shan, Ling; Bossers, Koen; Luchetti, Sabina; Balesar, Rawien; Lethbridge, Natasha; Chazot, Paul L; Bao, Ai-Min; Swaab, Dick F


    Earlier studies showed neuronal histamine production in the hypothalamic tuberomamillary nucleus to be unchanged in Parkinson's disease (PD), whereas the histamine levels and innervation in the substantia nigra (SN) increased. In the present study we used quantitative polymerase chain reaction (qPCR) to assess the changes in the histaminergic system in the SN, caudate nucleus (CN), and putamen (PU) in 7 PD patients and 7 controls. The messenger RNA (mRNA) expression of the histamine receptor-3 (H(3)R), which was localized immunocytochemically in the large pigmented neurons, was significantly decreased in the SN in PD, while histamine receptor-4 (H(4)R)-mRNA expression showed a significant increase in caudate nucleus and PU. In addition, significantly increased mRNA levels of histamine methyltransferase (HMT), a key enzyme involved in histamine metabolism, were found in the SN and in the PU in PD. Moreover, in the SN, the histamine methyltransferase-mRNA showed a strong negative correlation with PD disease duration. Our observations imply the presence of local changes in the histaminergic system that may contribute to PD pathology, and may thus provide a rationale for possible novel therapeutic strategies.

  17. Transient systemic inflammation does not alter the induction of tolerance to gastric autoantigens by migratory dendritic cells. (United States)

    Bourges, Dorothée; Ross, Ellen M; Allen, Stacey; Read, Simon; Houghton, Fiona J; Bedoui, Sammy; Boon, Louis; Gleeson, Paul A; van Driel, Ian R


    It has been proposed that activation of dendritic cells (DCs) presenting self-antigens during inflammation may lead to activation of autoreactive T cells and the development of autoimmunity. To test this hypothesis, we examined the presentation of the autoantigen recognized in autoimmune gastritis, gastric H(+)/K(+) ATPase, which is naturally expressed in the stomach and is constitutively presented in the stomach-draining lymph nodes. Systemic administration to mice of the TLR9 agonist CpG DNA, agonist anti-CD40 Ab, or TLR4 agonist LPS all failed to abrogate the process of peripheral clonal deletion of H(+)/K(+) ATPase-specific CD4 T cells or promote the development of autoimmune gastritis. We demonstrated that migratory DCs from the stomach-draining lymph nodes are the only DC subset capable of constitutively presenting the endogenous gastric H(+)/K(+) ATPase autoantigen in its normal physiological context. Analysis of costimulatory molecules indicated that, relative to resident DCs, migratory DCs displayed a partially activated phenotype in the steady state. Furthermore, migratory DCs were refractory to stimulation by transient exposure to TLR agonists, as they failed to upregulate costimulatory molecules, secrete significant amounts of inflammatory cytokines, or induce differentiation of effector T cells. Together, these data show that transient systemic inflammation failed to break tolerance to the gastric autoantigen, as migratory DCs presenting the gastric autoantigen remain tolerogenic under such conditions, demonstrating the robust nature of peripheral tolerance.

  18. Altered expression of talin 1 in peripheral immune cells points to a significant role of the innate immune system in spontaneous autoimmune uveitis. (United States)

    Degroote, Roxane L; Hauck, Stefanie M; Kremmer, Elisabeth; Amann, Barbara; Ueffing, Marius; Deeg, Cornelia A


    The molecular mechanism which enables activated immune cells to cross the blood-retinal barrier in spontaneous autoimmune uveitis is yet to be unraveled. Equine recurrent uveitis is the only spontaneous animal model allowing us to investigate the autoimmune mediated transformation of leukocytes in the course of this sight threatening disease. Hypothesizing that peripheral blood immune cells change their protein expression pattern in spontaneous autoimmune uveitis, we used DIGE to detect proteins with altered abundance comparing peripheral immune cells of healthy and ERU diseased horses. Among others, we found a significant downregulation of talin 1 in peripheral blood granulocytes of ERU specimen, pointing to changes in β integrin activation and indicating a significant role of the innate immune system in spontaneous autoimmune diseases.

  19. Docosahexaenoyl ethanolamide improves glucose uptake and alters endocannabinoid system gene expression in proliferating and differentiating C2C12 myoblasts

    Directory of Open Access Journals (Sweden)

    Jeffrey eKim


    Full Text Available Skeletal muscle is a major storage site for glycogen and a focus for understanding insulin resistance and type-2-diabetes. New evidence indicates that overactivation of the peripheral endocannabinoid system (ECS in skeletal muscle diminishes insulin sensitivity. Specific n-6 and n-3 polyunsaturated fatty acids (PUFA are precursors for the biosynthesis of ligands that bind to and activate the cannabinoid receptors. The function of the ECS and action of PUFA in skeletal muscle glucose uptake was investigated in proliferating and differentiated C2C12 myoblasts treated with either 25µM of arachidonate (AA or docosahexaenoate (DHA, 25µM of EC [anandamide (AEA, 2-arachidonoylglycerol (2-AG, docosahexaenoylethanolamide (DHEA], 1µM of CB1 antagonist NESS0327, and CB2 antagonist AM630. Compared to the BSA vehicle control cell cultures in both proliferating and differentiated myoblasts those treated with DHEA, the EC derived from the n-3 PUFA DHA, had higher 24 h glucose uptake, while AEA and 2-AG, the EC derived from the n-6 PUFA AA, had lower basal glucose uptake. Adenylyl cyclase mRNA was higher in myoblasts treated with DHA in both proliferating and differentiated states while those treated with AEA or 2-AG were lower compared to the control cell cultures. Western blot and qPCR analysis showed higher expression of the cannabinoid receptors in differentiated myoblasts treated with DHA while the opposite was observed with AA. These findings indicate a compensatory effect of DHA and DHEA compared to AA-derived ligands on the ECS and associated ECS gene expression and higher glucose uptake in myoblasts.Key Words: endocannabinoid system •C2C12 myoblasts cannabinoid receptors glucose uptake gene expression DHEA • polyunsaturated fatty acids

  20. System-based proteomic and metabonomic analysis of the Df(16)A+/− mouse identifies potential miR-185 targets and molecular pathway alterations (United States)

    Wesseling, H; Xu, B; Want, E J; Holmes, E; Guest, P C; Karayiorgou, M; Gogos, J A; Bahn, S


    Deletions on chromosome 22q11.2 are a strong genetic risk factor for development of schizophrenia and cognitive dysfunction. We employed shotgun liquid chromatography–mass spectrometry (LC-MS) proteomic and metabonomic profiling approaches on prefrontal cortex (PFC) and hippocampal (HPC) tissue from Df(16)A+/− mice, a model of the 22q11.2 deletion syndrome. Proteomic results were compared with previous transcriptomic profiling studies of the same brain regions. The aim was to investigate how the combined effect of the 22q11.2 deletion and the corresponding miRNA dysregulation affects the cell biology at the systems level. The proteomic brain profiling analysis revealed PFC and HPC changes in various molecular pathways associated with chromatin remodelling and RNA transcription, indicative of an epigenetic component of the 22q11.2DS. Further, alterations in glycolysis/gluconeogenesis, mitochondrial function and lipid biosynthesis were identified. Metabonomic profiling substantiated the proteomic findings by identifying changes in 22q11.2 deletion syndrome (22q11.2DS)-related pathways, such as changes in ceramide phosphoethanolamines, sphingomyelin, carnitines, tyrosine derivates and panthothenic acid. The proteomic findings were confirmed using selected reaction monitoring mass spectrometry, validating decreased levels of several proteins encoded on 22q11.2, increased levels of the computationally predicted putative miR-185 targets UDP-N-acetylglucosamine-peptide N-acetylglucosaminyltransferase 110 kDa subunit (OGT1) and kinesin heavy chain isoform 5A and alterations in the non-miR-185 targets serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform, neurofilament light chain and vesicular glutamate transporter 1. Furthermore, alterations in the proteins associated with mammalian target of rapamycin signalling were detected in the PFC and with glutamatergic signalling in the hippocampus. Based on the proteomic and metabonomic findings, we were

  1. Genetic alterations in systemic nodal and extranodal non-cutaneous lymphomas derived from mature T cells and natural killer cells. (United States)

    Boi, Michela; Stathis, Anastasios; Zucca, Emanuele; Inghirami, Giorgio; Bertoni, Francesco


    Mature (peripheral) T-cell and natural killer (NK)-cell lymphomas comprise a series of rather different neoplasms. Based on morphologic, immunophenotypic, genetic, and clinical data, the World Health Organization classification recognizes more than 20 entities or provisional entities. The variable clinical presentations, the objective recognition and pathological stratification, the difficulties regarding treatment, and the hardly predictable response to therapy indicate that the management of these entities requires novel tools. In contrast to B-cell lymphomas or precursor T-cell neoplasms, few recurrent translocations have been identified so far in T-cell non-Hodgkin's and NK-cell lymphomas. Additionally, some of the entities recognized by the World Health Organization classification are very rare and very scarce molecular data are available for T-cell lymphomas. Here, we have reviewed published reports focusing on the genetic lesions and gene expression profiling underlying systemic nodal and extranodal non-cutaneous mature T-cell and NK-cell lymphomas. We also provide a summary of new agents in clinical development and outline some future directions.

  2. Primary central nervous system degeneration in elderly patients. Characteristic imaging features; Primaere Degeneration des ZNS im Alter. Bildgebung charakteristischer Atrophiemuster

    Energy Technology Data Exchange (ETDEWEB)

    Weidauer, S.; Lanfermann, H. [Klinikum der Johann-Wolfgang-Goethe-Universitaet, Institut fuer Neuroradiologie, Frankfurt (Germany); Nichtweiss, M. [HANSE-Klinikum Wismar GmbH, Neurologische Klinik, Wismar (Germany)


    Despite further development of new magnetic resonance imaging techniques, e.g., diffusion tensor imaging and 1H magnetic resonance spectroscopy, structural imaging will continue to play a major role in the diagnosis of primary central nervous system degeneration in ageing. Characteristic imaging patterns of multisystem atrophies and primary dementias as well as differential diagnostic features are demonstrated. While such features may have high specificity, their sensitivity is low especially in cross-sectional studies. Longitudinal studies are the optimal method to characterize the dynamic neuroanatomical correlates of the disease. However, according to disease duration and progression, neuroimaging will show increased overlapping and convergence of pathological changes in multisystem atrophy as well as in dementia. (orig.) [German] Trotz der Weiterentwicklung innovativer magnetresonanztomographischer Methoden wie der Diffusionstensormessung und der 1H-Magnetresonanzspektroskopie hat die strukturelle Bildgebung nach wie vor einen zentralen Stellenwert in der Diagnostik altersassoziierter pathologischer Degenerationen des Zentralnervensystems. Es werden typische bildmorphologische Muster bei Multisystematrophien und primaer demenziellen Erkrankungen aufgezeigt und differenzialdiagnostische Merkmale dargestellt. Diese haben insbesondere bei Querschnittuntersuchungen eine hohe Spezifitaet, jedoch geringe Sensitivitaet. Verlaufs- oder Laengsschnittuntersuchungen koennen zwar einerseits die Dynamik und mitunter charakteristische Befunde besser darstellen, andererseits zeigt sich sowohl bei den Multisystematrophien mit initial betont motorischer Symptomatik als auch bei Demenzen mit zunehmender Krankheitsdauer eine Konvergenz und Ueberlappung der Atrophiemuster. (orig.)

  3. Alterations of systemic and muscle iron metabolism in human subjects treated with low-dose recombinant erythropoietin. (United States)

    Robach, Paul; Recalcati, Stefania; Girelli, Domenico; Gelfi, Cecilia; Aachmann-Andersen, Niels J; Thomsen, Jonas J; Norgaard, Anne M; Alberghini, Alessandra; Campostrini, Natascia; Castagna, Annalisa; Viganò, Agnese; Santambrogio, Paolo; Kempf, Tibor; Wollert, Kai C; Moutereau, Stéphane; Lundby, Carsten; Cairo, Gaetano


    The high iron demand associated with enhanced erythropoiesis during high-altitude hypoxia leads to skeletal muscle iron mobilization and decrease in myoglobin protein levels. To investigate the effect of enhanced erythropoiesis on systemic and muscle iron metabolism under nonhypoxic conditions, 8 healthy volunteers were treated with recombinant erythropoietin (rhEpo) for 1 month. As expected, the treatment efficiently increased erythropoiesis and stimulated bone marrow iron use. It was also associated with a prompt and considerable decrease in urinary hepcidin and a slight transient increase in GDF-15. The increased iron use and reduced hepcidin levels suggested increased iron mobilization, but the treatment was associated with increased muscle iron and L ferritin levels. The muscle expression of transferrin receptor and ferroportin was up-regulated by rhEpo administration, whereas no appreciable change in myoglobin levels was observed, which suggests unaltered muscle oxygen homeostasis. In conclusion, under rhEpo stimulation, the changes in the expression of muscle iron proteins indicate the occurrence of skeletal muscle iron accumulation despite the remarkable hepcidin suppression that may be mediated by several factors, such as rhEpo or decreased transferrin saturation or both.

  4. LRRK2 knockout mice have an intact dopaminergic system but display alterations in exploratory and motor co-ordination behaviors

    Directory of Open Access Journals (Sweden)

    Hinkle Kelly M


    Full Text Available Abstract Mutations in the LRRK2 gene are the most common cause of genetic Parkinson’s disease. Although the mechanisms behind the pathogenic effects of LRRK2 mutations are still not clear, data emerging from in vitro and in vivo models suggests roles in regulating neuronal polarity, neurotransmission, membrane and cytoskeletal dynamics and protein degradation. We created mice lacking exon 41 that encodes the activation hinge of the kinase domain of LRRK2. We have performed a comprehensive analysis of these mice up to 20 months of age, including evaluation of dopamine storage, release, uptake and synthesis, behavioral testing, dendritic spine and proliferation/neurogenesis analysis. Our results show that the dopaminergic system was not functionally comprised in LRRK2 knockout mice. However, LRRK2 knockout mice displayed abnormal exploratory activity in the open-field test. Moreover, LRRK2 knockout mice stayed longer than their wild type littermates on the accelerated rod during rotarod testing. Finally, we confirm that loss of LRRK2 caused degeneration in the kidney, accompanied by a progressive enhancement of autophagic activity and accumulation of autofluorescent material, but without evidence of biphasic changes.

  5. Object visibility alters the relative contribution of ventral visual stream and mirror neuron system to goal anticipation during action observation. (United States)

    Thioux, Marc; Keysers, Christian


    We used fMRI to study the effect of hiding the target of a grasping action on the cerebral activity of an observer whose task was to anticipate the size of the object being grasped. Activity in the putative mirror neuron system (pMNS) was higher when the target was concealed from the view of the observer and anticipating the size of the object being grasped requested paying attention to the hand kinematics. In contrast, activity in ventral visual areas outside the pMNS increased when the target was fully visible, and the performance improved in this condition. A repetition suppression analysis demonstrated that in full view, the size of the object being grasped by the actor was encoded in the ventral visual stream. Dynamic causal modeling showed that monitoring a grasping action increased the coupling between the parietal and ventral premotor nodes of the pMNS. The modulation of the functional connectivity between these nodes was correlated with the subject's capability to detect the size of hidden objects. In full view, synaptic activity increased within the ventral visual stream, and the connectivity with the pMNS was diminished. The re-enactment of observed actions in the pMNS is crucial when interpreting others' actions requires paying attention to the body kinematics. However, when the context permits, visual-spatial information processing may complement pMNS computations for improved action anticipation accuracy. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Effect of treatment with iloprost with or without bosentan on nailfold videocapillaroscopic alterations in patients with systemic sclerosis. (United States)

    Cestelli, Valentina; Manfredi, Andreina; Sebastiani, Marco; Praino, Emanuela; Cannarile, Francesca; Giuggioli, Dilia; Ferri, Clodoveo


    Vascular involvement plays a decisive role in systemic sclerosis (SSc) pathogenesis; it is responsible for some important clinical manifestations of the disease such as Raynaud's phenomenon and digital ulcers (DU). Bosentan, a dual receptor endothelin antagonist, and iloprost, often in combination therapy, seems to be able to interfere with the scleroderma microangiopathy. Aim of the study was to evaluate the effect of bosentan and iloprost on scleroderma microangiopathy, analyzed by means of capillaroscopic skin ulcer risk index (CSURI), in SSc patients treated for the prevention of DU. Nailfold videocapillaroscopy (NVC) was performed in 95 SSc patients, treated with iloprost alone (group 1) or combination therapy with iloprost and bosentan (group 2), at baseline and after one year. In all patients CSURI was calculated according to the formula "diameter × number of megacapillaries/(total number of capillaries)(2)": in addition, total number of capillaries, giant capillaries, micro-hemorrhages, disorganization of the vascular array, and ramified capillaries were evaluated by means of a semiquantitative score. After 12 months, we observed a reduction of the number of giant capillaries in both groups, while an increase of ramified capillaries was recorded only in group 2. CSURI improved slightly in group 2 without statistical significance; on the contrary, in group 1 a significant worsening was recorded (p ≤ 0.001). Our study confirms the effectiveness of bosentan, in combination with iloprost, in SSc microangiopathy observed to NVC. Moreover, the observed findings further support the role of CSURI in the evaluation and monitoring of SSc microangiopathy.

  7. A possible contribution of altered cathepsin B expression to the development of skin sclerosis and vasculopathy in systemic sclerosis.

    Directory of Open Access Journals (Sweden)

    Shinji Noda

    Full Text Available Cathepsin B (CTSB is a proteolytic enzyme potentially modulating angiogenic processes and extracellular matrix remodeling. While matrix metalloproteinases are shown to be implicated in tissue fibrosis and vasculopathy associated with systemic sclerosis (SSc, the role of cathepsins in this disease has not been well studied. The aim of this study is to evaluate the roles of CTSB in SSc. Serum pro-CTSB levels were determined by enzyme-linked immunosorbent assay in 55 SSc patients and 19 normal controls. Since the deficiency of transcription factor Fli1 in endothelial cells is potentially associated with the development of SSc vasculopathy, cutaneous CTSB expression was evaluated by immunostaining in Fli1(+/- and wild type mice as well as in SSc and control subjects. The effects of Fli1 gene silencing and transforming growth factor-β (TGF-β on CTSB expression were determined by real-time PCR in human dermal microvascular endothelial cells (HDMECs and dermal fibroblasts, respectively. Serum pro-CTSB levels were significantly higher in limited cutaneous SSc (lcSSc and late-stage diffuse cutaneous SSc (dcSSc patients than in healthy controls. In dcSSc, patients with increased serum pro-CTSB levels showed a significantly higher frequency of digital ulcers than those with normal levels. CTSB expression in dermal blood vessels was increased in Fli1(+/- mice compared with wild type mice and in SSc patients compared with healthy controls. Consistently, Fli1 gene silencing increased CTSB expression in HDMECs. In cultured dermal fibroblasts from early dcSSc, CTSB expression was decreased compared with normal fibroblasts and significantly reversed by TGF-β1 antisense oligonucleotide. In conclusion, up-regulation of endothelial CTSB due to Fli1 deficiency may contribute to the development of SSc vasculopathy, especially digital ulcers, while reduced expression of CTSB in lesional dermal fibroblasts is likely to be associated with skin sclerosis in early dcSSc.

  8. HIV-1 alters neural and glial progenitor cell dynamics in the central nervous system: coordinated response to opiates during maturation. (United States)

    Hahn, Yun Kyung; Podhaizer, Elizabeth M; Hauser, Kurt F; Knapp, Pamela E


    HIV-associated neurocognitive disorders (HANDs) are common sequelae of human immunodeficiency virus (HIV) infection, even when viral titers are well controlled by antiretroviral therapy. Evidence in patients and animal models suggests that neurologic deficits are increased during chronic opiate exposure. We have hypothesized that central nervous system (CNS) progenitor cells in both adult and developing CNS are affected by HIV infection and that opiates exacerbate these effects. To examine this question, neural progenitors were exposed to HIV-1 Tat(1-86) in the developing brain of inducible transgenic mice and in vitro. We examined whether Tat affected the proliferation or balance of progenitor populations expressing nestin, Sox2, and Olig2. Disease relevance was further tested by exposing human-derived progenitors to supernatant from HIV-1 infected monocytes. Studies concentrated on striatum, a region preferentially targeted by HIV and opiates. Results were similar among experimental paradigms. Tat or HIV exposure reduced the proliferation of undifferentiated (Sox2(+)) progenitors and oligodendroglial (Olig2(+)) progenitors. Coexposure to morphine exacerbated the effects of Tat or HIV-1(SF162) supernatant, but partially reversed HIV-1(IIIB) supernatant effects. Populations of Sox2(+) and Olig2(+) cells were also reduced by Tat exposure, although progenitor survival was unaffected. In rare instances, p24 immunolabeling was detected in viable human progenitors by confocal imaging. The vulnerability of progenitors is likely to distort the dynamic balance among neuron/glial populations as the brain matures, perhaps contributing to reports that neurologic disease is especially prevalent in pediatric HIV patients. Pediatric disease is atypical in developed regions but remains a serious concern in resource-limited areas where infection occurs commonly at birth and through breast feeding.

  9. Altered Cortical Thickness and Tract Integrity of the Mirror Neuron System and Associated Social Communication in Autism Spectrum Disorder. (United States)

    Chien, Hsiang-Yun; Gau, Susan Shur-Fen; Hsu, Yung-Chin; Chen, Yu-Jen; Lo, Yu-Chun; Shih, Yao-Chia; Tseng, Wen-Yih Isaac


    Previous studies using neural activity recording and neuroimaging techniques have reported functional deficits in the mirror neuron system (MNS) for individuals with autism spectrum disorder (ASD). However, a few studies focusing on gray and white matter structures of the MNS have yielded inconsistent results. The current study recruited adolescents and young adults with ASD (aged 15-26 years) and age-matched typically developing (TD) controls (aged 14-25 years). The cortical thickness (CT) and microstructural integrity of the tracts connecting the regions forming the classical MNS were investigated. High-resolution T1-weighted imaging and diffusion spectrum imaging were performed to quantify the CT and tract integrity, respectively. The structural covariance of the CT of the MNS regions revealed a weaker coordination of the MNS network in ASD. A strong correlation was found between the integrity of the right frontoparietal tracts and the social communication subscores measured by the Chinese version of the Social Communication Questionnaire. The results showed that there were no significant mean differences in the CTs and tract integrity between the ASD and TD groups, but revealed a moderate or even reverse age effect on the frontal MNS structures in ASD. In conclusion, aberrant structural coordination may be an underlying factor affecting the function of the MNS in ASD patients. The association between the right frontoparietal tracts and social communication performance implies a neural correlate of communication processing in the autistic brain. This study provides evidence of abnormal MNS structures and their influence on social communication in individuals with ASD.

  10. Comparison of Watermelon and Carbohydrate Beverage on Exercise-Induced Alterations in Systemic Inflammation, Immune Dysfunction, and Plasma Antioxidant Capacity

    Directory of Open Access Journals (Sweden)

    R. Andrew Shanely


    Full Text Available Consuming carbohydrate- and antioxidant-rich fruits during exercise as a means of supporting and enhancing both performance and health is of interest to endurance athletes. Watermelon (WM contains carbohydrate, lycopene, l-citrulline, and l-arginine. WM may support exercise performance, augment antioxidant capacity, and act as a countermeasure to exercise-induced inflammation and innate immune changes. Trained cyclists (n = 20, 48 ± 2 years participated in a randomized, placebo controlled, crossover study. Subjects completed two 75 km cycling time trials after either 2 weeks ingestion of 980 mL/day WM puree or no treatment. Subjects drank either WM puree containing 0.2 gm/kg carbohydrate or a 6% carbohydrate beverage every 15 min during the time trials. Blood samples were taken pre-study and pre-, post-, 1 h post-exercise. WM ingestion versus no treatment for 2-weeks increased plasma l-citrulline and l-arginine concentrations (p < 0.0125. Exercise performance did not differ between WM puree or carbohydrate beverage trials (p > 0.05, however, the rating of perceived exertion was greater during the WM trial (p > 0.05. WM puree versus carbohydrate beverage resulted in a similar pattern of increase in blood glucose, and greater increases in post-exercise plasma antioxidant capacity, l-citrulline, l-arginine, and total nitrate (all p < 0.05, but without differences in systemic markers of inflammation or innate immune function. Daily WM puree consumption fully supported the energy demands of exercise, and increased post-exercise blood levels of WM nutritional components (l-citrulline and l-arginine, antioxidant capacity, and total nitrate, but without an influence on post-exercise inflammation and changes in innate immune function.

  11. Elemental changes and alteration recorded by basaltic drill core samples recovered from in situ temperatures up to 345°C in the active, seawater-recharged Reykjanes geothermal system, Iceland (United States)

    Fowler, Andrew P. G.; Zierenberg, Robert A.


    Hydrothermal activity results in element exchanges between seawater and oceanic crust that contribute to many aspects of ocean chemistry; therefore, improving knowledge of the associated chemical processes is of global significance. Hydrothermally altered basaltic drill core samples from the seawater-recharged Reykjanes geothermal system in Iceland record elemental gains and losses similar to those observed in samples of hydrothermally altered oceanic crust. At Reykjanes, rocks originally emplaced on the seafloor were buried by continued volcanism and subsided to the current depths (>2250 m below surface). These rocks integrate temperature-dependent elemental gains and losses from multiple stages of hydrothermal alteration that correspond to chemical exchanges observed in rocks from different crustal levels of submarine hydrothermal systems. Specifically, these lithologies have gained U, Mg, Zn, and Pb and have lost K, Rb, Ba, Cu, and light rare earth elements (La through Eu). Alteration and elemental gains and losses in lithologies emplaced on the seafloor can only be explained by a complex multistage hydrothermal alteration history. Reykjanes dolerite intrusions record alteration similar to that reported for the sheeted dike section of several examples of oceanic crust. Specifically, Reykjanes dolerites have lost K, Rb, Ba, and Pb, and gained Cu. The Reykjanes drill core samples provide a unique analog for seawater-oceanic crust reactions actively occurring at high temperatures (275-345°C) beneath a seafloor hydrothermal system.

  12. Alteration of nuclear matrix-intermediate filament system and differential expression of nuclear matrix proteins during human hepatocarcinoma cell differentiation

    Institute of Scientific and Technical Information of China (English)

    Jian Tang; Jing-Wen Niu; Dong-Hui Xu; Zhi-Xing Li; Qi-Fu Li; Jin-An Chen


    accompanied by the configurational changes of nuclear matrix-intermediate filament (NM-IF)system and the compositional changes of nuclear matrix protein expression. These changes may be important morphological or functional indications of the cancer cell reversion.

  13. Alterations of hippocampal GAbaergic system contribute to development of spontaneous recurrent seizures in the rat lithium-pilocarpine model of temporal lobe epilepsy. (United States)

    André, V; Marescaux, C; Nehlig, A; Fritschy, J M


    Reorganization of excitatory and inhibitory circuits in the hippocampal formation following seizure-induced neuronal loss has been proposed to underlie the development of chronic seizures in temporal lobe epilepsy (TLE). Here, we investigated whether specific morphological alterations of the GABAergic system can be related to the onset of spontaneous recurrent seizures (SRS) in the rat lithium-pilocarpine model of TLE. Immunohistochemical staining for markers of interneurons and their projections, including parvalbumin (PV), calretinin (CR), calbindin (CB), glutamic acid decarboxylase (GAD), and type 1 GABA transporter (GAT1), was performed in brain sections of rats treated with lithium-pilocarpine and sacrificed after 24 h, during the silent phase (6 and 12 days), or after the onset of SRS (10-18 days after treatment). Semiquantitative analysis revealed a selective loss of interneurons in the stratum oriens of CA1, associated with a reduction of GAT1 staining in the stratum radiatum and stratum oriens. In contrast, interneurons in CA3 were largely preserved, although GAT1 staining was also reduced. These changes occurred within 6 days after treatment and were therefore insufficient to cause SRS. In the dentate gyrus, extensive cell loss occurred in the hilus. The pericellular innervation of granule cells by PV-positive axons was markedly reduced, although the loss of PV-interneurons was only partial. Most strikingly, the density of GABAergic axons, positive for both GAD and GAT1, was dramatically increased in the inner molecular layer. This change emerged during the silent period, but was most marked in animals with SRS. Finally, supernumerary CB-positive neurons were detected in the hilus, selectively in rats with SRS. These findings suggest that alterations of GABAergic circuits occur early after lithium-pilocarpine-induced status epilepticus and contribute to epileptogenesis. In particular, the reorganization of GABAergic axons in the dentate gyrus might

  14. Intestinal Dysbiosis Is Associated with Altered Short-Chain Fatty Acids and Serum-Free Fatty Acids in Systemic Lupus Erythematosus. (United States)

    Rodríguez-Carrio, Javier; López, Patricia; Sánchez, Borja; González, Sonia; Gueimonde, Miguel; Margolles, Abelardo; de Los Reyes-Gavilán, Clara G; Suárez, Ana


    Metabolic impairments are a frequent hallmark of systemic lupus erythematosus (SLE). Increased serum levels of free fatty acids (FFA) are commonly found in these patients, although the underlying causes remain elusive. Recently, it has been suggested that factors other than inflammation or clinical features may be involved. The gut microbiota is known to influence the host metabolism, the production of short-chain fatty acids (SCFA) playing a potential role. Taking into account that lupus patients exhibit an intestinal dysbiosis, we wondered whether altered FFA levels may be associated with the intestinal microbial composition in lupus patients. To this aim, total and specific serum FFA levels, fecal SCFA levels, and gut microbiota composition were determined in 21 SLE patients and 25 healthy individuals. The Firmicutes to Bacteroidetes (F/B) ratio was strongly associated with serum FFA levels in healthy controls (HC), even after controlling for confounders. However, this association was not found in lupus patients, where a decreased F/B ratio and increased FFA serum levels were noted. An altered production of SCFA was related to the intestinal dysbiosis in lupus, while SCFA levels paralleled those of serum FFA in HC. Although a different serum FFA profile was not found in SLE, specific FFA showed distinct patterns on a principal component analysis. Immunomodulatory omega-3 FFA were positively correlated to the F/B ratio in HC, but not in SLE. Furthermore, divergent associations were observed for pro- and anti-inflammatory FFA with endothelial activation biomarkers in lupus patients. Overall, these findings support a link between the gut microbial ecology and the host metabolism in the pathological framework of SLE. A potential link between intestinal dysbiosis and surrogate markers of endothelial activation in lupus patients is supported, FFA species having a pivotal role.

  15. Augmented expression and secretion of adipose-derived pigment epithelium-derived factor does not alter local angiogenesis or contribute to the development of systemic metabolic derangements. (United States)

    Lakeland, Thomas V; Borg, Melissa L; Matzaris, Maria; Abdelkader, Amany; Evans, Roger G; Watt, Matthew J


    Impaired coupling of adipose tissue expansion and vascularization is proposed to lead to adipocyte hypoxia and inflammation, which in turn contributes to systemic metabolic derangements. Pigment epithelium-derived factor (PEDF) is a powerful antiangiogenic factor that is secreted by adipocytes, elevated in obesity, and implicated in the development of insulin resistance. We explored the angiogenic and metabolic role of adipose-derived PEDF through in vivo studies of mice with overexpression of PEDF in adipocytes (PEDF-aP2). PEDF expression in white adipocytes and PEDF secretion from adipose tissue was increased in transgenic mice, but circulating levels of PEDF were not increased. Overexpression of PEDF did not alter vascularization, the partial pressure of O2, cellular hypoxia, or gene expression of inflammatory markers in adipose tissue. Energy expenditure and metabolic substrate utilization, body mass, and adiposity were not altered in PEDF-aP2 mice. Whole body glycemic control was normal as assessed by glucose and insulin tolerance tests, and adipocyte-specific glucose uptake was unaffected by PEDF overexpression. Adipocyte lipolysis was increased in PEDF-aP2 mice and associated with increased adipose triglyceride lipase and decreased perilipin 1 expression. Experiments conducted in mice rendered obese by high-fat feeding showed no differences between PEDF-aP2 and wild-type mice for body mass, adiposity, whole body energy expenditure, glucose tolerance, or adipose tissue oxygenation. Together, these data indicate that adipocyte-generated PEDF enhances lipolysis but question the role of PEDF as a major antiangiogenic or proinflammatory mediator in adipose tissue in vivo. Copyright © 2014 the American Physiological Society.

  16. SEAWAT model used to evaluate the potential effects of alterations to the hydrologic system on the distribution of salinity in the Biscayne aquifer in Broward County, Florida (United States)

    Hughes, Joseph D.; Sifuentes, Dorothy F.; White, Jeremy


    A three-dimensional, variable-density solute-transport model (SEAWAT) was developed to examine causes of saltwater intrusion and predict the effects of future alterations to the hydrologic system on salinity distribution in eastern Broward County, Florida. The model was calibrated to conditions from 1970 to 2012, the period for which data are most complete and reliable, and was used to simulate historical conditions from 1950 to 2012. The model was used to (1) evaluate the sensitivity of the salinity distribution in groundwater to sea-level rise and groundwater pumping , and (2) simulate the potential effects of increases in pumping, variable rates of sea-level rise, movement of a salinity control structure, and use of drainage recharge wells on the future distribution of salinity in the aquifer. This USGS data release contains all of the input and output files for the simulations described in the associated model documentation report ( This data release also includes (1) preprocessing python scripts and associated input data files for creating the sensitivity and scenarios runs, (2) flopy source code, and (3) SEAWAT (v4) source code. This groundwater model was created to examine causes of saltwater intrusion and predict the effects of future alterations to the hydrologic system on salinity distribution in eastern Broward County, Florida. The development of the model input and output files included in this data release are documented in U.S. Geological Survey Scientific Investigations Report 2016-5022 ( The models, along with pre- and post-processing tools, will run successfully only if the original directory structure is correctly restored. The model archive is broken into several pieces to reduce the likelihood of download timeouts. Instructions for reconstructing the original directory structure and running the models included in this data release and described in the model

  17. Physical, chemical and mineralogical evolution of the Tolhuaca geothermal system, southern Andes, Chile: Insights into the interplay between hydrothermal alteration and brittle deformation (United States)

    Sanchez-Alfaro, Pablo; Reich, Martin; Arancibia, Gloria; Pérez-Flores, Pamela; Cembrano, José; Driesner, Thomas; Lizama, Martin; Rowland, Julie; Morata, Diego; Heinrich, Christoph A.; Tardani, Daniele; Campos, Eduardo


    In this study, we unravel the physical, chemical and mineralogical evolution of the active Tolhuaca geothermal system in the Andes of southern Chile. We used temperature measurements in the deep wells and geochemical analyses of borehole fluid samples to constrain present-day fluid conditions. In addition, we reconstructed the paleo-fluid temperatures and chemistry from microthermometry and LA-ICP-MS analysis of fluid inclusions taken from well-constrained parageneses in vein samples retrieved from a ~ 1000 m borehole core. Based on core logging, mineralogical observations and fluid inclusions data we identify four stages (S1-S4) of progressive hydrothermal alteration. An early heating event (S1) was followed by the formation of a clay-rich cap in the upper zone (chemical analyses of fluid inclusions and borehole fluids reveal a significant change in chemical conditions during the evolution of Tolhuaca. Whereas borehole (present-day) fluids are rich in Au, B and As, but Cu-poor (B/Na ~ 100.5, As/Na ~ 10- 1.1, Cu/Na ~ 10- 4.2), the paleofluids trapped in fluid inclusions are Cu-rich but poor in B and As (B/Na ~ 10- 1, As/Na ~ 10- 2.5, Cu/Na ~ 10- 2.5 in average). We interpret the fluctuations in fluid chemistry at Tolhuaca as the result of transient supply of metal-rich, magmatically derived fluids where As, Au and Cu are geochemically decoupled. Since these fluctuating physical and chemical conditions at the reservoir produced a mineralogical vertical segmentation of the system that affects the mechanical and hydrological properties of host rock, we explored the effect of the development of a low-cohesion low-permeability clay cap on the conditions of fault rupture and on the long-term thermal structure of the system. These analyses were performed by using rock failure condition calculations and numerical simulations of heat and fluid flows. Calculations of the critical fluid pressures required to produce brittle rupture indicate that within the clay-rich cap, the

  18. [Altered states of consciousness]. (United States)

    Gora, E P


    The review of modern ideas concerning the altered states of consciousness is presented in this article. Various methods of entry into the altered states of consciousness are looked over. It is shown that the altered states of consciousness are insufficiently known, but important aspects of human being existence. The role of investigation of the altered states of consciousness for the creation of integrative scientific conception base is discussed.

