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Sample records for neurogenesis long-term potentiation

  1. Enhanced Dentate Neurogenesis after Brain Injury Undermines Long-Term Neurogenic Potential and Promotes Seizure Susceptibility

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    Eric J. Neuberger

    2017-09-01

    Full Text Available Hippocampal dentate gyrus is a focus of enhanced neurogenesis and excitability after traumatic brain injury. Increased neurogenesis has been proposed to aid repair of the injured network. Our data show that an early increase in neurogenesis after fluid percussion concussive brain injury is transient and is followed by a persistent decrease compared with age-matched controls. Post-injury changes in neurogenesis paralleled changes in neural precursor cell proliferation and resulted in a long-term decline in neurogenic capacity. Targeted pharmacology to restore post-injury neurogenesis to control levels reversed the long-term decline in neurogenic capacity. Limiting post-injury neurogenesis reduced early increases in dentate excitability and seizure susceptibility. Our results challenge the assumption that increased neurogenesis after brain injury is beneficial and show that early post-traumatic increases in neurogenesis adversely affect long-term outcomes by exhausting neurogenic potential and enhancing epileptogenesis. Treatments aimed at limiting excessive neurogenesis can potentially restore neuroproliferative capacity and limit epilepsy after brain injury.

  2. Long-term cognitive deficits accompanied by reduced neurogenesis after soman poisoning

    NARCIS (Netherlands)

    Joosen, M.J.A.; Jousma, E.; van den Boom, T.M.; Kuijpers, W.C.; Smit, A.B.; Lucassen, P.J.; van Helden, H.P.M.

    2009-01-01

    To date, treatment of organophosphate (OP) poisoning shows several shortcomings, and OP-victims might suffer from lasting cognitive deficits and sleep-wake disturbances. In the present study, long-term effects of soman poisoning on learning ability, memory and neurogenesis were investigated in rats,

  3. Long-term cognitive deficits accompanied by reduced neurogenesis after soman poisoning

    NARCIS (Netherlands)

    Joosen, M.J.A.; Jousma, E.; Boom, T.M. van den; Kuijpers, W.C.; Smit, A.B.; Lucassen, P.J.; Helden, H.P.M. van

    2009-01-01

    To date, treatment of organophosphate (OP) poisoning shows several shortcomings, and OP-victims might suffer from lasting cognitive deficits and sleep–wake disturbances. In the present study, long-term effects of soman poisoning on learning ability, memory and neurogenesis were investigated in rats,

  4. Early life stress and hippocampal neurogenesis in the neonate: sexual dimorphism, long term consequences and possible mediators. A minireview.

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    Naima eLajud

    2015-02-01

    Full Text Available Adverse early life experience decreases adult hippocampal neurogenesis and results in increased vulnerability to neuropsychiatric disorders. Despite that the effects of postnatal stress on neurogenesis have been widely studied in adult individuals, few efforts have been done to evaluate its immediate effects on the developing hippocampus. Moreover, it is not clear whether postnatal stress causes a differential impact in hippocampus development in male and female neonates that could be related to emotional deficits in adulthood. It has been proposed that the long term effects of early stress exposure rise from a persistent HPA axis activation during sensitive time windows; nevertheless the exact mechanisms and mediators remain unknown. Here, we summarize the immediate and late effects of early life stress on hippocampal neurogenesis in male and female rat pups, compare its later consequences in emotionality, and highlight some relevant mediator peptides that could be potentially involved in programming.

  5. Genetic Activation of ERK5 MAP Kinase Enhances Adult Neurogenesis and Extends Hippocampus-Dependent Long-Term Memory

    OpenAIRE

    Wang, Wenbin; Pan, Yung-Wei; Zou, Junhui; Li, Tan; Abel, Glen M.; Palmiter, Richard D.; Storm, Daniel R.; Xia, Zhengui

    2014-01-01

    Recent studies have shown that inhibition of adult neurogenesis impairs the formation of hippocampus-dependent memory. However, it is not known whether increasing adult neurogenesis affects the persistence of hippocampus-dependent long-term memory. Furthermore, signaling mechanisms that regulate adult neurogenesis are not fully defined. We recently reported that the conditional and targeted knock-out of ERK5 MAP kinase in adult neurogenic regions of the mouse brain attenuates adult neurogenes...

  6. Fornix deep brain stimulation induced long-term spatial memory independent of hippocampal neurogenesis.

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    Hescham, Sarah; Temel, Yasin; Schipper, Sandra; Lagiere, Mélanie; Schönfeld, Lisa-Maria; Blokland, Arjan; Jahanshahi, Ali

    2017-03-01

    Deep brain stimulation (DBS) is an established symptomatic treatment modality for movement disorders and constitutes an emerging therapeutic approach for the treatment of memory impairment. In line with this, fornix DBS has shown to ameliorate cognitive decline associated with dementia. Nonetheless, mechanisms mediating clinical effects in demented patients or patients with other neurological disorders are largely unknown. There is evidence that DBS is able to modulate neurophysiological activity in targeted brain regions. We therefore hypothesized that DBS might be able to influence cognitive function via activity-dependent regulation of hippocampal neurogenesis. Using stimulation parameters, which were validated to restore memory loss in a previous behavioral study, we here assessed long-term effects of fornix DBS. To do so, we injected the thymidine analog, 5-bromo-2'-deoxyuridine (BrdU), after DBS and perfused the animals 6.5 weeks later. A week prior to perfusion, memory performance was assessed in the water maze. We found that acute stimulation of the fornix improved spatial memory performance in the water maze when the probe trial was performed 1 h after the last training session. However, no evidence for stimulation-induced neurogenesis was found in fornix DBS rats when compared to sham. Our results suggest that fornix DBS improves memory functions independent of hippocampal neurogenesis, possibly through other mechanisms such as synaptic plasticity and acute neurotransmitter release.

  7. Short- and long-term treatment with modafinil differentially affects adult hippocampal neurogenesis.

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    Brandt, M D; Ellwardt, E; Storch, A

    2014-10-10

    The generation of new neurons in the dentate gyrus of the adult brain has been demonstrated in many species including humans and is suggested to have functional relevance for learning and memory. The wake promoting drug modafinil has popularly been categorized as a so-called neuroenhancer due to its positive effects on cognition. We here show that short- and long-term treatment with modafinil differentially effects hippocampal neurogenesis. We used different thymidine analogs (5-bromo-2-deoxyuridine (BrdU), chlorodeoxyuridine (CldU), iododeoxyuridine (IdU)) and labeling protocols to investigate distinct regulative events during hippocampal neurogenesis, namely cell proliferation and survival. Eight-week-old mice that were treated with modafinil (64mg/kg, i.p.) every 24h for 4days show increased proliferation in the dentate gyrus indicated by BrdU-labeling and more newborn granule cells 3weeks after treatment. Short-term treatment for 4days also enhanced the number of postmitotic calretinin-expressing progenitor cells that were labeled with BrdU 1week prior to treatment indicating an increased survival of new born immature granule cells. Interestingly, long-term treatment for 14days resulted in an increased number of newborn Prox1(+) granule cells, but we could not detect an additive effect of the prolonged treatment on proliferation and survival of newborn cells. Moreover, daily administration for 14days did not influence the number of proliferating cells in the dentate gyrus. Together, modafinil has an acute impact on precursor cell proliferation as well as survival but loses this ability during longer treatment durations. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  8. Nutritional deficit and Long Term Potentiation alterations

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    M. Petrosino

    2009-01-01

    Full Text Available In the present work we examined the ability of prenatally malnourished offspring to produce and maintain long-term potentiation (LTP of the perforant path/dentate granule cell synapse in freely moving rats at 15,30, and 90 days of age. Population spike amplitude (PSA was calculated from dentate field potential recordings prior to and at 15, 30, 60 min. and 3, 5, 18 and 24 h following tetanization of the perforant pathway. All animals of both malnourished and well-nourished diet groups at 15 days of age showed potentiation of PSA measures but the measures obtained from 15-day-old prenatally malnourished animals were significantly less than that of age-matched, well-nourished controls. At 30 days of age, remarkable effect of tetanization was likely observed from PSA measures for this age group followed much the same pattern. At 90 days of age, PSA measures obtained from malnourished animals decreased from pretetanization levels immediately following tetanization. At this age, however, at three hours time recordings, this measure growing up to a level which did not differ significantly from that of the control group. These results indicate that the width of tetanization induced enhancement of dentate granule cell response in preweanling rats (15-day-old animals is signifacantly affected fromgestational protein malnutrition and this trend is kept in animals tested at 30 and 90 days of age. The fact, however, that considerable limitation in LTP generation was gained from prenatally malnourished animals at 90 days of age, implying that dietary rehabilitation starting at birth is an intervention strategy not capable to imbrove the effects of the gestational stress.

  9. Conditional depletion of neurogenesis inhibits long-term recovery after experimental stroke in mice.

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    Xiaomei Wang

    Full Text Available We reported previously that ablation of doublecortin (DCX-immunopositive newborn neurons in mice worsens anatomical and functional outcome measured 1 day after experimental stroke, but whether this effect persists is unknown. We generated transgenic mice that express herpes simplex virus thymidine kinase under control of the DCX promoter (DCX-TK transgenic mice. DCX-expressing and recently divided cells in the rostral subventricular zone (SVZ and hippocampus of DCX-TK transgenic mice, but not wild-type mice, were specifically depleted after ganciclovir (GCV treatment for 14 days. Focal cerebral ischemia was induced by permanent distal middle cerebral artery occlusion (MCAO on day 14 of vehicle or GCV treatment, and mice were killed 12 weeks after MCAO. Infarct volume was significantly increased and neurologic deficits were more severe in GCV- compared to vehicle-treated DCX-TK transgenic mice at first 8 weeks, after depletion of DCX- and bromodeoxyuridine-immunoreactive cells in the SVZ and dentate gyrus following focal ischemia. Our results indicate that endogenous neurogenesis in a critical period following experimental stroke influences the course of long-term recovery.

  10. Impaired long-term memory retention: common denominator for acutely or genetically reduced hippocampal neurogenesis in adult mice.

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    Ben Abdallah, Nada M-B; Filipkowski, Robert K; Pruschy, Martin; Jaholkowski, Piotr; Winkler, Juergen; Kaczmarek, Leszek; Lipp, Hans-Peter

    2013-09-01

    In adult rodents, decreasing hippocampal neurogenesis experimentally using different approaches often impairs performance in hippocampus-dependent processes. Nonetheless, functional relevance of adult neurogenesis is far from being unraveled, and deficits so far described in animal models often lack reproducibility. One hypothesis is that such differences might be the consequence of the extent of the methodological specificity used to alter neurogenesis rather than the extent to which adult neurogenesis is altered. To address this, we focused on cranial irradiation, the most widely used technique to impair hippocampal neurogenesis and consequentially induce hippocampus-dependent behavioral deficits. To investigate the specificity of the technique, we thus exposed 4-5 months old female cyclin D2 knockout mice, a model lacking physiological levels of olfactory and hippocampal neurogenesis, to an X-ray dose of 10 Gy, reported to specifically affect transiently amplifying precursors. After a recovery period of 1.5 months, behavioral tests were performed and probed for locomotor activity, habituation, anxiety, and spatial learning and memory. Spatial learning in the Morris water maze was intact in all experimental groups. Although spatial memory retention assessed 24h following acquisition was also intact in all mice, irradiated wild type and cyclin D2 knockout mice displayed memory deficits one week after acquisition. In addition, we observed significant differences in tests addressing anxiety and locomotor activity dependent on the technique used to alter neurogenesis. Whereas irradiated mice were hyperactive regardless of their genotype, cyclin D2 knockout mice were hypoactive in most of the tests and displayed altered habituation. The present study emphasizes that different approaches aimed at decreasing adult hippocampal neurogenesis may result in distinct behavioral impairments related to locomotion and anxiety. In contrast, spatial long-term memory retention is

  11. Long-term potentiation and long-term depression: a clinical perspective

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    Timothy V.P. Bliss

    2011-01-01

    Full Text Available Long-term potentiation and long-term depression are enduring changes in synaptic strength, induced by specific patterns of synaptic activity, that have received much attention as cellular models of information storage in the central nervous system. Work in a number of brain regions, from the spinal cord to the cerebral cortex, and in many animal species, ranging from invertebrates to humans, has demonstrated a reliable capacity for chemical synapses to undergo lasting changes in efficacy in response to a variety of induction protocols. In addition to their physiological relevance, long-term potentiation and depression may have important clinical applications. A growing insight into the molecular mechanisms underlying these processes, and technological advances in non-invasive manipulation of brain activity, now puts us at the threshold of harnessing long-term potentiation and depression and other forms of synaptic, cellular and circuit plasticity to manipulate synaptic strength in the human nervous system. Drugs may be used to erase or treat pathological synaptic states and non-invasive stimulation devices may be used to artificially induce synaptic plasticity to ameliorate conditions arising from disrupted synaptic drive. These approaches hold promise for the treatment of a variety of neurological conditions, including neuropathic pain, epilepsy, depression, amblyopia, tinnitus and stroke.

  12. Quantification of long term emission potential from landfills

    NARCIS (Netherlands)

    Heimovaara, T.J.

    2011-01-01

    Novel approaches for the after-care of Municipal Solid Waste (MSW) landfills are based on technological measures to reduce the long term emission potential in a short time period. Biological degradation in landfills is a means to significantly reduce the long term emission potential. Leachate

  13. Long-term effects of an acute and systemic administration of LPS on adult neurogenesis and spatial memory

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    Jorge eValero

    2014-04-01

    Full Text Available The cognitive reserve is the capacity of the brain to maintain normal performance while exposed to insults or ageing. Increasing evidences point to a role for the interaction between inflammatory conditions and cognitive reserve status during Alzheimer's disease (AD progression. The production of new neurons along adult life can be considered as one of the components of the cognitive reserve. Interestingly, adult neurogenesis is decreased in mouse models of AD and following inflammatory processes. The aim of this work is to reveal the long-term impact of a systemic inflammatory event on memory and adult neurogenesis in wild type (WT and triple transgenic mouse model of AD (3xTg-AD.4 month-old mice were intraperitoneally injected once with saline or lipopolysaccharide (LPS and their performance on spatial memory analyzed with the Morris water maze (MWM test 7 weeks later. Our data showed that a single intraperitoneal injection with LPS has a long-term impact in the production of hippocampal neurons. Consistently, LPS-treated WT mice showed less doublecortin-positive neurons, less synaptic contacts in newborn neurons, and decreased dendritic volume and complexity. These surprising observations were accompanied with memory deficits. 3xTg-AD mice showed a decrease in new neurons in the dentate gyrus compatible with, although exacerbated, the pattern observed in WT LPS-treated mice. In 3xTg-AD mice, LPS injection did not significantly affected the production of new neurons but reduced their number of synaptic puncta and impaired memory performance, when compared to the observations made in saline-treated 3xTg-AD mice. These data indicate that LPS treatment induces a long-term impairment on hippocampal neurogenesis and memory. Our results show that acute neuroinflammatory events influence the production of new hippocampal neurons, affecting the cognitive reserve and leading to the development of memory deficits associated to Alzheimer's disease

  14. Learning-induced Glutamate Receptor Phosphorylation Resembles That Induced by Long Term Potentiation*

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    Shukla, Kajal; Kim, James; Blundell, Jacqueline; Powell, Craig M.

    2007-01-01

    Long term potentiation and long term depression of synaptic responses in the hippocampus are thought to be critical for certain forms of learning and memory, although until recently it has been difficult to demonstrate that long term potentiation or long term depression occurs during hippocampus-dependent learning. Induction of long term potentiation or long term depression in hippocampal slices in vitro modulates phosphorylation of the α-amino-3-hydrozy-5-methylisoxazole-4-propionic acid sub...

  15. Potential food-drug interactions in long-term care.

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    Anderson, Judy K; Fox, Jodie R

    2012-04-01

    Medication administration at mealtimes may result in food-drug interactions. Older adults are especially at risk of food-drug interactions leading to adverse drug effects and subtherapeutic responses. Research on potential food-drug interactions is limited and dated. This study examined the frequency of potential food-drug interactions in long-term care. Forty-nine percent of drugs administered at mealtimes had potential for interaction, with cardiovascular medications given most frequently. The frequency of potential interactions makes this phenomenon critically important to review. Collaboration between nurses and pharmacists may identify optimal medication scheduling. Nurses can enhance care by identifying strategies to limit interactions through knowledge and creative, collaborative administration schedules. Copyright 2012, SLACK Incorporated.

  16. Proton pump inhibitor therapy and potential long-term harm.

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    Corleto, Vito Domenico; Festa, Stefano; Di Giulio, Emilio; Annibale, Bruno

    2014-02-01

    This review summarizes the recent literature on the potential side-effects of proton pump inhibitors (PPIs) and known interactions with the metabolism/absorption of other drugs. Data confirm that PPIs are a very well tolerated drug class. Their high safety, efficacy and wide distribution lead to overuse, inappropriate dosage or excessive duration of treatment. Despite the absorption of micronutrients or other plausible effects on the development of bacterial infections linked to PPI-induced hypochlorhydria, it is difficult to demonstrate an association between PPI and specific symptoms. A possible negative effect of PPIs on bone integrity appears weak, but hypomagnesemia is likely a PPI drug class effect. A higher risk of Clostridium difficile infection and other infectious diseases such as small intestinal bacterial overgrowth and spontaneous bacterial peritonitis remain controversial in PPI users. However, the careful use of PPIs in cirrhotic or otherwise fragile patients is mandatory. Short-term or long-term PPI use may trigger microscopic colitis, and the management of this condition may include PPI withdrawal. The effect of PPIs on stimulating exocrine or endocrine gastric cell proliferation is poorly understood. A diagnostic delay or masking of diseases such as gastrinoma is difficult to evaluate. Short-term standard dose PPI treatment is low risk. Long-term PPI use may complicate health conditions by various mechanisms linked to PPIs and/or to hypochlorhydria.

  17. Hippocampal Focal Knockout of CBP Affects Specific Histone Modifications, Long-Term Potentiation, and Long-Term Memory

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    Barrett, Ruth M; Malvaez, Melissa; Kramar, Eniko; Matheos, Dina P; Arrizon, Abraham; Cabrera, Sara M; Lynch, Gary; Greene, Robert W; Wood, Marcelo A

    2011-01-01

    To identify the role of the histone acetyltransferase (HAT) CREB-binding protein (CBP) in neurons of the CA1 region of the hippocampus during memory formation, we examine the effects of a focal homozygous knockout of CBP on histone modifications, gene expression, synaptic plasticity, and long-term memory. We show that CBP is critical for the in vivo acetylation of lysines on histones H2B, H3, and H4. CBP's homolog p300 was unable to compensate for the loss of CBP. Neurons lacking CBP maintained phosphorylation of the transcription factor CREB, yet failed to activate CREB:CBP-mediated gene expression. Loss of CBP in dorsal CA1 of the hippocampus resulted in selective impairments to long-term potentiation and long-term memory for contextual fear and object recognition. Together, these results suggest a necessary role for specific chromatin modifications, selectively mediated by CBP in the consolidation of memories. PMID:21508930

  18. Observation of long term potentiation in papain-based memory devices

    KAUST Repository

    Bag, A.

    2014-06-01

    Biological synaptic behavior in terms of long term potentiation has been observed in papain-based (plant protein) memory devices (memristors) for the first time. Improvement in long term potentiation depends on pulse amplitude and width (duration). Continuous/repetitive dc voltage sweep leads to an increase in memristor conductivity leading to a long term memory in the \\'learning\\' processes.

  19. Inhibition of adult hippocampal neurogenesis disrupts contextual learning but spares spatial working memory, long-term conditional rule retention and spatial reversal.

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    Hernández-Rabaza, V; Llorens-Martín, M; Velázquez-Sánchez, C; Ferragud, A; Arcusa, A; Gumus, H G; Gómez-Pinedo, U; Pérez-Villalba, A; Roselló, J; Trejo, J L; Barcia, J A; Canales, J J

    2009-03-03

    Neurogenesis in the adult dentate gyrus (DG) of the hippocampus has been implicated in neural plasticity and cognition but the specific functions contributed by adult-born neurons remain controversial. Here, we have explored the relationship between adult hippocampal neurogenesis and memory function using tasks which specifically require the participation of the DG. In two separate experiments several groups of rats were exposed to fractionated ionizing radiation (two sessions of 7 Gy each on consecutive days) applied either to the whole brain or focally, aiming at a region overlying the hippocampus. The immunocytochemical assays showed that the radiation significantly reduced the expression of doublecortin (DCX), a marker for immature neurons, in the dorsal DG. Ultrastructural examination of the DG region revealed disruption of progenitor cell niches several weeks after the radiation. In the first experiment, whole-brain and focal irradiation reduced DCX expression by 68% and 43%, respectively. Whole-brain and focally-irradiated rats were unimpaired compared with control rats in a matching-to-place (MTP) working memory task performed in the T-maze and in the long-term retention of the no-alternation rule. In the second experiment, focal irradiation reduced DCX expression by 36% but did not impair performance on (1) a standard non-matching-to-place (NMTP) task, (2) a more demanding NMTP task with increasingly longer within-trial delays, (3) a long-term retention test of the alternation rule and (4) a spatial reversal task. However, rats irradiated focally showed clear deficits in a "purely" contextual fear-conditioning task at short and long retention intervals. These data demonstrate that reduced adult hippocampal neurogenesis produces marked deficits in the rapid acquisition of emotionally relevant contextual information but spares spatial working memory function, the long-term retention of acquired spatial rules and the ability to flexibly modify learned spatial

  20. Long-term performance potential of concentrated photovoltaic (CPV) systems

    KAUST Repository

    Burhan, Muhammad

    2017-07-17

    Owing to the diverse photovoltaic (PV) systems’ design and technology, as well as the dynamic nature of insolation data received on the aperture surfaces, the instantaneous output from a PV system fluctuates greatly. For accurate performance estimation of a large PV field, the long term performance as electrical output is a more rational approach over the conventional testing methods, such as at Standard Testing Conditions (STC) and at the Nominal Operating Cell Temperature (NOCT) available hitherto. In this paper, the long-term performances of concentrated PVs (Cassegrain reflectors and Fresnel lens) with 2-axes tracking and a variety of PV systems, namely the stationary flat-plate PV (mono-crystalline, poly-crystalline and thin-films CIS types), is presented over a period of one year for the merit comparison of system design, under the tropical weather conditions of Singapore. From the measured field performances, the total energy output of 240.2 kW h/m/year is recorded for CPV operation in Singapore, which is nearly two folds higher than the stationary PV panels.

  1. Long-Term Mild, rather than Intense, Exercise Enhances Adult Hippocampal Neurogenesis and Greatly Changes the Transcriptomic Profile of the Hippocampus.

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    Inoue, Koshiro; Okamoto, Masahiro; Shibato, Junko; Lee, Min Chul; Matsui, Takashi; Rakwal, Randeep; Soya, Hideaki

    2015-01-01

    Our six-week treadmill running training (forced exercise) model has revealed that mild exercise (ME) with an intensity below the lactate threshold (LT) is sufficient to enhance spatial memory, while intense exercise (IE) above the LT negates such benefits. To help understand the unrevealed neuronal and signaling/molecular mechanisms of the intensity-dependent cognitive change, in this rat model, we here investigated plasma corticosterone concentration as a marker of stress, adult hippocampal neurogenesis (AHN) as a potential contributor to this ME-induced spatial memory, and comprehensively delineated the hippocampal transcriptomic profile using a whole-genome DNA microarray analysis approach through comparison with IE. Results showed that only IE had the higher corticosterone concentration than control, and that the less intense exercise (ME) is better suited to improve AHN, especially in regards to the survival and maturation of newborn neurons. DNA microarray analysis using a 4 × 44 K Agilent chip revealed that ME regulated more genes than did IE (ME: 604 genes, IE: 415 genes), and only 41 genes were modified with both exercise intensities. The identified molecular components did not comprise well-known factors related to exercise-induced AHN, such as brain-derived neurotrophic factor. Rather, network analysis of the data using Ingenuity Pathway Analysis algorithms revealed that the ME-influenced genes were principally related to lipid metabolism, protein synthesis and inflammatory response, which are recognized as associated with AHN. In contrast, IE-influenced genes linked to excessive inflammatory immune response, which is a negative regulator of hippocampal neuroadaptation, were identified. Collectively, these results in a treadmill running model demonstrate that long-term ME, but not of IE, with minimizing running stress, has beneficial effects on increasing AHN, and provides an ME-specific gene inventory containing some potential regulators of this

  2. Long-Term Mild, rather than Intense, Exercise Enhances Adult Hippocampal Neurogenesis and Greatly Changes the Transcriptomic Profile of the Hippocampus

    Science.gov (United States)

    Inoue, Koshiro; Okamoto, Masahiro; Shibato, Junko; Lee, Min Chul; Matsui, Takashi; Rakwal, Randeep; Soya, Hideaki

    2015-01-01

    Our six-week treadmill running training (forced exercise) model has revealed that mild exercise (ME) with an intensity below the lactate threshold (LT) is sufficient to enhance spatial memory, while intense exercise (IE) above the LT negates such benefits. To help understand the unrevealed neuronal and signaling/molecular mechanisms of the intensity-dependent cognitive change, in this rat model, we here investigated plasma corticosterone concentration as a marker of stress, adult hippocampal neurogenesis (AHN) as a potential contributor to this ME-induced spatial memory, and comprehensively delineated the hippocampal transcriptomic profile using a whole-genome DNA microarray analysis approach through comparison with IE. Results showed that only IE had the higher corticosterone concentration than control, and that the less intense exercise (ME) is better suited to improve AHN, especially in regards to the survival and maturation of newborn neurons. DNA microarray analysis using a 4 × 44 K Agilent chip revealed that ME regulated more genes than did IE (ME: 604 genes, IE: 415 genes), and only 41 genes were modified with both exercise intensities. The identified molecular components did not comprise well-known factors related to exercise-induced AHN, such as brain-derived neurotrophic factor. Rather, network analysis of the data using Ingenuity Pathway Analysis algorithms revealed that the ME-influenced genes were principally related to lipid metabolism, protein synthesis and inflammatory response, which are recognized as associated with AHN. In contrast, IE-influenced genes linked to excessive inflammatory immune response, which is a negative regulator of hippocampal neuroadaptation, were identified. Collectively, these results in a treadmill running model demonstrate that long-term ME, but not of IE, with minimizing running stress, has beneficial effects on increasing AHN, and provides an ME-specific gene inventory containing some potential regulators of this

  3. Long-term potentiation promotes proliferation/survival and neuronal differentiation of neural stem/progenitor cells.

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    Taesup Cho

    Full Text Available Neural stem cell (NSC replacement therapy is considered a promising cell replacement therapy for various neurodegenerative diseases. However, the low rate of NSC survival and neurogenesis currently limits its clinical potential. Here, we examined if hippocampal long-term potentiation (LTP, one of the most well characterized forms of synaptic plasticity, promotes neurogenesis by facilitating proliferation/survival and neuronal differentiation of NSCs. We found that the induction of hippocampal LTP significantly facilitates proliferation/survival and neuronal differentiation of both endogenous neural progenitor cells (NPCs and exogenously transplanted NSCs in the hippocampus in rats. These effects were eliminated by preventing LTP induction by pharmacological blockade of the N-methyl-D-aspartate glutamate receptor (NMDAR via systemic application of the receptor antagonist, 3-[(R-2-carboxypiperazin-4-yl]-propyl-1-phosphonic acid (CPP. Moreover, using a NPC-neuron co-culture system, we were able to demonstrate that the LTP-promoted NPC neurogenesis is at least in part mediated by a LTP-increased neuronal release of brain-derived neurotrophic factor (BDNF and its consequent activation of tropomysosin receptor kinase B (TrkB receptors on NSCs. Our results indicate that LTP promotes the neurogenesis of both endogenous and exogenously transplanted NSCs in the brain. The study suggests that pre-conditioning of the host brain receiving area with a LTP-inducing deep brain stimulation protocol prior to NSC transplantation may increase the likelihood of success of using NSC transplantation as an effective cell therapy for various neurodegenerative diseases.