  19. Potential effects of alterations to the hydrologic system on the distribution of salinity in the Biscayne aquifer in Broward County, Florida (United States)

    Hughes, Joseph D.; Sifuentes, Dorothy F.; White, Jeremy T.


    To address concerns about the effects of water-resource management practices and rising sea level on saltwater intrusion, the U.S. Geological Survey in cooperation with the Broward County Environmental Planning and Community Resilience Division, initiated a study to examine causes of saltwater intrusion and predict the effects of future alterations to the hydrologic system on salinity distribution in eastern Broward County, Florida. A three-dimensional, variable-density solute-transport model was calibrated to conditions from 1970 to 2012, the period for which data are most complete and reliable, and was used to simulate historical conditions from 1950 to 2012. These types of models are typically difficult to calibrate by matching to observed groundwater salinities because of spatial variability in aquifer properties that are unknown, and natural and anthropogenic processes that are complex and unknown; therefore, the primary goal was to reproduce major trends and locally generalized distributions of salinity in the Biscayne aquifer. The methods used in this study are relatively new, and results will provide transferable techniques for protecting groundwater resources and maximizing groundwater availability in coastal areas. The model was used to (1) evaluate the sensitivity of the salinity distribution in groundwater to sea-level rise and groundwater pumping, and (2) simulate the potential effects of increases in pumping, variable rates of sea-level rise, movement of a salinity control structure, and use of drainage recharge wells on the future distribution of salinity in the aquifer.

  20. Flow cytometry of cerebrospinal fluid (CSF) lymphocytes: alterations of blood/CSF ratios of lymphocyte subsets in inflammation disorders of human central nervous system (CNS). (United States)

    Kleine, T O; Albrecht, J; Zöfel, P


    Flow cytometry was adapted to measure lymphocytes in human cerebrospinal fluid (CSF). The method was sufficiently precise, reproducible and accurate despite low cell counts. In lumbar CSF of controls with 500 to 3500 (10(3)/l) leukocytes, lymphocyte counts correlated with those in corresponding venous blood: blood/CSF ratios of approximately 2000 : 1 were found for total T cells (CD3+) and CD3+ HLA-DR-, CD3+4+, CD3+8+ subsets, ratios were increased for the lymphocyte subsets CD3+ HLA-DR+ blood-brain and blood-CSF barriers) to blood lymphocyte subsets which favor the transfer of T subsets. Correlation of the subset ratios to the CD3+ ratio indicates distinct barrier properties which changed differently with acute and subacute inflammations and neuroimmunological diseases of central nervous system (CNS) in lumbar or ventricular CSF, but not with simple protein barrier disturbance. HLA DR+ T ratios were higher than HLA DR- T ratios only with controls and some neuroimmunological diseases. Lymphocyte barrier characteristics were related to protein leakage situated at the same barriers, indicating for the lymphocyte subsets selective transfer routes in control subjects and non-selective routes in patients with CNS inflammation where altered ratios revealed a mixture of both routes.

  1. Alterations in the sugar metabolism and in the vacuolar system of mesophyll cells contribute to the desiccation tolerance of Haberlea rhodopensis ecotypes. (United States)

    Georgieva, K; Rapparini, F; Bertazza, G; Mihailova, G; Sárvári, É; Solti, Á; Keresztes, Á


    Haberlea rhodopensis belongs to the small group of resurrection plants having the unique ability to survive desiccation to air dry state retaining most of its chlorophyll content and then resume normal function upon rehydration. It prefers the shady valleys and northward facing slopes of limestone ridges in mountain zones with high average humidity. Nevertheless, it can be found rarely on rocks directly exposed to the sunlight, without the coverage of the canopy. In the present study, we follow the alterations in the subcellular organization of mesophyll cells and sugar metabolism upon desiccation of shade and sun H. rhodopensis plants. Composition and content of soluble carbohydrates during desiccation and rehydration were different in plants grown below the trees or on the sunny rocks. Sucrose, however, was dominating in both ecotypes. The amount of starch grains in chloroplasts was inversely related to that of sugars. Concomitantly with these changes, the number of vacuoles was multiplied in the cells. This can be explained by the development of small (secondary) vacuoles peripherally in the cytoplasm, rather than by the fragmentation of the single vacuole, proposed earlier in the literature. Accordingly, the centripetal movement of chloroplasts and other organelles may be a result of the dynamic changes in the vacuolar system. Upon rehydration, the inner vacuoles enlarged and the organelles returned to their normal position.

  2. MicroRNA expression profiles identify disease-specific alterations in systemic lupus erythematosus and primary Sjögren's syndrome (United States)

    Póliska, Szilárd; Szabó, Krisztina; Tarr, Tünde; Bálint, Bálint László; Szodoray, Péter


    The discovery of microRNAs (miRNAs) and their critical role in genetic control opened new avenues in understanding of various biological processes including immune cell lineage commitment, differentiation, proliferation and apoptosis. However, a given miRNA may have hundreds of different mRNA targets and a target might be regulated by multiple miRNAs, thus the characterisation of dysregulated miRNA expression profiles could give a better insight into the development of immunological disturbances in autoimmune diseases. The aim of our study was to examine the changes in miRNA expression profiles in patients with systemic lupus erythematosus (SLE) and primary Sjögren's syndrome (pSS). Eight SLE patients, 8 pSS patients and 7 healthy subjects were enrolled in the investigation. MiRNAs were isolated from peripheral blood mononuclear cells, and expression patterns were determined with Illumina next-generation sequencing technology. Since the immunopathogenesis of pSS and SLE encompasses pronounced B cell hyperactivity along with specific autoantibody production, we paid a special attention on the association between miRNA expression levels and altered peripheral B cell distribution. In SLE patients 135, while in pSS patients 26 miRNAs showed altered expression. Interestingly, the 25 miRNAs including miR-146a, miR-16 and miR-21, which were over-expressed in pSS patients, were found to be elevated in SLE group, as well. On the contrary, we observed the down-regulation of miR-150-5p, which is a novel and unique finding in pSS. Levels of several miRNAs over-expressed in SLE, were not changed in pSS, such as miR-148a-3p, miR-152, miR-155, miR-223, miR-224, miR-326 and miR-342. Expression levels of miR-223-5p, miR-150-5p, miR-155-5p and miR-342-3p, which miRNAs are potentially linked to B cell functions, showed associations with the B cell proportions within peripheral blood mononuclear cells. The observed differences in miRNA expression profiles and the better understanding

  3. Maternal consumption of organic trace minerals alters calf systemic and neutrophil mRNA and microRNA indicators of inflammation and oxidative stress. (United States)

    Jacometo, Carolina B; Osorio, Johan S; Socha, Michael; Corrêa, Marcio N; Piccioli-Cappelli, Fiorenzo; Trevisi, Erminio; Loor, Juan J


    Organic trace mineral (ORG) supplementation to dairy cows in substitution of sulfate (INO) sources has been associated with improvement in immune function during stressful states such as the peripartal period. However, the effect of supplemental ORG during pregnancy on the neonatal calf is unknown. Therefore, our aim was to investigate the effects of ORG supplementation during late pregnancy on the immune system and growth of the neonatal calf. Of specific interest was the evaluation of inflammation-related microRNA (miRNA) and target gene expression in blood neutrophils as indicators of possible nutritional programming. Forty multiparous cows were supplemented for 30d prepartum with 40 mg/kg of Zn, 20 mg/kg of Mn, 5 mg/kg of Cu, and 1mg/kg of Co from either organic (ORG) or sulfate (INO) sources (total diet contained supplemental 75 mg/kg of Zn, 65 mg/kg of Mn, 11 mg/kg of Cu, and 1 mg/kg of Co, and additional Zn, Mn, and Co provided by sulfates), and a subset of calves (n=8/treatment) was used for blood immunometabolic marker and polymorphonuclear leukocyte (PMNL) gene and miRNA expression analyses. Samples were collected at birth (before colostrum feeding), 1d (24 h after colostrum intake), and 7 and 21d of age. Data were analyzed as a factorial design with the PROC MIXED procedure of SAS. No differences were detected in BW, but maternal ORG tended to increase calf withers height. Calves from INO-fed cows had greater concentrations of blood glucose, GOT, paraoxonase, myeloperoxidase, and reactive oxygen metabolites. Antioxidant capacity also was greater in INO calves. The PMNL expression of toll-like receptor pathway genes indicated a pro-inflammatory state in INO calves, with greater expression of the inflammatory mediators MYD88, IRAK1, TRAF6, NFKB, and NFKBIA. The lower expression of miR-155 and miR-125b in ORG calves indicated the potential for maternal organic trace minerals in regulating the PMNL inflammatory response at least via alterations in mRNA and

  4. Chronic exposure to low levels of inorganic arsenic causes alterations in locomotor activity and in the expression of dopaminergic and antioxidant systems in the albino rat. (United States)

    Rodríguez, Verónica Mireya; Limón-Pacheco, Jorge Humberto; Carrizales, Leticia; Mendoza-Trejo, María Soledad; Giordano, Magda


    Several studies have associated chronic arsenicism with decreases in IQ and sensory and motor alterations in humans. Likewise, studies of rodents exposed to inorganic arsenic ((i)As) have found changes in locomotor activity, brain neurochemistry, behavioral tasks, oxidative stress, and in sensory and motor nerves. In the current study, male Sprague-Dawley rats were exposed to environmentally relevant doses of (i)As (0.05, 0.5 mg (i)As/L) and to a high dose (50 mg (i)As/L) in drinking water for one year. Hypoactivity and increases in the striatal dopamine content were found in the group treated with 50 mg (i)As/L. Exposure to 0.5 and 50 mg (i)As/L increased the total brain content of As. Furthermore, (i)As exposure produced a dose-dependent up-regulation of mRNA for Mn-SOD and Trx-1 and a down-regulation of DAR-D₂ mRNA levels in the nucleus accumbens. DAR-D₁ and Nrf2 mRNA expression were down-regulated in nucleus accumbens in the group exposed to 50 mg (i)As/L. Trx-1 mRNA levels were up-regulated in the cortex in an (i)As dose-dependent manner, while DAR-D₁ mRNA expression was increased in striatum in the 0.5 mg (i)As/L group. These results show that chronic exposure to low levels of arsenic causes subtle but region-specific changes in the nervous system, especially in antioxidant systems and dopaminergic elements. These changes became behaviorally evident only in the group exposed to 50 mg (i)As/L.

  5. Brain region-specific alterations in the gene expression of cytokines, immune cell markers and cholinergic system components during peripheral endotoxin-induced inflammation. (United States)

    Silverman, Harold A; Dancho, Meghan; Regnier-Golanov, Angelique; Nasim, Mansoor; Ochani, Mahendar; Olofsson, Peder S; Ahmed, Mohamed; Miller, Edmund J; Chavan, Sangeeta S; Golanov, Eugene; Metz, Christine N; Tracey, Kevin J; Pavlov, Valentin A


    Inflammatory conditions characterized by excessive peripheral immune responses are associated with diverse alterations in brain function, and brain-derived neural pathways regulate peripheral inflammation. Important aspects of this bidirectional peripheral immune-brain communication, including the impact of peripheral inflammation on brain region-specific cytokine responses, and brain cholinergic signaling (which plays a role in controlling peripheral cytokine levels), remain unclear. To provide insight, we studied gene expression of cytokines, immune cell markers and brain cholinergic system components in the cortex, cerebellum, brainstem, hippocampus, hypothalamus, striatum and thalamus in mice after an intraperitoneal lipopolysaccharide injection. Endotoxemia was accompanied by elevated serum levels of interleukin (IL)-1β, IL-6 and other cytokines and brain region-specific increases in Il1b (the highest increase, relative to basal level, was in cortex; the lowest increase was in cerebellum) and Il6 (highest increase in cerebellum; lowest increase in striatum) mRNA expression. Gene expression of brain Gfap (astrocyte marker) was also differentially increased. However, Iba1 (microglia marker) mRNA expression was decreased in the cortex, hippocampus and other brain regions in parallel with morphological changes, indicating microglia activation. Brain choline acetyltransferase (Chat ) mRNA expression was decreased in the striatum, acetylcholinesterase (Ache) mRNA expression was decreased in the cortex and increased in the hippocampus, and M1 muscarinic acetylcholine receptor (Chrm1) mRNA expression was decreased in the cortex and the brainstem. These results reveal a previously unrecognized regional specificity in brain immunoregulatory and cholinergic system gene expression in the context of peripheral inflammation and are of interest for designing future antiinflammatory approaches.

  6. Forced traffic in automatic milking systems effectively reduces the need to get cows, but alters eating behavior and does not improve milk yield of dairy cattle. (United States)

    Bach, A; Devant, M; Igleasias, C; Ferrer, A


    Eighty-five lactating Holstein dairy cows in loose housing conditions in 2 symmetrical pens, each containing 28 feeding places, 3 waterers, and 1 automatic milking system (AMS), were used to evaluate the effects of the traffic type imposed on lactating cows through an AMS on milking frequency, feeding behavior, and milk production. The study was a crossover design with 2 periods and 2 treatments. Each period lasted 3 mo, with 1 mo of adaptation within each period. All cows were fed a partial mixed ration twice daily and up to 3 kg/d of a concentrate during the visits to the AMS. Treatments consisted of allowing free traffic of cows throughout the pen or forcing cows to pass through the AMS to access the feed troughs (forced traffic). Individual eating behavior and feed consumption were continuously monitored throughout the study using a computerized system. Individual milk production was recorded at each milking, and milk composition was recorded monthly. In addition, the number of cows brought to the AMS was recorded. The number of daily meals was less, whereas meal duration and meal size were greater with forced traffic (6.6 +/- 0.3 meals/d, 20.4 +/- 0.65 min/meal, and 2.7 +/- 0.09 kg/meal, respectively) than with free traffic (10.1 +/- 0.3 meals/d, 15.7 +/- 0.65 min/meal, and 1.8 +/- 0.09 kg/meal, respectively). Total dry matter intake (21.1 +/- 0.5 and 20.4 +/- 0.58 kg/d, respectively) and milk production (29.8 +/- 0.79 and 30.9 +/- 0.79 kg/d, respectively) were similar in the 2 systems. The number of voluntary and total daily milkings was greater with forced traffic (2.4 +/- 0.04 and 2.5 +/- 0.06 milkings/d, respectively) than with free traffic (1.7 +/- 0.06 and 2.2 +/- 0.04 milkings/d, respectively). Forced traffic improved the number of voluntary milkings, but altered milk quality and eating behavior of dairy cattle.

  7. Hypothalamus-pituitary-thyroid axis disruption in rats with breast cancer is related to an altered endogenous oxytocin/insulin-regulated aminopeptidase (IRAP) system. (United States)

    Carrera-González, María Pilar; Ramírez-Expósito, María Jesús; de Saavedra, Jose Manuel Arias; Sánchez-Agesta, Rafael; Mayas, María Dolores; Martínez-Martos, Jose Manuel


    Associations of breast cancer with diseases of the thyroid have been repeatedly reported, but the mechanism underlying this association remains to be elucidated. It has been reported that oxytocin (OXT) attenuates the thyroid-stimulating hormone (TSH) release in response to thyrotrophin-releasing hormone (TRH) and decreased plasma levels of TSH as well as the thyroid hormones by an effect mediated by the central nervous system. Oxytocinase (IRAP) is the regulatory proteolytic enzyme reported to hydrolyze OXT. Changes in IRAP activity have been reported in both human breast cancer and N-methyl-nitrosourea (NMU)-induced rat mammary tumours. Here, we measure IRAP activity fluorometrically using cystyl-β-naphthylamide as the substrate, in the hypothalamus-pituitary-thyroid axis together with the circulating levels of OXT, and its relationship with circulating levels of TSH and free thyroxine (fT4), as markers of thyroid function in control rats and rats with breast cancer induced by NMU. We found decreased thyroid function in rats with breast cancer induced by NMU, supported by the existence of lower serum circulating levels of both TSH and fT4 than their corresponding controls. Concomitantly, we found a decrease of hypothalamic IRAP activity and an increase in circulating levels of OXT. We propose that breast cancer increases OXT pituitary release by decreasing its hypothalamic catabolism through IRAP activity, probably due to the alteration of the estrogenic endocrine status. Thus, high circulating levels of OXT decreased TSH release from the pituitary, and therefore, of thyroid hormones from the thyroid, supporting the association between breast cancer and thyroid function disruption.

  8. Common chromosomal fragile sites (CFS) may be involved in normal and traumatic cognitive stress memory consolidation and altered nervous system immunity. (United States)

    Gericke, G S


    Previous reports of specific patterns of increased fragility at common chromosomal fragile sites (CFS) found in association with certain neurobehavioural disorders did not attract attention at the time due to a shift towards molecular approaches to delineate neuropsychiatric disorder candidate genes. Links with miRNA, altered methylation and the origin of copy number variation indicate that CFS region characteristics may be part of chromatinomic mechanisms that are increasingly linked with neuroplasticity and memory. Current reports of large-scale double-stranded DNA breaks in differentiating neurons and evidence of ongoing DNA demethylation of specific gene promoters in adult hippocampus may shed new light on the dynamic epigenetic changes that are increasingly appreciated as contributing to long-term memory consolidation. The expression of immune recombination activating genes in key stress-induced memory regions suggests the adoption by the brain of this ancient pattern recognition and memory system to establish a structural basis for long-term memory through controlled chromosomal breakage at highly specific genomic regions. It is furthermore considered that these mechanisms for management of epigenetic information related to stress memory could be linked, in some instances, with the transfer of the somatically acquired information to the germline. Here, rearranged sequences can be subjected to further selection and possible eventual retrotranscription to become part of the more stable coding machinery if proven to be crucial for survival and reproduction. While linkage of cognitive memory with stress and fear circuitry and memory establishment through structural DNA modification is proposed as a normal process, inappropriate activation of immune-like genomic rearrangement processes through traumatic stress memory may have the potential to lead to undesirable activation of neuro-inflammatory processes. These theories could have a significant impact on the

  9. A review of mineral systems and associated tectonic settings of northern Xinjiang, NW China

    Directory of Open Access Journals (Sweden)

    Franco Pirajno


    Full Text Available In this paper we present a review of mineral systems in northern Xinjiang, NW China, focussing on the Tianshan, West and East Junggar and Altay orogenic belts, all of which are part of the greater Central Asian Orogenic Belt (CAOB. The CAOB is a complex collage of ancient microcontinents, island arcs, oceanic plateaux and oceanic plates, which were amalgamated and accreted in Early Palaeozoic to Early Permian times. The establishment of the CAOB collage was followed by strike-slip movements and affected by intraplate magmatism, linked to mantle plume activity, best exemplified by the 250 Ma Siberian Traps and the 280 Ma Tarim event. In northern Xinjiang, there are numerous and economically important mineral systems. In this contribution we describe a selection of representative mineral deposits, including subduction-related porphyry and epithermal deposits, volcanogenic massive sulphides and skarn systems. Shear zone-hosted Au lodes may have first formed as intrusion-related and subsequently re-worked during strike-slip deformation. Intraplate magmatism led to the emplacement of concentrically zoned (Alaskan-style mafic–ultramafic intrusions, many of which host orthomagmatic sulphide deposits. A huge belt of pegmatites in the Altay orogen, locally hosts world-class rare metal deposits. Roll-front, sandstone-hosted U mineralisation completes the rich mineral endowment of the northern Xinjiang terranes.

  10. Modelling the impacts of altered management practices, land use and climate changes on the water quality of the Millbrook catchment-reservoir system in South Australia. (United States)

    Nguyen, Hong Hanh; Recknagel, Friedrich; Meyer, Wayne; Frizenschaf, Jacqueline; Shrestha, Manoj Kumar


    Sustainable management of drinking water reservoirs requires taking into account the potential effects of their catchments' development. This study is an attempt to estimate the daily patterns of nutrients transport in the catchment - reservoir systems through the application of the ensemble of complementary models SWAT-SALMO. SWAT quantifies flow, nitrate and phosphate loadings originating in catchments before entering downstream reservoirs meanwhile SALMO determines phosphate, nitrate, and chlorophyll-a concentrations within the reservoirs. The study applies to the semi-arid Millbrook catchment-reservoir system that supplies drinking water to north-eastern suburbs of Adelaide, South Australia. The catchment hosts viti- and horticultural land uses. The warm-monomictic, mesotrophic reservoir is artificially aerated in summer. After validating the simulation results for both Millbrook catchment and reservoir, a comprehensive scenario analysis has been conducted to reveal cascading effects of altered management practices, land uses and climate conditions on water quality in the reservoir. Results suggest that the effect on reservoir condition in summer would be severe, most likely resulting in chlorophyll-a concentrations of greater than 40 μg/l if the artificial destratification was not applied from early summer. A 50% curbing of water diversion from an external pipeline to the catchment will slightly limit chlorophyll-a concentrations by 1.22% as an effect of reduced inflow phosphate loads. The simulation of prospective land use scenarios converting 50% of present pasture in the Millbrook catchment into residential and orchards areas indicates an increase of summer chlorophyll-a concentrations by 9.5-107.9%, respectively in the reservoir. Global warming scenarios based on the high emission simulated by SWAT-SALMO did result in earlier growth of chlorophyll-a but overall the effects on water quality in the Millbrook reservoir was not significant. However scenarios

  11. Risk of Impaired Control of Spacecraft/Associated Systems and Decreased Mobility Due to Vestibular/Sensorimotor Alterations Associated with Space Flight (United States)

    Bloomberg, Jacob J.; Reschke, Millard F.; Clément, Gilles R.; Mulavara, Ajitkumar P.; Taylor, Laura C.


    We examine the various dimensions of the Risk of Impaired Control of Spacecraft/Associated Systems and Decreased Mobility Due to Vestibular/Sensorimotor Alterations Associated with Space flight by reviewing the research and operational evidence demonstrating sensorimotor performance decrements during and after space flight. These sensorimotor performance decrements might affect vehicle and complex system control, including decreased visual acuity, eye-hand coordination, spatial and geographic orientation perception, and cognitive function. Sensorimotor performance decrements might also affect the ability to egress and walk away from the vehicle in case of an emergency or an extravehicular activity on a planetary surface. We also review the countermeasures that have been tested, including medication, prevention techniques and training exercises, physical rehabilitation, and mechanical devices. Furthermore, we identify the current knowledge and mitigation gaps that must be filled through further research and/or data mining efforts before the risk can be fully mitigated. We conclude that the true operational risks associated with the impacts of adaptive sensorimotor changes on mobility and crew abilities to control vehicles and other complex systems will only be estimable after the gaps have been filled and we have been able to accurately assess integrated performance in off-nominal operational settings. A large body of sensorimotor research data obtained from space flight experiments over the past half-century demonstrates significant decrements in oculomotor control, eye-hand coordination, spatial orientation, posture\\locomotor control and cognition during space flight missions. While these changes are most severe during and after G-transitions, the most crucial time for many critical operational tasks (e.g., landing and egress), only limited information is available to assess the operational impacts of these changes. Some of the operational observations are

  12. Image-Guided Analyses Reveal that Non-CD4 Splenocytes Contribute to CD4+ T Cell–Mediated Inflammation Leading to Islet Destruction by Altering Their Local Function and Not Systemic Trafficking Patterns

    Directory of Open Access Journals (Sweden)

    Mi-Heon Lee


    Full Text Available Recruitment of CD4+ T cells into islets is a critical component of islet inflammation (insulitis leading to type 1 diabetes; therefore, determining if conditions used to treat diabetes change their trafficking patterns is relevant to the outcome. Cotransfer of CD4+BDC2.5 (BDC cells with non-CD4 splenocytes obtained from newly diabetic NOD mice, but not when they are transferred alone, induces accelerated diabetes. It is unclear whether these splenocytes affect diabetes development by altering the systemic and/or local trafficking and proliferation patterns of BDC cells in target and nontarget tissues. To address these questions, we developed an animal model to visualize BDC cell trafficking and proliferation using whole-body in vivo bioluminescence imaging and used the images to direct tissue sampling for further analyses of the cell distribution within tissues. The whole-body, or macroscopic, trafficking patterns were not dramatically altered in both groups of recipient mice. However, the local patterns of cell distribution were distinct, which led to invasive insulitis only in cotransferred mice with an increased number of islet-infiltrating CD11b+ and CD11c+ cells. Taken together, the non-CD4 splenocytes act locally by promoting invasive insulitis without altering the systemic trafficking patterns or proliferation of BDC cells and thus contributing to diabetes by altering the localization within the tissue.

  13. Synthesis of the hydrogeological studies in the sedimentary basins Amazon and Solimões: the Aquifers Systems Içá-Solimões and Alter do Chão

    Directory of Open Access Journals (Sweden)

    José Geilson Alves Demétrio


    Full Text Available Geological maps and stratigraphic charts of the Amazon and Solimões sedimentary basins were reviewed, emphasizing the formations Alter do Chão, Içá and Solimões, the largest reserves of fresh groundwater in these basins. The lack of information on these formations was minimized by sample probe and stratigraphic profiles of construction, lithological and geophysical water and oil wells, obtained in the Base Operacional Geólogo Pedro de Moura, Urucu region, about 650 km southwest of Manaus (AM. In the Amazon Basin, the Aquifer System Alter do Chão is characterized by unconfined and confined aquifers, with transmissivity between 1.5 and 9.1 x 10-3 m2/s, indicated for public supply. In the Solimões Basin, this system is confined by Aquiclude Solimões, recovered by the I-Solimões Aquifers. The reserve is estimated as 33,000 km3. The Aquifer System Içá-Solimões, in Urucu, is unconfined-confined, with two aquifers hydraulically connected: the superficial, with top and bottom at depths near 20 and 70 m, respectively; and the deeper, between 50 and 120 m. With an outcrop area of 948,600 km2 in the Solimões Basin, the reservation of this system was estimated as 7,200 km3, less expressive than the Aquifer System Alter do Chão. The average hydrodynamic parameters were: T = 3 x 10-3 m2/s, S = 5 x 10-4 and K = 1 x 10-4 m/s, orders of magnitudes similar to those found in the aquifer Alter do Chão. Assessing the interrelationships and potential of these two regional aquifers sought to contribute to the hydrogeological knowledge in the Amazon Basin region, where researches on groundwater are still incipient.

  14. Impact of hydrothermal alteration on the U-Pb isotopic system of zircons from the Fangcheng syenites in the Qinling orogen, Henan Province, China

    Institute of Scientific and Technical Information of China (English)

    BAO Zhiwei; WANG Qiang; BAI Guodian; ZHAO Zhenhua


    Disturbance of the zircon U-Pb isotopic system has been investigated extensively, but mostly in lab, in the last decades. Here, we reported a field-based study on intensive sericitization, K-feldsparthization and the impacts of mylonitization on zircons from the Fangcheng syenites.The Fangcheng syenites occur in the eastern part of the Qinling orogen and consist mainly of aegirine-augite syenite, aegirine nepheline syenite, biotite syenite and hornblende nepheline syenite. Zircons from the slightly sericitized aegirine augite syenite are colorless, transparent crystals and exhibit well-developed oscillatory and sector zoning on the cathodoluminescence (CL) images which are typical of magmatic zircons from alkaline rocks. Zircon U-Pb determinations by laser ablation inductively coupled plasma mass spectrometry (LA-ICPMS) showed that the syenite was formed in Neoproterozoic time, the weighted average of 206Pb/238U ages is 844.3±1.6 Ma (MSWD=0.86). In contrast, the hydrothermally altered zircons (hydrothermal zircon) from the intensively sericitized, K-feldsparthized, and weakly mylonitized aegirine augite syenite are conglomerates, yellowish to brown in color, generally translucent and internally textureless. The CL and backscatter electron (BSE) images of hydrothermal zircons exhibit fractured, textureless or mosaic textures, and occasionally show "sponge texture" with the veinlets and inclusions of K-feldspar; however, relicts of magmatic oscillatory zoning can still be discerned locally in individual grains. LA-ICPMS analyses of the hydrothermal zircons demonstrated that the zircons are chemically inhomogeneous, with enhanced and widely varied Pb, U, and Th contents. The U and Th contents of the hydrothermal zircons are estimated to be 32×10-6-1550×10-6 and 188×10-6-4059×10-6, respectively, with Th/U ratios within the range of 0.7-44.9. 206Pb/238U apparent ages of the hydrothermal zircons are negatively correlated with the contents of U, and radiogenic and

  15. The Two-Component System ArlRS and Alterations in Metabolism Enable Staphylococcus aureus to Resist Calprotectin-Induced Manganese Starvation (United States)

    Radin, Jana N.; Párraga Solórzano, Paola K.; Kehl-Fie, Thomas E.


    During infection the host imposes manganese and zinc starvation on invading pathogens. Despite this, Staphylococcus aureus and other successful pathogens remain capable of causing devastating disease. However, how these invaders adapt to host-imposed metal starvation and overcome nutritional immunity remains unknown. We report that ArlRS, a global staphylococcal virulence regulator, enhances the ability of S. aureus to grow in the presence of the manganese-and zinc-binding innate immune effector calprotectin. Utilization of calprotectin variants with altered metal binding properties revealed that strains lacking ArlRS are specifically more sensitive to manganese starvation. Loss of ArlRS did not alter the expression of manganese importers or prevent S. aureus from acquiring metals. It did, however, alter staphylococcal metabolism and impair the ability of S. aureus to grow on amino acids. Further studies suggested that relative to consuming glucose, the preferred carbon source of S. aureus, utilizing amino acids reduced the cellular demand for manganese. When forced to use glucose as the sole carbon source S. aureus became more sensitive to calprotectin compared to when amino acids are provided. Infection experiments utilizing wild type and calprotectin-deficient mice, which have defects in manganese sequestration, revealed that ArlRS is important for disease when manganese availability is restricted but not when this essential nutrient is freely available. In total, these results indicate that altering cellular metabolism contributes to the ability of pathogens to resist manganese starvation and that ArlRS enables S. aureus to overcome nutritional immunity by facilitating this adaptation. PMID:27902777

  16. Modelling glass alteration in an altered argillaceous environment (United States)

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


    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

  17. Gestational Diabetes Alters Offspring DNA Methylation Profiles in Human and Rat: Identification of Key Pathways Involved in Endocrine System Disorders, Insulin Signaling, Diabetes Signaling, and ILK Signaling. (United States)

    Petropoulos, Sophie; Guillemin, Claire; Ergaz, Zivanit; Dimov, Sergiy; Suderman, Matthew; Weinstein-Fudim, Liza; Ornoy, Asher; Szyf, Moshe


    Gestational diabetes is associated with risk for metabolic disease later in life. Using a cross-species approach in rat and humans, we examined the hypothesis that gestational diabetes during pregnancy triggers changes in the methylome of the offspring that might be mediating these risks. We show in a gestation diabetes rat model, the Cohen diabetic rat, that gestational diabetes triggers wide alterations in DNA methylation in the placenta in both candidate diabetes genes and genome-wide promoters, thus providing evidence for a causal relationship between diabetes during pregnancy and DNA methylation alterations. There is a significant overlap between differentially methylated genes in the placenta and the liver of the rat offspring. Several genes differentially methylated in rat placenta exposed to maternal diabetes are also differentially methylated in the human placenta of offspring exposed to gestational diabetes in utero. DNA methylation changes inversely correlate with changes in expression. The changes in DNA methylation affect known functional gene pathways involved in endocrine function, metabolism, and insulin responses. These data provide support to the hypothesis that early-life exposures and their effects on metabolic disease are mediated by DNA methylation changes. This has important diagnostic and therapeutic implications.

  18. Preventive effect of CuCl₂ on behavioral alterations and mercury accumulation in central nervous system induced by HgCl2 in newborn rats. (United States)

    Moraes-Silva, L; Siqueira, L F; Oliveira, V A; Oliveira, C S; Ineu, R P; Pedroso, T F; Fonseca, M M; Pereira, M E


    This study investigated the benefits of Cu preexposition on Hg effects on behavioral tests, acetylcholinesterase (AChE) activity and Hg, and essential metal contents in the cerebrum and cerebellum of neonate rats. Wistar rats received (subcutaneous) saline or CuCl2 ·2H2O (6.9 mg/kg/day) when they were 3 to 7 days old and saline or HgCl2 (5.0 mg/kg/day) when they were 8 to 12 days old. Mercury exposure reduced the performance of rats in the negative geotaxis (3-13 days) and beaker test (17-20 days), inhibited cerebellum AChE activity (13 days), increased cerebrum and cerebellum Hg (13 days), cerebrum Cu (13 days), and cerebrum and cerebellum Zn levels (33 days). The performance of rats in the tail immersion and rotarod tests as well as Fe and Mg levels were not altered by treatments. Copper prevented all alterations induced by mercury. These results are important to open a new perspective of prevention and/or therapy for mercury exposure.

  19. Quantification of porosity evolution from unaltered to propylitic-altered granites: the 14C-PMMA method applied on the hydrothermal system of Lavras do Sul, Brazil

    Directory of Open Access Journals (Sweden)

    Everton M. Bongiolo


    Full Text Available This work is an application of the 14C-Polymethylmethacrylate method to compare the porosity evolution between unaltered and propylitic-altered granites, using samples from Lavras do Sul region, Brazil. This method, when coupled with optical and electronic petrography has the advantage over other methods to provide the quantification and identification of total and local porosity of rocks. From petrographic observations, different kinds of porous zones were identified and quantified (microfractures, grain boundaries, alteration of minerals, etc. Results show that unaltered granites have 0.5 to 0.6% porosity and propylitic-altered ones have 1.7 to 1.8% porosity, even between samples with different textures. Porosity of altered rocks increases mainly due to higher porosity of neoformed chlorite, calcite, sericite and microfractures. Field observations show that later phyllic alteration halos are wider in equigranular than in porphyritic granites, which could not be explained by different original porosity between those rocks. The observed differences of phyllic halos diffusion were controlled by structural and fluid/rock ratio variations between the equigranular and porphyritic granitic facies during the later hydrothermal stage.Este trabalho é uma aplicação do método 14C-polimetilmetacrilato na comparação da evolução da porosidade entre granitos não alterados e propilitizados, utilizando amostras da região de Lavras do Sul, Brasil. Este método, quando associado a análises por petrografia ótica, eletrônica e processamento digital de imagens tem a vantagem de fornecer, além da porosidade total, a quantificação e identificação da porosidade em locais específicos das rochas. A partir da petrografia foi possível identificar e quantificar os diferentes tipos de poros presentes nas rochas (microfraturas, limites de grãos, alteração de minerais, etc. Os resultados mostram que granitos não alterados têm porosidade de 0,5 a 0,6% e

  20. Music and Alterity Processes

    Directory of Open Access Journals (Sweden)

    Josep Martí


    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.

  1. Attention Alters Perceived Attractiveness. (United States)

    Störmer, Viola S; Alvarez, George A


    Can attention alter the impression of a face? Previous studies showed that attention modulates the appearance of lower-level visual features. For instance, attention can make a simple stimulus appear to have higher contrast than it actually does. We tested whether attention can also alter the perception of a higher-order property-namely, facial attractiveness. We asked participants to judge the relative attractiveness of two faces after summoning their attention to one of the faces using a briefly presented visual cue. Across trials, participants judged the attended face to be more attractive than the same face when it was unattended. This effect was not due to decision or response biases, but rather was due to changes in perceptual processing of the faces. These results show that attention alters perceived facial attractiveness, and broadly demonstrate that attention can influence higher-level perception and may affect people's initial impressions of one another.

  2. The presence of nodules on legume root systems can alter phenotypic plasticity in response to internal nitrogen independent of nitrogen fixation. (United States)

    Goh, Chooi-Hua; Nicotra, Adrienne B; Mathesius, Ulrike


    All higher plants show developmental plasticity in response to the availability of nitrogen (N) in the soil. In legumes, N starvation causes the formation of root nodules, where symbiotic rhizobacteria fix atmospheric N2 for the host in exchange for fixed carbon (C) from the shoot. Here, we tested whether plastic responses to internal [N] of legumes are altered by their symbionts. Glasshouse experiments compared root phenotypes of three legumes, Medicago truncatula, Medicago sativa and Trifolium subterraneum, inoculated with their compatible symbiont partners and grown under four nitrate levels. In addition, six strains of rhizobia, differing in their ability to fix N2 in M. truncatula, were compared to test if plastic responses to internal [N] were dependent on the rhizobia or N2 -fixing capability of the nodules. We found that the presence of rhizobia affected phenotypic plasticity of the legumes to internal [N], particularly in root length and root mass ratio (RMR), in a plant species-dependent way. While root length responses of M. truncatula to internal [N] were dependent on the ability of rhizobial symbionts to fix N2 , RMR response to internal [N] was dependent only on initiation of nodules, irrespective of N2 -fixing ability of the rhizobia strains.