  4. Compensation for PKMζ in long-term potentiation and spatial long-term memory in mutant mice.

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    Tsokas, Panayiotis; Hsieh, Changchi; Yao, Yudong; Lesburguères, Edith; Wallace, Emma Jane Claire; Tcherepanov, Andrew; Jothianandan, Desingarao; Hartley, Benjamin Rush; Pan, Ling; Rivard, Bruno; Farese, Robert V; Sajan, Mini P; Bergold, Peter John; Hernández, Alejandro Iván; Cottrell, James E; Shouval, Harel Z; Fenton, André Antonio; Sacktor, Todd Charlton

    2016-05-17

    PKMζ is a persistently active PKC isoform proposed to maintain late-LTP and long-term memory. But late-LTP and memory are maintained without PKMζ in PKMζ-null mice. Two hypotheses can account for these findings. First, PKMζ is unimportant for LTP or memory. Second, PKMζ is essential for late-LTP and long-term memory in wild-type mice, and PKMζ-null mice recruit compensatory mechanisms. We find that whereas PKMζ persistently increases in LTP maintenance in wild-type mice, PKCι/λ, a gene-product closely related to PKMζ, persistently increases in LTP maintenance in PKMζ-null mice. Using a pharmacogenetic approach, we find PKMζ-antisense in hippocampus blocks late-LTP and spatial long-term memory in wild-type mice, but not in PKMζ-null mice without the target mRNA. Conversely, a PKCι/λ-antagonist disrupts late-LTP and spatial memory in PKMζ-null mice but not in wild-type mice. Thus, whereas PKMζ is essential for wild-type LTP and long-term memory, persistent PKCι/λ activation compensates for PKMζ loss in PKMζ-null mice.

  5. Forebrain-specific glutamate receptor B deletion impairs spatial memory but not hippocampal field long-term potentiation.

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    Shimshek, Derya R; Jensen, Vidar; Celikel, Tansu; Geng, Yu; Schupp, Bettina; Bus, Thorsten; Mack, Volker; Marx, Verena; Hvalby, Øivind; Seeburg, Peter H; Sprengel, Rolf

    2006-08-16

    We demonstrate the fundamental importance of glutamate receptor B (GluR-B) containing AMPA receptors in hippocampal function by analyzing mice with conditional GluR-B deficiency in postnatal forebrain principal neurons (GluR-B(deltaFb)). These mice are as adults sufficiently robust to permit comparative cellular, physiological, and behavioral studies. GluR-B loss induced moderate long-term changes in the hippocampus of GluR-B(deltaFb) mice. Parvalbumin-expressing interneurons in the dentate gyrus and the pyramidal cells in CA3 were decreased in number, and neurogenesis in the subgranular zone was diminished. Excitatory synaptic CA3-to-CA1 transmission was reduced, although synaptic excitability, as quantified by the lowered threshold for population spike initiation, was increased compared with control mice. These changes did not alter CA3-to-CA1 long-term potentiation (LTP), which in magnitude was similar to LTP in control mice. The altered hippocampal circuitry, however, affected spatial learning in GluR-B(deltaFb) mice. The primary source for the observed changes is most likely the AMPA receptor-mediated Ca2+ signaling that appears after GluR-B depletion, because we observed similar alterations in GluR-B(QFb) mice in which the expression of Ca2+-permeable AMPA receptors in principal neurons was induced by postnatal activation of a Q/R-site editing-deficient GluR-B allele.

  6. Long-term potentiation in the hippocampal slice: evidence for stimulated secretion of newly synthesized proteins.

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    Duffy, C; Teyler, T J; Shashoua, V E

    1981-06-05

    Long-term potentiation of the hippocampal slice preparation results in an increase in the incorporation of labeled valine into the proteins destined for secretion into the extracellular medium. Double-labeling methods established that the increased secretion of the labeled proteins was limited to the potentiated region of a slice; incorporation of labeled valine was increased in the hippocampus if potentiation was through the Schaffer collaterals and in the dentate if potentiation was through the perforant path. Controls for nonspecific stimulation showed no changes. There appears to be a link between long-term potentiation and the metabolic processes that lead to protein synthesis in the hippocampal slice system.

  7. Long-term potentiation in the hippocampal slice: evidence for stimulated secretion of newly synthesized proteins

    Energy Technology Data Exchange (ETDEWEB)

    Duffy, C.; Teyler, T.J.; Shashoua, V.E.

    1981-06-01

    Long-term potentiation of the hippocampal slice preparation results in an increase in the incorporation of labeled valine into the proteins destined for secretion into the extracellular medium. Double-labeling methods established that the increased secretion of the labeled proteins was limited to the potentiated region of a slice; incorporation of labeled valine was increased in the hippocampus if potentiation was through the Schaffer collaterals and in the dentate if potentiation was through the perforant path. Controls for nonspecific stimulation showed no changes. There appears to be a link between long-term potentiation and the metabolic processes that lead to protein synthesis in the hippocampal slice system.

  8. Effects of long-term methylphenidate treatment in adolescent and adult rats on hippocampal shape, functional connectivity and adult neurogenesis

    NARCIS (Netherlands)

    van der Marel, K.; Bouet, V.; Meerhoff, G. F.; Freret, T.; Boulouard, M.; Dauphin, F.; Klomp, A.; Lucassen, P. J.; Homberg, J. R.; Dijkhuizen, R. M.; Reneman, L.

    2015-01-01

    Methylphenidate (MPH) is a widely prescribed stimulant drug for the treatment of attention deficit hyperactivity disorder (ADHD) in children and adolescents. Its use in this age group raises concerns regarding the potential interference with ongoing neurodevelopmental processes. Particularly the

  9. Long-Term Visuo-Gustatory Appetitive and Aversive Conditioning Potentiate Human Visual Evoked Potentials.

    Science.gov (United States)

    Christoffersen, Gert R J; Laugesen, Jakob L; Møller, Per; Bredie, Wender L P; Schachtman, Todd R; Liljendahl, Christina; Viemose, Ida

    2017-01-01

    Human recognition of foods and beverages are often based on visual cues associated with flavors. The dynamics of neurophysiological plasticity related to acquisition of such long-term associations has only recently become the target of investigation. In the present work, the effects of appetitive and aversive visuo-gustatory conditioning were studied with high density EEG-recordings focusing on late components in the visual evoked potentials (VEPs), specifically the N2-P3 waves. Unfamiliar images were paired with either a pleasant or an unpleasant juice and VEPs evoked by the images were compared before and 1 day after the pairings. In electrodes located over posterior visual cortex areas, the following changes were observed after conditioning: the amplitude from the N2-peak to the P3-peak increased and the N2 peak delay was reduced. The percentage increase of N2-to-P3 amplitudes was asymmetrically distributed over the posterior hemispheres despite the fact that the images were bilaterally symmetrical across the two visual hemifields. The percentage increases of N2-to-P3 amplitudes in each experimental subject correlated with the subject's evaluation of positive or negative hedonic valences of the two juices. The results from 118 scalp electrodes gave surface maps of theta power distributions showing increased power over posterior visual areas after the pairings. Source current distributions calculated from swLORETA revealed that visual evoked currents rose as a result of conditioning in five cortical regions-from primary visual areas and into the inferior temporal gyrus (ITG). These learning-induced changes were seen after both appetitive and aversive training while a sham trained control group showed no changes. It is concluded that long-term visuo-gustatory conditioning potentiated the N2-P3 complex, and it is suggested that the changes are regulated by the perceived hedonic valence of the US.

  10. BDNF Regains Function in Hippocampal Long-Term Potentiation Deficits Caused by Diencephalic Damage

    Science.gov (United States)

    Vedder, Lindsey C.; Savage, Lisa M.

    2017-01-01

    Thiamine deficiency (TD), commonly associated with chronic alcoholism, leads to diencephalic damage, hippocampal dysfunction, and spatial learning and memory deficits. We show a decrease in the magnitude of long-term potentiation (LTP) and paired-pulse facilitation (PPF) at CA3-CA1 synapses, independent of sex, following diencephalic damage…

  11. Long-term potentiation in spinal nociceptive pathways as a novel target for pain therapy.

    NARCIS (Netherlands)

    Ruscheweyh, R.; Wilder-Smith, O.H.G.; Drdla, R.; Liu, X.G.; Sandkuhler, J.

    2011-01-01

    Long-term potentiation (LTP) in nociceptive spinal pathways shares several features with hyperalgesia and has been proposed to be a cellular mechanism of pain amplification in acute and chronic pain states. Spinal LTP is typically induced by noxious input and has therefore been hypothesized to

  12. Neurophysiological Correlates of Nociceptive Heterosynaptic Long-Term Potentiation in Humans

    NARCIS (Netherlands)

    Broeke, E.N. van den; Rijn, C.M. van; Biurrun Manresa, J.A.; Andersen, O.K.; Arendt-Nielsen, L.; Wilder-Smith, O.H.G.

    2010-01-01

    Long-term potentiation (LTP) is a cellular model of synaptic plasticity and reflects an increase of synaptic strength. LTP is also present in the nociceptive system and is believed to be one of the key mechanisms involved in the manifestations of chronic pain. LTP manifested as an increased response

  13. Neurophysiological correlates of nociceptive heterosynaptic long-term potentiation in humans.

    NARCIS (Netherlands)

    Broeke, E.N. van den; Rijn, C.M. van; Biurrun Manresa, J.A.; Andersen, O.K.; Arendt-Nielsen, L.; Wilder-Smith, O.H.G.

    2010-01-01

    Long-term potentiation (LTP) is a cellular model of synaptic plasticity and reflects an increase of synaptic strength. LTP is also present in the nociceptive system and is believed to be one of the key mechanisms involved in the manifestations of chronic pain. LTP manifested as an increased response

  14. Role of nitric oxide in long-term potentiation of the rat medial vestibular nuclei.

    Science.gov (United States)

    Grassi, S; Pettorossi, V E

    2000-01-01

    In rat brainstem slices, we investigated the role of nitric oxide in long-term potentiation induced in the ventral portion of the medial vestibular nuclei by high-frequency stimulation of the primary vestibular afferents. The nitric oxide scavenger [2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide ] and the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester were administered before and after induction of potentiation. Both drugs completely prevented long-term potentiation, whereas they did not impede the potentiation build-up, or affect the already established potentiation. These results demonstrate that the induction, but not the maintenance of vestibular long-term potentiation, depends on the synthesis and release into the extracellular medium of nitric oxide. In addition, we analysed the effect of the nitric oxide donor sodium nitroprusside on vestibular responses. Sodium nitroprusside induced long-term potentiation, as evidenced through the field potential enhancement and unit peak latency decrease. This potentiation was impeded by D, L-2-amino-5-phosphonopentanoic acid, and was reduced under blockade of synaptosomal platelet-activating factor receptors by ginkgolide B and group I metabotropic glutamate receptors by (R,S)-1-aminoindan-1, 5-dicarboxylic acid. When reduced, potentiation fully developed following the washout of antagonist, demonstrating an involvement of platelet-activating factor and group I metabotropic glutamate receptors in its full development. Potentiation induced by sodium nitroprusside was also associated with a decrease in the paired-pulse facilitation ratio, which persisted under ginkgolide B, indicating that nitric oxide increases glutamate release independently of platelet-activating factor-mediated presynaptic events. We suggest that nitric oxide, released after the activation of N-methyl-D-aspartate receptors, acts as a retrograde messenger leading to an enhancement of glutamate release to a

  15. Whole-Body Exposure to (28)Si-Radiation Dose-Dependently Disrupts Dentate Gyrus Neurogenesis and Proliferation in the Short Term and New Neuron Survival and Contextual Fear Conditioning in the Long Term.

    Science.gov (United States)

    Whoolery, Cody W; Walker, Angela K; Richardson, Devon R; Lucero, Melanie J; Reynolds, Ryan P; Beddow, David H; Clark, K Lyles; Shih, Hung-Ying; LeBlanc, Junie A; Cole, Mara G; Amaral, Wellington Z; Mukherjee, Shibani; Zhang, Shichuan; Ahn, Francisca; Bulin, Sarah E; DeCarolis, Nathan A; Rivera, Phillip D; Chen, Benjamin P C; Yun, Sanghee; Eisch, Amelia J

    2017-11-01

    Astronauts traveling to Mars will be exposed to chronic low doses of galactic cosmic space radiation, which contains highly charged, high-energy (HZE) particles. (56)Fe-HZE-particle exposure decreases hippocampal dentate gyrus (DG) neurogenesis and disrupts hippocampal function in young adult rodents, raising the possibility of impaired astronaut cognition and risk of mission failure. However, far less is known about how exposure to other HZE particles, such as (28)Si, influences hippocampal neurogenesis and function. To compare the influence of (28)Si exposure on indices of neurogenesis and hippocampal function with previous studies on (56)Fe exposure, 9-week-old C57BL/6J and Nestin-GFP mice (NGFP; made and maintained for 10 or more generations on a C57BL/6J background) received whole-body (28)Si-particle-radiation exposure (0, 0.2 and 1 Gy, 300 MeV/n, LET 67 KeV/μ, dose rate 1 Gy/min). For neurogenesis assessment, the NGFP mice were injected with the mitotic marker BrdU at 22 h postirradiation and brains were examined for indices of hippocampal proliferation and neurogenesis, including Ki67(+), BrdU(+), BrdU(+)NeuN(+) and DCX(+) cell numbers at short- and long-term time points (24 h and 3 months postirradiation, respectively). In the short-term group, stereology revealed fewer Ki67(+), BrdU(+) and DCX(+) cells in 1-Gy-irradiated group relative to nonirradiated control mice, fewer Ki67(+) and DCX(+) cells in 0.2 Gy group relative to control group and fewer BrdU(+) and DCX(+) cells in 1 Gy group relative to 0.2 Gy group. In contrast to the clearly observed radiation-induced, dose-dependent reductions in the short-term group across all markers, only a few neurogenesis indices were changed in the long-term irradiated groups. Notably, there were fewer surviving BrdU(+) cells in the 1 Gy group relative to 0- and 0.2-Gy-irradiated mice in the long-term group. When the short- and long-term groups were analyzed by sex, exposure to radiation had a similar effect on

  16. Overcoming Long-Term Variability in Local Field Potentials Using an Adaptive Decoder.

    Science.gov (United States)

    Tadipatri, Vijay Aditya; Tewfik, Ahmed H; Pellizzer, Giuseppe; Ashe, James

    2017-02-01

    Long-term variability remains one of the major hurdles in using intracortical recordings like local field potentials for brain computer interfaces (BCI). Practical neural decoders need to overcome time instability of neural signals to estimate subject behavior accurately and faithfully over the long term. This paper presents a novel decoder that 1) characterizes each behavioral task (i.e., different movement directions under different force conditions) with multiple neural patterns and 2) adapts to the long-term variations in neural features by identifying the stable neural patterns. This adaptation can be performed in both an unsupervised and a semisupervised learning framework requiring minimal feedback from the user. To achieve generalization over time, the proposed decoder uses redundant sparse regression models that adapt to day-to-day variations in neural patterns. While this update requires no explicit feedback from the BCI user, any feedback (explicit or derived) to the BCI improves its performance. With this adaptive decoder, we investigated the effects of long-term neural modulation especially when subjects encountered new external forces against movement. The proposed decoder predicted eight hand-movement directions with an accuracy of 95% over two weeks (when there was no external forces); and 85% in later acquisition sessions spanning up to 42 days (when the monkeys countered external field forces). Since the decoder can operate with or without manual intervention, it could alleviate user frustration associated with BCI.