  3. Development of the main olfactory system and main olfactory epithelium-dependent male mating behavior are altered in Go-deficient mice (United States)

    Choi, Jung-Mi; Kim, Sung-Soo; Choi, Chan-Il; Cha, Hye Lim; Oh, Huy-Hyen; Ghil, Sungho; Lee, Young-Don; Birnbaumer, Lutz; Suh-Kim, Haeyoung


    In mammals, initial detection of olfactory stimuli is mediated by sensory neurons in the main olfactory epithelium (MOE) and the vomeronasal organ (VNO). The heterotrimeric GTP-binding protein Go is widely expressed in the MOE and VNO of mice. Early studies indicated that Go expression in VNO sensory neurons is critical for directing social and sexual behaviors in female mice [Oboti L, et al. (2014) BMC Biol 12:31]. However, the physiological functions of Go in the MOE have remained poorly defined. Here, we examined the role of Go in the MOE using mice lacking the α subunit of Go. Development of the olfactory bulb (OB) was perturbed in mutant mice as a result of reduced neurogenesis and increased cell death. The balance between cell types of OB interneurons was altered in mutant mice, with an increase in the number of tyrosine hydroxylase-positive interneurons at the expense of calbindin-positive interneurons. Sexual behavior toward female mice and preference for female urine odors by olfactory sensory neurons in the MOE were abolished in mutant male mice. Our data suggest that Go signaling is essential for the structural and functional integrity of the MOE and for specification of OB interneurons, which in turn are required for the transmission of pheromone signals and the initiation of mating behavior with the opposite sex. PMID:27625425

  4. Lipid Peroxidative Damage on Cisplatin Exposure and Alterations in Antioxidant Defense System in Rat Kidneys: A Possible Protective Effect of Selenium

    Directory of Open Access Journals (Sweden)

    Branka I. Ognjanović


    Full Text Available Cisplatin (Cis-diamminedichloroplatinum II, CP is an important chemotherapeutic agent, useful in the treatment of several cancers, but with several side effects such as nephrotoxicity. The present study investigated the possible protective effect of selenium (Se against CP-induced oxidative stress in the rat kidneys. Male Wistar albino rats were injected with a single dose of cisplatin (7 mg CP/kg b.m., i.p. and selenium (6 mg Se/kg b.m, as Na2SeO3, i.p., alone or in combination. The obtained results showed that CP increased lipid peroxidation (LPO and decreased reduced glutathione (GSH concentrations, suggesting the CP-induced oxidative stress, while Se treatment reversed this change to control values. Acute intoxication of rats with CP was followed by statistically significant decreased activity of antioxidant defense enzymes: superoxide dismutase (SOD, catalase (CAT, glutathione peroxidase (GSH-Px, glutathione reductase (GR and glutathione-S-transferase (GST. Treatment with Se reversed CP-induced alterations of antioxidant defense enzyme activities and significantly prevented the CP-induced kidney damage.

  5. Lipid peroxidative damage on Cisplatin exposure and alterations in antioxidant defense system in rat kidneys: a possible protective effect of selenium. (United States)

    Ognjanović, Branka I; Djordjević, Nataša Z; Matić, Miloš M; Obradović, Jasmina M; Mladenović, Jelena M; Stajn, Andraš Š; Saičić, Zorica S


    Cisplatin (Cis-diamminedichloroplatinum II, CP) is an important chemotherapeutic agent, useful in the treatment of several cancers, but with several side effects such as nephrotoxicity. The present study investigated the possible protective effect of selenium (Se) against CP-induced oxidative stress in the rat kidneys. Male Wistar albino rats were injected with a single dose of cisplatin (7 mg CP/kg b.m., i.p.) and selenium (6 mg Se/kg b.m, as Na(2)SeO(3), i.p.), alone or in combination. The obtained results showed that CP increased lipid peroxidation (LPO) and decreased reduced glutathione (GSH) concentrations, suggesting the CP-induced oxidative stress, while Se treatment reversed this change to control values. Acute intoxication of rats with CP was followed by statistically significant decreased activity of antioxidant defense enzymes: superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase (GR) and glutathione-S-transferase (GST). Treatment with Se reversed CP-induced alterations of antioxidant defense enzyme activities and significantly prevented the CP-induced kidney damage.

  6. Ressourcenorientierte Diagnostik im Alter


    Forstmeier, Simon; Maercker, Andreas


    Trotz der im Alter zunehmenden körperlichen, kognitiven und sozialen Verlusten bleibt das subjektive Wohlbefinden relativ stabil. Dies weist auf die vielen Ressourcen älterer Menschen hin. Dieser Artikel stellt für die klinische Ressourcendiagnostik relevante Verfahren vor und erläutert die zugrunde liegenden Konzepte. Berücksichtigt werden Aktivitäten und Erlebnisse als Ressourcen, emotionale Ressourcen (positiver Affekt, Lebenszufriedenheit, Selbstwerterleben, Lebensqualität), motivationale...

  7. The Hydrothermal System at Home Plate in Gusev Crater, Mars: Formation of High Silica Material by Acid-Sulfate Alteration of Basalt (United States)

    Morris, R. V.; Ming, D. W.; Gellert, R.; Yen, A.; Clark, B. C.; Gnaff, T. G.; Arvidson, R. E.; Squyres, S. W.


    The Alpha Particle X-ray Spectrometer (APXS) instrument on the Mars Exploration Rover (MER) Spirit measured three targets on or adjacent to Home Plate in Gusev Crater that have unusually high SiO2 concentrations (68% to 91%), unusually low FeO concentrations (1% to 7%, with total Fe as FeO), and unusually high TiO2/FeO ratios (0.2 to 1.2 by weight) [1]. Two targets (Kenosha Comets and Lefty Ganote) are located on high albedo soil (Gertrude Weise) that was exposed by the rover wheels, and one target is a float rock called Fuzzy Smith. Kenosha Comets has the highest SiO2 concentration, lowest FeO concentration, and highest TiO2/FeO ratio. Mineralogical evidence from the MER Miniature Thermal Emission Spectrometer (Mini-TES) suggests that the SiO2 is present as amorphous (noncrystalline) SiO2 at Gertrude Weise and nearby targets [2,3]. Mini-TES data were not acquired for Fuzzy Smith. Home Plate is considered to have an explosive volcanic origin, resulting when basaltic magma came into contact with ground water or ice [4]. Within 50 m to 1 km of Home Plate are sulfate rich soil deposits (Paso Robles class soils with 22-35% SO3) which are considered to be probable fumarolic and/or hydrothermal deposits associated with the volcanism [5]. We develop the model here, suggested by [5], that the high-silica materials are another manifestation of acid-sulfate processes associated with fumarolic and hydrothermal activity at Home Plate. This is done by analogy with basaltic materials altered by acid sulfate processes on the Island of Hawaii.

  8. 3-D seismic imaging of lithospheric fault-block structures, core complexes, alteration fronts, and hydrothermal systems along the Mid-Atlantic Ridge, Rainbow area (United States)

    Dunn, R. A.; Arai, R.; Eason, D. E.; Canales, J. P.; Sohn, R. A.


    Oceanic lithosphere formed along slow-spreading mid-ocean ridges is structurally and compositionally heterogeneous due to spatial and temporal variations in tectonic extension and magmatic accretion processes. Sorting out the different influences requires detailed imaging of the subsurface. The MARINER seismic and geophysical mapping experiment was designed to examine seafloor spreading across an area that includes a non-transform offset of the Mid-Atlantic Ridge, 36°14'N, the site of the Rainbow core complex and its associated hydrothermal vent field. Using seismic refraction data from this experiment, we constructed three-dimensional anisotropic tomographic images of the crust and upper mantle around the Rainbow area. Approaching Rainbow along the spreading ridges from either side, the seismic images reveal the onset of a clear ridge-parallel stripe-like structures, with alternating high- and low-velocities throughout the crust, correlated with changing lower crustal thickness and the locations of large normal faults. The pattern indicates that large normal faults rotate large blocks of the entire crust during tectonic stretching. Sitting within the ridge offset, the Rainbow core complex appears to be genetically related to neighboring fault blocks, and is largely an ultramafic exposure. Relatively low seismic velocities drape the core complex, having a sharp contact with higher-velocities below. The sharp contact may demarcate alteration (to serpentinite) and cracking fronts, since also draping the core complex are corresponding regions of high seismic anisotropy and high microseismicity, indicating pervasive cracking of its upper regions. The anisotropy and seismicity funnel upwards under the vent field, presumably marking the flow paths of vent fluids that cool melt lenses found to be intruded deep below the surface. The tomographic images reveal lithospheric structures in greater detail than previously possible, and when taken together with our other

  9. Neutralization of MMP-2 and TNFR1 Regulates the Severity of S. aureus-Induced Septic Arthritis by Differential Alteration of Local and Systemic Proinflammatory Cytokines in Mice. (United States)

    Sultana, Sahin; Adhikary, Rana; Bishayi, Biswadev


    . aureus infection-induced septic arthritis by altering the levels of cytokines.

  10. Four weeks of normobaric "live high-train low" do not alter muscular or systemic capacity for maintaining pH and K+ homeostasis during intense exercise

    DEFF Research Database (Denmark)

    Nordsborg, Nikolai B; Siebenmann, C; Jacobs, R A


    It was investigated if athletes subjected to 4 wk of living in normobaric hypoxia (3,000 m; 16 h/day) while training at 800-1,300 m ["live high-train low" (LHTL)] increase muscular and systemic capacity for maintaining pH and K(+) homeostasis as well as intense exercise performance. The design wa...

  11. Morphodynamics of an Anthropogenically Altered Dual-Inlet System: John’s Pass and Blind Pass, West-Central Florida, USA (United States)


    synchronized Real-Time-Kinematic ( RTK ) Global Positioning System ( GPS ) for position. In addition, monthly level-and-transit surveys using an electronic total...integrate hydrodynamics, sediment transport, and morphologic change through the coupling of two modules , CMS-Flow and CMS-Wave. The CMS was developed

  12. Altered gut microbiota and endocannabinoid system tone in obese and diabetic leptin-resistant mice: impact on apelin regulation in adipose tissue

    Directory of Open Access Journals (Sweden)

    Lucie eGeurts


    Full Text Available Growing evidence supports the role of gut microbiota in the development of obesity, type 2 diabetes and low-grade inflammation. The endocrine activity of adipose tissue has been found to contribute to the regulation of glucose homeostasis and low-grade inflammation. Among the key hormones produced by this tissue, apelin has been shown to regulate glucose homeostasis. Recently, it has been proposed that gut microbiota participate in adipose tissue metabolism via the endocannabinoid system and gut microbiota-derived compounds, namely lipopolysaccharide (LPS. We have investigated gut microbiota composition in obese and diabetic leptin-resistant mice (db/db by combining pyrosequencing and phylogenetic microarray analysis of 16S ribosomal RNA gene sequences. We observed a significant higher abundance of Firmicutes, Proteobacteria and Fibrobacteres phyla in db/db mice compared to lean mice. The abundance of 10 genera was significantly affected by the genotype. We identified the roles of the endocannabinoid system and LPS in the regulation of apelinergic system tone (apelin and APJ mRNA expression in genetic obese and diabetic mice. By using in vivo and in vitro models, we have demonstrated that both the endocannabinoid system and low-grade inflammation differentially regulate apelin and APJ mRNA expression in adipose tissue. Finally, deep-gut microbiota profiling revealed that the gut microbial community of type 2 diabetic mice is significantly different from that of their lean counterparts. This indicates specific relationships between the gut microbiota and the regulation of the apelinergic system. However, the exact roles of specific bacteria in shaping the phenotype of db/db mice remain to be determined.

  13. Resveratrol up-regulates the erythrocyte plasma membrane redox system and mitigates oxidation-induced alterations in erythrocytes during aging in humans. (United States)

    Pandey, Kanti Bhooshan; Rizvi, Syed Ibrahim


    Reactive oxygen/nitrogen species (ROS/RNS)-mediated oxidative damage followed by disturbed cellular homeostasis is involved in aging and related consequences. Lipid peroxidation, post-translational modifications of proteins, and an impaired defense system due to increased oxidative stress jeopardize cell fate and functions, resulting in cell senescence. Resveratrol, a natural stilbene, has extensively been reported to elicit a plethora of health-promoting effects. The present study carried out on 97 healthy human subjects (62 males and 35 females) of both sexes provides experimental evidence that resveratrol confers ability to up-regulate the plasma membrane redox system (PMRS) along with ascorbate free radical reductase, a compensatory system operating in the cell to maintain cellular redox state. Furthermore, resveratrol provided significant protection against lipid peroxidation and protein carbonylation and restored the cellular redox homeostasis measured in terms of glutathione (GSH) and sulfhydryl (-SH) group levels during oxidation injury in erythrocytes of different age groups in humans. Findings suggest a possible role of resveratrol in retardation of age-dependent oxidative stress.

  14. Malaria parasite infection compromises control of concurrent systemic non-typhoidal Salmonella infection via IL-10-mediated alteration of myeloid cell function. (United States)

    Lokken, Kristen L; Mooney, Jason P; Butler, Brian P; Xavier, Mariana N; Chau, Jennifer Y; Schaltenberg, Nicola; Begum, Ramie H; Müller, Werner; Luckhart, Shirley; Tsolis, Renée M


    Non-typhoidal Salmonella serotypes (NTS) cause a self-limited gastroenteritis in immunocompetent individuals, while children with severe Plasmodium falciparum malaria can develop a life-threatening disseminated infection. This co-infection is a major source of child mortality in sub-Saharan Africa. However, the mechanisms by which malaria contributes to increased risk of NTS bacteremia are incompletely understood. Here, we report that in a mouse co-infection model, malaria parasite infection blunts inflammatory responses to NTS, leading to decreased inflammatory pathology and increased systemic bacterial colonization. Blunting of NTS-induced inflammatory responses required induction of IL-10 by the parasites. In the absence of malaria parasite infection, administration of recombinant IL-10 together with induction of anemia had an additive effect on systemic bacterial colonization. Mice that were conditionally deficient for either myeloid cell IL-10 production or myeloid cell expression of IL-10 receptor were better able to control systemic Salmonella infection, suggesting that phagocytic cells are both producers and targets of malaria parasite-induced IL-10. Thus, IL-10 produced during the immune response to malaria increases susceptibility to disseminated NTS infection by suppressing the ability of myeloid cells, most likely macrophages, to control bacterial infection.

  15. Oxygen isotope exchange kinetics of mineral pairs in closed and open systems: Applications to problems of hydrothermal alteration of igneous rocks and Precambrian iron formations (United States)

    Gregory, R.T.; Criss, R.E.; Taylor, H.P.


    The systematics of stable-isotope exchange between minerals and fluids are examined in the context of modal mineralogical variations and mass-balance considerations, both in closed and in open systems. On mineral-pair ??18O plots, samples from terranes that have exchanged with large amounts of fluid typically map out steep positively-sloped non-equilibrium arrays. Analytical models are derived to explain these effects; these models allow for different exchange rates between the various minerals and the external fluids, as well as different fluid fluxes. The steep arrays are adequately modelled by calculated isochron lines that involve the whole family of possible exchange trajectories. These isochrons have initially-steep near-vertical positive slopes that rotate toward a 45?? equilibrium slope as the exchange process proceeds to completion. The actual data-point array is thus analogous to the hand of an "isotopic clock" that measures the duration of the hydrothermal episode. The dimensionless ratio of the volumetric fluid flux to the kinetic rate parameter ( u k) determines the shape of each individual exchange trajectory. In a fluid-buffered system ( u k ??? 1), the solutions to the equations: (1) are independent of the mole fractions of the solid phases; (2) correspond to Taylor's open-system water/rock equation; and (3) yield straight-line isochrons that have slopes that approach 1 f, where f is the fraction reacted of the more sluggishly exchanging mineral. The isochrons for this simple exchange model are closely congruent with the isochrons calculated for all of the more complex models, thereby simplifying the application of theory to actual hydrothermal systems in nature. In all of the models an order of magnitude of time (in units of kt) separates steep non-equilibrium arrays (e.g., slope ??? 10) from arrays approaching an equilibrium slope of unity on a ??-?? diagram. Because we know the approximate lifetimes of many hydrothermal systems from geologic and

  16. Perinatal asphyxia results in altered expression of the hippocampal acylethanolamide/endocannabinoid signaling system associated to memory impairments in postweaned rats. (United States)

    Blanco, Eduardo; Galeano, Pablo; Holubiec, Mariana I; Romero, Juan I; Logica, Tamara; Rivera, Patricia; Pavón, Francisco J; Suarez, Juan; Capani, Francisco; Rodríguez de Fonseca, Fernando


    Perinatal asphyxia (PA) is an obstetric complication that strongly affects the CNS. The endocannabinoid system (ECS) is a lipid transmitter system involved in several physiological processes including synaptic plasticity, neurogenesis, memory, and mood. Endocannabinoids, and other acylethanolamides (AEs) without endocannabinoid activity, have recently received growing attention due to their potential neuroprotective functions in neurological disorders, including cerebral ischemia. In the present study, we aimed to analyze the changes produced by PA in the major metabolic enzymes and receptors of the ECS/AEs in the hippocampus using a rodent model of PA. To induce PA, we removed uterine horns from ready-to-deliver rats and immersed them into a water bath during 19 min. Animals delivered spontaneously or by cesarean section were employed as controls. At 1 month of age, cognitive functions were assessed and immunohistochemical procedures were carried out to determine the expression of NeuN and glial fibrillary acidic protein, enzymes responsible for synthesis (DAGLα and NAPE-PLD) and degradation (FAAH) of ECS/AEs and their receptors (CB1 and PPARα) in the hippocampus. Postweaned asphyctic rats showed impaired recognition and spatial reference memory that were accompanied by hippocampal astrogliosis and changes in the expression of enzymes and receptors. The most remarkable findings in asphyctic rats were a decrease in the expression of NAPE-PLD and PPARα in both hippocampal areas CA1 and CA3. In addition, postweaned cesarean delivery rats showed an increase in the immunolabeling for FAAH in the hippocampal CA3 area. Since, NAPE-PLD and PPARα are proteins that participate in the biochemical process of AEs, specially the neuroprotective oleoylethanolamide, these results suggest that PA dysregulates this system. These data encourage conducting future studies using AEs as potential neuroprotective compounds in animal models of PA.

  17. Combined exposure to agriculture pesticides, paraquat and maneb, induces alterations in the N/OFQ-NOPr and PDYN/KOPr systems in rats: Relevance to sporadic Parkinson's disease. (United States)

    Bastías-Candia, Sussy; Di Benedetto, Manuela; D'Addario, Claudio; Candeletti, Sanzio; Romualdi, Patrizia


    Despite several years of research, the aetiology of Parkinson's disease (PD) is quite far from being solved. In PD, as well as in other neurodegenerative disorders, it has been proposed that the combination of multiple factors might contribute to the onset of the disease. Indeed, several authors have suggested that environmental factors, such as pollutants and chemicals, might be associated with the onset of several neurodegenerative disorders. On the other hand, several studies have described that the nociceptin/orphanin-NOP and prodynorphin-KOP opioid systems are implicated in the pathology of Parkinson's disease. Considering the nonrestricted commercial availability and common use of several pesticides, such as paraquat and maneb, in agriculture of less developed countries, the aim of our study was to investigate the involvement of nociceptin/orphanin-NOP and prodynorphin-KOP systems in a chronic paraquat and maneb animal model of Parkinson's disease. Our results showed that after paraquat/maneb (5/15 mg kg(-1) ) treatment, a significant reduction in tyrosine hydroxylase (TH) levels, the rate-limiting enzyme for dopamine synthesis, was observed. Also, the association of paraquat and maneb (5/15 mg kg(-1) ) induced an increase in nociceptin/orphanin and a decrease of prodynorphin gene expression levels in the substantia nigra with a down-regulation of NOP and KOP receptors after both treatments in the substantia nigra and caudate putamen. These data further confirm that paraquat and maneb toxicity can modulate gene expression of the nociceptin/orphanin-NOP receptor and prodynorphin-KOP receptor systems in the substantia nigra and caudate putamen, offering further support to the hypothesis that chronic exposure to these agrochemicals might be implicated in the mechanisms underlying sporadic Parkinson's disease. © 2013 Wiley Periodicals, Inc. Environ Toxicol 30: 656-663, 2015.

  18. Sublethal effect of silver and chromium in the green mussel Perna viridis with reference to alterations in oxygen uptake, filtration rate and membrane bound ATPase system as biomarkers. (United States)

    Vijayavel, K; Gopalakrishnan, S; Balasubramanian, M P


    Perna viridis is an ideal animal for studying the impairment caused by the effects of heavy metals that are often detected in coastal areas. Preliminary bioassay tests revealed that the lethal (LC(100)), median lethal (LC(50)) and sublethal (LC(0)) concentration of silver and chromium to P. viridis were 6.5, 4.0, 2.0 mg l(-1) and 4.5, 2.5, 1.0 mg l(-1), respectively. Toxic effect of silver and chromium was evaluated in the green mussel P. viridis, with reference to oxygen consumption, filtration rate and ATPase system in laboratory experiments. These parameters were selected as the end point of sublethal stress. Oxygen consumption and filtration rates were calculated as a measure of decline in the dissolved oxygen level and algal concentration (feed) in the aquaria water, respectively. Silver and chromium affects both oxygen consumption and filtration rate significantly (P<0.01) at 96 h when compared to control. The activity of ATPases system in the gills, hepatopancreas, ovary and muscle of mussels were inhibited by silver and chromium indicating that metals exerted significant toxic effect. The inhibition of Na(+)K(+) ATPase, Ca(2+) ATPase and Mg(2+) ATPase in the mussels were significant (P<0.05) for silver and highly significant (P<0.01) for chromium, which indicates that chromium was more toxic to mussels when compared to silver. The assessment of oxygen consumption, filtration and ATPases system can thus be used as a valid biomarker in aquatic ecotoxicology studies.

  19. Perinatal asphyxia results in altered expression of the hippocampal acylethanolamide/endocannabinoid signaling system associated to memory impairments in postweaned rats (United States)

    Blanco, Eduardo; Galeano, Pablo; Holubiec, Mariana I.; Romero, Juan I.; Logica, Tamara; Rivera, Patricia; Pavón, Francisco J.; Suarez, Juan; Capani, Francisco; Rodríguez de Fonseca, Fernando


    Perinatal asphyxia (PA) is an obstetric complication that strongly affects the CNS. The endocannabinoid system (ECS) is a lipid transmitter system involved in several physiological processes including synaptic plasticity, neurogenesis, memory, and mood. Endocannabinoids, and other acylethanolamides (AEs) without endocannabinoid activity, have recently received growing attention due to their potential neuroprotective functions in neurological disorders, including cerebral ischemia. In the present study, we aimed to analyze the changes produced by PA in the major metabolic enzymes and receptors of the ECS/AEs in the hippocampus using a rodent model of PA. To induce PA, we removed uterine horns from ready-to-deliver rats and immersed them into a water bath during 19 min. Animals delivered spontaneously or by cesarean section were employed as controls. At 1 month of age, cognitive functions were assessed and immunohistochemical procedures were carried out to determine the expression of NeuN and glial fibrillary acidic protein, enzymes responsible for synthesis (DAGLα and NAPE-PLD) and degradation (FAAH) of ECS/AEs and their receptors (CB1 and PPARα) in the hippocampus. Postweaned asphyctic rats showed impaired recognition and spatial reference memory that were accompanied by hippocampal astrogliosis and changes in the expression of enzymes and receptors. The most remarkable findings in asphyctic rats were a decrease in the expression of NAPE-PLD and PPARα in both hippocampal areas CA1 and CA3. In addition, postweaned cesarean delivery rats showed an increase in the immunolabeling for FAAH in the hippocampal CA3 area. Since, NAPE-PLD and PPARα are proteins that participate in the biochemical process of AEs, specially the neuroprotective oleoylethanolamide, these results suggest that PA dysregulates this system. These data encourage conducting future studies using AEs as potential neuroprotective compounds in animal models of PA. PMID:26578900

  20. Alterations in mitochondrial electron transport system activity in response to warm acclimation, hypoxia-reoxygenation and copper in rainbow trout, Oncorhynchus mykiss

    Energy Technology Data Exchange (ETDEWEB)

    Sappal, Ravinder [Department of Pathology and Microbiology, Atlantic Veterinary College, University of Prince Edward Island, Charlottetown, PE, C1A 4P3 (Canada); Department of Biomedical Sciences, Atlantic Veterinary College, University of Prince Edward Island, Charlottetown, PE, C1A 4P3 (Canada); MacDougald, Michelle [Faculty of Medicine, Memorial University of Newfoundland, Health Sciences Centre, Prince Philip Drive, St. John’s, NL, A1B 3V6 (Canada); Fast, Mark [Department of Pathology and Microbiology, Atlantic Veterinary College, University of Prince Edward Island, Charlottetown, PE, C1A 4P3 (Canada); Stevens, Don [Department of Biomedical Sciences, Atlantic Veterinary College, University of Prince Edward Island, Charlottetown, PE, C1A 4P3 (Canada); Kibenge, Fred [Department of Pathology and Microbiology, Atlantic Veterinary College, University of Prince Edward Island, Charlottetown, PE, C1A 4P3 (Canada); Siah, Ahmed [British Columbia Centre for Aquatic Health Sciences, 871A Island Highway, Campbell River, BC, V9W 2C2 (Canada); Kamunde, Collins, E-mail: [Department of Biomedical Sciences, Atlantic Veterinary College, University of Prince Edward Island, Charlottetown, PE, C1A 4P3 (Canada)


    Highlights: • Sequential inhibition and activation allows assessment of multiple segments of the electron transport system. • Warm acclimation and hypoxia-reoxygenation have global effects on the electron transport system. • Warm acclimation and hypoxia-reoxygenation sensitize the electron transport system to copper. • Thermal stress, hypoxia-reoxygenation and copper act additively to impair mitochondrial function. - Abstract: Fish expend significant amounts of energy to handle the numerous potentially stressful biotic and abiotic factors that they commonly encounter in aquatic environments. This universal requirement for energy singularizes mitochondria, the primary cellular energy transformers, as fundamental drivers of responses to environmental change. Our study probed the interacting effects of thermal stress, hypoxia-reoxygenation (HRO) and copper (Cu) exposure in rainbow trout to test the prediction that they act jointly to impair mitochondrial function. Rainbow trout were acclimated to 11 (controls) or 20 °C for 2 months. Liver mitochondria were then isolated and their responses in vitro to Cu (0–20 μM) without and with HRO were assessed. Sequential inhibition and activation of mitochondrial electron transport system (ETS) enzyme complexes permitted the measurement of respiratory activities supported by complex I–IV (CI–IV) in one run. The results showed that warm acclimation reduced fish and liver weights but increased mitochondrial protein indicating impairment of energy metabolism, increased synthesis of defense proteins and/or reduced liver water content. Whereas acute rise (11 → 20 °C) in temperature increased mitochondrial oxidation rates supported by CI–IV, warm acclimation reduced the maximal (state 3) and increased the basal (state 4) respiration leading to global uncoupling of oxidative phosphorylation (OXPHOS). HRO profoundly inhibited both maximal and basal respiration rates supported by CI–IV, reduced RCR for all except

  1. Histological alterations on the structure of the excretory renal system in tench (Tinca tinca) after exposure to 17-alpha-ethynylestradiol. (United States)

    Oropesa, A L; Jiménez, B; Fallola, C; Pula, H J; Cuesta, J M; Gómez, L


    This study describes the effects of 17-alpha-ethynylestradiol (EE2) on the structure of the excretory system of the kidney in tench. Adult male tench were exposed to sub-lethal doses of EE2 (50, 100 and 500 μg/kg b.w.) under semistatic conditions for a period of 30 days. The nephrosomatic index and histology (including a morphometric analysis) of the kidney were examined. Histopathological lesions in the kidney of exposed tench were: dilation of glomerular capillaries and increase in the area of the renal corpuscle, hyaline degeneration in the epithelial cells of the proximal tubules leading to necrotic changes, hemorrhages in the interstitial tissue and deposits of eosinophilic material. These lesions were observed with a greater degree of severity as the exposure doses were increased. These results indicate that long-term exposure to EE2 could produce clear negative effects on the excretory system of the kidney in tench and consequently on their physiological functions.

  2. Preference alters consumptive effects of predators: top-down effects of a native crab on a system of native and introduced prey.

    Directory of Open Access Journals (Sweden)

    Emily W Grason

    Full Text Available Top-down effects of predators in systems depend on the rate at which predators consume prey, and on predator preferences among available prey. In invaded communities, these parameters might be difficult to predict because ecological relationships are typically evolutionarily novel. We examined feeding rates and preferences of a crab native to the Pacific Northwest, Cancer productus, among four prey items: two invasive species of oyster drill (the marine whelks Urosalpinx cinerea and Ocenebra inornata and two species of oyster (Crassostrea gigas and Ostrea lurida that are also consumed by U. cinerea and O. inornata. This system is also characterized by intraguild predation because crabs are predators of drills and compete with them for prey (oysters. When only the oysters were offered, crabs did not express a preference and consumed approximately 9 juvenile oysters crab(-1 day(-1. We then tested whether crabs preferred adult drills of either U. cinerea or O. inornata, or juvenile oysters (C. gigas. While crabs consumed drills and oysters at approximately the same rate when only one type of prey was offered, they expressed a strong preference for juvenile oysters over drills when they were allowed to choose among the three prey items. This preference for oysters might negate the positive indirect effects that crabs have on oysters by crabs consuming drills (trophic cascade because crabs have a large negative direct effect on oysters when crabs, oysters, and drills co-occur.

  3. Gut Dendritic Cell Activation Links an Altered Colonic Microbiome to Mucosal and Systemic T Cell Activation in Untreated HIV-1 infection (United States)

    Dillon, SM; Lee, EJ; Kotter, CV; Austin, GL; Gianella, S; Siewe, B; Smith, DM; Landay, AL; McManus, MC; Robertson, CE; Frank, DN; McCarter, MD; Wilson, CC


    HIV-1-associated disruption of intestinal homeostasis is a major factor contributing to chronic immune activation and inflammation. Dendritic cells (DCs) are crucial in maintaining intestinal homeostasis, but the impact of HIV-1 infection on intestinal DC number and function has not been extensively studied. We compared the frequency and activation/maturation status of colonic myeloid DC (mDC) subsets (CD1c+ and CD1cneg) and plasmacytoid DCs in untreated HIV-1-infected subjects with uninfected controls. Colonic mDCs in HIV-1-infected subjects had increased CD40 but decreased CD83 expression, and CD40 expression on CD1c+ mDCs positively correlated with mucosal HIV-1 viral load, with mucosal and systemic cytokine production, and with frequencies of activated colon and blood T cells. Percent of CD83+CD1c+ mDCs negatively correlated with frequencies of IFN-γ-producing colon CD4+ and CD8+ T cells. CD40 expression on CD1c+ mDCs positively associated with abundance of high prevalence mucosal Prevotella copri and P. stercorea, but negatively associated with a number of low prevalence mucosal species including Rumminococcus bromii. CD1c+ mDC cytokine production was greater in response to in vitro stimulation with Prevotella species relative to R. bromii. These findings suggest that during HIV infection, colonic mDCs become activated upon exposure to mucosal pathobiont bacteria leading to mucosal and systemic immune activation. PMID:25921339

  4. Alterações funcionais do sistema estomatognático em pacientes com rinite alérgica: estudo caso-controle Functional alterations of the stomatognathic system in pacients with allergic rhinitis: case-control study

    Directory of Open Access Journals (Sweden)

    Catiane Maçaira de Lemos


    Full Text Available A respiração oral pode acarretar alterações estruturais e funcionais do sistema estomatognático. OBJETIVO: Verificar a presença de alterações das funções de respiração, mastigação, deglutição e fala em pacientes com rinite alérgica e relacioná-as com a intensidade dos sintomas da rinite. MATERIAL E MÉTODOS: Para este estudo prospectivo, foram avaliados 170 pacientes com faixa etária entre 6 e 55 anos de idade. Todos os pacientes passaram por avaliação otorrinolaringológica e fonoaudiológica. Foram colhidos os dados referentes às funções de respiração, mastigação, deglutição e fala e dados da consulta médica. Os dados foram comparados e analisados estatisticamente. RESULTADOS: A diferença dos escores de sinais e sintomas entre GR e GC mostrou-se estatisticamente significante. Quando comparada a presença de alteração nas funções estudadas entre GR e GC, foi observada diferença estatisticamente significante no modo respiratório e nos padrões de mastigação e deglutição. A correlação existente entre o escore de obstrução nasal e a presença de alteração funcional foi significante na análise do modo respiratório e do padrão de mastigação. CONCLUSÃO: O paciente com rinite alérgica apresenta alterações funcionais do sistema estomatognático e o aumento do escore de obstrução nasal pode ser considerado um indicativo destas alterações.Mouth breathing can cause structural and functional alterations to the stomatognathic system. AIM: the aim of this investigation was to study breathing, chewing, swallowing and speaking alterations present in patients with allergic rhinitis and associate it to rhinitis symptom intensity. MATERIALS AND METHODS: 170 patients between the ages of 6 and 55 years were prospectively evaluated in this study, all of them underwent both otorhinolaryngological and speech evaluation. Data on breathing, chewing, swallowing and speaking was gathered, as well as data from

  5. Low birth weight in response to salt restriction during pregnancy is not due to alterations in uterine-placental blood flow or the placental and peripheral renin-angiotensin system. (United States)

    Leandro, Sandra Márcia; Furukawa, Luzia Naôko Shinohara; Shimizu, Maria Heloisa Massola; Casarini, Dulce Elena; Seguro, Antonio Carlos; Patriarca, Giuliana; Coelho, Michella Soares; Dolnikoff, Miriam Sterman; Heimann, Joel Claudio


    A number of studies conducted in humans and in animals have observed that events occurring early in life are associated with the development of diseases in adulthood. Salt overload and restriction during pregnancy and lactation are responsible for functional (hemodynamic and hormonal) and structural alterations in adult offspring. Our group observed that lower birth weight and insulin resistance in adulthood is associated with salt restriction during pregnancy. On the other hand, perinatal salt overload is associated with higher blood pressure and higher renal angiotensin II content in adult offspring. Therefore, we hypothesised that renin-angiotensin system (RAS) function is altered by changes in sodium intake during pregnancy. Such changes may influence fetoplacental blood flow and thereby fetal nutrient supply, with effects on growth in utero and, consequently, on birth weight. Female Wistar rats were fed low-salt (LS), normal-salt (NS), or high-salt (HS) diet, starting before conception and continuing until day 19 of pregnancy. Blood pressure, heart rate, fetuses and dams' body weight, placentae weight and litter size were measured on day 19 of pregnancy. Cardiac output, uterine and placental blood flow were also determined on day 19. Expressions of renin-angiotensin system components and of the TNF-alpha gene were evaluated in the placentae. Plasma renin activity (PRA) and plasma and tissue angiotensin-converting enzyme (ACE) activity, as well as plasma and placental levels of angiotensins I, II, and 1-7 were measured. Body weight and kidney mass were greater in HS than in NS and LS dams. Food intake did not differ among the maternal groups. Placental weight was lower in LS dams than in NS and HS dams. Fetal weight was lower in the LS group than in the NS and HS groups. The PRA was greater in LS dams than in NS and HS dams, although ACE activity (serum, cardiac, renal, and placental) was unaffected by the level of sodium intake. Placental levels of

  6. Luminescence of thermally altered human skeletal remains

    NARCIS (Netherlands)

    Krap, Tristan; Nota, Kevin; Wilk, Leah; van de Goot, Frank; Ruijter, Jan; Duijst, Wilma; Oostra, Roelof Jan


    Literature on luminescent properties of thermally altered human remains is scarce and contradictory. Therefore, the luminescence of heated bone was systemically reinvestigated. A heating experiment was conducted on fresh human bone, in two different media, and cremated human remains were recovered

  7. Multisensory integration: how sound alters sight. (United States)

    Kerlin, Jess R; Shapiro, Kimron L


    What we hear can rapidly alter what we see. A new study provides evidence for a mechanism in which 10 Hz oscillations in the visual system define the time window for integrating auditory and visual information. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Zolpidem, A Clinical Hypnotic that Affects Electronic Transfer, Alters Synaptic Activity Through Potential Gaba Receptors in the Nervous System Without Significant Free Radical Generation

    Directory of Open Access Journals (Sweden)

    Peter Kovacic


    Full Text Available Zolpidem (trade name Ambien has attracted much interest as a sleep-inducing agent and also in research. Attention has been centered mainly on receptor binding and electrochemistry in the central nervous system which are briefly addressed herein. A novel integrated approach to mode of action is presented. The pathways to be discussed involve basicity, reduction potential, electrostatics, cell signaling, GABA receptor binding, electron transfer (ET, pharmacodynamics, structure activity relationships (SAR and side effects. The highly conjugated pyridinium salt formed by protonation of the amidine moiety is proposed to be the active form acting as an ET agent. Extrapolation of reduction potentials for related compounds supports the premise that zolpidem may act as an ET species in vivo. From recent literature reports, electrostatics is believed to play a significant role in drug action.

  9. Repetitive systemic morphine alters activity-dependent plasticity of Schaffer-collateral-CA1 pyramidal cell synapses: involvement of adenosine A1 receptors and adenosine deaminase. (United States)

    Sadegh, Mehdi; Fathollahi, Yaghoub


    The effectiveness of O-pulse stimulation (TPS) for the reversal of O-pattern primed bursts (PB)-induced long-term potentiation (LTP) were examined at the Schaffer-collateral-CA1 pyramidal cell synapses of hippocampal slices derived from rats chronically treated with morphine (M-T). The results showed that slices derived from both control and M-T rats had normal field excitatory postsynaptic potential (fEPSP)-LTP, whereas PS-LTP in slices from M-T rats was significantly greater than that from control slices. When morphine was applied in vitro to slices derived from rats chronically treated with morphine, the augmentation of PS-LTP was not seen. TPS given 30 min after LTP induction failed to reverse the fEPSP- or PS-LTP in both groups of slices. However, TPS delivered in the presence of long-term in vitro morphine caused the PS-LTP reversal. This effect was blocked by the adenosine A1 receptor (A1R) antagonist CPX (200 nM) and furthermore was enhanced by the adenosine deaminase (ADA) inhibitor EHNA (10 μM). Interestingly, TPS given 30 min after LTP induction in the presence of EHNA (10 μM) can reverse LTP in morphine-exposed control slices in vitro. These results suggest adaptive changes in the hippocampus area CA1 in particular in adenosine system following repetitive systemic morphine. Chronic in vivo morphine increases A1R and reduces ADA activity in the hippocampus. Consequently, adenosine can accumulate because of a stimulus train-induced activity pattern in CA1 area and takes the opportunity to work as an inhibitory neuromodulator and also to enable CA1 to cope with chronic morphine. In addition, adaptive mechanisms are differentially working in the dendrite layer rather than the somatic layer of hippocampal CA1.

  10. How temperature-dependent elasticity alters host rock/magmatic reservoir models: A case study on the effects of ice-cap unloading on shallow volcanic systems (United States)

    Bakker, Richard R.; Frehner, Marcel; Lupi, Matteo


    In geodynamic numerical models of volcanic systems, the volcanic basement hosting the magmatic reservoir is often assumed to exhibit constant elastic parameters with a sharp transition from the host rocks to the magmatic reservoir. We assess this assumption by deriving an empirical relation between elastic parameters and temperature for Icelandic basalts by conducting a set of triaxial compression experiments between 200 °C and 1000 °C. Results show a significant decrease of Young's modulus from ∼38 GPa to less than 4.7 GPa at around 1000 °C. Based on these laboratory data, we develop a 2D axisymmetric finite-element model including temperature-dependent elastic properties of the volcanic basement. As a case study, we use the Snæfellsjökull volcanic system, Western Iceland to evaluate pressure differences in the volcanic edifice and basement due to glacial unloading of the volcano. First, we calculate the temperature field throughout the model and assign elastic properties accordingly. Then we assess unloading-driven pressure differences in the magma chamber at various depths in models with and without temperature-dependent elastic parameters. With constant elastic parameters and a sharp transition between basement and magma chamber we obtain results comparable to other studies. However, pressure changes due to surface unloading become smaller when using more realistic temperature-dependent elastic properties. We ascribe this subdued effect to a transition zone around the magma chamber, which is still solid rock but with relatively low Young's modulus due to high temperatures. We discuss our findings in the light of volcanic processes in proximity to the magma chamber, such as roof collapse, dyke injection, or deep hydrothermal circulation. Our results aim at quantifying the effects of glacial unloading on magma chamber dynamics and volcanic activity.

  11. Time-dependent alterations in growth, photosynthetic pigments and enzymatic defense systems of submerged Ceratophyllum demersum during exposure to the cyanobacterial neurotoxin anatoxin-a

    Energy Technology Data Exchange (ETDEWEB)

    Ha, Mi-Hee; Pflugmacher, Stephan, E-mail:


    Highlights: •We examined time-dependent metabolic changes in C. demersum exposed to anatoxin-a. •Biotransformation and antioxidative defense mechanisms responded positively to anatoxin-a. •Decline in chlorophylls contents was detected in company with irreversible plant growth inhibition during exposure to anatoxin-a. •Anatoxin-a exhibits phytotoxic allelopathy by provoking oxidative stress. •Macrophytes may have interactions with anatoxin-a in aquatic environments. -- Abstract: Recently, aquatic macrophytes have been considered as promising tools for eco-friendly water management with a low running cost. However, only little information is available thus far regarding the metabolic capacity of macrophytes for coping with cyanobacterial toxins (cyanotoxins) in the aquatic environment. Cyanotoxins have become emerging contaminants of great concern due to the high proliferation of cyanobacteria (cyanobacterial bloom) accelerated by eutrophication and climate change. Anatoxin-a, one of the common and major cyanotoxins, is suggested as a high priority water pollutant for regulatory consideration owing to its notoriously rapid mode of action as a neurotoxin. In this study, the time-course metabolic regulation of the submerged macrophyte Ceratophyllum demersum (C. demersum) was investigated during exposure to anatoxin-a at an environmentally relevant concentration (15 μg/L). Biotransformation and antioxidative systems in C. demersum responded positively to anatoxin-a through the promoted synthesis of most of the involved enzymes within 8 h. Maximum enzyme activities were exhibited after 24 or 48 h of exposure to anatoxin-a. However, an apparent decline in enzyme activities was also observed at longer exposure duration (168 and 336 h) in company with high steady-state levels of cell internal H{sub 2}O{sub 2}, which showed its highest level after 48 h. Meanwhile, irreversible inhibitory influence on chlorophyll content (vitality) was noticed, whereas the ratio of

  12. Zolpidem, a clinical hypnotic that affects electronic transfer, alters synaptic activity through potential GABA receptors in the nervous system without significant free radical generation. (United States)

    Kovacic, Peter; Somanathan, Ratnasamy


    Zolpidem (trade name Ambien) has attracted much interest as a sleep-inducing agent and also in research. Attention has been centered mainly on receptor binding and electrochemistry in the central nervous system which are briefly addressed herein. A novel integrated approach to mode of action is presented. The pathways to be discussed involve basicity, reduction potential, electrostatics, cell signaling, GABA receptor binding, electron transfer (ET), pharmacodynamics, structure activity relationships (SAR) and side effects. The highly conjugated pyridinium salt formed by protonation of the amidine moiety is proposed to be the active form acting as an ET agent. Extrapolation of reduction potentials for related compounds supports the premise that zolpidem may act as an ET species in vivo. From recent literature reports, electrostatics is believed to play a significant role in drug action. The pyridinium cation displays molecular electrostatic potential which may well play a role energetically or as a bridging mechanism. An SAR analysis points to analogy with other physiologically active xenobiotics, namely benzodiazepines and paraquat in the conjugated iminium category. Inactivity of metabolites indicates that the parent is the active form of zolpidem. Absence of reactive oxygen species and oxidative stress is in line with minor side effects. In contrast, generally, the prior literature contains essentially no discussion of these fundamental biochemical relationships. Pharmacodynamics may play an important role. Concerning behavior at the blood-brain barrier, useful insight can be gained from investigations of the related cationic anesthetics that are structurally related to acetyl choline. Evidently, the neutral form of the drug penetrates the neuronal membrane, with the salt form operating at the receptor. The pathways of zolpidem have several clinical implications since the agent affects sedation, electroencephalographic activity, oxidative metabolites and

  13. Prenylation of a Rab1B mutant with altered GTPase activity is impaired in cell-free systems but not in intact mammalian cells. (United States)

    Wilson, A L; Sheridan, K M; Erdman, R A; Maltese, W A


    Previous studies have reached differing conclusions as to whether or not guanine-nucleotide-dependent conformational changes affect the ability of Rab proteins to undergo post-translational modification by Rab:geranylgeranyltransferase (Rab-GGTase). We now show that the ability of a Rab1B mutant [Q67L (Gln-67-->Leu)] with reduced intrinsic GTPase activity to undergo geranylgeranylation in cell-free assays depends on the guanine nucleotide composition of the system. When GTP is the predominant nucleotide in the assay, Rab1BQ67L is a poor substrate. However, when GDP is present and GTP is omitted, prenylation of the Q67L mutant is comparable with that of the wild-type (WT) protein. These studies, coupled with the poor prenylation of Rab1BWT in the presence of the non-hydrolysable GTP analogue guanosine 5'-[gamma-thio]triphosphate, support the notion that Rab-GGTase prefers substrates in the GDP conformation. When the abilities of Rab1BQ67L and Rab1BWT to undergo prenylation were compared by metabolic labelling of transiently expressed proteins in cultured human 293 cells, we did not observe a decline in prenylation of the mutant protein as predicted on the basis of the cell-free assays. Moreover, the Q67L mutant was comparable with the wild-type Rab1B in its ability to associate with co-expressed Rab GDP dissociation inhibitors in 293 cells. These findings raise the possibility that unidentified proteins present in intact cells may compensate for the reduced intrinsic GTPase activity of the Q67L mutant, allowing a significant proportion of the nascent Rab1BQ67L to assume a GDP conformation. The differential prenylation of Rab1BQ67L in cell-free systems versus intact cells underscores the importance of evaluating the post-translational modification of specific Rab mutants in vivo, where poorly characterized regulatory proteins may have a significant effect on GTPase activity or nucleotide exchange rates.

  14. The renin-angiotensin system: a target of and contributor to dyslipidemias, altered glucose homeostasis, and hypertension of the metabolic syndrome. (United States)

    Putnam, Kelly; Shoemaker, Robin; Yiannikouris, Frederique; Cassis, Lisa A


    The renin-angiotensin system (RAS) is an important therapeutic target in the treatment of hypertension. Obesity has emerged as a primary contributor to essential hypertension in the United States and clusters with other metabolic disorders (hyperglycemia, hypertension, high triglycerides, low HDL cholesterol) defined within the metabolic syndrome. In addition to hypertension, RAS blockade may also serve as an effective treatment strategy to control impaired glucose and insulin tolerance and dyslipidemias in patients with the metabolic syndrome. Hyperglycemia, insulin resistance, and/or specific cholesterol metabolites have been demonstrated to activate components required for the synthesis [angiotensinogen, renin, angiotensin-converting enzyme (ACE)], degradation (ACE2), or responsiveness (angiotensin II type 1 receptors, Mas receptors) to angiotensin peptides in cell types (e.g., pancreatic islet cells, adipocytes, macrophages) that mediate specific disorders of the metabolic syndrome. An activated local RAS in these cell types may contribute to dysregulated function by promoting oxidative stress, apoptosis, and inflammation. This review will discuss data demonstrating the regulation of components of the RAS by cholesterol and its metabolites, glucose, and/or insulin in cell types implicated in disorders of the metabolic syndrome. In addition, we discuss data supporting a role for an activated local RAS in dyslipidemias and glucose intolerance/insulin resistance and the development of hypertension in the metabolic syndrome. Identification of an activated RAS as a common thread contributing to several disorders of the metabolic syndrome makes the use of angiotensin receptor blockers and ACE inhibitors an intriguing and novel option for multisymptom treatment.

  15. Neural Crest Cell Implantation Restores Enteric Nervous System Function and Alters the Gastrointestinal Transcriptome in Human Tissue-Engineered Small Intestine

    Directory of Open Access Journals (Sweden)

    Christopher R. Schlieve


    Full Text Available Acquired or congenital disruption in enteric nervous system (ENS development or function can lead to significant mechanical dysmotility. ENS restoration through cellular transplantation may provide a cure for enteric neuropathies. We have previously generated human pluripotent stem cell (hPSC-derived tissue-engineered small intestine (TESI from human intestinal organoids (HIOs. However, HIO-TESI fails to develop an ENS. The purpose of our study is to restore ENS components derived exclusively from hPSCs in HIO-TESI. hPSC-derived enteric neural crest cell (ENCC supplementation of HIO-TESI establishes submucosal and myenteric ganglia, repopulates various subclasses of neurons, and restores neuroepithelial connections and neuron-dependent contractility and relaxation in ENCC-HIO-TESI. RNA sequencing identified differentially expressed genes involved in neurogenesis, gliogenesis, gastrointestinal tract development, and differentiated epithelial cell types when ENS elements are restored during in vivo development of HIO-TESI. Our findings validate an effective approach to restoring hPSC-derived ENS components in HIO-TESI and may implicate their potential for the treatment of enteric neuropathies.

  16. Neurobiological alterations in alcohol addiction: a review. (United States)

    Erdozain, Amaia M; Callado, Luis F


    The exact mechanism by which ethanol exerts its effects on the brain is still unknown. However, nowadays it is well known that ethanol interacts with specific neuronal membrane proteins involved in signal transmission, resulting in changes in neural activity. In this review different neurochemical alterations produced by ethanol are described. Primarily, ethanol interacts with two membrane receptors: GABAA and NMDA ion channel receptors. Ethanol enhances the GABA action and antagonizes glutamate action, therefore acting as a CNS depressant. In addition, ethanol affects most other neurochemical and endocrine systems. In regard to the brain reward system, both dopaminergic and opioid system are affected by this drug. Furthermore, the serotonergic, noradrenergic, corticotropin-releasing factor and cannabinoid systems seem to play an important role in the neurobiology of alcoholism. At last but not least, ethanol can also modulate cytoplasmic components, including the second messengers. We also review briefly the different actual and putative pharmacological treatments for alcoholism, based on the alterations produced by this drug.

  17. Altered Th17 cells and Th17/regulatory T-cell ratios indicate the subsequent conversion from undifferentiated connective tissue disease to definitive systemic autoimmune disorders. (United States)

    Szodoray, Peter; Nakken, Britt; Barath, Sandor; Csipo, Istvan; Nagy, Gabor; El-Hage, Fadi; Osnes, Liv T; Szegedi, Gyula; Bodolay, Edit


    A shift in the balance between Th17-cells and regulatory T-cells (Treg) is an important feature of systemic autoimmune diseases (SAID), and may also contribute to their development. Hereby, we assessed the distribution of peripheral Th17 and Treg-cells in patients with undifferentiated connective tissue disease (UCTD), the forerunner of SAIDs and followed these parameters during the development towards definitive SAIDs. Fifty-one UCTD patients were investigated and followed-up for 3 years. Flow cytometry was used to identify and follow three cell-populations: Th17-cells (CD4+IL-17+ T-cells), natural regulatory T-cells (CD4(+)CD25(bright)FoxP3(+); nTregs) and IL-10 producing Type-1 regulatory T-cells (CD4+IL-10+ T-cells; Tr1). Altogether 37.3% of these patients progressed into SAIDs. Th17-cells were increased in UCTD vs. controls, which further increased in those, whom developed SAIDs eventually. The Th17/nTreg ratio gradually increased from controls through UCTD patients, reaching the highest values in SAID-progressed patients. Regarding the Th17/Tr1 ratios, a similar tendency was observed moreover Th17/Tr1 could distinguish between UCTD patients with, or without subsequent SAID progression in a very early UCTD stage. Various immunoserological markers showed association with Th17 and Th17/nTreg at baseline, indicating the consecutive development of a distinct SAID. The derailed Th17/Treg balance may contribute to disease progression therefore could function as a prognostic marker.

  18. Maternal nicotine exposure during lactation alters food preference, anxiety-like behavior and the brain dopaminergic reward system in the adult rat offspring. (United States)

    Pinheiro, C R; Moura, E G; Manhães, A C; Fraga, M C; Claudio-Neto, S; Younes-Rapozo, V; Santos-Silva, A P; Lotufo, B M; Oliveira, E; Lisboa, P C


    The mesolimbic reward pathway is activated by drugs of abuse and palatable food, causing a sense of pleasure, which promotes further consumption of these substances. Children whose parents smoke are more vulnerable to present addictive-like behavior to drugs and food.We evaluated the association between maternal nicotine exposure during lactation with changes in feeding, behavior and in the dopaminergic reward system. On postnatal day (PN) 2,Wistar rat dams were implanted with minipumps releasing nicotine (N; 6 mg/kg/day, s.c.) or saline (C) for 14 days. On PN150 and PN160, offspring were divided into 4 groups for a food challenge: N and C that received standard chow(SC); and N and C that could freely self-select (SSD) between high-fat and high-sugar diets (HFD and HSD, respectively). Offspring were tested in the elevated plus maze (EPM) and open field (OF) arena on PN152–153. On PN170, offspring were euthanized for central dopaminergic analysis. SSD animals showed an increased food intake compared to SC ones and a preference for HFD. However, N-SSD animals consumed relatively more HSD than C-SSD ones. Regarding behavior, N animals showed an increase in the time spent in the EPM center and a reduction in relative activity in the OF center. N offspring presented lower dopamine receptor (D2R) and transporter (DAT) contents in the nucleus accumbens, and lower D2R in the arcuate nucleus. Postnatal exposure to nicotine increases preference for sugar and anxiety levels in the adult progeny possibly due to a decrease in dopaminergic action in the nucleus accumbens and arcuate nucleus.

  19. Differential contribution of plant-beneficial functions from Pseudomonas kilonensis F113 to root system architecture alterations in Arabidopsis thaliana and Zea mays. (United States)

    Vacheron, Jordan; Desbrosses, Guilhem; Renoud, Sébastien; Padilla-Aguilar, Rosa-Maria; Walker, Vincent; Muller, Daniel; Prigent-Combaret, Claire


    Fluorescent pseudomonads are playing key roles in plant-bacteria symbiotic interactions due to the multiple plant-beneficial functions (PBFs) they are harboring. The relative contributions of PBFs to plant-stimulatory effects of the well-known PGPR Pseudomonas kilonensis F113 (formerly P. fluorescens F113) were investigated using a genetic approach. To this end, several deletion mutants were constructed: simple mutants ΔphlD (impaired in the biosynthesis of 2,4-diacetylphloroglucinol [DAPG]), ΔacdS (deficient in 1-aminocyclopropane-1-carboxylate [ACC] deaminase activity), Δgcd (glucose dehydrogenase deficient, impaired in phosphate solubilization), and ΔnirS (nitrite reductase deficient) and a quadruple mutant (deficient in the 4 PBFs mentioned above). Every PBF activity was quantified in the wild-type strain and the five deletion mutants. This approach revealed few functional interactions between PBFs in vitro. In particular, biosynthesis of glucose dehydrogenase severely reduced the production of DAPG. Contrariwise, the DAPG production impacted positively, but to a lesser extent, phosphate solubilization. Inoculation of the F113 wild-type strain on Arabidopsis thaliana Col-0 and maize seedlings modified the root architecture of both plants. Mutant strain inoculations revealed that the relative contribution of each PBF differed according to the measured plant traits, and that F113 plant-stimulatory effects did not correspond to the sum of each PBF relative contribution. Indeed, two PBF genes (ΔacdS and ΔnirS) had a significant impact on root system architecture from both model plants, whether in in vitro and in vivo conditions. The current work underlined that few F113 PBFs seem to interact between each other in the free-living bacterial cells, whereas they control in concert Arabidopsis thaliana and maize growth and development.

  20. Alterations in physiology and anatomy during pregnancy. (United States)

    Tan, Eng Kien; Tan, Eng Loy


    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.

  1. What is needed to understand feedback mechanisms from agricultural and climate changes that can alter the hydrological system and the transport of sediments and agricultural chemicals? (United States)

    Coupe, Richard; Payraudeau, Sylvain; Babcsányi, Izabella; Imfeld, Gwenaël


    Modern agriculture activities are constantly changing as producers try to produce a crop, keep their soils fertile, control pests, and prevent contamination of air and water resources. Because most of the world's arable land is already in production we must become more efficient if we are to feed and clothe the world's growing population as well as do this in a sustainable manner; leaving a legacy of fertile soil and clean water resources for our descendants. The objective of this paper is to demonstrate the importance of historical datasets and of developing new strategies to understand the effects of changing agricultural systems on the environment. Scientists who study agriculture and its effects on water must constantly adapt their strategies and evaluate how changing agricultural activities impact the environment. As well as understand from historical datasets on hydrology and agriculture how a changing climate or agricultural activity such as a change in tillage method might impact the processes that determine the movement of agricultural chemicals off of the target site. The 42.7 ha Hohrain (Rouffach, Alsace, France) vineyard experimental catchment offers several examples of how scientists have used historical data from this catchment to understand how the transport of agricultural chemicals may change due to a changing climate as well as how new strategies are developed for understanding the transport of agricultural chemicals. Runoff is a major process of pesticide transport from agricultural land to downstream aquatic ecosystems. The impact of rainfall characteristics on the transport of runoff-related pesticides is crucial to understanding how to prevent or minimize their movement now, but also in understanding how climate change might affect runoff. If we understand how rainfall characteristics affect the transport of pesticides, we can use climate change models to predict how those characteristics might change in the future and be better prepared for

  2. Disruption of glucocorticoid receptors in the noradrenergic system leads to BDNF up-regulation and altered serotonergic transmission associated with a depressive-like phenotype in female GR(DBHCre) mice. (United States)

    Chmielarz, Piotr; Kreiner, Grzegorz; Kot, Marta; Zelek-Molik, Agnieszka; Kowalska, Marta; Bagińska, Monika; Daniel, Władysława Anna; Nalepa, Irena


    Recently, we have demonstrated that conditional inactivation of glucocorticoid receptors (GRs) in the noradrenergic system, may evoke depressive-like behavior in female but not male mutant mice (GR(DBHCre) mice). The aim of the current study was to dissect how selective ablation of glucocorticoid signaling in the noradrenergic system influences the previously reported depressive-like phenotype and whether it might be linked to neurotrophic alterations or secondary changes in the serotonergic system. We demonstrated that selective depletion of GRs enhances brain derived neurotrophic factor (BDNF) expression in female but not male GR(DBHCre) mice on both the mRNA and protein levels. The possible impact of the mutation on brain noradrenergic and serotonergic systems was addressed by investigating the tissue neurotransmitter levels under basal conditions and after acute restraint stress. The findings indicated a stress-provoked differential response in tissue noradrenaline content in the GR(DBHCre) female but not male mutant mice. An analogous gender-specific effect was identified in the diminished content of 5-hydroxyindoleacetic acid, the main metabolite of serotonin, in the prefrontal cortex, which suggests down-regulation of this monoamine system in female GR(DBHCre) mice. The lack of GR also resulted in an up-regulation of alpha2-adrenergic receptor (α2-AR) density in the female but not male mutants in the locus coeruleus. We have also confirmed the utility of the investigated model in pharmacological studies, which demonstrates that the depressive-like phenotype of GR(DBHCre) female mice can be reversed by antidepressant treatment with desipramine or fluoxetine, with the latter drug evoking more pronounced effects. Overall, our study validates the use of female GR(DBHCre) mice as an interesting and novel genetic tool for the investigation of the cross-connected mechanisms of depression that is not only based on behavioral phenotypes.

  3. Genetic Alterations in Glioma

    Energy Technology Data Exchange (ETDEWEB)

    Bralten, Linda B. C.; French, Pim J., E-mail: [Department of Neurology, Erasmus University Medical Center, Erasmus University Rotterdam, Dr Molewaterplein 50, 3000 CA, Rotterdam (Netherlands)


    Gliomas are the most common type of primary brain tumor and have a dismal prognosis. Understanding the genetic alterations that drive glioma formation and progression may help improve patient prognosis by identification of novel treatment targets. Recently, two major studies have performed in-depth mutation analysis of glioblastomas (the most common and aggressive subtype of glioma). This systematic approach revealed three major pathways that are affected in glioblastomas: The receptor tyrosine kinase signaling pathway, the TP53 pathway and the pRB pathway. Apart from frequent mutations in the IDH1/2 gene, much less is known about the causal genetic changes of grade II and III (anaplastic) gliomas. Exceptions include TP53 mutations and fusion genes involving the BRAF gene in astrocytic and pilocytic glioma subtypes, respectively. In this review, we provide an update on all common events involved in the initiation and/or progression across the different subtypes of glioma and provide future directions for research into the genetic changes.

  4. Music alters visual perception.

    Directory of Open Access Journals (Sweden)

    Jacob Jolij

    Full Text Available BACKGROUND: Visual perception is not a passive process: in order to efficiently process visual input, the brain actively uses previous knowledge (e.g., memory and expectations about what the world should look like. However, perception is not only influenced by previous knowledge. Especially the perception of emotional stimuli is influenced by the emotional state of the observer. In other words, how we perceive the world does not only depend on what we know of the world, but also by how we feel. In this study, we further investigated the relation between mood and perception. METHODS AND FINDINGS: We let observers do a difficult stimulus detection task, in which they had to detect schematic happy and sad faces embedded in noise. Mood was manipulated by means of music. We found that observers were more accurate in detecting faces congruent with their mood, corroborating earlier research. However, in trials in which no actual face was presented, observers made a significant number of false alarms. The content of these false alarms, or illusory percepts, was strongly influenced by the observers' mood. CONCLUSIONS: As illusory percepts are believed to reflect the content of internal representations that are employed by the brain during top-down processing of visual input, we conclude that top-down modulation of visual processing is not purely predictive in nature: mood, in this case manipulated by music, may also directly alter the way we perceive the world.

  5. Altered Perspectives: Immersive Environments (United States)

    Shipman, J. S.; Webley, P. W.


    Immersive environments provide an exciting experiential technology to visualize the natural world. Given the increasing accessibility of 360o cameras and virtual reality headsets we are now able to visualize artistic principles and scientific concepts in a fully immersive environment. The technology has become popular for photographers as well as designers, industry, educational groups, and museums. Here we show a sci-art perspective on the use of optics and light in the capture and manipulation of 360o images and video of geologic phenomena and cultural heritage sites in Alaska, England, and France. Additionally, we will generate intentionally altered perspectives to lend a surrealistic quality to the landscapes. Locations include the Catacombs of Paris, the Palace of Versailles, and the Northern Lights over Fairbanks, Alaska. Some 360o view cameras now use small portable dual lens technology extending beyond the 180o fish eye lens previously used, providing better coverage and image quality. Virtual reality headsets range in level of sophistication and cost, with the most affordable versions using smart phones and Google Cardboard viewers. The equipment used in this presentation includes a Ricoh Theta S spherical imaging camera. Here we will demonstrate the use of 360o imaging with attendees being able to be part of the immersive environment and experience our locations as if they were visiting themselves.

  6. Network community structure alterations in adult schizophrenia: identification and localization of alterations. (United States)

    Lerman-Sinkoff, Dov B; Barch, Deanna M


    A growing body of literature suggests functional connectivity alterations in schizophrenia. While findings have been mixed, evidence points towards a complex pattern of hyper-connectivity and hypo-connectivity. This altered connectivity can be represented and analyzed using the mathematical frameworks provided by graph and information theory to represent functional connectivity data as graphs comprised of nodes and edges linking the nodes. One analytic technique in this framework is the determination and analysis of network community structure, which is the grouping of nodes into linked communities or modules. This data-driven technique finds a best-fit structure such that nodes in a given community have greater connectivity with nodes in their community than with nodes in other communities. These community structure representations have been found to recapitulate known neural-systems in healthy individuals, have been used to identify novel functional systems, and have identified and localized community structure alterations in a childhood onset schizophrenia cohort. In the present study, we sought to determine whether community structure alterations were present in an adult onset schizophrenia cohort while stringently controlling for sources of imaging artifacts. Group level average graphs in healthy controls and individuals with schizophrenia exhibited visually similar network community structures and high amounts of normalized mutual information (NMI). However, testing of individual subject community structures identified small but significant alterations in community structure with alterations being driven by changes in node community membership in the somatosensory, auditory, default mode, salience, and subcortical networks.

  7. Happiness, Deprivation and the Alter Ego


    Paolo Verme


    The paper focuses on satisfaction with income and proposes a utility model built on two value systems, the `Ego' system - described as one own income assessment relatively to one own past and future income - and the `Alter' system - described as one own income assessment relatively to a reference group. We show how the union of these two value systems and the use of relative deprivation measures can lead to a model able to accommodate a wide range of theories on income and happiness. The mode...

  8. Deposition and alteration of carbonaceous series within a Neotethyan rift at the western boundary of the Arabian plate: The late Permian Um Irna Formation, NW Jordan, a petroleum system

    Energy Technology Data Exchange (ETDEWEB)

    Dill, H.G.; Kus, J. [Federal Institute for Geosciences and Natural Resources, P.O. Box 51 01 53 D-30631 Hannover (Germany); Bechtel, A.; Gratzer, R. [Department of Applied Geosciences and Geophysics, University of Leoben, Peter Tunner Strasse 5, A-8700 Leoben (Austria); Abu Hamad, A.M.B. [Geology Department, University of Jordan, Amman 11942 (Jordan)


    During the late Permian (Kungurian to Kazanian) a Neotethyan rift basin evolved at the western boundary of the Arabian Plate, in what is called today the Dead Sea Valley of western Jordan. The break-up of Pangaea was accompanied by low-sinuosity sandy braided- to meandering-fluvial drainage systems which were fed by the uplift of the Arabian Shield and by poorly aerated swamps and ponds that concentrated plant debris of the Cathaysian floral province in the Um Irna Formation. These proximal wet fan sediments are overlain by a dry fan characterized by extensive reddish floodplain deposits, anastomosing channel systems and paleosols. The wet fan is underlain by Cambrian sandstones. These units serve as the top and bottom seals of the OM-bearing system of the Um Irna Formation. The sedimentary rocks of the OM-bearing Um Irna Formation underwent supergene, diagenetic and epigenetic hydrothermal alteration under an elevated geothermal gradient. The temperature increased from the time of deposition of the wet to the time of deposition of the dry fan and caused remobilization of manganese already pre-concentrated in the Cambrian footwall rocks of the rift basin. The anomalous heat regime may be accounted for as a predecessor stage of the Dead Sea Rift which is still active today. Oil seeps are found along faults and fractures near this deep-seated lineamentary fault zone. The deposition and alteration of the organic matter in this late Permian rift are of great consequence for oil generation in the region. Organic petrographic investigations revealed that organic-rich terrestrial carbonaceous and coal rich sediments of mainly of type III kerogen are dominant in the Um Irna Formation. In addition, aquatic liptinite rich sedimentary input (fresh water lake and/or lacustrine swamp) of type I kerogen is also noted. Coal derived organic matter occurs in the form of coaly particles with ranks from subbituminous A to high volatile bituminous C. Higher plant-derived macerals as

  9. Axioms Altered With Research (United States)


    Prevention (CDC): Acinetobacter baumannii infections among patients at military medical facilities treating injured U.S. service members, 2002–2004. MMWR...outbreak of multidrug-resistant Acinetobacter baumannii -calcoaceticus complex infection in the US military health care system associated with military...operations in Iraq. Clin Infect Dis 2007;44(12):1577-1584. 10. Turton JF, Kaufmann ME, Gill MJ, et al: Comparison of Acinetobacter baumannii isolates from

  10. Pulmonary alterations in cocaine users

    Directory of Open Access Journals (Sweden)

    Mário Terra Filho

    Full Text Available CONTEXT: Brazilian researchers have recently recognized a marked increase in the number of people using abusable drugs and the consequences of this habit. It has become a major public health problem in a potentially productive segment of the general population. In the last few years, several medical articles have given special emphasis to pulmonary complications related to cocaine use. This review is based on this information and experience acquired with groups of cocaine users. OBJECTIVE: To present to physicians the pulmonary aspects of cocaine use and warn about the various effects this drug has on the respiratory system, stressing those related to long-term use. DESIGN: Narrative review. METHOD: Pulmonary complications are described. These may include infections (Staphylococcus aureus, pulmonary tuberculosis, acquired immunodeficiency syndrome/aids, etc., aspiration pneumonia, lung abscess, empyema, septic embolism, non-cardiogenic pulmonary edema, barotrauma, pulmonary granulomatosis, bronchiolitis obliterans and organizing pneumonia, pneumonitis and interstitial fibrosis, pneumonitis hypersensitivity, lung infiltrates and eosinophilia in individuals with bronchial hyperreactivity, diffuse alveolar hemorrhage, vasculitis, pulmonary infarction, pulmonary hypertension and alterations in gas exchange. It is concluded that physicians should give special attention to the various pulmonary and clinical manifestations related to cocaine use, particularly in young patients.

  11. Genetic alteration in hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Yoo Chul; Kang, Tae Woong; Lee, Jin Oh [Korea Cancer Center Hospital of Korea Atomic Energy Research Institute, Seoul (Korea, Republic of)


    Cancer of stomach, colon and liver are a group of the most common cancer in Korea. However, results with current therapeutic modalities are still unsatisfactory. The intensive efforts have been made to understand basic pathogenesis and to find better therapeutic tools for the treatment of this miserable disease. We studied the alteration of tumor suppressor genes and oncogenes in hepatocellular carcinoma in Korea. We found that alteration of Rb gene, APC were 33 %, 13 % respectively. But alterations of oncogenes such as myc, ras and mdm2 were rarely found. Our results suggests that HBV may act as oncogenic role in hepatocarcinogenesis instead of oncogenes. 6 figs, 2 tabs. (Author).

  12. Epigenetic alterations in gastric carcinogenesis

    Institute of Scientific and Technical Information of China (English)

    In-Seon CHOI; Tsung-Teh WU


    Gastric cancer is believed to result in part from the accumulation of multiple genetic alterations leading to oncogene overexpression and tumor suppressor loss. Epigenetic alterations as a distinct and crucial mechanism to silence a variety of methylated tissue-specific and imprinted genes, have been extensively studied in gastric carcinoma and play important roles in gastric carcinogenesis. This review will briefly discuss the basic aspects of DNA methylation and CpG island methylation, in particular the epigenetic alterations of certain critical genes implicated in gastric carcinogenesis and its relevance of clinical implications.

  13. 参数可变的无线式冲击波超压测试系统的研究%Study on parameter-alterable and wireless shock wave overpressure measuring system

    Institute of Scientific and Technical Information of China (English)

    赵岩; 杜红棉; 马铁华


    Memorized measurement is extensively applied in the overpressure measurement. In the shock wave overpressure field measurement, overpressure peak and time-domain pulse width are changing with TNT equivalent and the distance between measuring point and ground zero. Difference between short and long distance overpressure peak and time-domain pulse width will be score of time to increase the precision and flexibility of the test system, a parameter-alterable and wireless shock wave overpressure measuring system is presented. This system sets the wireless parameter( range, sampling frequency, trigger level)to many sensor nodes by wireless Zig Bee module. The feasibility and superiority of this system have been tested and verified by the theoretical calculation on overpressure test and the analysis on the data of the shooting range test.%存储式测试在冲击波超压测试中应用多.在冲击波超压场测试中,超压峰值和时域脉宽随着TNT当量的大小和测点距爆心的距离的大小变化而变化,近距离和远距离之间超压峰值以及时域脉宽近几十倍之差,为提高测试系统的精度和测试系统的灵活性,提出了一种参数可变的无线式冲击波超压测试系统,此系统主要由无线zig Bee模块对多个传感器节点进行无线参数设置(量程设置、采样频率设置、触发电平设置等),通过冲击波超压测试理论计算和靶场实验数据的分析,验证了该系统设计方案的可行性和优越性.