  17. Learning, memory and long-term potentiation are altered in Nedd4 heterozygous mice.

    Science.gov (United States)

    Camera, Daria; Coleman, Harold A; Parkington, Helena C; Jenkins, Trisha A; Pow, David V; Boase, Natasha; Kumar, Sharad; Poronnik, Philip

    2016-04-15

    The consolidation of short-term memory into long-term memory involves changing protein level and activity for the synaptic plasticity required for long-term potentiation (LTP). AMPA receptor trafficking is a key determinant of LTP and recently ubiquitination by Nedd4 has been shown to play an important role via direct action on the GluA1 subunit, although the physiological relevance of these findings are yet to be determined. We therefore investigated learning and memory in Nedd4(+/-) mice that have a 50% reduction in levels of Nedd4. These mice showed decreased long-term spatial memory as evidenced by significant increases in the time taken to learn the location of and subsequently find a platform in the Morris water maze. In contrast, there were no significant differences between Nedd4(+/+) and Nedd4(+/-) mice in terms of short-term spatial memory in a Y-maze test. Nedd4(+/-) mice also displayed a significant reduction in post-synaptic LTP measured in hippocampal brain slices. Immunofluorescence of Nedd4 in the hippocampus confirmed its expression in hippocampal neurons of the CA1 region. These findings indicate that reducing Nedd4 protein by 50% significantly impairs LTP and long-term memory thereby demonstrating an important role for Nedd4 in these processes. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Modelling bidirectional modulations in synaptic plasticity: A biochemical pathway model to understand the emergence of long term potentiation (LTP) and long term depression (LTD).

    Science.gov (United States)

    He, Yao; Kulasiri, Don; Samarasinghe, Sandhya

    2016-08-21

    Synaptic plasticity induces bidirectional modulations of the postsynaptic response following a synaptic transmission. The long term forms of synaptic plasticity, named long term potentiation (LTP) and long term depression (LTD), are critical for the antithetic functions of the memory system, memory formation and removal, respectively. A common Ca(2+) signalling upstream triggers both LTP and LTD, and the critical proteins and factors coordinating the LTP/LTD inductions are not well understood. We develop an integrated model based on the sub-models of the indispensable synaptic proteins in the emergence of synaptic plasticity to validate and understand their potential roles in the expression of synaptic plasticity. The model explains Ca(2+)/calmodulin (CaM) complex dependent coordination of LTP/LTD expressions by the interactions among the indispensable proteins using the experimentally estimated kinetic parameters. Analysis of the integrated model provides us with insights into the effective timescales of the key proteins and we conclude that the CaM pool size is critical for the coordination between LTP/LTD expressions. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Molecular constraints on synaptic tagging and maintenance of long-term potentiation: a predictive model.

    Science.gov (United States)

    Smolen, Paul; Baxter, Douglas A; Byrne, John H

    2012-01-01

    Protein synthesis-dependent, late long-term potentiation (LTP) and depression (LTD) at glutamatergic hippocampal synapses are well characterized examples of long-term synaptic plasticity. Persistent increased activity of protein kinase M ζ (PKMζ) is thought essential for maintaining LTP. Additional spatial and temporal features that govern LTP and LTD induction are embodied in the synaptic tagging and capture (STC) and cross capture hypotheses. Only synapses that have been "tagged" by a stimulus sufficient for LTP and learning can "capture" PKMζ. A model was developed to simulate the dynamics of key molecules required for LTP and LTD. The model concisely represents relationships between tagging, capture, LTD, and LTP maintenance. The model successfully simulated LTP maintained by persistent synaptic PKMζ, STC, LTD, and cross capture, and makes testable predictions concerning the dynamics of PKMζ. The maintenance of LTP, and consequently of at least some forms of long-term memory, is predicted to require continual positive feedback in which PKMζ enhances its own synthesis only at potentiated synapses. This feedback underlies bistability in the activity of PKMζ. Second, cross capture requires the induction of LTD to induce dendritic PKMζ synthesis, although this may require tagging of a nearby synapse for LTP. The model also simulates the effects of PKMζ inhibition, and makes additional predictions for the dynamics of CaM kinases. Experiments testing the above predictions would significantly advance the understanding of memory maintenance.

  20. Molecular constraints on synaptic tagging and maintenance of long-term potentiation: a predictive model.

    Directory of Open Access Journals (Sweden)

    Paul Smolen

    Full Text Available Protein synthesis-dependent, late long-term potentiation (LTP and depression (LTD at glutamatergic hippocampal synapses are well characterized examples of long-term synaptic plasticity. Persistent increased activity of protein kinase M ζ (PKMζ is thought essential for maintaining LTP. Additional spatial and temporal features that govern LTP and LTD induction are embodied in the synaptic tagging and capture (STC and cross capture hypotheses. Only synapses that have been "tagged" by a stimulus sufficient for LTP and learning can "capture" PKMζ. A model was developed to simulate the dynamics of key molecules required for LTP and LTD. The model concisely represents relationships between tagging, capture, LTD, and LTP maintenance. The model successfully simulated LTP maintained by persistent synaptic PKMζ, STC, LTD, and cross capture, and makes testable predictions concerning the dynamics of PKMζ. The maintenance of LTP, and consequently of at least some forms of long-term memory, is predicted to require continual positive feedback in which PKMζ enhances its own synthesis only at potentiated synapses. This feedback underlies bistability in the activity of PKMζ. Second, cross capture requires the induction of LTD to induce dendritic PKMζ synthesis, although this may require tagging of a nearby synapse for LTP. The model also simulates the effects of PKMζ inhibition, and makes additional predictions for the dynamics of CaM kinases. Experiments testing the above predictions would significantly advance the understanding of memory maintenance.

  1. Opiate Analgesics as Negative Modulators of Adult Hippocampal Neurogenesis: Potential Implications in Clinical Practice

    Directory of Open Access Journals (Sweden)

    Valeria Bortolotto

    2017-05-01

    Full Text Available During the past decade, studies of the mechanisms and functional implications of adult hippocampal neurogenesis (ahNG have significantly progressed. At present, it is proposed that adult born neurons may contribute to a variety of hippocampal-related functions, including specific cognitive aspects and mood regulation. Several groups focussed on the factors that regulate proliferation and fate determination of adult neural stem/progenitor cells (NSC/NPC, including clinically relevant drugs. Opiates were the first drugs shown to negatively impact neurogenesis in the adult mammalian hippocampus. Since that initial report, a vast array of information has been collected on the effect of opiate drugs, by either modulating proliferation of stem/progenitor cells or interfering with differentiation, maturation and survival of adult born neurons. The goal of this review is to critically revise the present state of knowledge on the effect of opiate drugs on the different developmental stages of ahNG, as well as the possible underlying mechanisms. We will also highlight the potential impact of deregulated hippocampal neurogenesis on patients undergoing chronic opiate treatment. Finally, we will discuss the differences in the negative impact on ahNG among clinically relevant opiate drugs, an aspect that may be potentially taken into account to avoid long-term deregulation of neural plasticity and its associated functions in the clinical practice.

  2. Potentially inappropriate prescriptions for older patients in long-term care

    Directory of Open Access Journals (Sweden)

    Laurin Danielle

    2004-10-01

    Full Text Available Abstract Background Inappropriate medication use is a major healthcare issue for the elderly population. This study explored the prevalence of potentially inappropriate prescriptions (PIPs in long-term care in metropolitan Quebec. Methods A cross sectional chart review of 2,633 long-term care older patients of the Quebec City area was performed. An explicit criteria list for PIPs was developed based on the literature and validated by a modified Delphi method. Medication orders were reviewed to describe prescribing patterns and to determine the prevalence of PIPs. A multivariate analysis was performed to identify predictors of PIPs. Results Almost all residents (94.0% were receiving one or more prescribed medication; on average patients had 4.8 prescribed medications. A majority (54.7% of treated patients had a potentially inappropriate prescription (PIP. Most common PIPs were drug interactions (33.9% of treated patients, followed by potentially inappropriate duration (23.6%, potentially inappropriate medication (14.7% and potentially inappropriate dosage (9.6%. PIPs were most frequent for medications of the central nervous system (10.8% of prescribed medication. The likelihood of PIP increased significantly as the number of drugs prescribed increased (odds ratio [OR]: 1.38, 95% confidence interval [CI]: 1.33 – 1.43 and with the length of stay (OR: 1.78, CI: 1.43 – 2.20. On the other hand, the risk of receiving a PIP decreased with age. Conclusion Potentially inappropriate prescribing is a serious problem in the highly medicated long-term care population in metropolitan Quebec. Use of explicit criteria lists may help identify the most critical issues and prioritize interventions to improve quality of care and patient safety.

  3. Long term hydrogen production potential of concentrated photovoltaic (CPV) system in tropical weather of Singapore

    KAUST Repository

    Burhan, Muhammad

    2016-08-23

    Concentrated photovoltaic (CPV) system provides highest solar energy conversion efficiency among all the photovoltaic technologies and provides the most suitable option to convert solar energy into hydrogen, as future sustainable energy carrier. So far, only conventional flat plate PV systems are being used for almost all of the commercial applications. However, most of the studies have only shown the maximum efficiency of hydrogen production using CPV. In actual field conditions, the performance of CPV-Hydrogen system is affected by many parameter and it changes continuously during whole day operation. In this paper, the daily average and long term performances are proposed to analyze the real field potential of the CPV-Hydrogen system, which is of main interest for designers and consumers. An experimental setup is developed and a performance model is proposed to investigate the average and long term production potential of CPV-Hydrogen system. The study is carried out in tropical weather of Singapore. The maximum CPV efficiency of 27-28% and solar to hydrogen (STH) efficiency of 18%, were recorded. In addition, the CPV-Hydrogen system showed the long term average efficiency of 15.5%, for period of one year (12-months), with electrolyser rating of 47 kWh/kg and STH production potential of 218 kWh/kg. Based upon the DNI availability, the system showed hydrogen production potential of 0.153-0.553 kg/m/month, with average production of 0.43 kg/m/month. However, CPV-Hydrogen system has shown annual hydrogen production potential of 5.162 kg/m/year in tropical weather of Singapore.

  4. Disinhibition mediates a form of hippocampal long-term potentiation in area CA1.

    Directory of Open Access Journals (Sweden)

    Jake Ormond

    Full Text Available The hippocampus plays a central role in memory formation in the mammalian brain. Its ability to encode information is thought to depend on the plasticity of synaptic connections between neurons. In the pyramidal neurons constituting the primary hippocampal output to the cortex, located in area CA1, firing of presynaptic CA3 pyramidal neurons produces monosynaptic excitatory postsynaptic potentials (EPSPs followed rapidly by feedforward (disynaptic inhibitory postsynaptic potentials (IPSPs. Long-term potentiation (LTP of the monosynaptic glutamatergic inputs has become the leading model of synaptic plasticity, in part due to its dependence on NMDA receptors (NMDARs, required for spatial and temporal learning in intact animals. Using whole-cell recording in hippocampal slices from adult rats, we find that the efficacy of synaptic transmission from CA3 to CA1 can be enhanced without the induction of classic LTP at the glutamatergic inputs. Taking care not to directly stimulate inhibitory fibers, we show that the induction of GABAergic plasticity at feedforward inhibitory inputs results in the reduced shunting of excitatory currents, producing a long-term increase in the amplitude of Schaffer collateral-mediated postsynaptic potentials. Like classic LTP, disinhibition-mediated LTP requires NMDAR activation, suggesting a role in types of learning and memory attributed primarily to the former and raising the possibility of a previously unrecognized target for therapeutic intervention in disorders linked to memory deficits, as well as a potentially overlooked site of LTP expression in other areas of the brain.