  14. Pathophysiology of hypertension: interactions between macro and microvascular alterations through endothelial dysfunction. (United States)

    Yannoutsos, Alexandra; Levy, Bernard I; Safar, Michel E; Slama, Gerard; Blacher, Jacques


    Hypertension is a multifactorial systemic chronic disorder through functional and structural macrovascular and microvascular alterations. Macrovascular alterations are featured by arterial stiffening, disturbed wave reflection and altered central to peripheral pulse pressure amplification. Microvascular alterations, including altered wall-to-lumen ratio of larger arterioles, vasomotor tone abnormalities and network rarefaction, lead to disturbed tissue perfusion and susceptibility to ischemia. Central arterial stiffness and microvascular alterations are common denominators of organ damages. Vascular alterations are intercorrelated, amplifying the haemodynamic load and causing further damage in the arterial network. A plausible precursor role of vascular alterations in incident hypertension provides new insights for preventive and therapeutic strategies targeting macro and microvasculature. Cumulative metabolic burden and oxidative stress lead to chronic endothelial injury, promoting structural and functional vascular alterations, especially in the microvascular network. Pathophysiology of hypertension may then be revisited, based on both macrovascular and microvascular alterations, with a precursor role of endothelial dysfunction for the latter.

  15. Hypergravity-induced altered behavior in Drosophila (United States)

    Hosamani, Ravikumar; Wan, Judy; Marcu, Oana; Bhattacharya, Sharmila


    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

  16. Complement Activation Alters Platelet Function (United States)


    Award Number: W81XWH-12-1-0523 TITLE: Complement Activation Alters Platelet Function PRINCIPAL INVESTIGATOR: George Tsokos, M.D. CONTRACTING...Activation Alters Platelet Function 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-12-1-0523 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) George Tsokos, M.D...a decreased level of disease. Further studies will expand upon these observations better outlining the function of platelets in the injury associated

  17. Luminescence of thermally altered human skeletal remains. (United States)

    Krap, Tristan; Nota, Kevin; Wilk, Leah S; van de Goot, Franklin R W; Ruijter, Jan M; Duijst, Wilma; Oostra, Roelof-Jan


    Literature on luminescent properties of thermally altered human remains is scarce and contradictory. Therefore, the luminescence of heated bone was systemically reinvestigated. A heating experiment was conducted on fresh human bone, in two different media, and cremated human remains were recovered from a modern crematory. Luminescence was excited with light sources within the range of 350 to 560 nm. The excitation light was filtered out by using different long pass filters, and the luminescence was analysed by means of a scoring method. The results show that temperature, duration and surrounding medium determine the observed emission intensity and bandwidth. It is concluded that the luminescent characteristic of bone can be useful for identifying thermally altered human remains in a difficult context as well as yield information on the perimortem and postmortem events.

  18. Pneumatic tube system transport does not alter platelet function in optical and whole blood aggregometry, prothrombin time, activated partial thromboplastin time, platelet count and fibrinogen in patients on anti-platelet drug therapy (United States)

    Enko, Dietmar; Mangge, Harald; Münch, Andreas; Niedrist, Tobias; Mahla, Elisabeth; Metzler, Helfried; Prüller, Florian


    Introduction The aim of this study was to assess pneumatic tube system (PTS) alteration on platelet function by the light transmission aggregometry (LTA) and whole blood aggregometry (WBA) method, and on the results of platelet count, prothrombin time (PT), activated partial thromboplastin time (APTT), and fibrinogen. Materials and methods Venous blood was collected into six 4.5 mL VACUETTE® 9NC coagulation sodium citrate 3.8% tubes (Greiner Bio-One International GmbH, Kremsmünster, Austria) from 49 intensive care unit (ICU) patients on dual anti-platelet therapy and immediately hand carried to the central laboratory. Blood samples were divided into 2 Groups: Group 1 samples (N = 49) underwent PTS (4 m/s) transport from the central laboratory to the distant laboratory and back to the central laboratory, whereas Group 2 samples (N = 49) were excluded from PTS forces. In both groups, LTA and WBA stimulated with collagen, adenosine-5’-diphosphate (ADP), arachidonic acid (AA) and thrombin-receptor-activated-peptide 6 (TRAP-6) as well as platelet count, PT, APTT, and fibrinogen were performed. Results No statistically significant differences were observed between blood samples with (Group 1) and without (Group 2) PTS transport (P values from 0.064 – 0.968). The AA-induced LTA (bias: 68.57%) exceeded the bias acceptance limit of ≤ 25%. Conclusions Blood sample transportation with computer controlled PTS in our hospital had no statistically significant effects on platelet aggregation determined in patients with anti-platelet therapy. Although AA induced LTA showed a significant bias, the diagnostic accuracy was not influenced. PMID:28392742

  19. The use of an In House Scoring System Scale versus Glasgow Coma Scale in non-traumatic altered states of consciousness patients: can it be used for triaging patients in Southeast Asian developing countries? (United States)

    Maheswaran, M; Adnan, W A W; Ahmad, R; Ab Rahman, N H N; Naing, N N; Abdullah, J


    Non-traumatic Altered States of Consciousness (ASC) are a non-specific consequence of various etiologies, and are normally monitored by Glasgow Coma Scale (GCS). The GCS gives varriable results among untrained emergency medicine personel in developing countries where English is not the first language. An In House Scoring System (IHSS) scale was made by the first author for the purpose of triaging so as to quickly asses patients when seen by medical personel. This IHSS scale was compared to the GCS to determine it's specificity and sensitivity in the accident and emergency department (ED) of Hospital University Sains Malaysia (HUSM). All patients with non-traumatic ASC were selected by purposive sampling according to pre-determined criteria. Patients were evaluated by the two systems, IHSS and GCS, by emergency physicians who were on call. Patient demographics, clinical features, investigations, treatment given and outcomes were collected and followed for a period of 14 days. A total of 221 patients with non-traumatic ASC were studied, 54.3% were males. The mean age of the patients was 56 years old. The mean overall GCS score on presentation to the ED was 10.3. The mean duration of ASC was 11.6 hours. One hundred thirty patients (58.8%) experienced ASC secondary to general or focal cerebral disorders. The mortality rate was 40.3% 2 weeks after the ED visit. Fifty-four point three percent of the patients were awake and considered to have good outcomes while 45.7% of the patients had poor outcomes (comatose or dead) 2 weeks after the ED visit. The mean overall GCS score, verbal and motor subscores as well as the IHSS had significantly decreased (worsened) after treatment in the ED. A poor IHSS scale, hypertension, current smoking, abnormal pupillary reflexes and acidosis were associated with a worse 2-week outcome. The mean age and WBC count was lower and the mean overall GCS score and eye, verbal and motor subscores were higher as well as those having a lower IHSS

  20. 2015 Sensorimotor Risk Standing Review Panel Evidence and Status Review For: the Risk of Impaired Control of Spacecraft/Associated Systems and Decreased Mobility Due to Vestibular/Sensorimotor Alterations Associated with Spaceflight (United States)

    Steinberg, Susan


    The 2015 Sensorimotor Risk Standing Review Panel (from here on referred to as the SRP) participated in a WebEx/teleconference with members of the Human Health Countermeasures (HHC) Element, representatives from the Human Research Program (HRP), NASA Headquarters, and NASA Research and Education Support Services (NRESS) on December 17, 2015 (list of participants is in Section VI of this report). The SRP reviewed the new Evidence Report for the Risk of Impaired Control of Spacecraft/Associated Systems and Decreased Mobility Due to Vestibular/Sensorimotor Alterations Associated with Spaceflight (from here on referred to as the 2015 Sensorimotor Evidence Report), and also received a status review of the Risk. The opening section of the 2015 Sensorimotor Evidence Report provides written descriptions of various incidents that have occurred during space missions. In most of these incidents, the main underlying contributing factors are not easy to identify unambiguously. For example, in section 1.9, a number of falls occurred while astronauts were walking on the moon. It is not clear to the SRP, however, why they fell. It is only possible to extrapolate from likely specific psychophysical or physiological abnormalities, but how these abnormalities were determined, and how they were directly responsible for the falls is unclear to the SRP. Section 2.1.2 on proprioception is very interesting, but the functional significance of the abnormalities detected is not clear. The SRP sees this as a problem throughout the report: a mapping between the component abnormalities identified and the holistic behaviors that are most relevant, for example, controlling the vehicle, and locomotion during egress, is generally lacking. The SRP thinks the cognitive section is too strongly focused on vestibular functioning. The SRP questions the notion that the main cognitive effects are mainly attributable to reversible vestibular changes induced by spaceflight. The SRP thinks that there can also

  1. [Neurocutaneous syndrome with hair alterations]. (United States)

    Camacho-Martínez, F


    There are multiple neurocutaneous syndromes that may show hair alterations such as the interglabellar peak or 'widow's peak', which is an alteration of the hair implantation, in addition to the genohypotrichosis, hypertrichosis and hair shaft dysplasias. In this chapter we will focus on the latter. Out of the unspecific hair shaft dysplasias the only ones showing neurological alterations are trichorrhexis invaginata, observed in the syndrome of Netherton. Among the specific dysplasias we would like to point out monilethrix, and very especially the moniliform hair syndrome, the trichorrhexis nodosa, the pili torti and trichotiodystrophy. The latter is actually a group of syndromes which associates a series of diverse symptoms that have in common hair brittleness, fertility problems and physical and mental retardation, and they constitute the basic syndrome know as 'BIDS syndrome.

  2. Altering embryonic cardiac dynamics with optical pacing. (United States)

    Peterson, L M; McPheeters, M; Barwick, L; Gu, S; Rollins, A M; Jenkins, M W


    Several studies have shown that altering blood flow early in development leads to congenital heart defects. In these studies the perturbations to hemodynamics were very gross manipulations (vessel ligation, conotruncal banding, etc.) that would be inappropriate for probing the delicate mechanisms responsible for mechanically-transduced signaling. Also, these perturbations lacked feedback from a monitoring system to determine the exact degree of alteration and the location of its effect. Here, we employed optical pacing (OP) to alter the heart rate in quail embryos and optical coherence tomography (OCT) to measure the resultant shear forces on the endocardium. OP is a new technique utilizing pulsed 1.851 µm infrared laser light to noninvasively capture the heart rate to the pulse frequency of the laser without the use of exogenous agents. To measure shear stress on the endocardium, we extended our previous OCT algorithms to enable the production of 4-D shear maps. 4-D shear maps allowed observation of the spatial and temporal distribution of shear stress. Employing both OCT and OP, we were able to develop perturbation protocols that increase regurgitant flow and greatly modify the oscillatory shear index (OSI) in a region of the heart tube where future valves will develop. Regurgitant flow has been linked with valve development and precise perturbations may allow one to determine the role of hemodynamics in valvulogenesis.

  3. Neck muscle fatigue alters upper limb proprioception. (United States)

    Zabihhosseinian, Mahboobeh; Holmes, Michael W R; Murphy, Bernadette


    Limb proprioception is an awareness by the central nervous system (CNS) of the location of a limb in three-dimensional space and is essential for movement and postural control. The CNS uses the position of the head and neck when interpreting the position of the upper limb, and altered input from neck muscles may affect the sensory inputs to the CNS and consequently may impair the awareness of upper limb joint position. The purpose of this study was to determine whether fatigue of the cervical extensors muscles (CEM) using a submaximal fatigue protocol alters the ability to recreate a previously presented elbow angle with the head in a neutral position. Twelve healthy individuals participated. CEM activity was examined bilaterally using surface electromyography, and kinematics of the elbow joint was measured. The fatigue protocol included an isometric neck extension task at 70 % of maximum until failure. Joint position error increased following fatigue, demonstrating a significant main effect of time (F 2, 18 = 19.41, p ≤ 0.0001) for absolute error. No significant differences were found for variable error (F 2, 18 = 0.27, p = 0.76) or constant error (F 2, 18 = 1.16 of time, p ≤ 0.33). This study confirms that fatigue of the CEM can reduce the accuracy of elbow joint position matching. This suggests that altered afferent input from the neck subsequent to fatigue may impair upper limb proprioception.

  4. [Alterity in psychopathologic languages. 3: the sex of words]. (United States)

    Fernandez-Zoïla, A


    This study of alterity in psychopathological language includes three parts: 1) The double without dialogue; 2) The ego(s) in the soliloguy; and here: 3) The sex of words. Two clinical cases (an asexuation delusion, an agressive misogyny) show the systemic interrelations in one of their sides only. The relations between neurosis, perversion, psychosis are operating into the sexuation and into the insatured dialogical structure of language. Enclosed alterity in language is the specific fact of psychopathology.

  5. Hypersexuality or altered sexual preference following brain injury.


    Miller, B.L.; Cummings, J L; McIntyre, H.; Ebers, G; Grode, M


    Eight patients are described in whom either hypersexuality (four cases) or change in sexual preference (four cases) occurred following brain injury. In this series disinhibition of sexual activity and hypersexuality followed medial basal-frontal or diencephalic injury. This contrasted with the patients demonstrating altered sexual preference whose injuries involved limbic system structures. In some patients altered sexual behaviour may be the presenting or dominant feature of brain injury.

  6. Aqueous alteration on main-belt asteroids (United States)

    Fornasier, S.; Lantz, C.; Barucci, M.; Lazzarin, M.


    The study of aqueous alteration is particularly important for unraveling the processes occurring during the earliest times in Solar System history, as it can give information both on the thermal processes and on the localization of water sources in the asteroid belt, and for the associated astrobiological implications. The aqueous alteration process produces the low temperature (< 320 K) chemical alteration of materials by liquid water which acts as a solvent and produces materials like phyllosilicates, sulphates, oxides, carbonates, and hydroxides. This means that liquid water was present in the primordial asteroids, produced by the melting of water ice by heating sources, very probably by ^{26}Al decay. Hydrated minerals have been found mainly on Mars surface, on primitive main-belt asteroids (C, G, B, F, and P-type, following the classification scheme by Tholen, 1984) and possibly also on few transneptunian objects. Reflectance spectroscopy of aqueous altered asteroids shows absorption features in the 0.6-0.9 and 2.5-3.5-micron regions, which are diagnostic of, or associated with, hydrated minerals. In this work, we investigate the aqueous alteration process on a large sample of 600 visible spectra of C-complex asteroids available in the literature. We analyzed all these spectra in a similar way to characterize the absorption-band parameters (band center, depth, and width) and spectral slope, and to look for possible correlations between the aqueous alteration process and the asteroids taxonomic classes, orbital elements, heliocentric distances, albedo, and sizes. We find that 4.6 % of P, 7.7 % of F, 9.8 % of B, 50.5 % of C, and 100 % of the G-type asteroids have absorption bands in the visible region due to hydrated silicates. Our analysis shows that the aqueous alteration sequence starts from the P-type objects, practically unaltered, and increases through the P → F → B → C → G asteroids, these last being widely aqueously altered, strengthening thus

  7. Art as Alterity in Education (United States)

    Zhao, Guoping


    In education, art has often been perceived as entertainment and decoration and is the first subject to go when there are budget cuts or test-score pressures. Drawing on Emmanuel Lévinas's idea of the primacy of radical alterity that breaks the totality of our being, enables self-transformation and ethics, and ensures community as a totality…

  8. Exposure to chronic early-life stress lastingly alters the adipose tissue, the leptin system and changes the vulnerability to western-style diet later in life in mice. (United States)

    Yam, K Y; Naninck, E F G; Abbink, M R; la Fleur, S E; Schipper, L; van den Beukel, J C; Grefhorst, A; Oosting, A; van der Beek, E M; Lucassen, P J; Korosi, A


    Early-life stress (ES) increases the vulnerability to develop psychopathologies and cognitive decline in adulthood. Interestingly, this is often comorbid with metabolic disorders, such as obesity. However, it is unclear whether ES leads to lasting metabolic changes and to what extent this is associated with the ES-induced cognitive impairments. Here, we used an established chronic ES mouse model (from postnatal day (P) 2 to P9) to investigate the short- and long-term effects of ES exposure on parameters of the adipose tissue and the leptin system (i.e. circulating levels and gene expression of leptin and its receptor) in both sexes. Immediately following ES, the offspring exhibited reductions in white adipose tissue (WAT) mass, plasma leptin levels and in leptin mRNA expression in WAT. Furthermore, ES exposure led to increased brown adipose tissue and browning of WAT, which was evident by a drastic increase in uncoupling protein 1 mRNA expression in the inguinal WAT at P9. Notably, the ES-induced reductions in WAT mass, plasma leptin and leptin expression in WAT were sustained into adulthood and were accompanied by changes in body fat distribution, such as a higher ratio between mesenteric WAT and other WATs. Interestingly, while ES exposure increased leptin receptor mRNA expression in the choroid plexus, it was unaltered in the hippocampus. This suggests an adaptation to maintain central leptin homeostasis following ES exposure. In addition, chronic ES exposure resulted in the well-established cognitive impairment in object recognition performance during adulthood, which correlated positively with reductions in WAT mass observed in male, but not in female mice. Finally, to assess if ES leads to a different metabolic phenotype in a moderate obesogenic environment, we measured body fat accumulation of control and ES-exposed mice in response to a moderate western-style diet (WSD) that was provided during adulthood. ES-exposed mice subjected to WSD exhibit a higher

  9. Alteraç��es dos atributos físicos de um Latossolo Vermelho submetido a diferentes sistemas de manejo Physical attribute alterations of an Oxisol under different tillage systems

    Directory of Open Access Journals (Sweden)

    Jose Luiz Rodrigues Torres


    Full Text Available O cultivo do solo pode alterar alguns atributos físicos em relação ao solo não cultivado. Diante disso, neste estudo objetivou-se verificar as alterações provocadas pelos sistemas de uso do solo sobre alguns atributos físicos de um Latossolo Vermelho no Triângulo Mineiro. Os tratamentos utilizados foram: Campo nativo (CN (testemunha; preparo convencional do solo (PC; pastagem irrigada de braquiária sob pastejo rotacionado tipo VoIsin (PT e Semeadura direta (SD. Utilizou-se o delineamento inteiramente casualizado, com 4 repetições, onde foram avaliados os seguintes atributos físicos: densidade do solo (Ds, volume total de poros (VTP, microporosidade (MI, macroporosidade (MA, condutividade hidráulica saturada (Kθ, resistência mecânica do solo à penetração (RP e o índice de sensibilidade (Is. Nas áreas sob PC, SD e PT não foram observadas alterações significativas com relação aos atributos físicos avaliados. Para as profundidades avaliadas só ocorreram diferenças significativas entre as profundidades de 0,0 - 0,05 e a de 0,15 a 0,20 m para os parâmetros Ds e VTP. PC, SD, PT e CN apresentaram valores médios de volumes de MA próximos ou superiores daquele considerado ideal (0,33 dm-3dm-3. Apenas no CN não ocorreu valores maiores que 2 MPa. No CN, PC, e SD não ocorreram limitações ao desenvolvimento das culturas até a profundidade de 0,08 m. O Is calculado para os atributos CC e Kθ nos sistemas PC e PT demonstraram o efeito prejudicial desses sistemas de manejo sobre a estrutura do solo, quando comparados ao SD.The cultivation of the soil may alter some physical attributes compared to non cultivated soil. The objective of this study to verify changes caused by land use systems on some physical attributes of an Oxisol in the Triângulo Mineiro. The used treatments were: Native field (CN (control; Conventional preparation of the soil (PC; Irrigated pasture of brachiaria under pasture alternate (PT and Direct tillage

  10. [Factors that alter taste perception]. (United States)

    Maffeis, E R; Silva-Netto, C R


    Dysfunction of taste perception is a significant problem for many individuals. Taste anomalies may affect health not only by directly affecting liquid and solid food intake, but also by creating a state of depression due to the loss of an important source of pleasure. Many factors alter taste perception, such as lesions of the oral mucosa, cigarette smoking, radiation, chemotherapy, renal disease, hepatitis, leprosy, hormones, nutrition, use of dentures, medications, and aging. Gum or ice chewing may temporarily help loss of taste. Patients should be encouraged to chew their food thoroughly, alternating the sides of the mouth, or alternating different foods. Unfortunately, in many cases there is no cure for this alteration, and patience is then the only possibility.

  11. Fantastic alterities and The Sandman



    This article explores the ways in which the comics medium enhances our understanding of literary models of the Fantastic. It examines the presence and depiction of multiple worlds in Neil Gaiman’s The Sandman, with specific reference to the role of the comics medium and its denial of mimesis when creating such alterities. \\ud \\ud It initially uses literature review to establish a contemporary working model of the Fantastic, taking as its basis the framework devised by Tzvetan Todorov, and inc...

  12. Buccal alterations in diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Negrato Carlos


    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.

  13. Oral alterations among chemical dependents

    Directory of Open Access Journals (Sweden)

    Estela Vanessa COLODEL


    Full Text Available Introduction: It has been daily observed a significant increase ofchemical dependent individuals, as well as the lack of depth on thisissue in the dentistry area. Nevertheless many times the dentalclinicians are the first professionals to diagnose possible alterations,which appear due to the consumption of tobacco, alcohol and other illicit drugs. Objectives: To make a literature review of oral alterations and to identify them on a specific group of persons, which are addicted to different types of drugs. Material and methods: The clinical history of the selected individuals was added to the answers of a questionnaire,comprising the data of the present research. Results: Besides other minor soft tissue alterations, a high prevalence of caries and periodontal diseases were found in the studied population. Conclusion: It was concluded that the role of the dental clinician is very important to the health rehabilitation of drug addicts, individuals with physical and mental disorders that need specific oral care, which sometimes is neglected.

  14. Learning arm/hand coordination with an altered visual input. (United States)

    Iftime Nielsen, Simona Denisia; Dosen, Strahinja; Popović, Mirjana B; Popović, Dejan B


    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.

  15. Menstrual and gonadal functional alterations in systemic lupus erythematosus in adult females%月经及性腺功能在成年女性系统性红斑狼疮中的变化

    Institute of Scientific and Technical Information of China (English)

    曹智君; 叶志中; 董慧娟; 陈杰; 尹志华


    目的 探讨月经及性腺功能在成年女性系统性红斑狼疮(SLE)中的变化.方法 对先后在本院就诊的SLE患者及在本院进行健康体验的正常对照者进行临床资料收集,详细记录入选研究对象的月经及生育情况,检测研究对象血中性激素水平.结果 在入选的192例成年女性SLE患者中,78例(41%)患者出现月经异常,并且患者月经异常的情况表现为多种模式.在100例健康对照者中,仅19例(19%)患者出现月经异常.和健康对照者相比,SLE患者组的性激素E2、P、T明显下降,FSH、LH及PRL的水平均明显升高(P<0.05).与无月经异常表现的SLE患者相比,有月经异常表现的SLE患者的起病年龄相对较小、SLEDAI积分相对较高、使用过烷化剂的比例相对较高、服用激素的平均剂量相对较大,两组的性腺功能差异无统计学意义(P>0.05).结论 SLE患者中出现月经异常的比例显著高于健康对照者,有月经异常的SLE患者临床表现具有一定的特点,虽然SLE患者的性腺功能存在异常,但未见其与SLE的月经异常相关.%Objective To investigate menstrual and gonadal functional alterations in systemic lupus erythematosus (SLE) in adult females. Methods The clinical data of 192 consecutive patients who fulfilled f6ur or more of the ACR 1997 revised criteria for SLE (the SLE patients) were studied and compared with 100 age-matched healthy controls, including menstrual function, gonadal function, ad serum Sex Hormone Levels. Results 78 (41%) SLE patients and 19 (19%) healthy individuals presented menstrual abnormalities. The level of E2, P, T significantly decreased and the level of FSH, LH, PRL significantly increased in SLE patients, compared with that if the healthy controls (P< 0.05). Younger disease-onset age, higher SLEDAI score, higher use of alkylating agent, and higher dose of glucosteroid therapy were found in patients with menstrual abnormalities than in patients without

  16. Altering prolactin concentrations in sows. (United States)

    Farmer, C


    Prolactin has a multiplicity of actions, but it is of particular importance in gestating and lactating animals. In sows, it is involved in the control of mammary development and also holds essential roles in the lactogenic and galactopoietic processes. Furthermore, low circulating concentrations of prolactin are associated with the agalactia syndrome. The crucial role of prolactin makes it important to understand the various factors that can alter its secretion. Regulation of prolactin secretion is largely under the negative control of dopamine, and dopamine agonists consistently decrease prolactin concentrations in sows. On the other hand, injections of dopamine antagonists can enhance circulating prolactin concentrations. Besides pharmacologic agents, many other factors can also alter prolactin concentrations in sows. The use of Chinese-derived breeds, for instance, leads to increased prolactin concentrations in lactating sows compared with standard European white breeds. Numerous husbandry and feeding practices also have a potential impact on prolactin concentrations in sows. Factors, such as provision of nest-building material prepartum, housing at farrowing, high ambient temperature, stress, transient weaning, exogenous thyrotropin-releasing factor, exogenous growth hormone-releasing factor, nursing frequency, prolonged photoperiod, fasting, increased protein and/or energy intake, altered energy sources, feeding high-fiber diets, sorghum ergot or plant extracts, were all studied with respect to their prolactinemic properties. Although some of these practices do indeed affect circulating prolactin concentrations, none leads to changes as drastic as those brought about by dopamine agonists or antagonists. It appears that the numerous factors regulating prolactin concentrations in sows are still not fully elucidated, and that studies to develop novel applicable ways of increasing prolactin concentrations in sows are warranted. Crown Copyright © 2015. Published

  17. Field guide to hydrothermal alteration in the White River altered area and in the Osceola Mudflow, Washington (United States)

    John, David A.; Rytuba, James J.; Ashley, Roger P.; Blakely, Richard J.; Vallance, James W.; Newport, Grant R.; Heinemeyer, Gary R.


    The Cenozoic Cascades arcs of southwestern Washington are the product of long-lived, but discontinuous, magmatism beginning in the Eocene and continuing to the present (for example, Christiansen and Yeats, 1992). This magmatism is the result of subduction of oceanic crust beneath the North American continent. The magmatic rocks are divided into two subparallel, north-trending continental-margin arcs, the Eocene to Pliocene Western Cascades, and the Quaternary High Cascades, which overlies, and is east of, the Western Cascades. Both arcs are calc-alkaline and are characterized by voluminous mafic lava flows (mostly basalt to basaltic andesite compositions) and scattered large stratovolcanoes of mafic andesite to dacite compositions. Silicic volcanism is relatively uncommon. Quartz diorite to granite plutons are exposed in more deeply eroded parts of the Western Cascades Arc (for example, Mount Rainier area and just north of Mt. St. Helens). Hydrothermal alteration is widespread in both Tertiary and Quaternary igneous rocks of the Cascades arcs. Most alteration in the Tertiary Western Cascades Arc resulted from hydrothermal systems associated with small plutons, some of which formed porphyry copper and related deposits, including copper-rich breccia pipes, polymetallic veins, and epithermal gold-silver deposits. Hydrothermal alteration also is present on many Quaternary stratovolcanoes of the High Cascades Arc. On some High Cascades volcanoes, this alteration resulted in severely weakened volcanic edifices that were susceptible to failure and catastrophic landslides. Most notable is the sector collapse of the northeast side of Mount Rainier that occurred about 5,600 yr. B.P. This collapse resulted in formation of the clay-rich Osceola Mudflow that traveled 120 km down valley from Mount Rainier to Puget Sound covering more than 200 km2. This field trip examines several styles and features of hydrothermal alteration related to Cenozoic magmatism in the Cascades arcs

  18. Examination of chloritization of biotite as a tool for reconstructing the physicochemical parameters of mineralization and associated alteration in the Zafarghand porphyry copper system, Ardestan, Central Iran: mineral-chemistry and stable isotope analyses (United States)

    Aminroayaei Yamini, Maryam; Tutti, Faramarz; Aminoroayaei Yamini, Mohammad Reza; Ahmadian, Jamshid; Wan, Bo


    The chloritization of biotite and stable isotopes of silicate have been studied for the Zafarghand porphyry copper deposit, Ardestan, Iran. The studied area, in the central part of the Urumieh-Dokhtar magmatic belt, contains porphyry-style Cu mineralization and associated hydrothermal alteration within the Miocene (19-26 Ma, Zircon U-Pb age) granodioritc stock and adjacent andesitic to rhyodacitic volcanic rocks (ca. 56 Ma, zircon U-Pb age). The primary and secondary biotite that formed during potassic alteration in this porphyry and these volcanic host rocks are variably chloritized. Chloritization of biotite pseudomorphically is characterized by an increase in MgO, FeOt, and MnO, with decreasing in SiO2, K2O, and TiO2. Based on the Ti-in-biotite geothermometer of Henry et al. (Am Mineral 90:316-328, 2005) and Al-in-chlorite geothermometer of Cathelineau (Clay Miner 23:417-485, 1988), crystallization temperatures of primary biotite representative of magmatic conditions and later chloritization temperature range from 617° to 675 °C ± 24 °C and 177° to 346 °C, respectively. Calculated isotopic compositions of fluids that chloritized primary and secondary biotite display isotopic compositions of 1.1 to 1.7 per mil for δ18O and -19.9 to -20.5 per mil for δD consistent with meteoric water. Sericite, barren, and A-type-quartz veins from phyllic alteration were produced by mixed magmatic and meteoric water with δ18O values from -2.8 to 2.5 and δD values of ˜ -23 per mil; the narrow range of δD values of the propylitic epidote may be due to a meteoric water with δ18O values from 0.8 to 1.6 and δD values from -14.6 to -16.9 per mil.

  19. Elevated ozone alters soybean-virus interaction. (United States)

    Bilgin, Damla D; Aldea, Mihai; O'Neill, Bridget F; Benitez, Marisol; Li, Min; Clough, Steven J; DeLucia, Evan H


    Increasing concentrations of ozone (O(3)) in the troposphere affect many organisms and their interactions with each other. To analyze the changes in a plant-pathogen interaction, soybean plants were infected with Soybean mosaic virus (SMV) while they were fumigated with O(3). In otherwise natural field conditions, elevated O(3) treatment slowed systemic infection and disease development by inducing a nonspecific resistance against SMV for a period of 3 weeks. During this period, the negative effect of virus infection on light-saturated carbon assimilation rate was prevented by elevated O(3) exposure. To identify the molecular basis of a soybean nonspecific defense response, high-throughput gene expression analysis was performed in a controlled environment. Transcripts of fungal, bacterial, and viral defense-related genes, including PR-1, PR-5, PR-10, and EDS1, as well as genes of the flavonoid biosynthesis pathways (and concentrations of their end products, quercetin and kaempherol derivatives) increased in response to elevated O(3). The drastic changes in soybean basal defense response under altered atmospheric conditions suggest that one of the elements of global change may alter the ecological consequences and, eventually, coevolutionary relationship of plant-pathogen interactions in the future.

  20. Natal Host Plants Can Alter Herbivore Competition (United States)

    Pan, Huipeng; Preisser, Evan L.; Su, Qi; Jiao, Xiaoguo; Xie, Wen; Wang, Shaoli; Wu, Qingjun


    Interspecific competition between herbivores is widely recognized as an important determinant of community structure. Although researchers have identified a number of factors capable of altering competitive interactions, few studies have addressed the influence of neighboring plant species. If adaptation to/ epigenetic effects of an herbivore’s natal host plant alter its performance on other host plants, then interspecific herbivore interactions may play out differently in heterogeneous and homogenous plant communities. We tested wether the natal host plant of a whitefly population affected interactions between the Middle-east Asia Minor 1 (MEAM1) and Mediterranean (MED) cryptic species of the whitefly Bemisia tabaci by rearing the offspring of a cabbage-derived MEAM1 population and a poinsettia-derived MED population together on three different host plants: cotton, poinsettia, and cabbage. We found that MED dominated on poinsettia and that MEAM1 dominated on cabbage, results consistent with previous research. MED also dominated when reared with MEAM1 on cotton, however, a result at odds with multiple otherwise-similar studies that reared both species on the same natal plant. Our work provides evidence that natal plants affect competitive interactions on another plant species, and highlights the potential importance of neighboring plant species on herbivore community composition in agricultral systems. PMID:28030636

  1. Natal Host Plants Can Alter Herbivore Competition. (United States)

    Pan, Huipeng; Preisser, Evan L; Su, Qi; Jiao, Xiaoguo; Xie, Wen; Wang, Shaoli; Wu, Qingjun; Zhang, Youjun


    Interspecific competition between herbivores is widely recognized as an important determinant of community structure. Although researchers have identified a number of factors capable of altering competitive interactions, few studies have addressed the influence of neighboring plant species. If adaptation to/ epigenetic effects of an herbivore's natal host plant alter its performance on other host plants, then interspecific herbivore interactions may play out differently in heterogeneous and homogenous plant communities. We tested wether the natal host plant of a whitefly population affected interactions between the Middle-east Asia Minor 1 (MEAM1) and Mediterranean (MED) cryptic species of the whitefly Bemisia tabaci by rearing the offspring of a cabbage-derived MEAM1 population and a poinsettia-derived MED population together on three different host plants: cotton, poinsettia, and cabbage. We found that MED dominated on poinsettia and that MEAM1 dominated on cabbage, results consistent with previous research. MED also dominated when reared with MEAM1 on cotton, however, a result at odds with multiple otherwise-similar studies that reared both species on the same natal plant. Our work provides evidence that natal plants affect competitive interactions on another plant species, and highlights the potential importance of neighboring plant species on herbivore community composition in agricultral systems.

  2. Pesticide Exposures May Alter Mouth Bacteria (United States)

    ... fullstory_162249.html Pesticide Exposures May Alter Mouth Bacteria Study of Washington farm workers finds alterations persist ... News) -- Pesticide exposure may change the makeup of bacteria in the mouths of farm workers, a new ...

  3. Detection Of Alterations In Audio Files Using Spectrograph Analysis

    Directory of Open Access Journals (Sweden)

    Anandha Krishnan G


    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.

  4. Mineralogy and stable isotope geochemistry of hydrothermally altered oceanic rocks (United States)

    Stakes, D.S.; O'Neil, J.R.


    Mineralogical and isotopic variations observed in altered glassy and crystalline rocks from the East Pacific Rise and the Mid-Atlantic Ridge provide information about the temperatures of alteration and seawater/rock ratios for various hydrothermal regimes within the oceanic crust. A systematic increase in alteration temperature is evident for the glassy rocks in the sequence: (1) nontronite and celadonite vesicle fillings (35??C), (2) saponite-rich pillow breccias (130-170??C), (3) calcite-rich greenstone breccias and epidote-rich greenstone (200-350??C). These results include the highest temperatures thus far reported for saponite formation. The "seawater-dominated" hydrothermal alteration process that formed the saponite-rich pillow breccias is characterized by high water/rock ratios (>50:1), low to moderate temperatures, a seawater origin of most of the carbon in vein calcites (??13 C ??? 0) and the predominance of Fe-rich saponite and calcite as secondary phases. Greenstones (chlorite-quartz-epidote) and greenstone breccias (chlorite-quartz-albite-calcite) are altered in a "rock-dominated" system with lower water/rock ratios (50:1 to isotopic composition to alter the overlying glassy rocks to the observed mineralogies as well as being the source of metal-rich deposits associated with the oceanic spreading centers. ?? 1982.

  5. A kernel version of multivariate alteration detection

    DEFF Research Database (Denmark)

    Nielsen, Allan Aasbjerg; Vestergaard, Jacob Schack


    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....

  6. Immunological alterations in hepatitis C virus infection. (United States)

    Calvaruso, Vincenza; Craxì, Antonio


    A higher prevalence of immunological processes has recently been reported in patients with hepatitis C virus (HCV) infection, focusing the attention of physicians and researchers on the close association between HCV and immune disorders. HCV lymphotropism represents the most important step in the pathogenesis of virus-related immunological diseases and experimental, virologic, and clinical evidence has demonstrated a trigger role for HCV both in systemic autoimmune diseases, such as rheumatoid arthritis, Sjögren syndrome, hemolytic anemia and severe thrombocytopenia, and in organ-specific autoimmune diseases, such as autoimmune hepatitis, thyroid disorders and diabetes. This review will outline the principal aspects of such HCV-induced immunological alterations, focusing on the prevalence of these less characterized HCV extrahepatic manifestations.

  7. Alteration of the Specificity of PstⅠRestriction Endonuclease

    Institute of Scientific and Technical Information of China (English)


    The influence of factors on the substrate-specificity of Pst Ⅰ restriction endonuclease has been studied with the method of electrophoresis. The results show that, the specificity of Pst Ⅰ almost can not be influenced by the single alteration of the concentration of Tris*HCl, Mg2+ or Na+ in the reaction system, but it can be altered by the reduction of any two of them. The specificity can not be altered by the single alteration of pH or the replacement of Mg2+ with Mn2+. The addition of glycerol or dimethylsulphoxide (DMSO) to the reaction system results in the relaxation of the substrate-specificity of Pst Ⅰ , but dimethylmethylformide, glycol and ethyl alcohol can not bring about the alteration of Pst Ⅰ specificity. Through the method of cloning and sequencing, the nucleotides of No.1 and 6 in the recognition sequence of Pst Ⅰ have changed (1C→A or 6G→T). Used with the enzyme analysis of an artificially synthetic DNA segment containing a special sequence, the nucleotides of No.1 and 6 have both changed (1C→A and 6G→T). The recognition sequence of Pst Ⅰ is speculated to be changed from CTGCA↓G to TGCA↓.