  5. Assessment of tumourigenic potential in long-term cryopreserved human adipose-derived stem cells.

    Science.gov (United States)

    Yong, Kar Wey; Safwani, Wan Kamarul Zaman Wan; Xu, Feng; Zhang, Xiaohui; Choi, Jane Ru; Abas, Wan Abu Bakar Wan; Omar, Siti Zawiah; Azmi, Mat Adenan Noor; Chua, Kien Hui; Pingguan-Murphy, Belinda

    2017-08-01

    Cryopreservation represents an efficient way to preserve human mesenchymal stem cells (hMSCs) at early culture/passage, and allows pooling of cells to achieve sufficient cells required for off-the-shelf use in clinical applications, e.g. cell-based therapies and regenerative medicine. To fully apply cryopreserved hMSCs in a clinical setting, it is necessary to evaluate their biosafety, e.g. chromosomal abnormality and tumourigenic potential. To date, many studies have demonstrated that cryopreserved hMSCs display no chromosomal abnormalities. However, the tumourigenic potential of cryopreserved hMSCs has not yet been evaluated. In the present study, we cryopreserved human adipose-derived mesenchymal stem cells (hASCs) for 3 months, using a slow freezing method with various cryoprotective agents (CPAs), followed by assessment of the tumourigenic potential of the cryopreserved hASCs after thawing and subculture. We found that long-term cryopreserved hASCs maintained normal levels of the tumour suppressor markers p53, p21, p16 and pRb, hTERT, telomerase activity and telomere length. Further, we did not observe significant DNA damage or signs of p53 mutation in cryopreserved hASCs. Our findings suggest that long-term cryopreserved hASCs are at low risk of tumourigenesis. These findings aid in establishing the biosafety profile of cryopreserved hASCs, and thus establishing low hazardous risk perception with the use of long-term cryopreserved hASCs for future clinical applications. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  6. Intelligent power wheelchair use in long-term care: potential users' experiences and perceptions.

    Science.gov (United States)

    Rushton, Paula W; Mortenson, Ben W; Viswanathan, Pooja; Wang, Rosalie H; Miller, William C; Hurd Clarke, Laura

    2017-10-01

    Long-term care (LTC) residents with cognitive impairments frequently experience limited mobility and participation in preferred activities. Although a power wheelchair could mitigate some of these mobility and participation challenges, this technology is often not prescribed for this population due to safety concerns. An intelligent power wheelchair (IPW) system represents a potential intervention that could help to overcome these concerns. The purpose of this study was to explore a) how residents experienced an IPW that used three different modes of control and b) what perceived effect the IPW would have on their daily lives. We interviewed 10 LTC residents with mild or moderate cognitive impairment twice, once before and once after testing the IPW. Interviews were conducted using a semi-structured interview guide, audio recorded and transcribed verbatim for thematic analyses. Our analyses identified three overarching themes: (1) the difference an IPW would make, (2) the potential impact of the IPW on others and (3) IPW-related concerns. Findings from this study confirm the need for and potential benefits of IPW use in LTC. Future studies will involve testing IPW improvements based on feedback and insights from this study. Implications for rehabilitation Intelligent power wheelchairs may enhance participation and improve safety and feelings of well-being for long-term care residents with cognitive impairments. Intelligent power wheelchairs could potentially have an equally positive impact on facility staff, other residents, and family and friends by decreasing workload and increasing safety.

  7. Potential multiple steady-states in the long-term carbon cycle

    OpenAIRE

    Tennenbaum, Stephen; Berezovskaya, Faina; Schwartzman, David

    2013-01-01

    In our modeling of the long-term carbon cycle we find potential multiple steady-states in Phanerozoic climates. We include the effects of biotic enhancement of weathering on land, organic carbon burial, oxidation of reduced organic carbon in terrestrial sediments and the variation of biotic productivity with temperature, finding a second stable steady-state appearing between 20 and 50 oC. The very warm early Triassic climate as well as an oceanic anoxic event in the late Cretaceous may be the...

  8. Postsynaptic signal transduction models for long-term potentiation and depression

    Directory of Open Access Journals (Sweden)

    Tiina Manninen

    2010-12-01

    Full Text Available More than a hundred biochemical species, activated by neurotransmitters binding to transmembrane receptors, are important in long-term potentiation and depression. To investigate which species and interactions are critical for synaptic plasticity, many computational postsynaptic signal transduction models have been developed. The models range from simple models with a single reversible reaction to detailed models with several hundred kinetic reactions. In this study, more than a hundred models are reviewed, and their features are compared and contrasted so that similarities and differences are more readily apparent. The models are classified according to the type of synaptic plasticity that is modeled (long-term potentiation or long-term depression and whether they include diffusion or electrophysiological phenomena. Other characteristics that discriminate the models include the phase of synaptic plasticity modeled (induction, expression, or maintenance and the simulation method used (deterministic or stochastic method. We find that models are becoming increasingly sophisticated, by including stochastic properties, integrating with electrophysiological properties of entire neurons, or incorporating diffusion of signaling molecules. Simpler models continue to be developed because they are computationally efficient and allow theoretical analysis. The more complex models permit investigation of mechanisms underlying specific properties and experimental verification of model predictions. Nonetheless, it is difficult to fully comprehend the evolution of these models because (1 several models are not described in detail in the publications, (2 only a few models are provided in existing model databases, and (3 comparison to previous models is lacking. We conclude that the value of these models for understanding molecular mechanisms of synaptic plasticity is increasing and will be enhanced further with more complete descriptions and sharing of the

  9. Low-carbohydrate diets: what are the potential short- and long-term health implications?

    Science.gov (United States)

    Bilsborough, Shane A; Crowe, Timothy C

    2003-01-01

    Low-carbohydrate diets for weight loss are receiving a lot of attention of late. Reasons for this interest include a plethora of low-carbohydrate diet books, the over-sensationalism of these diets in the media and by celebrities, and the promotion of these diets in fitness centres and health clubs. The re-emergence of low-carbohydrate diets into the spotlight has lead many people in the general public to question whether carbohydrates are inherently 'bad' and should be limited in the diet. Although low-carbohydrate diets were popular in the 1970s they have resurged again yet little scientific fact into the true nature of how these diets work or, more importantly, any potential for serious long-term health risks in adopting this dieting practice appear to have reached the mainstream literature. Evidence abounds that low-carbohydrate diets present no significant advantage over more traditional energy-restricted, nutritionally balanced diets both in terms of weight loss and weight maintenance. Studies examining the efficacy of using low-carbohydrate diets for long-term weight loss are few in number, however few positive benefits exist to promote the adoption of carbohydrate restriction as a realistic, and more importantly, safe means of dieting. While short-term carbohydrate restriction over a period of a week can result in a significant loss of weight (albeit mostly from water and glycogen stores), of serious concern is what potential exists for the following of this type of eating plan for longer periods of months to years. Complications such as heart arrhythmias, cardiac contractile function impairment, sudden death, osteoporosis, kidney damage, increased cancer risk, impairment of physical activity and lipid abnormalities can all be linked to long-term restriction of carbohydrates in the diet. The need to further explore and communicate the untoward side-effects of low-carbohydrate diets should be an important public health message from nutrition professionals.

  10. Exogenous glutamate induces short and long-term potentiation in the rat medial vestibular nuclei.

    Science.gov (United States)

    Grassi, S; Frondaroli, A; Pessia, M; Pettorossi, V E

    2001-08-08

    In rat brain stem slices, high concentrations of exogenous glutamate induce long-term potentiation (LTP) of the field potentials evoked in the medial vestibular nuclei (MVN) by vestibular afferent stimulation. At low concentrations, glutamate can also induce short-term potentiation (STP), indicating that LTP and STP are separate events depending on the level of glutamatergic synapse activation. LTP and STP are prevented by blocking NMDA receptors and nitric oxide (NO) synthesis. Conversely, blocking platelet-activating factor (PAF) and group I metabotropic glutamate receptors only prevents the full development of LTP. Moreover, in the presence of blocking agents, glutamate causes transient inhibition, suggesting that when potentiation is impeded, exogenous glutamate can activate presynaptic mechanisms that reduce glutamate release.

  11. A role for protein phosphatases 1, 2A, and 2B in cerebellar long-term potentiation

    NARCIS (Netherlands)

    A. Belmeguenai (Amor); C.R.W. Hansel (Christian)

    2005-01-01

    textabstractCerebellar parallel fiber (PF)-Purkinje cell (PC) synapses can undergo postsynaptically expressed long-term depression (LTD) or long-term potentiation (LTP). PF-LTD induction requires the coactivity of the PF and CF (climbing fiber) inputs to PCs and a concomitant

  12. Long-term antibiotic delivery by chitosan-based composite coatings with bone regenerative potential

    Science.gov (United States)

    Ordikhani, F.; Simchi, A.

    2014-10-01

    Composite coatings with bone-bioactivity and drug-eluting capacity are considered as promising materials for titanium bone implants. In this work, drug-eluting chitosan-bioactive glass coatings were fabricated by a single-step electrophoretic deposition technique. Drug-loading and -releasing capacity of the composite coatings were carried out using the vancomycin antibiotic. Uniform coatings with a thickness of ∼55 μm containing 23.7 wt% bioactive glass particles and various amounts of the antibiotic (380-630 μg/cm2) were produced. The coatings were bioactive in terms of apatite-forming ability in simulated body fluid and showed favorable cell adhesion and growth. In vitro biological tests also indicated that the composite coatings had better cellular affinity than pristine chitosan coatings. The in vitro elution kinetics of the composite coating revealed an initial burst release of around 40% of the drug within the first elution step of 1 h and following by a continuous eluting over 4 weeks, revealing long-term drug-delivering potential. Antibacterial tests using survival assay against Gram-positive Staphylococcus aureus bacteria determined the effect of vancomycin release on reduction of infection risk. Almost no bacteria were survived on the coatings prepared from the EPD suspension containing ≥0.5 g/l vancomycin. The developed chitosan-based composite coatings with bone bioactivity and long-term drug-delivery ability may be potentially useful for metallic implants to reduce infection risk.

  13. Cholinergic pairing with visual activation results in long-term enhancement of visual evoked potentials.

    Directory of Open Access Journals (Sweden)

    Jun Il Kang

    Full Text Available Acetylcholine (ACh contributes to learning processes by modulating cortical plasticity in terms of intensity of neuronal activity and selectivity properties of cortical neurons. However, it is not known if ACh induces long term effects within the primary visual cortex (V1 that could sustain visual learning mechanisms. In the present study we analyzed visual evoked potentials (VEPs in V1 of rats during a 4-8 h period after coupling visual stimulation to an intracortical injection of ACh analog carbachol or stimulation of basal forebrain. To clarify the action of ACh on VEP activity in V1, we individually pre-injected muscarinic (scopolamine, nicotinic (mecamylamine, alpha7 (methyllycaconitine, and NMDA (CPP receptor antagonists before carbachol infusion. Stimulation of the cholinergic system paired with visual stimulation significantly increased VEP amplitude (56% during a 6 h period. Pre-treatment with scopolamine, mecamylamine and CPP completely abolished this long-term enhancement, while alpha7 inhibition induced an instant increase of VEP amplitude. This suggests a role of ACh in facilitating visual stimuli responsiveness through mechanisms comparable to LTP which involve nicotinic and muscarinic receptors with an interaction of NMDA transmission in the visual cortex.

  14. Pharmacological Rescue of Long-Term Potentiation in Alzheimer Diseased Synapses.

    Science.gov (United States)

    Prieto, G Aleph; Trieu, Brian H; Dang, Cindy T; Bilousova, Tina; Gylys, Karen H; Berchtold, Nicole C; Lynch, Gary; Cotman, Carl W

    2017-02-01

    Long-term potentiation (LTP) is an activity-dependent and persistent increase in synaptic transmission. Currently available techniques to measure LTP are time-intensive and require highly specialized expertise and equipment, and thus are not well suited for screening of multiple candidate treatments, even in animal models. To expand and facilitate the analysis of LTP, here we use a flow cytometry-based method to track chemically induced LTP by detecting surface AMPA receptors in isolated synaptosomes: fluorescence analysis of single-synapse long-term potentiation (FASS-LTP). First, we demonstrate that FASS-LTP is simple, sensitive, and models electrically induced LTP recorded in intact circuitries. Second, we conducted FASS-LTP analysis in two well-characterized Alzheimer's disease (AD) mouse models (3xTg and Tg2576) and, importantly, in cryopreserved human AD brain samples. By profiling hundreds of synaptosomes, our data provide the first direct evidence to support the idea that synapses from AD brain are intrinsically defective in LTP. Third, we used FASS-LTP for drug evaluation in human synaptosomes. Testing a panel of modulators of cAMP and cGMP signaling pathways, FASS-LTP identified vardenafil and Bay-73-6691 (phosphodiesterase-5 and -9 inhibitors, respectively) as potent enhancers of LTP in synaptosomes from AD cases. These results indicate that our approach could provide the basis for protocols to study LTP in both healthy and diseased human brains, a previously unattainable goal. Learning and memory depend on the ability of synapses to strengthen in response to activity. Long-term potentiation (LTP) is a rapid and persistent increase in synaptic transmission that is thought to be affected in Alzheimer's disease (AD). However, direct evidence of LTP deficits in human AD brain has been elusive, primarily due to methodological limitations. Here, we analyze LTP in isolated synapses from AD brain using a novel approach that allows testing LTP in cryopreserved

  15. Identification of compounds that potentiate CREB signaling as possible enhancers of long-term memory

    Science.gov (United States)

    Xia, Menghang; Huang, Ruili; Guo, Vicky; Southall, Noel; Cho, Ming-Hsuang; Inglese, James; Austin, Christopher P.; Nirenberg, Marshall

    2009-01-01

    Many studies have implicated the cAMP Response Element Binding (CREB) protein signaling pathway in long-term memory. To identify small molecule enhancers of CREB activation of gene expression, we screened ≈73,000 compounds, each at 7–15 concentrations in a quantitative high-throughput screening (qHTS) format, for activity in cells by assaying CREB mediated β-lactamase reporter gene expression. We identified 1,800 compounds that potentiated CREB mediated gene expression, with potencies as low as 16 nM, comprising 96 structural series. Mechanisms of action were systematically determined, and compounds that affect phosphodiesterase 4, protein kinase A, and cAMP production were identified, as well as compounds that affect CREB signaling via apparently unidentified mechanisms. qHTS folowed by interrogation of pathway targets is an efficient paradigm for lead generation for chemical genomics and drug development. PMID:19196967

  16. Spatial learning and long-term potentiation of mutant mice lacking D-amino-acid oxidase.

    Science.gov (United States)

    Maekawa, Masao; Watanabe, Masashi; Yamaguchi, Shigeki; Konno, Ryuichi; Hori, Yuuichi

    2005-09-01

    We evaluated the role of D-amino-acid oxidase on spatial learning and long-term potentiation (LTP) in the hippocampus, since this enzyme metabolizes D-amino-acids, some of which enhance the N-methyl-D-aspartate receptor functions. The Morris water maze learning and the LTP in the CA1 area of the hippocampal slice were observed in wild-type mice and mutant mice lacking D-amino-acid oxidase. The mutant mice showed significantly shorter platform search times in the water maze and significantly larger hippocampal LTPs than the wild-type mice. These results suggest that the abundant D-amino-acids in the mutant mouse brain facilitate hippocampal LTP and spatial learning.

  17. Tyrosine phosphatase STEP is a tonic brake on induction of long-term potentiation.

    Science.gov (United States)

    Pelkey, Kenneth A; Askalan, Rand; Paul, Surojit; Kalia, Lorraine V; Nguyen, Tri Hung; Pitcher, Graham M; Salter, Michael W; Lombroso, Paul J

    2002-03-28

    The functional roles of protein tyrosine phosphatases (PTPs) in the developed CNS have been enigmatic. Here we show that striatal enriched tyrosine phosphatase (STEP) is a component of the N-methyl-D-aspartate receptor (NMDAR) complex. Functionally, exogenous STEP depressed NMDAR single-channel activity in excised membrane patches. STEP also depressed NMDAR-mediated synaptic currents whereas inhibiting endogenous STEP enhanced these currents. In hippocampal slices, administering STEP into CA1 neurons did not affect basal glutamatergic transmission evoked by Schaffer collateral stimulation but prevented tetanus-induced long-term potentiation (LTP). Conversely, inhibiting STEP in CA1 neurons enhanced transmission and occluded LTP induction through an NMDAR-, Src-, and Ca(2+)-dependent mechanism. Thus, STEP acts as a tonic brake on synaptic transmission by opposing Src-dependent upregulation of NMDARs.

  18. Receptor protein tyrosine phosphatase alpha is essential for hippocampal neuronal migration and long-term potentiation

    DEFF Research Database (Denmark)

    Petrone, Angiola; Battaglia, Fortunato; Wang, Cheng

    2003-01-01

    Despite clear indications of their importance in lower organisms, the contributions of protein tyrosine phosphatases (PTPs) to development or function of the mammalian nervous system have been poorly explored. In vitro studies have indicated that receptor protein tyrosine phosphatase alpha (RPTPa....... However, these synapses are unable to undergo long-term potentiation. Mice lacking RPTPalpha also underperform in the radial-arm water-maze test. These studies identify RPTPalpha as a key mediator of neuronal migration and synaptic plasticity....... neuronal migration. The migratory abnormality likely results from a radial glial dysfunction rather than from a neuron-autonomous defect. In spite of this aberrant development, basic synaptic transmission from the Schaffer collateral pathway to CA1 pyramidal neurons remains intact in Ptpra(-/-) mice...

  19. A model of late long-term potentiation simulates aspects of memory maintenance.

    Directory of Open Access Journals (Sweden)

    Paul Smolen

    Full Text Available Late long-term potentiation (L-LTP denotes long-lasting strengthening of synapses between neurons. L-LTP appears essential for the formation of long-term memory, with memories at least partly encoded by patterns of strengthened synapses. How memories are preserved for months or years, despite molecular turnover, is not well understood. Ongoing recurrent neuronal activity, during memory recall or during sleep, has been hypothesized to preferentially potentiate strong synapses, preserving memories. This hypothesis has not been evaluated in the context of a mathematical model representing ongoing activity and biochemical pathways important for L-LTP. In this study, ongoing activity was incorporated into two such models - a reduced model that represents some of the essential biochemical processes, and a more detailed published model. The reduced model represents synaptic tagging and gene induction simply and intuitively, and the detailed model adds activation of essential kinases by Ca(2+. Ongoing activity was modeled as continual brief elevations of Ca(2+. In each model, two stable states of synaptic strength/weight resulted. Positive feedback between synaptic weight and the amplitude of ongoing Ca(2+ transients underlies this bistability. A tetanic or theta-burst stimulus switches a model synapse from a low basal weight to a high weight that is stabilized by ongoing activity. Bistability was robust to parameter variations in both models. Simulations illustrated that prolonged periods of decreased activity reset synaptic strengths to low values, suggesting a plausible forgetting mechanism. However, episodic activity with shorter inactive intervals maintained strong synapses. Both models support experimental predictions. Tests of these predictions are expected to further understanding of how neuronal activity is coupled to maintenance of synaptic strength. Further investigations that examine the dynamics of activity and synaptic maintenance can be

  20. Developmental expression of inhibitory synaptic long-term potentiation in the lateral superior olive

    Directory of Open Access Journals (Sweden)

    Vibhakar C. Kotak

    2014-06-01

    Full Text Available Principal neurons of the lateral superior olivary nucleus (LSO respond selectively to interaural level differences (ILD. To perform this computation, LSO neurons integrate excitatory synaptic drive from the ipsilateral ear with inhibitory synaptic drive from the contralateral ear via the medial nucleus of the trapezoid body (MNTB. Previous research demonstrated that inhibitory terminals from the MNTB to the LSO are eliminated during development. Furthermore, MNTB synapses display an activity- and age-dependent long-term depression (iLTD which may contribute to inhibitory synapse elimination. However, inhibitory synapses that are stabilized become stronger. Here, we asked whether MNTB synapses displayed activity-dependent strengthening. Whole-cell recordings were obtained from LSO neurons in a gerbil brain slice before and after hearing onset. The inhibitory MNTB afferents were stimulated at a low rate, similar to spontaneous discharge rates observed in vivo. The MNTB-evoked inhibitory responses were strengthened by 40-300% when synaptic activity was coupled with postsynaptic membrane depolarization, exogenous glutamate application, or activation of ipsilateral excitatory synaptic inputs. This inhibitory long-term potentiation (iLTP was associated with increased spontaneous inhibitory postsynaptic current (IPSC amplitude and frequency. One hour after iLTP induction, IPSCs could not be de-potentiated by the MNTB stimulation pattern that induces iLTD in control slices. iLTP could only be induced after hearing onset (>P12, and was blocked in the presence of a GABAB receptor antagonist. Together, these results suggest a developmental period during which the induction of iLTP depends on the conjoint activation of GABAB receptors and postsynaptic depolarization. We propose that iLTP may support stabilization of un-pruned MNTB connections and contribute to the emergence of ILD processing in the mature LSO.

  1. Colorado Plateau Rapid Ecoregion Assessment Change Agents - Development - Current, Near-Term, and Long-Term Potential High Landscape Development

    Data.gov (United States)

    Bureau of Land Management, Department of the Interior — This map shows areas of high current, near-term, and long-term potential landscape development, based on factors such as urban areas, agriculture, roads, and energy...

  2. Postsynaptic Signal Transduction Models for Long-Term Potentiation and Depression

    Science.gov (United States)

    Manninen, Tiina; Hituri, Katri; Kotaleski, Jeanette Hellgren; Blackwell, Kim T.; Linne, Marja-Leena

    2010-01-01

    More than a hundred biochemical species, activated by neurotransmitters binding to transmembrane receptors, are important in long-term potentiation (LTP) and long-term depression (LTD). To investigate which species and interactions are critical for synaptic plasticity, many computational postsynaptic signal transduction models have been developed. The models range from simple models with a single reversible reaction to detailed models with several hundred kinetic reactions. In this study, more than a hundred models are reviewed, and their features are compared and contrasted so that similarities and differences are more readily apparent. The models are classified according to the type of synaptic plasticity that is modeled (LTP or LTD) and whether they include diffusion or electrophysiological phenomena. Other characteristics that discriminate the models include the phase of synaptic plasticity modeled (induction, expression, or maintenance) and the simulation method used (deterministic or stochastic). We find that models are becoming increasingly sophisticated, by including stochastic properties, integrating with electrophysiological properties of entire neurons, or incorporating diffusion of signaling molecules. Simpler models continue to be developed because they are computationally efficient and allow theoretical analysis. The more complex models permit investigation of mechanisms underlying specific properties and experimental verification of model predictions. Nonetheless, it is difficult to fully comprehend the evolution of these models because (1) several models are not described in detail in the publications, (2) only a few models are provided in existing model databases, and (3) comparison to previous models is lacking. We conclude that the value of these models for understanding molecular mechanisms of synaptic plasticity is increasing and will be enhanced further with more complete descriptions and sharing of the published models. PMID:21188161

  3. Steatohepatitis secondary to long-term glucocorticoid treatment for congenital adrenal hyperplasia: a potential diagnostic pitfall.

    Science.gov (United States)

    Ding, Xianzhong; Thung, Swan N; Grewal, Priya

    2013-11-01

    A 24-year-old woman with congenital adrenal hyperplasia (CAH) was referred for evaluation of elevated liver enzyme activities over the preceding 6 months. The patient was diagnosed with CAH at the age 12 when she presented with irregular menses and hirsutism. Since then, she had been on dexamethasone to maintain a normal menstrual cycle and prevent hirsutism and acne. She had no history of chronic liver disease and drank alcohol socially. An extensive workup for other treatable causes of liver disease was unrevealing. Therefore, a liver biopsy was performed, which revealed extensive ballooned degenerative hepatocytes containing Mallory-Denk hyalines. The ballooned hepatocytes were located predominantly in centrilobular areas and without any accompanying steatosis. Even though the histopathologic features are most compatible with alcoholic and/or nonalcoholic steatohepatitis, it was not supported by the patient's medical history and clinical presentation. The patient had a normal body mass index and only occasional alcohol use. Based on the biopsy finding and clinical presentation, we postulated that the abnormal liver enzyme and pathological features seen on the liver biopsy were secondary to CAH and long-term use of glucocorticoid. A few studies have shown that patients with CAH often develop metabolic abnormalities and insulin resistance, particularly women treated with glucocorticoid for several years. To our knowledge, this is the first report describing steatohepatitis secondary to CAH and prolonged glucocorticoid treatment. It is important to be aware that steatohepatitis can develop in these patients due to long-term glucocorticoid use and potentially lead to progressive liver damage. Furthermore, in patients with CAH who develop abnormal liver enzyme activities a liver biopsy is warranted to assess for steatohepatitis and any associated fibrosis. If indeed fibrosis is already present, a consultation with the endocrinologist should be undertaken in an effort

  4. Involvement of microglia activation in the lead induced long-term potentiation impairment.

    Directory of Open Access Journals (Sweden)

    Ming-Chao Liu

    Full Text Available Exposure of Lead (Pb, a known neurotoxicant, can impair spatial learning and memory probably via impairing the hippocampal long-term potentiation (LTP as well as hippocampal neuronal injury. Activation of hippocampal microglia also impairs spatial learning and memory. Thus, we raised the hypothesis that activation of microglia is involved in the Pb exposure induced hippocampal LTP impairment and neuronal injury. To test this hypothesis and clarify its underlying mechanisms, we investigated the Pb-exposure on the microglia activation, cytokine release, hippocampal LTP level as well as neuronal injury in in vivo or in vitro model. The changes of these parameters were also observed after pretreatment with minocycline, a microglia activation inhibitor. Long-term low dose Pb exposure (100 ppm for 8 weeks caused significant reduction of LTP in acute slice preparations, meanwhile, such treatment also significantly increased hippocampal microglia activation as well as neuronal injury. In vitro Pb-exposure also induced significantly increase of microglia activation, up-regulate the release of cytokines including tumor necrosis factor-alpha (TNF-α, interleukin-1β (IL-1β and inducible nitric oxide synthase (iNOS in microglia culture alone as well as neuronal injury in the co-culture with hippocampal neurons. Inhibiting the microglia activation with minocycline significantly reversed the above-mentioned Pb-exposure induced changes. Our results showed that Pb can cause microglia activation, which can up-regulate the level of IL-1β, TNF-α and iNOS, these proinflammatory factors may cause hippocampal neuronal injury as well as LTP deficits.

  5. Long-term variability of the thunderstorm and hail potential in Europe

    Science.gov (United States)

    Mohr, Susanna; Kunz, Michael; Speidel, Johannes; Piper, David

    2016-04-01

    Severe thunderstorms and associated hazardous weather events such as hail frequently cause considerable damage to buildings, crops, and automobiles, resulting in large monetary costs in many parts of Europe and the world. To relate single extreme hail events to the historic context and to estimate their return periods and possible trends related to climate change, long-term statistics of hail events are required. Due to the local-scale nature of hail and a lack of suitable observation systems, however, hailstorms are not captured reliably and comprehensively for a long period of time. In view of this fact, different proxies (indirect climate data) obtained from sounding stations and regional climate models can be used to infer the probability and intensity of thunderstorms or hailstorms. In contrast to direct observational data, such proxies are available homogeneously over a long time period. The aim of the study is to investigate the potential for severe thunderstorms and their changes over past decades. Statistical analyses of sounding data show that the convective potential over the past 20 - 30 years has significantly increased over large parts of Central Europe, making severe thunderstorms more likely. A similar picture results from analyses of weather types that are most likely associated with damaging hailstorms. These weather patterns have increased, even if only slightly but nevertheless statistically significantly, in the time period from 1971 to 2000. To improve the diagnostics of hail events in regional climate models, a logistic hail model has been developed by means of a multivariate analysis method. The model is based on a combination of appropriate hail-relevant meteorological parameters. The output of the model is a new index that estimates the potential of the atmosphere for hailstorm development, referred to as potential hail index (PHI). Applied to a high-resolved reanalysis run for Europe driven by NCEP/NCAR1, long-term changes of the PHI for

  6. Long-term, stable behavior of local field potentials during brain machine interface use.

    Science.gov (United States)

    Scheid, Michael R; Flint, Robert D; Wright, Zachary A; Slutzky, Marc W

    2013-01-01

    Local field potentials (LFPs) have the potential to provide robust, long-lasting control signals for brain-machine interfaces (BMIs). Moreover, they have been hypothesized to be a stable signal source. Here we assess the long-term stability of LFPs and multi-unit spikes (MSPs) in two monkeys using both LFP-based and MSP-based, biomimetic BMIs to control a computer cursor. The monkeys demonstrated highly accurate performance using both the LFP- and MSP-based BMIs. This performance remained high for 11 and 6 months, respectively, without adapting or retraining. We evaluated the stability of the LFP features and MSPs themselves by building, in each session, linear decoders of the BMI-controlled cursor velocity using single features or single MSPs. We then used these single-feature decoders to decode BMI-controlled cursor velocity in the last session. Many of the LFP features and MSPs showed stably-high correlations with the cursor velocity over the entire study period. This implies that the monkeys were able to maintain a stable mapping between either motor cortical field potentials or multi-spike potentials and BMI-controlled outputs.