  8. Genetic alterations in pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Muhammad Wasif Saif; Lena Karapanagiotou; Kostas Syrigos


    The diagnosis of pancreatic cancer is devastating for patients and their relatives as the incidence rate is approximately the same as mortality rate. Only a small percentage, which ranges from 0.4% to 4% of patients who have been given this diagnosis, will be alive at five years. At the time of diagnosis, 80% of pancreatic cancer patients have unresectable or metastatic disease.Moreover, the therapeutic alternatives offered by chemotherapy or radiotherapy are few, if not zero. For all these reasons, there is an imperative need of analyzing and understanding the primitive lesions that lead to invasive pancreatic adenocarcinoma. Molecular pathology of these lesions is the key of our understanding of the mechanisms underlying the development of this cancer and will probably help us in earlier diagnosis and better therapeutic results. This review focuses on medical research on pancreatic cancer models and the underlying genetic alterations.

  9. Genetic alterations in pancreatic carcinoma

    Directory of Open Access Journals (Sweden)

    Schmid Roland M


    Full Text Available Abstract Cancer of the exocrine pancreas represents the fifth leading cause of cancer death in the Western population with an average survival after diagnosis of 3 to 6 months and a five-year survival rate under 5%. Our understanding of the molecular carcinogenesis has improved in the last few years due to the development of novel molecular biological techniques. Pancreatic cancer is a multi-stage process resulting from the accumulation of genetic changes in the somatic DNA of normal cells. In this article we describe major genetic alterations of pancreatic cancer, mutations in the proto-oncogene K-RAS and the tumor suppressors INK4A, TP53 and DPC4/SMAD4. The accumulation of these genetic changes leads to a profound disturbance in cell cycle regulation and continuous growth. The knowledge of the underlying molecular mechanisms will offer new therapeutic and diagnostic options and hopefully improve the outcome of this aggressive disease.

  10. Epigenetic alterations underlying autoimmune diseases. (United States)

    Aslani, Saeed; Mahmoudi, Mahdi; Karami, Jafar; Jamshidi, Ahmad Reza; Malekshahi, Zahra; Nicknam, Mohammad Hossein


    Recent breakthroughs in genetic explorations have extended our understanding through discovery of genetic patterns subjected to autoimmune diseases (AID). Genetics, on the contrary, has not answered all the conundrums to describe a comprehensive explanation of causal mechanisms of disease etiopathology with regard to the function of environment, sex, or aging. The other side of the coin, epigenetics which is defined by gene manifestation modification without DNA sequence alteration, reportedly has come in to provide new insights towards disease apprehension through bridging the genetics and environmental factors. New investigations in genetic and environmental contributing factors for autoimmunity provide new explanation whereby the interactions between genetic elements and epigenetic modifications signed by environmental agents may be responsible for autoimmune disease initiation and perpetuation. It is aimed through this article to review recent progress attempting to reveal how epigenetics associates with the pathogenesis of autoimmune diseases.

  11. Epigenetic Alterations in Muscular Disorders

    Directory of Open Access Journals (Sweden)

    Chiara Lanzuolo


    Full Text Available Epigenetic mechanisms, acting via chromatin organization, fix in time and space different transcriptional programs and contribute to the quality, stability, and heritability of cell-specific transcription programs. In the last years, great advances have been made in our understanding of mechanisms by which this occurs in normal subjects. However, only a small part of the complete picture has been revealed. Abnormal gene expression patterns are often implicated in the development of different diseases, and thus epigenetic studies from patients promise to fill an important lack of knowledge, deciphering aberrant molecular mechanisms at the basis of pathogenesis and diseases progression. The identification of epigenetic modifications that could be used as targets for therapeutic interventions could be particularly timely in the light of pharmacologically reversion of pathological perturbations, avoiding changes in DNA sequences. Here I discuss the available information on epigenetic mechanisms that, altered in neuromuscular disorders, could contribute to the progression of the disease.

  12. Window to 'Clovis's' Altered Past (United States)


    This image taken by the Mars Exploration Rover Spirit shows a rock outcrop dubbed 'Clovis.' The rock was discovered to be softer than other rocks studied so far at Gusev Crater after the rover easily ground a hole (center) into it with its rock abrasion tool. An analysis of the interior of the hole with the rover's alpha particle X-ray spectrometer found higher concentrations of sulfur, bromine and chlorine compared to basaltic, or volcanic, rocks at Gusev. This might indicate that Clovis was chemically altered, and that fluids once flowed through the rock depositing these elements. Spirit's solar panels can be seen in the foreground. This image was taken by the rover's navigation camera on sol 205 (July 31, 2004).

  13. Self-alteration in HRI

    DEFF Research Database (Denmark)

    Yamazaki, Ryuji; Nørskov, Marco

    Humanlike androids are being developed with the ambition to be immersed into our daily life and meet us on an equal level in social interaction. The possibilities and limitations of these types of robots can potentially change societies and Human-Robot Interaction might affect the very way in which...... and Denmark, we examine how Telenoid, a new type of teleoperated android robot designed as a minimalistic human, affect people in the real world. We introduce Telenoid to real-world as the fields of elderly care and child education by focusing on the social aspects of the android robot that might facilitate...... the ways in which our subjectivity can be innerly transformed, decentred, in other words, self-altered. In our trials so far, we have been investigating the potential of teleoperated androids, which are embodied telecommunication media with humanlike appearances. By conducting pilot studies in Japan...

  14. The Chutzpah Factor in Altered States of Consciousness (United States)

    Pelletier, Kenneth; Peper, Erik


    Discusses the "chutzpah factor", the ability to transcend fear and enter into the unknown, in altered states of consciousness, especially in what are known as "adept" individuals. Examines the powerful effect a person's belief system has upon what he or she is able to do and endure. (Editor/RK)

  15. Review on environmental alterations propagating from aquatic to terrestrial ecosystems. (United States)

    Schulz, Ralf; Bundschuh, Mirco; Gergs, René; Brühl, Carsten A; Diehl, Dörte; Entling, Martin H; Fahse, Lorenz; Frör, Oliver; Jungkunst, Hermann F; Lorke, Andreas; Schäfer, Ralf B; Schaumann, Gabriele E; Schwenk, Klaus


    Terrestrial inputs into freshwater ecosystems are a classical field of environmental science. Resource fluxes (subsidy) from aquatic to terrestrial systems have been less studied, although they are of high ecological relevance particularly for the receiving ecosystem. These fluxes may, however, be impacted by anthropogenically driven alterations modifying structure and functioning of aquatic ecosystems. In this context, we reviewed the peer-reviewed literature for studies addressing the subsidy of terrestrial by aquatic ecosystems with special emphasis on the role that anthropogenic alterations play in this water-land coupling. Our analysis revealed a continuously increasing interest in the coupling of aquatic to terrestrial ecosystems between 1990 and 2014 (total: 661 studies), while the research domains focusing on abiotic (502 studies) and biotic (159 studies) processes are strongly separated. Approximately 35% (abiotic) and 25% (biotic) of the studies focused on the propagation of anthropogenic alterations from the aquatic to the terrestrial system. Among these studies, hydromorphological and hydrological alterations were predominantly assessed, whereas water pollution and invasive species were less frequently investigated. Less than 5% of these studies considered indirect effects in the terrestrial system e.g. via food web responses, as a result of anthropogenic alterations in aquatic ecosystems. Nonetheless, these very few publications indicate far-reaching consequences in the receiving terrestrial ecosystem. For example, bottom-up mediated responses via soil quality can cascade over plant communities up to the level of herbivorous arthropods, while top-down mediated responses via predatory spiders can cascade down to herbivorous arthropods and even plants. Overall, the current state of knowledge calls for an integrated assessment on how these interactions within terrestrial ecosystems are affected by propagation of aquatic ecosystem alterations. To fill

  16. Diagenetic alteration in low-Mg calcite from macrofossils

    DEFF Research Database (Denmark)

    Ullmann, Clemens Vinzenz; Korte, Christoph


    microscopy) and chemical (trace element abundances, isotopic ratios) screening techniques used to assess the alteration degree of low-Mg calcite macrofossils and summarize the findings on diagenetic trends observed for elemental and isotopic systems in such materials. For a robust evaluation...... of the preservation state of biogenic calcite, it is advisable to combine a set of complementary techniques. Absolute limiting values of element and isotope ratios for discarding diagenetically altered materials cannot be universally applied, but should rather be evaluated on a case to case basis. The evaluation can...

  17. Novel BRAF Alteration in a Sporadic Pilocytic Astrocytoma

    Directory of Open Access Journals (Sweden)

    Sonika Dahiya


    Full Text Available Pilocytic astrocytoma (PA is the most frequently encountered glial tumor (glioma or astrocytoma in children. Recent studies have identified alterations in the BRAF serine/threonine kinase gene as the likely causative mutation in these childhood brain tumors. The majority of these genetic changes involve chromosome 7q34 tandem duplication, resulting in aberrant BRAF fusion transcripts. In this paper, we describe a novel KIAA1549:BRAF fusion transcript in a sporadic PA tumor associated with increased ERK activation and review the spectrum of BRAF genetic alterations in this common pediatric low-grade central nervous system neoplasm.

  18. Temperatures of aqueous alteration on carbonaceous chondrite parent bodies


    Guo, W; Perronnet, M.; Zolensky, M.E.; Eiler, J. M.


    Aqueous alteration of primitive meteorites is among the earliest and the most widespread geological processes in the solar system. A better understanding of these processes would help us constrain the early evolution condition of the solar system and test models of thermal and chemical evolution of planetesimals. In this study, we extended our previous work on CM chondrites by further applying carbonate clumped isotope thermometry to other types of carbonaceous chondrites (G...

  19. Altered brain reward circuits in eating disorders: chicken or egg? (United States)

    Frank, Guido K W


    The eating disorders anorexia nervosa (AN) and bulimia nervosa (BN) are severe psychiatric disorders with high mortality. Our knowledge about the neurobiology of eating disorders is very limited, and the question remains whether alterations in brain structure or function in eating disorders are state related, remnants of the illness or premorbid traits. The brain reward system is a relatively well-characterized brain circuitry that plays a central role in the drive to eat and individuals with current or past eating disorders showed alterations in those pathways compared to controls. Here we propose that structural and functional alterations in the insula and frontal cortex, including orbitofrontal and cingulate regions, areas that contribute to reward and anxiety processing, could predispose to developing an eating disorder and that adaptive changes in those circuits in response to malnutrition or repeated binge eating and purging could further promote illness behavior, hinder recovery and contribute to relapse.

  20. Epigenetic Alterations in Parathyroid Cancers

    Directory of Open Access Journals (Sweden)

    Chiara Verdelli


    Full Text Available Parathyroid cancers (PCas are rare malignancies representing approximately 0.005% of all cancers. PCas are a rare cause of primary hyperparathyroidism, which is the third most common endocrine disease, mainly related to parathyroid benign tumors. About 90% of PCas are hormonally active hypersecreting parathormone (PTH; consequently patients present with complications of severe hypercalcemia. Pre-operative diagnosis is often difficult due to clinical features shared with benign parathyroid lesions. Surgery provides the current best chance of cure, though persistent or recurrent disease occurs in about 50% of patients with PCas. Somatic inactivating mutations of CDC73/HRPT2 gene, encoding parafibromin, are the most frequent genetic anomalies occurring in PCas. Recently, the aberrant DNA methylation signature and microRNA expression profile have been identified in PCas, providing evidence that parathyroid malignancies are distinct entities from parathyroid benign lesions, showing an epigenetic signature resembling some embryonic aspects. The present paper reviews data about epigenetic alterations in PCas, up to now limited to DNA methylation, chromatin regulators and microRNA profile.

  1. Epigenetic Alterations in Parathyroid Cancers (United States)

    Verdelli, Chiara; Corbetta, Sabrina


    Parathyroid cancers (PCas) are rare malignancies representing approximately 0.005% of all cancers. PCas are a rare cause of primary hyperparathyroidism, which is the third most common endocrine disease, mainly related to parathyroid benign tumors. About 90% of PCas are hormonally active hypersecreting parathormone (PTH); consequently patients present with complications of severe hypercalcemia. Pre-operative diagnosis is often difficult due to clinical features shared with benign parathyroid lesions. Surgery provides the current best chance of cure, though persistent or recurrent disease occurs in about 50% of patients with PCas. Somatic inactivating mutations of CDC73/HRPT2 gene, encoding parafibromin, are the most frequent genetic anomalies occurring in PCas. Recently, the aberrant DNA methylation signature and microRNA expression profile have been identified in PCas, providing evidence that parathyroid malignancies are distinct entities from parathyroid benign lesions, showing an epigenetic signature resembling some embryonic aspects. The present paper reviews data about epigenetic alterations in PCas, up to now limited to DNA methylation, chromatin regulators and microRNA profile. PMID:28157158

  2. Hindlimb unloading alters ligament healing (United States)

    Provenzano, Paolo P.; Martinez, Daniel A.; Grindeland, Richard E.; Dwyer, Kelley W.; Turner, Joanne; Vailas, Arthur C.; Vanderby, Ray Jr


    We investigated the hypothesis that hindlimb unloading inhibits healing in fibrous connective tissue such as ligament. Male rats were assigned to 3- and 7-wk treatment groups with three subgroups each: sham control, ambulatory healing, and hindlimb-suspended healing. Ambulatory and suspended animals underwent surgical rupture of their medial collateral ligaments, whereas sham surgeries were performed on control animals. After 3 or 7 wk, mechanical and/or morphological properties were measured in ligament, muscle, and bone. During mechanical testing, most suspended ligaments failed in the scar region, indicating the greatest impairment was to ligament and not to bone-ligament insertion. Ligament testing revealed significant reductions in maximum force, ultimate stress, elastic modulus, and low-load properties in suspended animals. In addition, femoral mineral density, femoral strength, gastrocnemius mass, and tibialis anterior mass were significantly reduced. Microscopy revealed abnormal scar formation and cell distribution in suspended ligaments with extracellular matrix discontinuities and voids between misaligned, but well-formed, collagen fiber bundles. Hence, stress levels from ambulation appear unnecessary for formation of fiber bundles yet required for collagen to form structurally competent continuous fibers. Results support our hypothesis that hindlimb unloading impairs healing of fibrous connective tissue. In addition, this study provides compelling morphological evidence explaining the altered structure-function relationship in load-deprived healing connective tissue.

  3. K isotopes as a tracer of seafloor hydrothermal alteration. (United States)

    Parendo, Christopher A; Jacobsen, Stein B; Wang, Kun


    At ocean spreading ridges, circulation of seawater through rock at elevated temperatures alters the chemical and isotopic composition of oceanic crust. Samples obtained from drilling into ocean floor and from ophiolites have demonstrated that certain isotope systems, such as (18)O/(16)O and (87)Sr/(86)Sr, are systematically modified in hydrothermally altered oceanic crust. Although K is known to be mobile during hydrothermal alteration, there have not yet been any K-isotope analyses of altered oceanic crustal materials. Moreover, the (41)K/(39)K of seawater was recently found to be significantly higher than that of igneous rocks, so the addition of seawater K to oceanic crust would be expected to generate (41)K/(39)K variations in affected rocks. Here, we report high-precision (41)K/(39)K measurements for samples from the Bay of Islands ophiolite, and we document large variations in (41)K/(39)K, covarying with previous determinations of (87)Sr/(86)Sr. Our data indicate that analytically resolvable (41)K/(39)K effects arise in oceanic crust as a result of hydrothermal alteration. This finding raises the possibility that (41)K/(39)K can be used as an effective tracer of oceanic crust recycled into the mantle, as a diagnostic criterion by which to identify ancient fragments of oceanic crust, and as a constraint on the flux of K between oceanic crust and seawater.

  4. Modulatory Effect of Taurine on 7,12-Dimethylbenz(a)Anthracene-Induced Alterations in Detoxification Enzyme System, Membrane Bound Enzymes, Glycoprotein Profile and Proliferative Cell Nuclear Antigen in Rat Breast Tissue. (United States)

    Vanitha, Manickam Kalappan; Baskaran, Kuppusamy; Periyasamy, Kuppusamy; Selvaraj, Sundaramoorthy; Ilakkia, Aruldoss; Saravanan, Dhiravidamani; Venkateswari, Ramachandran; Revathi Mani, Balasundaram; Anandakumar, Pandi; Sakthisekaran, Dhanapal


    The modulatory effect of taurine on 7,12-dimethylbenz(a)anthracene (DMBA)-induced breast cancer in rats was studied. DMBA (25 mg/kg body weight) was administered to induce breast cancer in rats. Protein carbonyl levels, activities of membrane bound enzymes (Na(+) /K(+) ATPase, Ca(2+) ATPase, and Mg(2+) ATPase), phase I drug metabolizing enzymes (cytochrome P450, cytochrome b5, NADPH cytochrome c reductase), phase II drug metabolizing enzymes (glutathione-S-transferase and UDP-glucuronyl transferase), glycoprotein levels, and proliferative cell nuclear antigen (PCNA) were studied. DMBA-induced breast tumor bearing rats showed abnormal alterations in the levels of protein carbonyls, activities of membrane bound enzymes, drug metabolizing enzymes, glycoprotein levels, and PCNA protein expression levels. Taurine treatment (100 mg/kg body weight) appreciably counteracted all the above changes induced by DMBA. Histological examination of breast tissue further supported our biochemical findings. The results of the present study clearly demonstrated the chemotherapeutic effect of taurine in DMBA-induced breast cancer.

  5. Hydrothermal alteration in oceanic ridge volcanics: A detailed study at the Galapagos Fossil Hydrothermal Field (United States)

    Ridley, W.I.; Perfit, M.R.; Josnasson, I.R.; Smith, M.F.


    The Galapagos Fossil Hydrothermal Field is composed of altered oceanic crust and extinct hydrothermal vents within the eastern Galapagos Rift between 85??49???W and 85??55???W. The discharge zone of the hydrothermal system is revealed along scarps, thus providing an opportunity to examine the uppermost mineralized, and highly altered interior parts of the crust. Altered rocks collected in situ by the submersible ALVIN show complex concentric alteration zones. Microsamples of individual zones have been analysed for major/minor, trace elements, and strontium isotopes in order to describe the complex compositional details of the hydrothermal alteration. Interlayered chlorite-smectite and chlorite with disequilibrium compositions dominate the secondary mineralogy as replacement phases of primary glass and acicular pyroxene. Phenocrysts and matrix grains of plagioclase are unaffected during alteration. Using a modification of the Gresens' equation we demonstrate that the trivalent rare earth elements (REEs) are relatively immobile, and calculate degrees of enrichment and depletion in other elements. Strontium isotopic ratios increase as Sr concentrations decrease from least-altered cores to most-altered rims and cross-cutting veins in individual samples, and can be modeled by open system behaviour under low fluid-rock ratio (metal sulfides beneath the seafloor is probably a result of fluid mixing and cooling. If, as suggested here, the discharge zone alteration occurred under relatively low fluid-rock ratios, then this shallow region must play an important role in determining the exit composition of vent fluids in marine hydrothermal systems. ?? 1994.

  6. Rural Electric Network Alteration Spurs Cable Production

    Institute of Scientific and Technical Information of China (English)


    <正>Most aluminum cable enterprises in Yunnan and Zhejiang focus their production capacity on overhead cables needed in rural electric network alteration. During the 12th Five-Year Plan period, China launched the rural electric network alteration & upgrade project. As of the middle of 2011, the budget of the central government for the rural electric network alteration & upgrade project planned by the National Development and Reform Commission has reached up to RMB 64.96 billion.

  7. Altered Glutathione Redox State in Schizophrenia

    Directory of Open Access Journals (Sweden)

    Jeffrey K. Yao


    Full Text Available Altered antioxidant status has been reported in schizophrenia. The glutathione (GSH redox system is important for reducing oxidative stress. GSH, a radical scavenger, is converted to oxidized glutathione (GSSG through glutathione peroxidase (GPx, and converted back to GSH by glutathione reductase (GR. Measurements of GSH, GSSG and its related enzymatic reactions are thus important for evaluating the redox and antioxidant status. In the present study, levels of GSH, GSSG, GPx and GR were assessed in the caudate region of postmortem brains from schizophrenic patients and control subjects (with and without other psychiatric disorders. Significantly lower levels of GSH, GPx, and GR were found in schizophrenic group than in control groups without any psychiatric disorders. Concomitantly, a decreased GSH:GSSG ratio was also found in schizophrenic group. Moreover, both GSSG and GR levels were significantly and inversely correlated to age of schizophrenic patients, but not control subjects. No significant differences were found in any GSH redox measures between control subjects and individuals with other types of psychiatric disorders. There were, however, positive correlations between GSH and GPx, GSH and GR, as well as GPx and GR levels in control subjects without psychiatric disorders. These positive correlations suggest a dynamic state is kept in check during the redox coupling under normal conditions. By contrast, lack of such correlations in schizophrenia point to a disturbance of redox coupling mechanisms in the antioxidant defense system, possibly resulting from a decreased level of GSH as well as age-related decreases of GSSG and GR activities.

  8. Altered mental status and endocrine diseases. (United States)

    Park, Elizabeth; Abraham, Michael K


    Although the altered mental status is a common presentation in the emergency department, altered mental status caused by endocrine emergencies is rare. The altered patient could have an endocrine cause that can quickly improve with appropriate diagnosis and interventions. When dealing with limited information and an obtunded patient, it is important to have a broad differential diagnosis, pick up on the physical examination findings, and evaluate laboratory abnormalities that could suggest an underlying endocrine emergency. This article outlines the findings and provides a description of altered patients with endocrine emergencies to facilitate the diagnosis and treatment in the emergency department.

  9. Avian assemblages on altered grasslands (United States)

    Knopf, Fritz L.


    Grasslands comprise 17% of the North American landscape but provide primary habitat for only 5% of native bird species. On the Great Plains, grasslands include an eastern component of tall grasses and a western component of short grasses, both of which have been regionally altered by removing native grazers, plowing sod, draining wetlands, and encouraging woody vegetation. As a group, populations of endemic bird species of the grasslands have declined more than others (including neotropical migrants) in the last quarter century. Individually, populations of the Upland Sandpiper and McCown’s Longspur have increased; the wetlands-associated Marbled Godwit and Wilson’s Phalarope appear stable; breeding ranges are shifting for the Ferruginous Hawk, Mississippi Kite, Short-eared Owl, Upland Sandpiper, Horned Lark, Vesper, Savannah, and Henslow’s sparrows, and Western Meadowlark; breeding habitats are disappearing locally for Franklin’s Gull, Dickcissel, Henslow’s and Grasshopper sparrows. Lark Bunting, and Eastern Meadowlark; and populations are declining throughout the breeding ranges for Mountain Plover, and Cassin’s and Clay-colored sparrows. Declines of these latter three species, and also the Franklin’s Gull, presumably are due to ecological phenomena on their respective wintering areas. Unlike forest species that winter in the neotropics, most birds that breed in the North American grasslands also winter on the continent and problems driving declines in grassland species are associated almost entirely with North American processes. Contemporary programs and initiatives hold promise for the conservation of breeding habitats for these birds. Ecological ignorance of wintering habits and habitats clouds the future of the endemic birds of grasslands, especially those currently experiencing widespread declines across breeding locales.

  10. Alteração física e morfológica em solos cultivados sob sistema tradicional de manejo Physical and morphological alterations in cultivated soil under traditional management system

    Directory of Open Access Journals (Sweden)

    Jorge Luís Nascimento Soares


    Full Text Available O presente trabalho foi realizado numa área agrícola situada no município de Bariri (SP, em área cultivada com citros (Citrus sinensis, onde foram estudadas algumas alterações pedológicas decorrentes de um longo período de exploração agrícola com sistema tradicional de manejo do solo. Foi estabelecida uma condição de seqüência topográfica para que pudesse ser avaliada a importância da posição dos solos no relevo sobre as modificações de alguns dos seus atributos físicos. As observações foram realizadas em campo e laboratório, em perfis verticais situados nos terços: superior, médio e inferior da encosta em um Latossolo Vermelho com alguns atributos avaliados estatisticamente por meio de teste de comparação de médias. Houve alterações na densidade do solo e da macroporosidade, principalmente nas posições mais baixas do relevo. Nestas posições, mais argilosas, há preenchimento dos espaços vazios, com a formação de estrutura em blocos, ocorrendo concomitantemente com a estrutura microagregada. Os tratos culturais promoveram grandes alterações na estrutura dos solos, mesmo em camadas relativamente profundas. O estudo ressaltou a importância de observações morfológicas detalhadas dos perfis de solo, em virtude da grande variabilidade dos atributos pedológicos a uma curta distância, sendo observados, num mesmo horizonte do perfil, setores compactados ao lado de bolsões desagregados, o que atesta a necessidade de serem considerados tanto os gradientes verticais (em cada perfil como os laterais (ao longo da toposseqüência no estudo das variações temporais dos parâmetros pedológicos.Some of the pedologic alterations resulting from traditional soil management methods were studied in an area cultivated with citrus (Citrus sinensis in a farm in Bariri County, State of São Paulo, Brazil. A toposequence was established to evaluate the effect of the position in the landscape on changes in soil physical

  11. Naloxone treatment alters gene expression in the mesolimbic reward system in 'junk food' exposed offspring in a sex-specific manner but does not affect food preferences in adulthood. (United States)

    Gugusheff, J R; Ong, Z Y; Muhlhausler, B S


    We have previously reported that the opioid receptor blocker, naloxone, is less effective in reducing palatable food intake in offspring exposed to a maternal cafeteria diet during the perinatal period, implicating a desensitization of the central opioid pathway in the programming of food preferences. The present study aimed to investigate the effect of a maternal cafeteria diet and naloxone treatment on the development of the mesolimbic reward pathway and food choices in adulthood. We measured mRNA expression of key components of the reward pathway (mu-opioid receptor, proenkephalin, tyrosine hydroxylase, D1 and D2 receptors and the dopamine active transporter (DAT)) in the nucleus accumbens (NAc) and ventral tegmental area (VTA) of the offspring of control and cafeteria fed (JF) dams at weaning and after a 10-day naloxone treatment post-weaning and determined food preferences in adulthood in the remaining offspring. Naloxone treatment decreased the expression of DAT by 8.2 fold in female control offspring but increased it by 4.3 fold in female offspring of JF dams relative to the saline-injected reference groups. Proenkephalin mRNA expression was higher in the NAc of female JF offspring compared to controls, independent of naloxone treatment (Pfood preferences in adulthood in either control or JF offspring. These data indicate that prenatal exposure to a cafeteria diet alters the impact of opioid signaling blockade in the early post-weaning period on gene expression in the central reward pathway in a sex specific manner, but that these changes in gene expression do not appear to have any persistent impact on food preferences in adulthood. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. [The role of alterations in the brain signaling systems regulated by insulin, IGF-1 and leptin in the transition of impaired glucose tolerance to overt type 2 diabetes mellitus]. (United States)

    Shpakov, A O


    One of the crucial factors leading to the development of pre-diabetes and type 2 diabetes mellitus (DM2) are the disturbances in the brain hormonal signaling systems regulated by insulin, insulin-like growth factor-1 (IGF-1) and leptin. The causes of these disturbances are the changes in the redox balance and lipid metabolism leading to lipotoxicity and endoplasmic reticulum stress in neuronal cells, as well as the dysfunctions in neurotransmitter systems of the brain that are functionally associated with insulin, IGF-1 and leptin signaling systems. The identification of molecular disturbances in insulin, IGF-1 and leptin systems of the brain in pre-diabetes and DM2 can be used for early diagnostics of these diseases, and to develop new strategies for preventive treatment of DM2 at the pre-diabetic stage. In the review, the literature data and the results of own investigations concerning the changes in the insulin, IGF-1 and leptin systems of the brain in pre-diabetes and DM2 and their role in the etiology and pathogenesis of DM2 are analyzed, and the approaches to restore the functional activity of these systems are discussed.

  13. Altered morphology of the nucleus accumbens in persistent developmental stuttering. (United States)

    Neef, Nicole E; Bütfering, Christoph; Auer, Tibor; Metzger, F Luise; Euler, Harald A; Frahm, Jens; Paulus, Walter; Sommer, Martin


    Neuroimaging studies in persistent developmental stuttering repeatedly report altered basal ganglia functions. Together with thalamus and cerebellum, these structures mediate sensorimotor functions and thus represent a plausible link between stuttering and neuroanatomy. However, stuttering is a complex, multifactorial disorder. Besides sensorimotor functions, emotional and social-motivational factors constitute major aspects of the disorder. Here, we investigated cortical and subcortical gray matter regions to study whether persistent developmental stuttering is also linked to alterations of limbic structures. The study included 33 right-handed participants who stutter and 34 right-handed control participants matched for sex, age, and education. Structural images were acquired using magnetic resonance imaging to estimate volumetric characteristics of the nucleus accumbens, hippocampus, amygdala, pallidum, putamen, caudate nucleus, and thalamus. Volumetric comparisons and vertex-based shape comparisons revealed structural differences. The right nucleus accumbens was larger in participants who stutter compared to controls. Recent theories of basal ganglia functions suggest that the nucleus accumbens is a motivation-to-movement interface. A speaker intends to reach communicative goals, but stuttering can derail these efforts. It is therefore highly plausible to find alterations in the motivation-to-movement interface in stuttering. While behavioral studies of stuttering sought to find links between the limbic and sensorimotor system, we provide the first neuroimaging evidence of alterations in the limbic system. Thus, our findings might initialize a unified neurobiological framework of persistent developmental stuttering that integrates sensorimotor and social-motivational neuroanatomical circuitries. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Gray matter alterations in first-admission adolescents with schizophrenia. (United States)

    Henze, Romy; Brunner, Romuald; Thiemann, Ulf; Parzer, Peter; Richterich, Andreas; Essig, Marco; Resch, Franz; Stieltjes, Bram


    Imaging studies of patients with schizophrenia have described a variety of cerebral alterations. However, long-term medication and the chronicity of the disorder may have contributed substantially to these alterations. Studies examining patients in the early stages of the disorder reduce the possibility of such confounding factors but are rare. In light of this, the aim of the present study was to examine adolescents in the early stages of the disorder to observe primary structural brain abnormalities. Gray and white matter were measured in 13 adolescents with schizophrenia and 13 healthy controls matched for age, gender, handedness, and school type using voxel-based morphometry. Subjects with schizophrenia displayed decreased gray matter in the cerebellar vermis, and alterations in the left putamen and in several parts of the visual system. These findings support cerebellar involvement in the pathogenesis of schizophrenia, and the alterations observed in several parts of the visual system may provide insights into the nature of hallucinations and delusional interpretations. © 2010 by the American Society of Neuroimaging.

  15. Altered States of Consciousness and Alcohol. (United States)

    Jones, Ben Morgan; And Others

    This document contains the reports of research at a symposium on "Altered States of Consciousness and Alcohol." The participants primarily agreed that alcohol induces an altered state of consciousness similar to other drugs, but that this phenomenon has not been explicitly stated due to the current interest in newer and more novel drugs. The…

  16. Simulation of rock mass balance of two typical altered rocks in Wulong gold deposit of Liaoning, China

    Institute of Scientific and Technical Information of China (English)


    Wulong gold deposit hosted in granite and fine-grained diorite dikes, is a typical gold deposit of quartz vein type. Granite and fine-grained diorite dikes in the ore deposit were altered by metallogenic fluid.Based on the altered zoning, the samples of petrochemistry were collected and major and trace elements were analyzed systematically. Calculation of rock mass balance shows that the major elements (SiO2, K2 O, P2O5,Fe2 O3) in the two typical altered rocks are clearly added into the altered system, and that trace elements (V,Y, Zr, Ni, Co, Sr) assume an increasing and decreasing tendencies in the altered granite and altered diorite dike, respectively. The fluid/rock ratios are 30.17-181.00 and 115.44-692.67 respectively for altered granite and altered diorite dike, they have profoundly effects on metallogenesis.

  17. Helminth Parasites Alter Protection against Plasmodium Infection

    Directory of Open Access Journals (Sweden)

    Víctor H. Salazar-Castañon


    Full Text Available More than one-third of the world’s population is infected with one or more helminthic parasites. Helminth infections are prevalent throughout tropical and subtropical regions where malaria pathogens are transmitted. Malaria is the most widespread and deadliest parasitic disease. The severity of the disease is strongly related to parasite density and the host’s immune responses. Furthermore, coinfections between both parasites occur frequently. However, little is known regarding how concomitant infection with helminths and Plasmodium affects the host’s immune response. Helminthic infections are frequently massive, chronic, and strong inductors of a Th2-type response. This implies that infection by such parasites could alter the host’s susceptibility to subsequent infections by Plasmodium. There are a number of reports on the interactions between helminths and Plasmodium; in some, the burden of Plasmodium parasites increased, but others reported a reduction in the parasite. This review focuses on explaining many of these discrepancies regarding helminth-Plasmodium coinfections in terms of the effects that helminths have on the immune system. In particular, it focuses on helminth-induced immunosuppression and the effects of cytokines controlling polarization toward the Th1 or Th2 arms of the immune response.

  18. Helminth Parasites Alter Protection against Plasmodium Infection (United States)

    Salazar-Castañon, Víctor H.; Legorreta-Herrera, Martha


    More than one-third of the world's population is infected with one or more helminthic parasites. Helminth infections are prevalent throughout tropical and subtropical regions where malaria pathogens are transmitted. Malaria is the most widespread and deadliest parasitic disease. The severity of the disease is strongly related to parasite density and the host's immune responses. Furthermore, coinfections between both parasites occur frequently. However, little is known regarding how concomitant infection with helminths and Plasmodium affects the host's immune response. Helminthic infections are frequently massive, chronic, and strong inductors of a Th2-type response. This implies that infection by such parasites could alter the host's susceptibility to subsequent infections by Plasmodium. There are a number of reports on the interactions between helminths and Plasmodium; in some, the burden of Plasmodium parasites increased, but others reported a reduction in the parasite. This review focuses on explaining many of these discrepancies regarding helminth-Plasmodium coinfections in terms of the effects that helminths have on the immune system. In particular, it focuses on helminth-induced immunosuppression and the effects of cytokines controlling polarization toward the Th1 or Th2 arms of the immune response. PMID:25276830

  19. Atrazine exposure elicits copy number alterations in the zebrafish genome. (United States)

    Wirbisky, Sara E; Freeman, Jennifer L


    Atrazine is an agricultural herbicide used throughout the Midwestern United States that frequently contaminates potable water supplies resulting in human exposure. Using the zebrafish model system, an embryonic atrazine exposure was previously reported to decrease spawning rates with an increase in progesterone and ovarian follicular atresia in adult females. In addition, alterations in genes associated with distinct molecular pathways of the endocrine system were observed in brain and gonad tissue of the adult females and males. Current hypotheses for mechanistic changes in the developmental origins of health and disease include genetic (e.g., copy number alterations) or epigenetic (e.g., DNA methylation) mechanisms. As such, in the current study we investigated whether an atrazine exposure would generate copy number alterations (CNAs) in the zebrafish genome. A zebrafish fibroblast cell line was used to limit detection to CNAs caused by the chemical exposure. First, cells were exposed to a range of atrazine concentrations and a crystal violet assay was completed, showing confluency decreased by ~60% at 46.3μM. Cells were then exposed to 0, 0.463, 4.63, or 46.3μM atrazine and array comparative genomic hybridization completed. Results showed 34, 21, and 44 CNAs in the 0.463, 4.63, and 46.3μM treatments, respectively. Furthermore, CNAs were associated with previously reported gene expression alterations in adult male and female zebrafish. This study demonstrates that atrazine exposure can generate CNAs that are linked to gene expression alterations observed in adult zebrafish exposed to atrazine during embryogenesis providing a mechanism of the developmental origins of atrazine endocrine disruption. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Alterations of the visual pathways in congenital blindness

    DEFF Research Database (Denmark)

    Ptito, Maurice; Schneider, Fabien C G; Paulson, Olaf B


    We used whole brain MRI voxel-based morphometry (VBM) to study the anatomical organization of the visual system in congenitally blind (CB) adults. Eleven CB without a history of visual perception were compared with 21 age- and sex-matched normal-sighted controls (NS). CB showed significant atrophy...... of the geniculo-striate system, encompassing the optic nerves, the optic chiasm, the optic radiations and the primary visual cortex (BA17). The volume decrease in BA17 reached 25% in both hemispheres. The pulvinar and its projections to the associative visual areas were also dramatically altered, BA18....../19 and the middle temporal cortex (MT) showing volume reductions of up to 20%. Additional significant white matter alterations were observed in the inferior longitudinal tract and in the posterior part of the corpus callosum, which links the visual areas of both hemispheres. Our data indicate that the afferent...