  7. On the role of nitric oxide in hippocampal long-term potentiation.

    Science.gov (United States)

    Bon, Christelle L M; Garthwaite, John

    2003-03-01

    Nitric oxide (NO) functions in several types of synaptic plasticity, including hippocampal long-term potentiation (LTP), in which it may serve as a retrograde messenger after postsynaptic NMDA receptor activation. In accordance with a prediction of this hypothesis, and with previous findings using guinea pig tissue, exogenous NO, when paired with a short tetanus (ST) to afferent fibers, generated a stable NMDA receptor-independent potentiation of rat CA1 hippocampal synaptic transmission that occluded LTP. Contrary to predictions, however, the pairing-induced potentiation was abolished in the presence of NO synthase inhibitors, indicating that endogenous NO is required for exogenous NO to facilitate LTP. Periodic application of NO while endogenous NO synthesis was blocked indicated that a tonic low level is necessary on both sides of the NO-ST pairing for the plasticity to occur. A similar dependence on tonic NO seems to extend to LTP, because application of an NO synthase inhibitor 5 min after tetanic stimulation blocked LTP as effectively as adding it beforehand. The posttetanus time window during which NO operated was restricted to learning behavior.

  8. Involvement of CX3CL1/CX3CR1 signaling in spinal long term potentiation.

    Science.gov (United States)

    Bian, Chao; Zhao, Zhi-Qi; Zhang, Yu-Qiu; Lü, Ning

    2015-01-01

    The long-term potentiation (LTP) of spinal C-fiber-evoked field potentials is considered as a fundamental mechanism of central sensitization in the spinal cord. Accumulating evidence has showed the contribution of spinal microglia to spinal LTP and pathological pain. As a key signaling of neurons-microglia interactions, the involvement of CX3CL1/CX3CR1 signaling in pathological pain has also been investigated extensively. The present study examined whether CX3CL1/CX3CR1 signaling plays a role in spinal LTP. The results showed that 10-trains tetanic stimulation (100 Hz, 2s) of the sciatic nerve (TSS) produced a significant LTP of C-fiber-evoked field potentials lasting for over 3 h in the rat spinal dorsal horn. Blockade of CX3CL1/CX3CR1 signaling with an anti-CX3CR1 neutralizing antibody (CX3CR1 AB) markedly suppressed TSS-induced LTP. Exogenous CX3CL1 significantly potentiated 3-trains TSS-induced LTP in rats. Consistently, spinal LTP of C-fiber-evoked field potentials was also induced by TSS (100 Hz, 1s, 4 trains) in all C57BL/6 wild type (WT) mice. However, in CX3CR1-/- mice, TSS failed to induce LTP and behavioral hypersensitivity, confirming an essential role of CX3CR1 in spinal LTP induction. Furthermore, blockade of IL-18 or IL-23, the potential downstream factors of CX3CL1/CX3CR1 signaling, with IL-18 BP or anti-IL-23 neutralizing antibody (IL-23 AB), obviously suppressed spinal LTP in rats. These results suggest that CX3CL1/CX3CR1 signaling is involved in LTP of C-fiber-evoked field potentials in the rodent spinal dorsal horn.

  9. Involvement of CX3CL1/CX3CR1 signaling in spinal long term potentiation.

    Directory of Open Access Journals (Sweden)

    Chao Bian

    Full Text Available The long-term potentiation (LTP of spinal C-fiber-evoked field potentials is considered as a fundamental mechanism of central sensitization in the spinal cord. Accumulating evidence has showed the contribution of spinal microglia to spinal LTP and pathological pain. As a key signaling of neurons-microglia interactions, the involvement of CX3CL1/CX3CR1 signaling in pathological pain has also been investigated extensively. The present study examined whether CX3CL1/CX3CR1 signaling plays a role in spinal LTP. The results showed that 10-trains tetanic stimulation (100 Hz, 2s of the sciatic nerve (TSS produced a significant LTP of C-fiber-evoked field potentials lasting for over 3 h in the rat spinal dorsal horn. Blockade of CX3CL1/CX3CR1 signaling with an anti-CX3CR1 neutralizing antibody (CX3CR1 AB markedly suppressed TSS-induced LTP. Exogenous CX3CL1 significantly potentiated 3-trains TSS-induced LTP in rats. Consistently, spinal LTP of C-fiber-evoked field potentials was also induced by TSS (100 Hz, 1s, 4 trains in all C57BL/6 wild type (WT mice. However, in CX3CR1-/- mice, TSS failed to induce LTP and behavioral hypersensitivity, confirming an essential role of CX3CR1 in spinal LTP induction. Furthermore, blockade of IL-18 or IL-23, the potential downstream factors of CX3CL1/CX3CR1 signaling, with IL-18 BP or anti-IL-23 neutralizing antibody (IL-23 AB, obviously suppressed spinal LTP in rats. These results suggest that CX3CL1/CX3CR1 signaling is involved in LTP of C-fiber-evoked field potentials in the rodent spinal dorsal horn.

  10. Sauroxine reduces memory retention in rats and impairs hippocampal long-term potentiation generation.

    Science.gov (United States)

    Vallejo, Mariana; Carlini, Valeria; Gabach, Laura; Ortega, M G; L Cabrera, José; de Barioglio, Susana Rubiales; Pérez, Mariela; Agnese, Alicia M

    2017-07-01

    In the present paper it was investigated the role of sauroxine, an alkaloid of Phlegmariurus saururus, as a modulator of some types of learning and memory, considering the potential nootropic properties previously reported for the alkaloid extract and the main alkaloid sauroine. Sauroxine was isolated by means of an alkaline extraction, purified by several chromatographic techniques, and assayed in electrophysiological experiments on rat hippocampus slices, tending towards the elicitation of the long-term potentiation (LTP) phenomena. It was also studied the effects of intrahippocampal administration of sauroxine on memory retention in vivo using a Step-down test. Being the bio distribution of a drug an important parameter to be considered, the concentration of sauroxine in rat brain was determined by GLC-MS. Sauroxine blocked LTP generation at both doses used, 3.65 and 3.610 -2 μM. In the behavioral test, the animals injected with this alkaloid (3.6510 -3 nmol) exhibited a significant decrease on memory retention compared with control animals. It was also showed that sauroxine reached the brain (3.435μg/g tissue), after an intraperitoneal injection, displaying its ability to cross the blood-brain barrier. Thus, sauroxine demonstrated to exert an inhibition on these mnemonic phenomena. The effect here established for 1 is defeated by other constituents according to the excellent results obtained for P. saururus alkaloid extract as well as for the isolated alkaloid sauroine. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  11. Overexpression of Protein Kinase Mζ in the Hippocampus Enhances Long-Term Potentiation and Long-Term Contextual But Not Cued Fear Memory in Rats.

    Science.gov (United States)

    Schuette, Sven R M; Fernández-Fernández, Diego; Lamla, Thorsten; Rosenbrock, Holger; Hobson, Scott

    2016-04-13

    The persistently active protein kinase Mζ (PKMζ) has been found to be involved in the formation and maintenance of long-term memory. Most of the studies investigating PKMζ, however, have used either putatively unselective inhibitors or conventional knock-out animal models in which compensatory mechanisms may occur. Here, we overexpressed an active form of PKMζ in rat hippocampus, a structure highly involved in memory formation, and embedded in several neural networks. We investigated PKMζ's influence on synaptic plasticity using electrophysiological recordings of basal transmission, paired pulse facilitation, and LTP and combined this with behavioral cognitive experiments addressing formation and retention of both contextual memory during aversive conditioning and spatial memory during spontaneous exploration. We demonstrate that hippocampal slices overexpressing PKMζ show enhanced basal transmission, suggesting a potential role of PKMζ in postsynaptic AMPAR trafficking. Moreover, the PKMζ-overexpressing slices augmented LTP and this effect was not abolished by protein-synthesis blockers, indicating that PKMζ induces enhanced LTP formation in a protein-synthesis-independent manner. In addition, we found selectively enhanced long-term memory for contextual but not cued fear memory, underlining the theory of the hippocampus' involvement in the contextual aspect of aversive reinforced tasks. Memory for spatial orientation during spontaneous exploration remained unaltered, suggesting that PKMζ may not affect the neural circuits underlying spontaneous tasks that are different from aversive tasks. In this study, using an overexpression strategy as opposed to an inhibitor-based approach, we demonstrate an important modulatory role of PKMζ in synaptic plasticity and selective memory processing. Most of the literature investigating protein kinase Mζ (PKMζ) used inhibitors with selectivity that has been called into question or conventional knock-out animal

  12. Both NR2A and NR2B Subunits of the NMDA Receptor Are Critical for Long-Term Potentiation and Long-Term Depression in the Lateral Amygdala of Horizontal Slices of Adult Mice

    Science.gov (United States)

    Muller, Tobias; Albrecht, Doris; Gebhardt, Christine

    2009-01-01

    The lateral nucleus of the amygdala (LA) is implicated in emotional and social behaviors. We recently showed that in horizontal brain slices, activation of NMDA receptors (NMDARs) is a requirement for persistent synaptic alterations in the LA, such as long-term potentiation (LTP) and long-term depression (LTD). In the LA, NR2A- and NR2B-type NMDRs…

  13. Discovering long-term potentiation (LTP) - recollections and reflections on what came after.

    Science.gov (United States)

    Lømo, T

    2017-07-18

    Chance events led me to a lifelong career in scientific research. They paved the way for being the first to see long-term potentiation of synaptic efficiency (LTP) in Per Andersen's laboratory in Oslo in 1966. Here I describe my way to this discovery and the experiments with Tim Bliss in 1968-1969 that led to Bliss and Lømo, 1973. Surprisingly, we later failed to reproduce these results. I discuss possible reasons for this failure, which made us both leave LTP research, in my case for good, in Tim's case for several years. After 30 years of work in a different field, I renewed my interest in the hippocampus and LTP in the early 2000s and published, for the first time, results that I had obtained 40 years earlier. Here I present my take on how interest in and research on LTP evolved after the early years. This includes a discussion of the functions of hippocampus as seen in those early days, the case of patient H.M., Donald Hebb's place in the story, the search for 'memory molecules' such as PKMζ, and the primary site for LTP expression (pre- and/or post-synaptic?). Throughout, I reflect on my life in science, how science is done and what drives it. The reflections are quite personal and I admit to mixed feelings about broadcasting them. © 2017 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

  14. Long-term potentiation in spinal nociceptive pathways as a novel target for pain therapy

    Directory of Open Access Journals (Sweden)

    Liu Xian-Guo

    2011-03-01

    Full Text Available Abstract Long-term potentiation (LTP in nociceptive spinal pathways shares several features with hyperalgesia and has been proposed to be a cellular mechanism of pain amplification in acute and chronic pain states. Spinal LTP is typically induced by noxious input and has therefore been hypothesized to contribute to acute postoperative pain and to forms of chronic pain that develop from an initial painful event, peripheral inflammation or neuropathy. Under this assumption, preventing LTP induction may help to prevent the development of exaggerated postoperative pain and reversing established LTP may help to treat patients who have an LTP component to their chronic pain. Spinal LTP is also induced by abrupt opioid withdrawal, making it a possible mechanism of some forms of opioid-induced hyperalgesia. Here, we give an overview of targets for preventing LTP induction and modifying established LTP as identified in animal studies. We discuss which of the various symptoms of human experimental and clinical pain may be manifestations of spinal LTP, review the pharmacology of these possible human LTP manifestations and compare it to the pharmacology of spinal LTP in rodents.

  15. Exposure of mouse to high gravitation forces induces long-term potentiation in the hippocampus.

    Science.gov (United States)

    Ishii, Masamitsu; Tomizawa, Kazuhito; Matsushita, Masayuki; Matsui, Hideki

    2004-06-01

    The central nervous system is highly plastic and has been shown to undergo both transient and chronic adaptive changes in response to environmental influences. The purpose of this study was to investigate the effect of hypergravic field on long-term potentiation (LTP) in the mouse hippocampus. Exposure of mice to 4G fields for 48 h had no effect on input-output coupling during extracellular stimulation of Schaffer collaterals and paired pulse facilitation, suggesting that the hypergravic exposure had no detrimental effect on basal neurotransmission in the hippocampus. However, the exposure to 4G fields for 48 h significantly induced LTP compared with the control mouse hippocampus. In contrast, no significant changes of late-phase LTP (L-LTP) were found in the hippocampi of mice exposed to the hypergravic field. Exposure of mice to 4G fields for 48 h enhanced AMPA receptor phosphorylation but not cyclic AMP-responsive element binding protein (CREB) phosphorylation. These results suggest that exposure to hyperdynamic fields influences the synaptic plasticity in the hippocampus.