  1. Calcium signaling in plant cells in altered gravity (United States)

    Kordyum, E. L.


    tension → alterations in the physicochemical properties of the membrane → changes in membrane permeability, ion transport, membrane-bound enzyme activity, etc. → metabolism rearrangements → physiological responses. An analysis of data available on biological effects of altered gravity at the cellular level allows one to conclude that microgravity environment appears to affect cytoskeleton, carbohydrate and lipid metabolism, cell wall biogenesis via changes in enzyme activity and protein expression, with involvement of regulatory Ca 2+ messenger system. Changes in Ca 2+ influx/efflux and possible pathways of Ca 2+ signaling in plant cell biochemical regulation in altered gravity are discussed.

  2. Impact of Medicare's prospective payment system on hospitals, skilled nursing facilities, and home health agencies: how the Balanced Budget Act of 1997 may have altered service patterns for Medicare providers. (United States)

    Kulesher, Robert R


    The prospective payment system is one of many changes in reimbursement that has affected the delivery of health care. Originally developed for the payment of inpatient hospital services, it has become a major factor in how all health insurance is reimbursed. The policy implications extend beyond the Medicare program and affect the entire health care delivery system. Initially implemented in 1982 for payments to hospitals, prospective payment system was extended to payments for skilled nursing facility and home health agency services by the Balanced Budget Act of 1997. The intent of the Balanced Budget Act was to bring into balance the federal budget through reductions in spending. The decisions that providers have made to mitigate the impact are a function of ownership type, organizational mission, and current level of Medicare participation. This article summarizes the findings of several initial studies on the Balanced Budget Act's impact and discusses how changes in Medicare reimbursement policy have influenced the delivery of health care for the general public and for Medicare beneficiaries.

  3. Altered dynamics of forest recovery under a changing climate. (United States)

    Anderson-Teixeira, Kristina J; Miller, Adam D; Mohan, Jacqueline E; Hudiburg, Tara W; Duval, Benjamin D; Delucia, Evan H


    Forest regeneration following disturbance is a key ecological process, influencing forest structure and function, species assemblages, and ecosystem-climate interactions. Climate change may alter forest recovery dynamics or even prevent recovery, triggering feedbacks to the climate system, altering regional biodiversity, and affecting the ecosystem services provided by forests. Multiple lines of evidence - including global-scale patterns in forest recovery dynamics; forest responses to experimental manipulation of CO2 , temperature, and precipitation; forest responses to the climate change that has already occurred; ecological theory; and ecosystem and earth system models - all indicate that the dynamics of forest recovery are sensitive to climate. However, synthetic understanding of how atmospheric CO2 and climate shape trajectories of forest recovery is lacking. Here, we review these separate lines of evidence, which together demonstrate that the dynamics of forest recovery are being impacted by increasing atmospheric CO2 and changing climate. Rates of forest recovery generally increase with CO2 , temperature, and water availability. Drought reduces growth and live biomass in forests of all ages, having a particularly strong effect on seedling recruitment and survival. Responses of individual trees and whole-forest ecosystems to CO2 and climate manipulations often vary by age, implying that forests of different ages will respond differently to climate change. Furthermore, species within a community typically exhibit differential responses to CO2 and climate, and altered community dynamics can have important consequences for ecosystem function. Age- and species-dependent responses provide a mechanism by which climate change may push some forests past critical thresholds such that they fail to recover to their previous state following disturbance. Altered dynamics of forest recovery will result in positive and negative feedbacks to climate change. Future research


    Directory of Open Access Journals (Sweden)

    Sunita eMathur


    Full Text Available Background: Chronic obstructive pulmonary disease (COPD is a respiratory disease associated with a systemic inflammatory response. Peripheral muscle dysfunction has been well characterized in individuals with COPD and results from a complex interaction between systemic and local factors. Objective: In this narrative review, we will describe muscle wasting in people with COPD, the associated structural changes, muscle regenerative capacity and possible mechanisms for muscle wasting. We will also discuss how structural changes relate to impaired muscle function and mobility in people with COPD. Key Observations: Approximately 30-40% of individuals with COPD experience muscle mass depletion. Furthermore, muscle atrophy is a predictor of physical function and mortality in this population. Associated structural changes include a decreased proportion and size of type-I fibers, reduced oxidative capacity and mitochondrial density mainly in the quadriceps. Observations related to impaired muscle regenerative capacity in individuals with COPD include a lower proportion of central nuclei in the presence or absence of muscle atrophy and decreased maximal telomere length, which has been correlated with reduced muscle cross-sectional area. Potential mechanisms for muscle wasting in COPD may include excessive production of reactive oxygen species, altered amino acid metabolism and lower expression of peroxisome proliferator-activated receptors-gamma-coactivator 1-alpha mRNA. Despite a moderate relationship between muscle atrophy and function, impairments in oxidative metabolism only seems weakly related to muscle function. Conclusion: This review article demonstrates the cellular modifications in the peripheral muscle of people with COPD and describes the evidence of its relationship to muscle function. Future research will focus on rehabilitation strategies to improve muscle wasting and maximize function.

  5. Neural Alterations in Acquired Age-Related Hearing Loss

    Directory of Open Access Journals (Sweden)

    Raksha Anand Mudar


    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.

  6. Topics in space gerontology: Effects of altered gravity and the problem of biological age (United States)

    Economos, A. C.


    The use of altered gravity experimentation as a gerontological research tool is examined and a rationale for a systems approach to the adaptation to spaceflight is presented. The dependence of adaptation capacity on biological age is also discussed.


    Although earthworms are known to influence agroecosystem processes, there are relatively few long-term studies addressing population dynamics under cropping systems in which earthworm populations were intentionally altered. We assessed earthworm communities from fall 1994 to spr...

  8. Uranium-induced sensory alterations in the zebrafish Danio rerio

    Energy Technology Data Exchange (ETDEWEB)

    Faucher, K., E-mail: [Laboratoire d' ecotoxicologie des radionucleides (LECO), Institut de Radioprotection et Surete Nucleaire, Centre de Cadarache, Batiment 186, BP3, 13115 Saint Paul lez Durance (France); Floriani, M.; Gilbin, R.; Adam-Guillermin, C. [Laboratoire d' ecotoxicologie des radionucleides (LECO), Institut de Radioprotection et Surete Nucleaire, Centre de Cadarache, Batiment 186, BP3, 13115 Saint Paul lez Durance (France)


    The effect of chronic exposure to uranium ions (UO{sub 2}{sup 2+}) on sensory tissues including the olfactory and lateral line systems was investigated in zebrafish (Danio rerio) using scanning electron microscopy. The aim of this study was to determine whether exposure to uranium damaged sensory tissues in fish. The fish were exposed to uranium at the concentration of 250 {mu}g l{sup -1} for 10 days followed by a depuration period of 23 days. Measurements of uranium uptake in different fish organs: olfactory rosettes and bulbs, brain, skin, and muscles, were also determined by ICP-AES and ICP-MS during the entire experimental period. The results showed that uranium displayed a strong affinity for sensory structures in direct contact with the surrounding medium, such as the olfactory and lateral line systems distributed on the skin. A decreasing gradient of uranium concentration was found: olfactory rosettes > olfactory bulbs > skin > muscles > brain. At the end of the experiment, uranium was present in non-negligible quantities in sensory tissues. In parallel, fish exposed to uranium showed severe sensory tissue alterations at the level of the olfactory and lateral line systems. In both sensory systems, the gross morphology was altered and the sensory hair cells were significantly damaged very early after the initiation of exposure (from the 3rd day). At the end of the experiment, after 23 days of depuration, the lateral line system still displayed slight tissue alterations, but approximately 80% of the neuromasts in this system had regenerated. In contrast, the olfactory system took more time to recover, as more than half of the olfactory rosettes observed remained destroyed at the end of the experiment. This study showed, for the first time, that uranium is able to damage fish sensory tissues to such an extent that tissue regeneration is delayed.

  9. Obesity and arterial compliance alterations. (United States)

    Seifalian, Alexander M; Filippatos, Theodosios D; Joshi, Jatin; Mikhailidis, Dimitri P


    Obesity is associated with increased cardiovascular disease (CVD) risk, especially when excess body fat is distributed preferentially within the abdominal region. Obese subjects usually have increased arterial stiffness compared with non-obese subjects of similar age. The factors associated with increased arterial stiffness in obesity include endothelial dysfunction (decreased nitric oxide bioavailability), impaired smooth muscle cell function, insulin resistance, as well as elevated cholesterol and C-peptide levels. Furthermore, visceral fat, the adipose tissue-related renin-angiotensin-aldosterone system and hyperleptinaemia contribute to the obesity-associated impaired arterial compliance. Weight loss improves CVD risk factors and arterial compliance. Because increased arterial stiffness is a marker of CVD risk these findings support the concept that the presence of obesity has vascular implications.

  10. Global Brain Gene Expression Analysis Links Glutamatergic and GABAergic Alterations to Suicide and Major Depression


    Adolfo Sequeira; Firoza Mamdani; Carl Ernst; Vawter, Marquis P.; Bunney, William E.; Veronique Lebel; Sonia Rehal; Tim Klempan; Alain Gratton; Chawki Benkelfat; Rouleau, Guy A.; Naguib Mechawar; Gustavo Turecki


    BACKGROUND: Most studies investigating the neurobiology of depression and suicide have focused on the serotonergic system. While it seems clear that serotonergic alterations play a role in the pathogenesis of these major public health problems, dysfunction in additional neurotransmitter systems and other molecular alterations may also be implicated. Microarray expression studies are excellent screening tools to generate hypotheses about additional molecular processes that may be at play. In t...

  11. Radiolytic Alteration of Biosignatures on Mars (United States)

    Quinn, R. C.


    When exposed to ionizing radiation, a complex distribution of redox states and reactive intermediates form in both perchlorate and nitrate salts. These reactive species then act to alter the forms of organic biosignatures preserved on Mars.

  12. Effect of low dose electron beam irradiation on the alteration layer formed during nuclear glass leaching (United States)

    Mougnaud, S.; Tribet, M.; Renault, J.-P.; Jollivet, P.; Panczer, G.; Charpentier, T.; Jégou, C.


    This investigation concerns borosilicate glass leaching mechanisms and the evolution of alteration layer under electron beam irradiation. A simple glass doped with rare earth elements was selected in order to access mechanistic and structural information and better evaluate the effects of irradiation. It was fully leached in initially pure water at 90 °C and at high glass surface area to solution volume ratio (S/V = 20 000 m-1) in static conditions. Under these conditions, the system quickly reaches the residual alteration rate regime. A small particle size fraction (2-5 μm) was sampled in order to obtain a fairly homogeneous altered material enabling the use of bulk characterization methods. External irradiations with 10 MeV electrons up to a dose of 10 MGy were performed either before or after leaching, to investigate respectively the effect of initial glass irradiation on its alteration behavior and the irradiation stability of the alteration layer. Glass dissolution rate was analyzed by regular leachate samplings and the alteration layer structure was characterized by Raman, luminescence (continuous or time-resolved), and 29Si MAS NMR and EPR spectroscopy. It was shown that the small initial glass evolutions under irradiation did not induce any modification of the leaching kinetic nor of the structure of the alteration layer. The alteration process seemed to "smooth over" the created defects. Otherwise, the alteration layer and initial glass appeared to have different behaviors under irradiation. No Eu3+ reduction was detected in the alteration layer after irradiation and the defect creation efficiency was much lower than for initial glass. This can possibly be explained by the protective role of pore water contained in the altered material (∼20%). Moreover, a slight depolymerization of the silicon network of the altered glass under irradiation with electrons was evidenced, whereas in the initial glass it typically repolymerizes.

  13. AFFECT: Altered-Fidelity Framework for Enhancing Cognition and Training

    Directory of Open Access Journals (Sweden)

    Ryan Patrick McMahan


    Full Text Available In this paper, we present a new framework for analyzing and designing virtual reality (VR techniques. This framework is based on two concepts—system fidelity (i.e., the degree with which real-world experiences are reproduced by a system and memory (i.e., the formation and activation of perceptual, cognitive, and motor networks of neurons. The premise of the framework is to manipulate an aspect of system fidelity in order to assist a stage of memory. We call it the Altered-Fidelity Framework for Enhancing Cognition and Training (AFFECT. AFFECT provides nine categories of approaches to altering system fidelity to positively affect learning or training. These categories are based on the intersections of three aspects of system fidelity (interaction fidelity, scenario fidelity, and display fidelity and three stages of memory (encoding, implicit retrieval, and explicit retrieval. In addition to discussing the details of our new framework, we show how AFFECT can be used as a tool for analyzing and categorizing VR techniques designed to facilitate learning or training. We also demonstrate how AFFECT can be used as a design space for creating new VR techniques intended for educational and training systems.

  14. Natal Host Plants Can Alter Herbivore Competition


    Pan, Huipeng; Evan L. Preisser; Su, Qi; Jiao, Xiaoguo; Xie, Wen; Wang, Shaoli; Wu, Qingjun; Zhang, Youjun


    Interspecific competition between herbivores is widely recognized as an important determinant of community structure. Although researchers have identified a number of factors capable of altering competitive interactions, few studies have addressed the influence of neighboring plant species. If adaptation to/ epigenetic effects of an herbivore’s natal host plant alter its performance on other host plants, then interspecific herbivore interactions may play out differently in heterogeneous and h...

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

    Directory of Open Access Journals (Sweden)

    O'Dhaniel A Mullette-Gillman


    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.

  16. Sleep deprivation alters choice strategy without altering uncertainty or loss aversion preferences. (United States)

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


    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.

  17. Calcium signaling alterations, oxidative stress, and autophagy in aging. (United States)

    Ureshino, Rodrigo Portes; Rocha, Katiucha Karolina; Lopes, Guiomar Silva; Bincoletto, Cláudia; Smaili, Soraya Soubhi


    Aging is a multi-factorial process that may be associated with several functional and structural deficits which can evolve into degenerative diseases. In this review, we present data that may depict an expanded view of molecular aging theories, beginning with the idea that reactive oxygen species (ROS) are the major effectors in this process. In addition, we have correlated the importance of autophagy as a neuroprotective mechanism and discussed a link between age-related molecules, Ca(2+) signaling, and oxidative stress. There is evidence suggesting that alterations in Ca(2+) homeostasis, including mitochondrial Ca(2+) overload and alterations in electron transport chain (ETC) complexes, which increase cell vulnerability, are linked to oxidative stress in aging. As much as Ca(2+) signaling is altered in aged cells, excess ROS can be produced due to an ineffective coupling of mitochondrial respiration. Damaged mitochondria might not be removed by the macroautophagic system, which is hampered in aging by lipofuscin accumulation, boosting ROS generation, damaging DNA, and, ultimately, leading to apoptosis. This process can lead to altered protein expression (such as p53, Sirt1, and IGF-1) and progress to cell death. This cycle can lead to increased cell vulnerability in aging and contribute to an increased susceptibility to degenerative processes. A better understanding of Ca(2+) signaling and molecular aging alterations is important for preventing apoptosis in age-related diseases. In addition, caloric restriction, resveratrol and autophagy modulation appear to be predominantly cytoprotective, and further studies of this process are promising in age-related disease therapeutics.

  18. Modulation of Quorum Sensing in Acylhomoserine Lactone-Producing or -Degrading Tobacco Plants Leads to Alteration of Induced Systemic Resistance Elicited by the Rhizobacterium Serratia marcescens 90-166. (United States)

    Ryu, Choong-Min; Choi, Hye Kyung; Lee, Chi-Ho; Murphy, John F; Lee, Jung-Kee; Kloepper, Joseph W


    Numerous root-associated bacteria (rhizobacteria) are known to elicit induced systemic resistance (ISR) in plants. Bacterial cell-density-dependent quorum sensing (QS) is thought to be important for ISR. Here, we investigated the role of QS in the ISR elicited by the rhizobacterium, Serratia marcescens strain 90-166, in tobacco. Since S. marcescens 90-166 produces at least three QS signals, QS-mediated ISR in strain 90-166 has been difficult to understand. Therefore, we investigated the ISR capacity of two transgenic tobacco (Nicotiana tabacum) plants that contained either bacterial acylhomoserine lactone-producing (AHL) or -degrading (AiiA) genes in conjunction with S. marcescens 90-166 to induce resistance against bacterial and viral pathogens. Root application of S. marcescens 90-166 increased ISR to the bacterial pathogens, Pectobacterium carotovorum subsp. carotovorum and Pseudomonas syringae pv. tabaci, in AHL plants and decreased ISR in AiiA plants. In contrast, ISR to Cucumber mosaic virus was reduced in AHL plants treated with S. marcescens 90-166 but enhanced in AiiA plants. Taken together, these data indicate that QS-dependent ISR is elicited by S. marcescens 90-166 in a pathogen-dependent manner. This study provides insight into QS-dependent ISR in tobacco elicited by S. marcescens 90-166.

  19. Modulation of Quorum Sensing in Acylhomoserine Lactone-Producing or -Degrading Tobacco Plants Leads to Alteration of Induced Systemic Resistance Elicited by the Rhizobacterium Serratia marcescens 90-166

    Directory of Open Access Journals (Sweden)

    Choong-Min Ryu


    Full Text Available Numerous root-associated bacteria (rhizobacteria are known to elicit induced systemic resistance (ISR in plants. Bacterial cell-density-dependent quorum sensing (QS is thought to be important for ISR. Here, we investigated the role of QS in the ISR elicited by the rhizobacterium, Serratia marcescens strain 90–166, in tobacco. Since S. marcescens 90–166 produces at least three QS signals, QS-mediated ISR in strain 90–166 has been difficult to understand. Therefore, we investigated the ISR capacity of two transgenic tobacco (Nicotiana tabacum plants that contained either bacterial acylhomoserine lactone-producing (AHL or -degrading (AiiA genes in conjunction with S. marcescens 90–166 to induce resistance against bacterial and viral pathogens. Root application of S. marcescens 90–166 increased ISR to the bacterial pathogens, Pectobacterium carotovorum subsp. carotovorum and Pseudomonas syringae pv. tabaci, in AHL plants and decreased ISR in AiiA plants. In contrast, ISR to Cucumber mosaic virus was reduced in AHL plants treated with S. marcescens 90–166 but enhanced in AiiA plants. Taken together, these data indicate that QS-dependent ISR is elicited by S. marcescens 90–166 in a pathogen-dependent manner. This study provides insight into QS-dependent ISR in tobacco elicited by S. marcescens 90–166.

  20. Optical tweezers reveal how proteins alter replication (United States)

    Chaurasiya, Kathy

    Single molecule force spectroscopy is a powerful method that explores the DNA interaction properties of proteins involved in a wide range of fundamental biological processes such as DNA replication, transcription, and repair. We use optical tweezers to capture and stretch a single DNA molecule in the presence of proteins that bind DNA and alter its mechanical properties. We quantitatively characterize the DNA binding mechanisms of proteins in order to provide a detailed understanding of their function. In this work, we focus on proteins involved in replication of Escherichia coli (E. coli ), endogenous eukaryotic retrotransposons Ty3 and LINE-1, and human immunodeficiency virus (HIV). DNA polymerases replicate the entire genome of the cell, and bind both double-stranded DNA (dsDNA) and single-stranded DNA (ssDNA) during DNA replication. The replicative DNA polymerase in the widely-studied model system E. coli is the DNA polymerase III subunit alpha (DNA pol III alpha). We use optical tweezers to determine that UmuD, a protein that regulates bacterial mutagenesis through its interactions with DNA polymerases, specifically disrupts alpha binding to ssDNA. This suggests that UmuD removes alpha from its ssDNA template to allow DNA repair proteins access to the damaged DNA, and to facilitate exchange of the replicative polymerase for an error-prone translesion synthesis (TLS) polymerase that inserts nucleotides opposite the lesions, so that bacterial DNA replication may proceed. This work demonstrates a biophysical mechanism by which E. coli cells tolerate DNA damage. Retroviruses and retrotransposons reproduce by copying their RNA genome into the nuclear DNA of their eukaryotic hosts. Retroelements encode proteins called nucleic acid chaperones, which rearrange nucleic acid secondary structure and are therefore required for successful replication. The chaperone activity of these proteins requires strong binding affinity for both single- and double-stranded nucleic

  1. Epigenetic Alterations Associated with War Trauma and Childhood Maltreatment. (United States)

    Ramo-Fernández, Laura; Schneider, Anna; Wilker, Sarah; Kolassa, Iris-Tatjana


    Survivors of war trauma or childhood maltreatment are at increased risk for trauma-spectrum disorders such as post-traumatic stress disorder (PTSD). In addition, traumatic stress has been associated with alterations in the neuroendocrine and the immune system, enhancing the risk for physical diseases. Traumatic experiences might even affect psychological as well as biological parameters in the next generation, i.e. traumatic stress might have transgenerational effects. This article outlines how epigenetic processes, which represent a pivotal biological mechanism for dynamic adaptation to environmental challenges, might contribute to the explanation of the long-lasting and transgenerational effects of trauma. In particular, epigenetic alterations in genes regulating the hypothalamus-pituitary-adrenal axis as well as the immune system have been observed in survivors of childhood and adult trauma. These changes could result in enduring alterations of the stress response as well as the physical health risk. Furthermore, the effects of parental trauma could be transmitted to the next generation by parental distress and the pre- and postnatal environment, as well as by epigenetic marks transmitted via the germline. While epigenetic research has a high potential of advancing our understanding of the consequences of trauma, the findings have to be interpreted with caution, as epigenetics only represent one piece of a complex puzzle of interacting biological and environmental factors. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  2. Histochemical alterations in colorectal carcinoma and adenoma in Egyptian patients

    Institute of Scientific and Technical Information of China (English)

    Saber A Sakr; Moshira M Abdel-Wahed; Asmaa G Abdou; Eman K El-Adely


    Objective:To evaluate the histochemical alterations inDNA and total carbohydrates, in colorectal cancer cells. Methods:This study was carried out on 48 colorectal carcinoma and 10 adenoma specimens. Hematoxylin and Eosin staining was carried out for histopathological examination to confirm the diagnosis and to evaluate the histopathological characteristics of tumor. Histologic grade and pathologic stage was assessed according to TNM staging system. Staging was also assessed according to original Dukes’ staging system.DNA was demonstrated by Feulgen method and carbohydrates were demonstrated by periodic acid Schiff’s reaction. Results:Adenoma cases showed that the cells lining the glands of the polyp have more crowded, irregular and darker nuclei (hyperchromatic), anisonucleosis, abnormal mitotic figures with prominent nucleoli and variability in the size and shape of nuclei. Colorectal carcinoma cases showed a condensation and reduction in the size of a cell nucleus associated with hyperchromatosis, pyknotic nuclei, abnormal mitotic figures, anisonucleosis, irregular nuclear membrane and inequality in the size of the nuclei (Pleomorphosis). There was a statistical significant differences between adenoma and carcinoma regarding number of mitotic cells (P = 0.03) that was in favour of malignant group. Adenoma and colorectal carcinoma cases showed periodic acid Schiff’s reactivity with different degree. Conclusions:These histochemical alterations can be so characteristic of a given tumor type and stage that they are used in cancer diagnosis and might also be related to the altered functional properties of cancer cells.

  3. Histochemical alterations in colorectal carcinoma and adenoma in Egyptian patients

    Directory of Open Access Journals (Sweden)

    Saber A Sakr


    Full Text Available Objective: To evaluate the histochemical alterations in DNA and total carbohydrates, in colorectal cancer cells. Methods: This study was carried out on 48 colorectal carcinoma and 10 adenoma specimens. Hematoxylin and Eosin staining was carried out for histopathological examination to confirm the diagnosis and to evaluate the histopathological characteristics of tumor. Histologic grade and pathologic stage was assessed according to TNM staging system. Staging was also assessed according to original Dukes’ staging system. DNA was demonstrated by Feulgen method and carbohydrates were demonstrated by periodic acid Schiff’s reaction. Results: Adenoma cases showed that the cells lining the glands of the polyp have more crowded, irregular and darker nuclei (hyperchromatic, anisonucleosis, abnormal mitotic figures with prominent nucleoli and variability in the size and shape of nuclei. Colorectal carcinoma cases showed a condensation and reduction in the size of a cell nucleus associated with hyperchromatosis, pyknotic nuclei, abnormal mitotic figures, anisonucleosis, irregular nuclear membrane and inequality in the size of the nuclei (Pleomorphosis. There was a statistical significant differences between adenoma and carcinoma regarding number of mitotic cells (P = 0.03 that was in favour of malignant group. Adenoma and colorectal carcinoma cases showed periodic acid Schiff’s reactivity with different degree. Conclusions: These histochemical alterations can be so characteristic of a given tumor type and stage that they are used in cancer diagnosis and might also be related to the altered functional properties of cancer cells.

  4. Characterization of Cardiovascular Alterations Induced by Different Chronic Cisplatin Treatments

    Directory of Open Access Journals (Sweden)

    Esperanza Herradón


    Full Text Available In the last years, many clinical studies have revealed that some cisplatin-treated cancer survivors have a significantly increased risk of cardiovascular events, being cisplatin-induced cardiovascular toxicity an increasing concern. The aim of the present work was to evaluate the cardiovascular alterations induced by different chronic cisplatin treatments, and to identify some of the mechanisms involved. Direct blood pressure, basal cardiac (left ventricle and coronary arteries and vascular (aortic and mesenteric functions were evaluated in chronic (5 weeks saline- or cisplatin-treated male Wistar rats. Three different doses of cisplatin were tested (1, 2, and 3 mg/kg/week. Alterations in cardiac and vascular tissues were also investigated by immunohistochemistry, Western Blot, and or quantitative RT-PCR analysis. Cisplatin treatment provoked a significant modification of arterial blood pressure, heart rate, and basal cardiac function at the maximum dose tested. However, vascular endothelial dysfunction occurred at lower doses. The expression of collagen fibers and conexin-43 were increased in cardiac tissue in cisplatin-treated rats with doses of 2 and 3 mg/kg/week. The expression of endothelial nitric oxide synthase was also modified in cardiac and vascular tissues after cisplatin treatment. In conclusion, chronic cisplatin treatment provokes cardiac and vascular toxicity in a dose-dependent manner. Besides, vascular endothelial dysfunction occurs at lower doses than cardiac and systemic cardiovascular toxicity. Moreover, some structural changes in cardiac and vascular tissues are also patent even before any systemic cardiovascular alterations.

  5. The altered expression of inflammation-related molecules and secretion of IL-6 and IL-8 by HUVEC from newborns with maternal inactive systemic lupus erythematosus is modified by estrogens. (United States)

    Rodriguez, E; Guevara, J; Paez, A; Zapata, E; Collados, M T; Fortoul, T I; Lopez-Marure, R; Masso, F; Montaño, L F


    Systemic lupus erythematosus (SLE) predominantly affects women, especially those in reproductive age. Genetic contributions to disease susceptibility as well as immune dysregulation, particularly persistent inflammatory responses, are considered essential features. Our aim was to determine whether human umbilical vein endothelial cells (HUVEC) isolated from healthy newborns to women with inactive SLE show inflammation-related abnormalities that might lead to an early development of SLE in the offsprings. HUVEC isolated from six women with inactive SLE were stimulated with 2.5 ng/mL of TNF-alpha and/or physiological and pharmacological doses of 17-I(2) estradiol (E2). Then the expression of VCAM-1, ICAM-1, E-selectin, toll-like receptor-9 (TLR-9), heat shock protein 70 (HSP70) and HSP90 were measured. The concentrations of IL-6, IL-8, and IL-10 were also determined in maternal serum and in TNF-alpha stimulated and non-stimulated HUVEC culture supernatant. HUVEC from children with no family history of autoimmune disease served as controls. Our results showed that in HUVEC from SLE+ mothers, a constitutively low expression of adhesion molecules was enhanced by TNF-alpha treatment. The E2 (1 ng/mL) increased the expression of adhesion molecules but had no effect upon TNF-alpha-treated cells. IL-6 was constitutively higher in SLE+ HUVEC, whereas IL-8 was lower; E2 treatment diminished the latter. The E2 had no effect upon IL-6 and IL-8 secretions in TNF-alpha-treated cells. SLE+ HUVEC showed a disordered cytoskeleton and overexpressed HSP70, HSP90, and TLR-9. Our results indicate that endothelial cells of newborns to SLE+ mothers are in a proinflammatory condition which can be upregulated by estrogens.

  6. A novel intronic cAMP response element modulator (CREM) promoter is regulated by activator protein-1 (AP-1) and accounts for altered activation-induced CREM expression in T cells from patients with systemic lupus erythematosus. (United States)

    Rauen, Thomas; Benedyk, Konrad; Juang, Yuang-Taung; Kerkhoff, Claus; Kyttaris, Vasileios C; Roth, Johannes; Tsokos, George C; Tenbrock, Klaus


    The transcriptional repressor cAMP response element modulator (CREM) α has important roles in normal T cell physiology and contributes to aberrant T cell function in patients with systemic lupus erythematosus (SLE). Recently, we characterized a specificity protein-1-dependent promoter located upstream of the CREM gene that accounts for increased basal CREM expression in SLE T cells and reflects disease activity. Here, we identify a novel intronic CREM promoter (denoted P2) in front of the second exon of the CREM gene that harbors putative binding sites for TATA-binding proteins and the transcriptional activator AP-1. DNA binding studies, chromatin immunoprecipitation, and reporter assays confirmed the functional relevance of these sites, and T cell activation through CD3/CD28 stimulation or phorbol 12-myristate 13-acetate/ionomycin treatment enhances P2 promoter activity. Although the basal CREM levels are increased in T cells from SLE patients compared with healthy controls, there are remarkable differences in the regulation of CREM expression in response to T cell activation. Whereas T cells from healthy individuals display increased CREM expression after T cell activation, most likely through AP-1-dependent up-regulation of the P2 promoter, SLE T cells fail to further increase their basal CREM levels upon T cell activation due to a decreased content of the AP-1 family member c-Fos. Because CREM trans-represses c-fos transcription in SLE T cells, we propose an autoregulatory feedback mechanism between CREM and AP-1. Our findings extend the understanding of CREM gene regulation in the context of T cell activation and disclose another difference in the transcriptional machinery in SLE T cells.

  7. No Differences Between Alter G-Trainer And Active And Passive Recovery Strategies On Isokinetic Strength, Systemic Oxidative Stress And Perceived Muscle Soreness After Exercise-Induced Muscle Damage. (United States)

    Cooke, Matthew B; Nix, Carrie; Greenwood, Lori; Greenwood, Mike


    The incidence of muscle injuries is prevalent in elite sport athletes as well as weekend warriors and strategies that safely and effectively hasten recovery are highly desirable. The purpose of this study was to examine the differences between three recovery methods after eliciting muscle damage in recreationally active men relative to maximal isokinetic contractions, perceived muscle soreness and psychological mood states. Twenty-five recreationally active men (22.15±3.53yrs, 75.75±11.91kg, 180.52±7.3cm) were randomly matched by VO2 peak (53.86±6.65ml·kg·min) and assigned to one of three recovery methods: Anti-gravity Treadmill (G-Trainer) (N = 8), Conventional Treadmill (N = 8) or Static Stretching (N = 9). Recovery methods were performed 30 minutes, 24, 48 and 72 hours following a 45 minute downhill run. Following eccentrically-biased running, no significant differences were noted in isokinetic knee flexion and extension peak torque, systemic markers of muscle damage, oxidative stress and lipid peroxidation such as serum creatine kinase (CK), superoxide dismutase (SOD), and malondialdehyde (MDA), respectively, and subjective ratings of perceived muscle soreness between recovery methods. The G-Trainer group did however display a higher mood state as indicated by the Profile of Mood State global scores at 24 hours post-exercise when compared to the conventional treadmill recovery group (p=0.035). The improved mood state following the use of the anti-gravity treadmill may provide clinical relevance to other populations.

  8. A high multivitamin diet fed to Wistar rat dams during pregnancy increases maternal weight gain later in life and alters homeostatic, hedonic and peripheral regulatory systems of energy balance. (United States)

    Pannia, Emanuela; Cho, Clara E; Kubant, Ruslan; Sánchez-Hernández, Diana; Huot, Pedro S P; Chatterjee, Diptendu; Fleming, Alison; Anderson, G Harvey


    High multivitamin (10-fold, HV) and high folic acid (Fol) diets fed to pregnant Wistar rats increase body weight and characteristics of the metabolic syndrome in their offspring. Our objective was to determine the effects of a HV maternal diet on dams and whether methyl vitamins contribute to these effects. Pregnant Wistar rats were fed AIN-93G diets containing either (1) recommended multivitamins (RV, control), (2) HV, (3) HV with recommended Fol (HVRF; 1-fold Fol), or (4) RV with high methyl group vitamins (HMethyl; 10-fold Fol, vitamin B12 and B6). All groups were fed a RV diet during lactation until weaning and a RV high fat (HF; 60% fat) diet for 16 weeks post-weaning. The HV, HVRF and HMethyl diet fed dams gained 45% more weight from 2 to 15 weeks post-weaning and their weight gain (WG) was positively associated with cumulative post-weaning food intake (FI). However, only HV dams had a reduced preference for a sucrose solution, lower mesolimbic dopamine (DA) turnover in the nucleus accumbens (NAc), and higher expression of several genes involved in FI regulation in the arcuate nucleus of the hypothalamus (ARC). Energy conserving peroxisome proliferator-activated receptor (Ppar)-γ in adipose and -α in liver was also greater in these dams consistent with their WG. In conclusion, HV, HVRF and HMethyl maternal diets exacerbate maternal WG when dams are exposed to a HF diet post-weaning. However, the diets differed in their effects on central and peripheral regulatory systems of energy balance. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. 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

  10. Constraints on mineralisation and hydrothermal alteration in the Nalunaq gold deposit, South Greenland

    DEFF Research Database (Denmark)

    Bell, Robin-Marie Fairbairn

    -and - medium grained amphibolite of the Nanortalik Nappe. Detailed petrographic and geochronological studies have revealed a multi-stage hydrothermal alteration system, with alteration pre-and post-dating gold mineralisation. The hydrothermal alteration records a transition from upper-amphibolite facies...... to lower greenschist facies metamorphic conditions, over a period of 40 million years. The development of the hydrothermal alteration can be correlated to deformation events in the wider Palaeoproterozoic Ketilidian Orogen. Petrographic thin section analysis has shown that sulphidation, saussuritization...... and hydrolysis reactions are important in locally precipitating gold, which may suggest an Au(HS)2- transport complex for gold. A c. 20 cm wide biotite-arsenopyrite alteration zone surrounds the gold-quartz veins locally, and denotes areas of high-gold grades. Implicit 3-Dimentional modelling has revealed...

  11. The mineralogical characteristics of the hydrothermal types alteration from Nistru ore deposit, Baia Mare metallogenetic district

    Directory of Open Access Journals (Sweden)

    Floarea Damian


    Full Text Available The hydrothermal alteration types, which have affected intrusive and volcanic rocks from Nistru ore deposit, are related to fluids composition varied in their evolution within hydrothermal systems. The early stage of the hydrothermal activity has produced extensive propylitisation and potassic alteration (orthoclase, biotite, sericite associated with the central part of the quartz-micromonzodioritic porphyry stock. The late stage of the fluids differentiation is determined by the hydrogen-ion metasomatism (phyllic alteration, argillic alteration, characterized by a large vertical variation. The hydrogen-ion metasomatism is associated with the bor metasomatism, generated by acid solutions and at a high temperature. The vertical and lateral zoning character of the hydrothermal alterations is related to differences in rock composition and variation in physical-chemical conditions during the periods of subvolcanic intrusion and mineralization.

  12. Alterações morfológicas no sistema radicular do milho induzidas por fungos micorrízicos e fósforo Morphological alterations on root system of maize induced by mycorrhizal fungi and phosphorus

    Directory of Open Access Journals (Sweden)

    Wellington Bressan


    Full Text Available O objetivo deste trabalho, conduzido em casa de vegetação, foi avaliar os efeitos da inoculação de fungos micorrízicos arbusculares (Glomus etunicatum e Glomus clarum e da adição de níveis de P (0, 50, 100 e 200 mg/kg de solo sobre a morfologia do sistema radicular do milho (Zea mays L., cultivar BR 201, e a concentração de P na planta, em duas épocas de colheita (18 e 104 dias após semeadura em solo Latossolo Vermelho-Escuro distrófico desinfestado com Bromex. O experimento foi realizado na Embrapa-Centro Nacional de Pesquisa de Milho e Sorgo, Sete Lagoas, MG. A inoculação de fungos micorrízicos aumentou o peso das raízes secas, o número de raízes laterais primárias e secundárias, e o teor de P na planta, porém reduziu a relação peso das raízes secas/peso da parte aérea seca e o número de pêlos radiculares. Esses efeitos foram dependentes das doses de P aplicadas ao solo e da espécie de fungo micorrízico. O peso das raízes secas das plantas micorrizadas mostrou correlação significativa (PThe objective of this research, carried out under greenhouse conditions was to evaluate the effect of mycorrhizal fungi (Glomus etunicatum and Glomus clarum inoculation and P levels (0, 50, 100 e 200 mg/kg of soil on maize (Zea mays L. root system morphology, cultivar BR 201, and P plant concentration in two harvest period (18 and 104 days after sowing in disinfested dystrophic Dark-Red Latosol. The experiment was carried out under greenhouse conditions at Embrapa-Centro Nacional de Pesquisa de Milho e Sorgo, in Sete Lagoas, Minas Gerais, Brazil. Inoculation with mycorrhizal fungi increased root dry weight, number of first and second order lateral roots and P concentration in the plant, but decreased root/shoot dry weight ratio and number of root hairs. These effects were affected by P concentration in the soil and by mycorrhizal fungi species. Root dry weight of inoculated plants showed significative (P<=0.05 correlation to

  13. Boldine Prevents Renal Alterations in Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Romina Hernández-Salinas


    Full Text Available Diabetic nephropathy alters both structure and function of the kidney. These alterations are associated with increased levels of reactive oxygen species, matrix proteins, and proinflammatory molecules. Inflammation decreases gap junctional communication and increases hemichannel activity leading to increased membrane permeability and altering tissue homeostasis. Since current treatments for diabetic nephropathy do not prevent renal damage, we postulated an alternative treatment with boldine, an alkaloid obtained from boldo with antioxidant, anti-inflammatory, and hypoglycemic effects. Streptozotocin-induced diabetic and control rats were treated or not treated with boldine (50 mg/Kg/day for ten weeks. In addition, mesangial cells were cultured under control conditions or in high glucose concentration plus proinflammatory cytokines, with or without boldine (100 µmol/L. Boldine treatment in diabetic animals prevented the increase in glycemia, blood pressure, renal thiobarbituric acid reactive substances and the urinary protein/creatinine ratio. Boldine also reduced alterations in matrix proteins and markers of renal damage. In mesangial cells, boldine prevented the increase in oxidative stress, the decrease in gap junctional communication, and the increase in cell permeability due to connexin hemichannel activity induced by high glucose and proinflammatory cytokines but did not block gap junction channels. Thus boldine prevented both renal and cellular alterations and could be useful for preventing tissue damage in diabetic subjects.

  14. Alterations of the Erythrocyte Membrane during Sepsis

    Directory of Open Access Journals (Sweden)

    Yasmina Serroukh


    Full Text Available Erythrocytes have been long considered as “dead” cells with transport of oxygen (O2 as their only function. However, the ability of red blood cells (RBCs to modulate the microcirculation is now recognized as an important additional function. This capacity is regulated by a key element in the rheologic process: the RBC membrane. This membrane is a complex unit with multiple interactions between the extracellular and intracellular compartments: blood stream, endothelium, and other blood cells on the one hand, and the intracytoplasmic compartment with possible rapid adaptation of erythrocyte metabolism on the other. In this paper, we review the alterations in the erythrocyte membrane observed in critically ill patients and the influence of these alterations on the microcirculatory abnormalities observed in such patients. An understanding of the mechanisms of RBC rheologic alterations in sepsis and their effects on blood flow and on oxygen transport may be important to help reduce morbidity and mortality from severe sepsis.

  15. Altered global brain signal in schizophrenia (United States)

    Yang, Genevieve J.; Murray, John D.; Repovs, Grega; Cole, Michael W.; Savic, Aleksandar; Glasser, Matthew F.; Pittenger, Christopher; Krystal, John H.; Wang, Xiao-Jing; Pearlson, Godfrey D.; Glahn, David C.; Anticevic, Alan


    Neuropsychiatric conditions like schizophrenia display a complex neurobiology, which has long been associated with distributed brain dysfunction. However, no investigation has tested whether schizophrenia shows alterations in global brain signal (GS), a signal derived from functional MRI and often discarded as a meaningless baseline in many studies. To evaluate GS alterations associated with schizophrenia, we studied two large chronic patient samples (n = 90, n = 71), comparing them to healthy subjects (n = 220) and patients diagnosed with bipolar disorder (n = 73). We identified and replicated increased cortical power and variance in schizophrenia, an effect predictive of symptoms yet obscured by GS removal. Voxel-wise signal variance was also increased in schizophrenia, independent of GS effects. Both findings were absent in bipolar patients, confirming diagnostic specificity. Biologically informed computational modeling of shared and nonshared signal propagation through the brain suggests that these findings may be explained by altered net strength of overall brain connectivity in schizophrenia. PMID:24799682

  16. Genetic and epigenetic alterations in pancreatic carcinogenesis. (United States)

    Delpu, Yannick; Hanoun, Naïma; Lulka, Hubert; Sicard, Flavie; Selves, Janick; Buscail, Louis; Torrisani, Jérôme; Cordelier, Pierre


    Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers worldwide. Despite significant progresses in the last decades, the origin of this cancer remains unclear and no efficient therapy exists. PDAC does not arise de novo: three remarkable different types of pancreatic lesions can evolve towards pancreatic cancer. These precursor lesions include: Pancreatic intraepithelial neoplasia (PanIN) that are microscopic lesions of the pancreas, Intraductal Papillary Mucinous Neoplasms (IPMN) and Mucinous Cystic Neoplasms (MCN) that are both macroscopic lesions. However, the cellular origin of these lesions is still a matter of debate. Classically, neoplasm initiation or progression is driven by several genetic and epigenetic alterations. The aim of this review is to assemble the current information on genetic mutations and epigenetic disorders that affect genes during pancreatic carcinogenesis. We will further discuss the interest of the genetic and epigenetic alterations for the diagnosis and prognosis of PDAC. Large genetic alterations (chromosomal deletion/amplification) and single point mutations are well described for carcinogenesis inducers. Mutations classically occur within key regions of the genome. Consequences are various and include activation of mitogenic pathways or silencing of apoptotic processes. Alterations of K-RAS, P16 and DPC4 genes are frequently observed in PDAC samples and have been described to arise gradually during carcinogenesis. DNA methylation is an epigenetic process involved in imprinting and X chromosome inactivation. Alteration of DNA methylation patterns leads to deregulation of gene expression, in the absence of mutation. Both genetic and epigenetic events influence genes and non-coding RNA expression, with dramatic effects on proliferation, survival and invasion. Besides improvement in our fundamental understanding of PDAC development, highlighting the molecular alterations that occur in pancreatic carcinogenesis could

  17. Streamflow alteration at selected sites in Kansas (United States)

    Juracek, Kyle E.; Eng, Ken


    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.

  18. Portrét-Alter ego


    BUČKOVÁ, Michaela


    The bachelor work is focused in the topic of alter ego in art, mainly in portrait and self- portrait. This work is diveded in two parts-theory and practical part. In the first part I´m interested in ?alter ego?- where it comes form, history (shamanism), these days ( body modification). In the sekond part I´m interested in person (as a whole unit), psychology and psychoanalysis. In the end of the theory I remember (notice) an author, who works with simile topics. In the practical part I descri...

  19. Preterm birth and structural brain alterations in early adulthood

    Directory of Open Access Journals (Sweden)

    Chiara Nosarti


    Full Text Available Alterations in cortical development and impaired neurodevelopmental outcomes have been described following very preterm (VPT birth in childhood and adolescence, but only a few studies to date have investigated grey matter (GM and white matter (WM maturation in VPT samples in early adult life. Using voxel-based morphometry (VBM we studied regional GM and WM volumes in 68 VPT-born individuals (mean gestational age 30 weeks and 43 term-born controls aged 19–20 years, and their association with cognitive outcomes (Hayling Sentence Completion Test, Controlled Oral Word Association Test, Visual Reproduction test of the Wechsler Memory Scale-Revised and gestational age. Structural MRI data were obtained with a 1.5 Tesla system and analysed using the VBM8 toolbox in SPM8 with a customized study-specific template. Similarly to results obtained at adolescent assessment, VPT young adults compared to controls demonstrated reduced GM volume in temporal, frontal, insular and occipital areas, thalamus, caudate nucleus and putamen. Increases in GM volume were noted in medial/anterior frontal gyrus. Smaller subcortical WM volume in the VPT group was observed in temporal, parietal and frontal regions, and in a cluster centred on posterior corpus callosum/thalamus/fornix. Larger subcortical WM volume was found predominantly in posterior brain regions, in areas beneath the parahippocampal and occipital gyri and in cerebellum. Gestational age was associated with GM and WM volumes in areas where VPT individuals demonstrated GM and WM volumetric alterations, especially in temporal, parietal and occipital regions. VPT participants scored lower than controls on measures of IQ, executive function and non-verbal memory. When investigating GM and WM alterations and cognitive outcome scores, subcortical WM volume in an area beneath the left inferior frontal gyrus accounted for 14% of the variance of full-scale IQ (F = 12.9, p < 0.0001. WM volume in posterior corpus

  20. Hydrothermal alteration of impact melt sheets with implications for Mars (United States)

    Newsom, H. E.


    A model of the interaction of water with an impact melt sheet is constructed to explain the presence of hydrothermal alteration, fluid flow channels, and the redistribution of volatile elements in terrestrial melt sheets. A calculation of the amount of water vaporized beneath a melt sheet with a large fraction of melt results in a maximum total steam/melt sheet ratio of 23% by weight. The model also applies to Martian impact melt sheets, which have a total volume greater than a global layer 60 m thick. Hydrothermal circulation of steam in Martian melt sheets may have produced iron-rich alteration clays, ferric hydroxides, and near-surface accumulations of salts. The ability of vapor-dominated hydrothermal systems to concentrate sulfate relative to chloride is consistent with the high sulfate to chloride ratio found in the Martian soil by the Viking landers. A major fraction of the Martian soil may consist of the erosion products of hydrothermally altered impact melt sheets.

  1. Alterations of intestinal barrier and microbiota in chronic kidney disease. (United States)

    Sabatino, Alice; Regolisti, Giuseppe; Brusasco, Irene; Cabassi, Aderville; Morabito, Santo; Fiaccadori, Enrico


    Recent studies have highlighted the close relationship between the kidney and the gastrointestinal (GI) tract--frequently referred to as the kidney--gut axis--in patients with chronic kidney disease (CKD). In this regard, two important pathophysiological concepts have evolved: (i) production and accumulation of toxic end-products derived from increased bacterial fermentation of protein and other nitrogen-containing substances in the GI tract, (ii) translocation of endotoxins and live bacteria from gut lumen into the bloodstream, due to damage of the intestinal epithelial barrier and quantitative/qualitative alterations of the intestinal microbiota associated with the uraemic milieu. In both cases, these gut-centred alterations may have relevant systemic consequences in CKD patients, since they are able to trigger chronic inflammation, increase cardiovascular risk and worsen uraemic toxicity. The present review is thus focused on the kidney-gut axis in CKD, with special attention to the alterations of the intestinal barrier and the local microbiota (i.e. the collection of microorganisms living in a symbiotic coexistence with their host in the intestinal lumen) and their relationships to inflammation and uraemic toxicity in CKD. Moreover, we will summarize the most important clinical data suggesting the potential for nutritional modulation of gut-related inflammation and intestinal production of noxious by-products contributing to uraemic toxicity in CKD patients.

  2. Tea tree oil-induced transcriptional alterations in Staphylococcus aureus. (United States)

    Cuaron, Jesus A; Dulal, Santosh; Song, Yang; Singh, Atul K; Montelongo, Cesar E; Yu, Wanqin; Nagarajan, Vijayaraj; Jayaswal, Radheshyam K; Wilkinson, Brian J; Gustafson, John E


    Tea tree oil (TTO) is a steam distillate of Melaleuca alternifolia that demonstrates broad-spectrum antibacterial activity. This study was designed to document how TTO challenge influences the Staphylococcus aureus transcriptome. Overall, bioinformatic analyses (S. aureus microarray meta-database) revealed that both ethanol and TTO induce related transcriptional alterations. TTO challenge led to the down-regulation of genes involved with energy-intensive transcription and translation, and altered the regulation of genes involved with heat shock (e.g. clpC, clpL, ctsR, dnaK, groES, groEL, grpE and hrcA) and cell wall metabolism (e.g. cwrA, isaA, sle1, vraSR and vraX). Inactivation of the heat shock gene dnaK or vraSR which encodes a two-component regulatory system that responds to peptidoglycan biosynthesis inhibition led to an increase in TTO susceptibility which demonstrates a protective role for these genes in the S. aureus TTO response. A gene (mmpL) encoding a putative resistance, nodulation and cell division efflux pump was also highly induced by TTO. The principal antimicrobial TTO terpene, terpinen-4-ol, altered ten genes in a transcriptional direction analogous to TTO. Collectively, this study provides additional insight into the response of a bacterial pathogen to the antimicrobial terpene mixture TTO.

  3. Activated oxygen alters cerebral microvascular responses in newborn pigs

    Energy Technology Data Exchange (ETDEWEB)

    Leffler, C.W.; Busiia, D.W.; Armstead, W.M.; Mirro, R.; Thelin, O. (Univ. of Tennessee, Memphis (United States))


    In piglets, cerebral ischemia/reperfusion blocks prostanoid dependent cerebral vasodilation to hypercapnia (CO{sub 2}) and hypotension but not prostanoid independent dilation to isoproterenol (Isu) or constriction to norepinephrine (NE). Ischemia/reperfusion increases activated-O{sub 2} production by piglet brains. Using cranial windows in piglets, the authors investigated the hypothesis that activated oxygen can block prostanoid dependent cerebral vasodilator responses to CO{sub 2} and hypotension without altering responses to Isu and NE. Exposure to an activated oxygen generating system of xanthine oxidase, hypoxanthine, and Fe that made about 3 times the activated-O{sub 2} on the brain surface as ischemia/reperfusion caused reversible pial arteriolar dilation. After exposure, pial arteriolar dilation was reduced to CO{sub 2} and hypotension but not to Isu. NE constrictor responses were also unaltered. H{sub 2}O{sub 2} or H{sub 2}O{sub 2} + Fe caused constriction followed by reversible dilation. After exposure, pial arteriolar dilation in response to CO{sub 2} and hypotension was not altered. However, addition of xanthine oxidase and hypoxanthine with H{sub 2}O{sub 2} and Fe totally eliminated pial arteriolar dilator responses to CO{sub 2} and hypotension but did not decrease dilation caused by Isu or constriction caused by NE. The authors conclude that activated oxygen could produce the altered prostanoid dependent pial arteriolar responses observed following ischemia in piglets.

  4. [Cytopathological alterations and risk factors for uterine cervical neoplasm]. (United States)

    de Melo, Simone Cristina Castanho Sabaini; Prates, Letícia; Carvalho, Maria Dalva de Barros; Marcon, Sonia Silva; Pelloso, Sandra Marisa


    The aim of the present study was to verify the occurrence of citopathological alterations and risk factors of Uterine Cervical Neoplasm in women attended by SUS--the Public Healthcare System--in a district situated in the North of Paraná State, Brazil from 2001 to 2006. It was a descriptive transversal observational study. The data collection consisted in collection of test results from medical records and interviews. It was achieved 6.356 tests and, 1.02% (65) of the women examined presented alterations. From the tests made 4.869 (70,8%) were from women aged between 25 and 59 years. And 38,5% of the tests presented Cervical Intraepithelial Neoplasm (CIN) I, 32,3% CIN II, 18,5% CIN I and Human Papiloma Virus (HPV). It was interviewed 25 women from the total sample. Most of them presented a risk factor as: smoking habits, sexually transmitted diseases, use of hormonal contraceptive, number of sexual partners, early sexual intercourse. This study concludes that is required educative and more effective actions in order to reduce the alterations, meanly among teenagers.

  5. Di-octyl phthalate induced altered host resistance: Viral and protozoal models in mice

    Energy Technology Data Exchange (ETDEWEB)

    Dogra, R.K.S.; Khanna, S.; Srivastava, S.N.; Shukla, L.; Shanker, R. (Industrial Toxicology Research Centre, Lucknow (India)); Chandra, K.; Chandra, S.; Katiyar, J.C. (Central Drug Research Institute, Lucknow (India))


    Among industrially important chemicals, the effect of phthalate ester plasticizers on host resistance and immune surveillance to disease has not been well studied. Our recent studies with Di-ccetyl phthalate (DOP) have demonstrated lymphoid organotoxicity, alteration in the functioning of immune system and altered host resistance to a hookworm parasite (Nippostrongylus brasiliensis) in rodents. These observations suggested that DOP, probably through its effect on immune system, could result in altered host resistance to infection. The present studies were, therefore, undertaken to further assess the altered host resistance in DOP treated mice when challenged with either a virus (encephalomyocarditis) or a protozoal (plasmodium) infection, to delineate the possible contribution of phthalate-induced state of immunomodulation to infections.

  6. Coarctation induces alterations in basement membranes in the cardiovascular system

    DEFF Research Database (Denmark)

    Lipke, D W; McCarthy, K J; Elton, T S


    A coarctation hypertensive rat model was used to examine the effects of elevated blood pressure on basement membrane component synthesis by cardiac myocytes and aorta using immunohistochemistry and Northern blot analysis. Carotid arterial pressure increased immediately on coarctation, and left ve...

  7. Comprehensive Evaluation of Altered Systemic Metabolism and Pancreatic Cancer Risk (United States)


    Major Task 4: Generate and analyze metabolites related to branched chain amino acid ( BCAA ) metabolism. 3 Major Task 4 included analyses of...branched chain amino acid ( BCAA ) catabolic products (months 10-15), quality control of data (months 16-17), and analysis of BCAA catabolic products with...pancreatic cancer development (months 18-23). We have completed measurement of BCAA catabolic products in our plasma samples and have begun the

  8. An overlooked effect of systemic anticholinergics: alteration on accommodation amplitude

    Directory of Open Access Journals (Sweden)

    Mehmet Ali Sekeroglu


    Full Text Available AIM: To investigate the effect of oral solifenacin succinate, tolterodine-L-tartarate and oxybutinin hydrochloride (HCl on accommodation amplitude. METHODS: Female overactive bladder syndrome (OAB patients who were planned to use oral anticholinergics, patients that uses solifenacin succinate 5 mg (Group I, n=25, tolterodine-L-tartarate 4 mg (Group II, n=25, and oxybutinin HCl 5 mg b.i.d (Group III, n=25 and age matched healthy female subjects (Group IV, n=25 were recruited and complete ophthalmological examination and accommodation amplitude assessment were done at baseline and 4wk after initiation of treatment. RESULTS: The mean age of 100 consecutive female subjects was 51.6±5.7 (40-60y and there were no statistically significant difference with regard to the mean age (P=0.107 and baseline accommodation amplitude (P=0.148 between study groups. All treatment groups showed a significant decrease in accommodation amplitude following a 4-week course of anticholinergic treatment (P=0.008 in Group I, P=0.002 in Group II, P=0.001 in Group III, but there was no statistically significant difference in Group IV (P=0.065. CONCLUSION: A 4-week course of oral anticholinergic treatment have statistically significant effect on accommodation amplitude. Clinicians should avoid both overestimating this result, as this would unnecessarily restrict therapeutic possibilities, and also underestimating it which may lead to drug intolerance.

  9. Alteration of the CP/M-86 Operating System. (United States)


    al,cl out clata,al ;transmitter vi±±er is errpty ret ;tqen return adata LISTOUT: ;list device output re t LISTST: ;Poll. list status ;not, Iiplenentea...offset read2+5 mov lbxb .al Inc bx -no0v [bil an nrov big ofVSet reaL 76 ca~ll execute ,re af t rac C2 .7ov I e a P se;!rnert es ;5etup far jump vector

  10. Comprehensive Evaluation of Altered Systemic Metabolism and Pancreatic Cancer Risk (United States)


    Rev. 8-98) Prescribed by ANSI Std . Z39.18 Table of Contents Page 1. Introduction………………………………………………………….1 2. Keywords…………………………………………………………….1 3...contributions, as well as the following state cancer registries for their help: Alabama, Arizona, Arkansas, California, Colorado, Connecticut, Delaware

  11. Modeling Human Perception of Orientation in Altered Gravity

    Directory of Open Access Journals (Sweden)

    Torin K. Clark


    Full Text Available Altered gravity environments, such as those experienced by astronauts, impact spatial orientation perception and can lead to spatial disorientation and sensorimotor impairment. To more fully understand and quantify the impact of altered gravity on orientation perception, several mathematical models have been proposed. The utricular shear, tangent, and the idiotropic vector models aim to predict static perception of tilt in hyper-gravity. Predictions from these prior models are compared to the available data, but are found to systematically err from the perceptions experimentally observed. Alternatively, we propose a modified utricular shear model for static tilt perception in hyper-gravity. Previous dynamic models of vestibular function and orientation perception are limited to 1 G. Specifically, they fail to predict the characteristic overestimation of roll tilt observed in hyper-gravity environments. To address this, we have proposed a modification to a previous observer-type canal otolith interaction model based upon the hypothesis that the central nervous system treats otolith stimulation in the utricular plane differently than stimulation out of the utricular plane. Here we evaluate our modified utricular shear and modified observer models in four altered gravity motion paradigms: a static roll tilt in hyper-gravity, b static pitch tilt in hyper-gravity, c static roll tilt in hypo-gravity, and d static pitch tilt in hypo-gravity. The modified models match available data in each of the conditions considered. Our static modified utricular shear model and dynamic modified observer model may be used to help quantitatively predict astronaut perception of orientation in altered gravity environments.

  12. Tributyltin exposure alters cytokine levels in mouse serum. (United States)

    Lawrence, Shanieek; Pellom, Samuel T; Shanker, Anil; Whalen, Margaret M


    Tributyltin (TBT), a toxic environmental contaminant, has been widely utilized for various industrial, agricultural and household purposes. Its usage has led to a global contamination and its bioaccumulation in aquatic organisms and terrestrial mammals. Previous studies suggest that TBT has debilitating effects on the overall immune function of animals, rendering them more vulnerable to diseases. TBT (at concentrations that have been detected in human blood) alters secretion of inflammatory cytokines from human lymphocytes ex vivo. Thus, it is important to determine if specified levels of TBT can alter levels of cytokines in an in vivo system. Mice were exposed to biologically relevant concentrations of TBT (200, 100 or 25 nM final concentrations). The quantitative determination of interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL2, IL5, IL7, IL12βp40, IL13, IL15, keratinocyte chemoattractant (KC), macrophage inflammatory protein 1β (MIP), MIP2 and regulated on activation normal T-cell-expressed and secreted (RANTES) was performed in mouse sera by MAGPIX analysis and Western blot. Results indicated alterations (both decreases and increases) in several cytokines. The pro-inflammatory cytokines IFNγ, TNFα, IL-1β, IL-2, IL5, IL12βp40 and IL-15 were altered as were the chemokines MIP-1 and RANTES and the anti-inflammatory cytokine IL-13. Increases in IFNγ and TNFα were seen in the serum of mice exposed to TBT for less than 24 h. Levels of IL1β, IL-12 βp40, IL-5 and IL-15 were also modulated in mouse serum, depending on the specific experiment and exposure level. IL-2 was consistently decreased in mouse serum when animals were exposed to TBT. There were also TBT-induced increases in MIP-1β, RANTES and IL-13. These results from human and murine samples clearly suggest that TBT exposures modulate the secretion inflammatory cytokines.

  13. Igneous Hydrothermal Alteration and Ore-Forming Processes in the Land's End Granite, Nanjizal


    Eik, Marte


    This study addresses the hydrothermal alteration and mineralization related to a system of tourmaline-quartz veins intersecting biotite-granite in Nanjizal, in the Land s End granites of the cornubian batholith. Nanjizal is an important site as it is one of the few locations in the southern segment of the Land s End Granite where magmatic-hydrothermal tin mineralizations have been mined. The aim is to identify the alteration-patterns and their correlation with hydrothermal ore-forming events ...

  14. Connective tissue alteration in abdominal wall hernia

    DEFF Research Database (Denmark)

    Henriksen, N A; Yadete, D H; Sørensen, Lars Tue


    The aetiology and pathogenesis of abdominal wall hernia formation is complex. Optimal treatment of hernias depends on a full understanding of the pathophysiological mechanisms involved in their formation. The aim of this study was to review the literature on specific collagen alterations in abdom...

  15. Diabetic rat testes: morphological and functional alterations. (United States)

    Ricci, G; Catizone, A; Esposito, R; Pisanti, F A; Vietri, M T; Galdieri, M


    Reproductive dysfunction is a consequence of diabetes, but the underlying mechanisms are poorly understood. This study investigated the histological and molecular alterations in the testes of rats injected with streptozotocin at prepuperal (SPI rats) and adult age (SAI rats) to understand whether diabetes affects testicular tissue with different severity depending on the age in which this pathological condition starts. The testes of diabetic animals showed frequent abnormal histology, and seminiferous epithelium cytoarchitecture appeared altered as well as the occludin distribution pattern. The early occurrence of diabetes increased the percentage of animals with high number of damaged tubules. The interstitial compartment of the testes was clearly hypertrophic in several portions of the organs both in SPI and SAI rats. Interestingly, fully developed Leydig cells were present in all the treated animals although abnormally distributed. Besides the above-described damages, we found a similar decrease in plasma testosterone levels both in SPI and SAI rats. Oxidative stress (OS) is involved in the pathogenesis of various diabetic complications, and in our experimental models we found that manganese superoxide dismutase was reduced in diabetic animals. We conclude that in STZ-induced diabetes, the altered spermatogenesis, more severe in SPI animals, is possibly due to the effect of OS on Leydig cell function which could cause the testosterone decrease responsible for the alterations found in the seminiferous epithelium of diabetic animals.

  16. Acting: An Altered State of Consciousness. (United States)

    Scheiffele, Eberhard


    Uses notions from the field Psychology of Consciousness, including an explanation of how psychologists define and investigate Altered States of Consciousness (ASCs). Argues that actors routinely enter an ASC. Establishes acting as a way to enter an ASC and discusses why theater artists, educators, and advocates need to be aware of both the dangers…

  17. Psychobiology of Altered States of Consciousness (United States)

    Vaitl, Dieter; Birbaumer, Niels; Gruzelier, John; Jamieson, Graham A.; Kotchoubey, Boris; Kubler, Andrea; Lehmann, Dietrich; Miltner, Wolfgang H. R.; Ott, Ulrich; Sammer, Gebhard; Strauch, Inge; Strehl, Ute; Wackermann, Jiri; Weiss, Thomas


    The article reviews the current knowledge regarding altered states of consciousness (ASC) (a) occurring spontaneously, (b) evoked by physical and physiological stimulation, (c) induced by psychological means, and (d) caused by diseases. The emphasis is laid on psychological and neurobiological approaches. The phenomenological analysis of the…

  18. Reorientation from Altered States: Please, More Carefully. (United States)

    Heikkinen, Charles A.


    Claims counselors too often appear to forget to reorient clients from altered states of consciousness used in counseling and that failure to reorient can result in unnecessary discomfort for clients. Provides suggestions for when and how to reorient to avoid unwanted, lingering aftereffects. (Author/ABL)

  19. Altered Images: The Camera, Computer, & Beyond. (United States)

    Stieglitz, Mary

    The speech contained in this document originally accompanied a slide presentation on the altered photographic image. The discussion examines the links between photographic tradition and contemporary visual imaging, the current transformation of visual imaging by the computer, and the effects of digital imaging on visual arts. Photography has a…

  20. Gold mobility during Palaeoarchaean submarine alteration (United States)

    Hofmann, Axel; Pitcairn, Iain; Wilson, Allan


    Seafloor alteration provides large amounts of solutes to the hydrosphere. In order to investigate gold mobility during water-rock interaction prior to 3-billion-years ago, low detection limit analysis of Au concentrations was carried out on rocks from marine alteration zones. Stratiform zones recording low-temperature (≤150 °C) seafloor alteration are a characteristic feature of greenstone belts older than 3.0 Ga. Hydrothermal processes were operating on, and immediately below, the seafloor, giving rise to extensive silicification of sub-seafloor volcanic rocks and silicification of seafloor sediments. In order to investigate gold mobility during silicification, unaltered and variably silicified volcanic rocks and associated cherts from Palaeoarchaean greenstone successions (c. 3.4 Ga) of South Africa were analyzed. Results show mobility of gold during silicification of mafic/ultramafic rocks and transfer to the Archaean ocean. Some gold was incorporated into carbonaceous marine sediments overlying the alteration zones. A combination of pervasive silicification, rarity of black shales, and low gold content in komatiites can explain the low mineralization potential of Palaeoarchaean greenstone belts for orogenic gold deposits.

  1. Psychobiology of Altered States of Consciousness (United States)

    Vaitl, Dieter; Birbaumer, Niels; Gruzelier, John; Jamieson, Graham A.; Kotchoubey, Boris; Kubler, Andrea; Lehmann, Dietrich; Miltner, Wolfgang H. R.; Ott, Ulrich; Sammer, Gebhard; Strauch, Inge; Strehl, Ute; Wackermann, Jiri; Weiss, Thomas


    The article reviews the current knowledge regarding altered states of consciousness (ASC) (a) occurring spontaneously, (b) evoked by physical and physiological stimulation, (c) induced by psychological means, and (d) caused by diseases. The emphasis is laid on psychological and neurobiological approaches. The phenomenological analysis of the…

  2. Olfactory alterations in patients with multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Sergio Semeraro Jordy

    Full Text Available ABSTRACT This cross-sectional study involves 100 multiple sclerosis (MS and 100 non-MS patients, under the age of 60 years old, with nasal obstruction, traumatic brain injury, previous rhinoplasty or neurosurgery, and so forth. Objective To assess olfactory function using the Connecticut test and verify correlations between olfactory alteration, disease duration and the Expanded Disability Status Scale (EDSS. Methods One hundred MS patients and 100 healthy control patients responded to a questionnaire. Those with olfactory alteration underwent a facial CT to exclude other causes. Results Thirty-two percent of patients showed alterations, compared with 3% in the healthy control group. Patients having EDSS above 4, showed a 5.2-times increased risk of dysfunction. Patients over 38 years of age have a 2.2-times increased risk over younger patients. Conclusions Because MS patients are likely to experience olfactory alterations, this study is a useful tool in follow-up care, although more studies are necessary to evaluate the correlations in MS evolution.

  3. Altered gut microbiota in Rett syndrome. (United States)

    Strati, Francesco; Cavalieri, Duccio; Albanese, Davide; De Felice, Claudio; Donati, Claudio; Hayek, Joussef; Jousson, Olivier; Leoncini, Silvia; Pindo, Massimo; Renzi, Daniela; Rizzetto, Lisa; Stefanini, Irene; Calabrò, Antonio; De Filippo, Carlotta


    The human gut microbiota directly affects human health, and its alteration can lead to gastrointestinal abnormalities and inflammation. Rett syndrome (RTT), a progressive neurological disorder mainly caused by mutations in MeCP2 gene, is commonly associated with gastrointestinal dysfunctions and constipation, suggesting a link between RTT's gastrointestinal abnormalities and the gut microbiota. The aim of this study was to evaluate the bacterial and fungal gut microbiota in a cohort of RTT subjects integrating clinical, metabolomics and metagenomics data to understand if changes in the gut microbiota of RTT subjects could be associated with gastrointestinal abnormalities and inflammatory status. Our findings revealed the occurrence of an intestinal sub-inflammatory status in RTT subjects as measured by the elevated values of faecal calprotectin and erythrocyte sedimentation rate. We showed that, overall, RTT subjects harbour bacterial and fungal microbiota altered in terms of relative abundances from those of healthy controls, with a reduced microbial richness and dominated by microbial taxa belonging to Bifidobacterium, several Clostridia (among which Anaerostipes, Clostridium XIVa, Clostridium XIVb) as well as Erysipelotrichaceae, Actinomyces, Lactobacillus, Enterococcus, Eggerthella, Escherichia/Shigella and the fungal genus Candida. We further observed that alterations of the gut microbiota do not depend on the constipation status of RTT subjects and that this dysbiotic microbiota produced altered short chain fatty acids profiles. We demonstrated for the first time that RTT is associated with a dysbiosis of both the bacterial and fungal component of the gut microbiota, suggesting that impairments of MeCP2 functioning favour the establishment of a microbial community adapted to the costive gastrointestinal niche of RTT subjects. The altered production of short chain fatty acids associated with this microbiota might reinforce the constipation status of RTT

  4. Alteration patterns and structural controls of the El Espino IOCG mining district, Chile (United States)

    Lopez, G. P.; Hitzman, M. W.; Nelson, E. P.


    The El Espino IOCG mining district is characterized by several mineralized bodies the largest of which is the El Espino deposit, which has an estimated geologic resource of 123 Mt at 0.66 % Cu and 0.24 g/t Au. Mineralized bodies are distributed in a 7 × 10 km2 area throughout a 1,000-m vertical section. They range from single veins to stockworks and breccias to manto-type deposits. The ore bodies are hosted primarily by volcanic, volcaniclastic, and sedimentary rocks of the Early Cretaceous Arqueros and Quebrada Marquesa formations, with a few mineralized zones within Late Cretaceous dioritic intrusions. The fault and vein architecture shows that El Espino IOCG system was localized within a dilatational jog along a major transtensional dextral fault system. Sodic alteration (albite) is the most extensive style of alteration in the district, and it is bounded by major NS-NNE trending faults. Sodic-calcic (epidote-albite) alteration occurs at deep to medium elevations (1,000-500 m) and grades inward into calcic alteration. Calcic alteration surrounds dioritic intrusions of the Llahuin plutonic suite. Significant iron oxides are associated with later calcic alteration associations (actinolite-epidote-hematite). The upper portions of the alteration system (0-500 m) display hydrolytic alteration associations with abundant hematite. Hydrolytic veins are feeders to zones of manto-type alteration and mineralization within favorable volcano-sedimentary lithologies that formed El Espino deposit. Sulfides are largely confined to calcic and hydrolytic alteration associations. Hydrothermal fluids responsible for hematite and sulfide mineralization had salinities between 32 and 34 wt% NaCleq and temperature of approximately 425 °C at an estimated depth of 3-4 km. Geochronological U-Pb and 40Ar/39Ar data indicate that hydrothermal alteration was coeval with magmatic intrusive activity. One particular dioritic intrusion (88.5 Ma) preceded the calcic stage (88.4 Ma), which was

  5. Study of nuclear glasses alteration gel and synthesis of some model gels; Etude du gel d`alteration des verres nucleaires et synthese de gels modeles

    Energy Technology Data Exchange (ETDEWEB)

    Ricol, S.


    This work deals with the general problem of alteration of the reference nuclear glass R7T7. Attention is paid particularly to the altered layer formed at the glass surface during alteration process. In opposition to previous works, related essentially to glass dissolution kinetics based on chemical analyses of lixiviated elements, this thesis deals with alteration problems through structural studies of the reference glass and derived gel. This approach allows the determination of mechanisms for the gel formation and a better understanding of the behaviour of glasses towards lixiviation. Both approaches appeared complementary. Based on several spectroscopic techniques, this work showed the particular role of cations such as calcium, zirconium and iron. Studies of silica-based synthetic gels showed the synergic effect of formers cation and of one highly coordinated cation. The variation of the wavenumber related to Si-O-Si asymmetric stretching vibration can be correlated to O/Si ratio for ternary systems Si/Na/Zr. On the contrary, the Si losses of the materials depend on the number of non-bridging oxygen atoms. In the perspective of long-term behaviour, the alteration gel presents better characteristics than initial glass. It is therefore a highly stable material in static conditions. In the same way, synthetic gels are materials with very low solubilities (much lower than the alteration