  16. Long-term potentiation in spinal nociceptive pathways as a novel target for pain therapy

    Science.gov (United States)

    2011-01-01

    Long-term potentiation (LTP) in nociceptive spinal pathways shares several features with hyperalgesia and has been proposed to be a cellular mechanism of pain amplification in acute and chronic pain states. Spinal LTP is typically induced by noxious input and has therefore been hypothesized to contribute to acute postoperative pain and to forms of chronic pain that develop from an initial painful event, peripheral inflammation or neuropathy. Under this assumption, preventing LTP induction may help to prevent the development of exaggerated postoperative pain and reversing established LTP may help to treat patients who have an LTP component to their chronic pain. Spinal LTP is also induced by abrupt opioid withdrawal, making it a possible mechanism of some forms of opioid-induced hyperalgesia. Here, we give an overview of targets for preventing LTP induction and modifying established LTP as identified in animal studies. We discuss which of the various symptoms of human experimental and clinical pain may be manifestations of spinal LTP, review the pharmacology of these possible human LTP manifestations and compare it to the pharmacology of spinal LTP in rodents. PMID:21443797

  17. Gating of long-term potentiation by nicotinic acetylcholine receptors at the cerebellum input stage.

    Directory of Open Access Journals (Sweden)

    Francesca Prestori

    Full Text Available The brain needs mechanisms able to correlate plastic changes with local circuit activity and internal functional states. At the cerebellum input stage, uncontrolled induction of long-term potentiation or depression (LTP or LTD between mossy fibres and granule cells can saturate synaptic capacity and impair cerebellar functioning, which suggests that neuromodulators are required to gate plasticity processes. Cholinergic systems innervating the cerebellum are thought to enhance procedural learning and memory. Here we show that a specific subtype of acetylcholine receptors, the α7-nAChRs, are distributed both in cerebellar mossy fibre terminals and granule cell dendrites and contribute substantially to synaptic regulation. Selective α7-nAChR activation enhances the postsynaptic calcium increase, allowing weak mossy fibre bursts, which would otherwise cause LTD, to generate robust LTP. The local microperfusion of α7-nAChR agonists could also lead to in vivo switching of LTD to LTP following sensory stimulation of the whisker pad. In the cerebellar flocculus, α7-nAChR pharmacological activation impaired vestibulo-ocular-reflex adaptation, probably because LTP was saturated, preventing the fine adjustment of synaptic weights. These results show that gating mechanisms mediated by specific subtypes of nicotinic receptors are required to control the LTD/LTP balance at the mossy fibre-granule cell relay in order to regulate cerebellar plasticity and behavioural adaptation.

  18. Short-term plasticity and long-term potentiation mimicked in single inorganic synapses

    Science.gov (United States)

    Ohno, Takeo; Hasegawa, Tsuyoshi; Tsuruoka, Tohru; Terabe, Kazuya; Gimzewski, James K.; Aono, Masakazu

    2011-08-01

    Memory is believed to occur in the human brain as a result of two types of synaptic plasticity: short-term plasticity (STP) and long-term potentiation (LTP; refs , , , ). In neuromorphic engineering, emulation of known neural behaviour has proven to be difficult to implement in software because of the highly complex interconnected nature of thought processes. Here we report the discovery of a Ag2S inorganic synapse, which emulates the synaptic functions of both STP and LTP characteristics through the use of input pulse repetition time. The structure known as an atomic switch, operating at critical voltages, stores information as STP with a spontaneous decay of conductance level in response to intermittent input stimuli, whereas frequent stimulation results in a transition to LTP. The Ag2S inorganic synapse has interesting characteristics with analogies to an individual biological synapse, and achieves dynamic memorization in a single device without the need of external preprogramming. A psychological model related to the process of memorizing and forgetting is also demonstrated using the inorganic synapses. Our Ag2S element indicates a breakthrough in mimicking synaptic behaviour essential for the further creation of artificial neural systems that emulate characteristics of human memory.

  19. Cytokines and cytokine networks target neurons to modulate long-term potentiation.

    Science.gov (United States)

    Prieto, G Aleph; Cotman, Carl W

    2017-04-01

    Cytokines play crucial roles in the communication between brain cells including neurons and glia, as well as in the brain-periphery interactions. In the brain, cytokines modulate long-term potentiation (LTP), a cellular correlate of memory. Whether cytokines regulate LTP by direct effects on neurons or by indirect mechanisms mediated by non-neuronal cells is poorly understood. Elucidating neuron-specific effects of cytokines has been challenging because most brain cells express cytokine receptors. Moreover, cytokines commonly increase the expression of multiple cytokines in their target cells, thus increasing the complexity of brain cytokine networks even after single-cytokine challenges. Here, we review evidence on both direct and indirect-mediated modulation of LTP by cytokines. We also describe novel approaches based on neuron- and synaptosome-enriched systems to identify cytokines able to directly modulate LTP, by targeting neurons and synapses. These approaches can test multiple samples in parallel, thus allowing the study of multiple cytokines simultaneously. Hence, a cytokine networks perspective coupled with neuron-specific analysis may contribute to delineation of maps of the modulation of LTP by cytokines. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Endocannabinoid-Dependent Long-Term Potentiation of Synaptic Transmission at Rat Barrel Cortex.

    Science.gov (United States)

    Maglio, Laura Eva; Noriega-Prieto, José Antonio; Maraver, Maria Jesús; Fernández de Sevilla, David

    2017-03-01

    Brain-derived neurotrophic factor (BDNF) plays a critical role in modulating plasticity in sensory cortices. Indeed, a BDNF-dependent long-term potentiation (LTP) at distal basal excitatory synapses of Layer 5 pyramidal neurons (L5PNs) has been demonstrated in disinhibited rat barrel cortex slices. Although it is well established that this LTP requires the pairing of excitatory postsynaptic potentials (PSPs) with Ca2+ spikes, its induction when synaptic inhibition is working remains unexplored. Here we show that low-frequency stimulation at basal dendrites of L5PNs is able to trigger a PSP followed by an action potential (AP) and a slow depolarization (termed PSP-Ca2+ response) in thalamocortical slices without blocking synaptic inhibition. We demonstrate that AP barrage-mediated release of endocannabinoids (eCBs) from the recorded L5PNs induces PSP-Ca2+ response facilitation and BDNF-dependent LTP. Indeed, this LTP requires the type 1 cannabinoid receptors activation, is prevented by postsynaptic intracellular 1,2-bis(2-aminophenoxy) ethane-N,N,N,N'-tetraacetic acid (BAPTA) or the anandamide membrane transporter inhibitor AM404, and only occurs in L5PNs neurons showing depolarization-induced suppression of inhibition. Additionally, electrical stimulation at the posteromedial thalamic nucleus induced similar response and LTP. These results reveal a novel form of eCB-dependent LTP at L5PNs that could be relevant in the processing of sensory information in the barrel cortex. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  1. Effects of voluntary exercise on hippocampal long-term potentiation in morphine-dependent rats.

    Science.gov (United States)

    Miladi-Gorji, H; Rashidy-Pour, A; Fathollahi, Y; Semnanian, S; Jadidi, M

    2014-01-03

    This study was designed to examine the effect of voluntary exercise on hippocampal long-term potentiation (LTP) in morphine-dependent rats. The rats were randomly distributed into the saline-sedentary (Sal/Sed), the dependent-sedentary, the saline-exercise (Sal/Exc), and the dependent-exercise (D/Exc) groups. The Sal/Exc and the D/Exc groups were allowed to freely exercise in a running wheel for 10 days. The Sal/Sed and the morphine-sedentary groups were kept sedentary for the same extent of time. Morphine (10 mg/kg) was injected bi-daily (12 h interval) during 10 days of voluntary exercise. On day 11, 2h after the morphine injection, the in vivo LTP in the dentate gyrus of the hippocampus was examined. The theta frequency primed bursts were delivered to the perforant path for induction of LTP. Population spike (PS) amplitude and the field excitatory post-synaptic potentials (fEPSP) slope were measured as indices of increase in synaptic efficacy. Chronic morphine increased the mean basal EPSP, and augmented PS-LTP. Exercise significantly increased the mean baseline EPSP and PS responses, and augmented PS-LTP in both saline and morphine-treated groups. Moreover, the increase of PS-LTP in the morphine-exercise group was greater (22.5%), but not statistically significant, than that of the Sal/Exc group. These results may imply an additive effect between exercise and morphine on mechanisms of synaptic plasticity. Such an interaction between exercise and chronic morphine may influence cognitive functions in opiate addicts. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

  2. Simvastatin enhances hippocampal long-term potentiation in C57BL/6 mice

    Science.gov (United States)

    Mans, Robert A.; Chowdhury, Nazma; Cao, Dongfeng; McMahon, Lori L.; Li, Ling

    2010-01-01

    Statins inhibit 3-hydroxy-3-methylglutaryl CoA reductase (HMG-CoA), the rate-limiting enzyme in the cholesterol biosynthetic pathway, and they are widely used to control plasma cholesterol levels and prevent cardiovascular disease. However, emerging evidence indicates that the beneficial effects of statins extend to the central nervous system. Statins have been shown to improve the outcome of stroke and traumatic brain injury, and statin use has been associated with a reduced prevalence of Alzheimer’s disease (AD) and dementia. However, prospective studies with statins in AD have produced mixed results. Recently, we reported that simvastatin, a widely used statin in humans, enhances learning and memory in non-transgenic mice as well as in transgenic mice with AD-like pathology on a mixed genetic background. However, the cellular and molecular mechanisms underlying the beneficial effects of simvastatin on learning and memory remain elusive. The present study was undertaken to investigate the effect of acute simvastatin treatment on hippocampal long-term potentiation (LTP), a cellular model of learning and memory, in brain slices from C57BL/6 mice. Our results demonstrate that a prolonged in vitro simvastatin treatment for 2-4 hrs, but not a short-term 20-min exposure, significantly increases the magnitude of LTP at CA3-CA1 synapses without altering basal synaptic transmission or the paired-pulse facilitation ratio in hippocampal slices. Furthermore, we show that phosphorylation of Akt (protein kinase B) is increased significantly in the CA1 region following 2-hour treatment with simvastatin, and that inhibition of Akt phosphorylation suppresses the simvastatin-induced enhancement of LTP. These findings suggest activation of Akt as a molecular pathway for augmented hippocampal LTP by simvastatin treatment, and implicate enhancement of hippocampal LTP as a potential cellular mechanism underlying the beneficial effects of simvastatin on cognitive function. PMID

  3. Enhanced hippocampal long-term potentiation and fear memory in Btbd9 mutant mice.

    Directory of Open Access Journals (Sweden)

    Mark P DeAndrade

    Full Text Available Polymorphisms in BTBD9 have recently been associated with higher risk of restless legs syndrome (RLS, a neurological disorder characterized by uncomfortable sensations in the legs at rest that are relieved by movement. The BTBD9 protein contains a BTB/POZ domain and a BACK domain, but its function is unknown. To elucidate its function and potential role in the pathophysiology of RLS, we generated a line of mutant Btbd9 mice derived from a commercial gene-trap embryonic stem cell clone. Btbd9 is the mouse homolog of the human BTBD9. Proteins that contain a BTB/POZ domain have been reported to be associated with synaptic transmission and plasticity. We found that Btbd9 is naturally expressed in the hippocampus of our mutant mice, a region critical for learning and memory. As electrophysiological characteristics of CA3-CA1 synapses of the hippocampus are well characterized, we performed electrophysiological recordings in this region. The mutant mice showed normal input-output relationship, a significant impairment in pre-synaptic activity, and an enhanced long-term potentiation. We further performed an analysis of fear memory and found the mutant mice had an enhanced cued and contextual fear memory. To elucidate a possible molecular basis for these enhancements, we analyzed proteins that have been associated with synaptic plasticity. We found an elevated level of dynamin 1, an enzyme associated with endocytosis, in the mutant mice. These results suggest the first identified function of Btbd9 as being involved in regulating synaptic plasticity and memory. Recent studies have suggested that enhanced synaptic plasticity, analogous to what we have observed, in other regions of the brain could enhance sensory perception similar to what is seen in RLS patients. Further analyses of the mutant mice will help shine light on the function of BTBD9 and its role in RLS.

  4. Long-term visuo-gustatory appetitive and aversive conditioning potentiate human visual evoked potentials

    DEFF Research Database (Denmark)

    Christoffersen, Gert R.J.; Laugesen, Jakob L.; Møller, Per

    2017-01-01

    and aversive visuo-gustatory conditioning were studied with high density EEG-recordings focusing on late components in the visual evoked potentials (VEPs), specifically the N2-P3 waves. Unfamiliar images were paired with either a pleasant or an unpleasant juice and VEPs evoked by the images were compared...

  5. Long-Term Visuo-Gustatory Appetitive and Aversive Conditioning Potentiate Human Visual Evoked Potentials

    DEFF Research Database (Denmark)

    Christoffersen, Gert Rene Juul; Laugesen, Jakob Lund; Møller, Per

    2017-01-01

    and aversive visuo-gustatory conditioning were studied with high density EEG-recordings focusing on late components in the visual evoked potentials (VEPs), specifically the N2-P3 waves. Unfamiliar images were paired with either a pleasant or an unpleasant juice and VEPs evoked by the images were compared...

  6. Transplant professionals vary in the long-term medical risks they communicate to potential living kidney donors: an international survey.

    Science.gov (United States)

    Housawi, A A; Young, A; Boudville, N; Thiessen-Philbrook, H; Muirhead, N; Rehman, F; Parikh, C R; Al-Obaidli, A; El-Triki, A; Garg, A X

    2007-10-01

    Discussing long-term medical risks with potential living donors is a vital aspect of informed consent. We considered whether there are global practice variations in the information communicated to potential living kidney donors. Transplant professionals participated in a survey to determine which long-term risks are communicated to potential living kidney donors. Self-administered questionnaires were distributed in person and by electronic mail. We surveyed 203 practitioners from 119 cities in 35 different countries. Sixty-three percent of participants were nephrologists, and 27% were surgeons. Risks of hypertension, proteinuria or kidney failure requiring dialysis were frequently discussed (usually over 80% of practitioners discussed each medical condition). However, many practitioners do not believe these risks are increased after donation, with surgeons being less convinced of long-term sequelae compared with nephrologists (P professionals vary in the long-term risks they communicate to potential donors. Improving consensus will enhance decision-making, and emphasize best practices which maintain good, long-term donor health.

  7. The Potential for Long-Term Impacts of Extreme Events in the Front Range of Colorado

    Science.gov (United States)

    Losleben, M. V.; Caine, N.; Flanagan, C.; McKnight, D.; Monson, R.

    2005-12-01

    Extreme climatic events can trigger a cascade of events, or cause a step function change, in environmental systems that changes the balance of one or more environmental systems, such as bio-, geo-, hydro-, or chemical. They occur at all spatial, temporal, and intensity scales, some easily measurable, others more difficult. Moreover, not all extreme events have lasting environmental impacts. Whether they foreset the environmental clock or not is dependent on the particular system sensitivity in the geographic area of interest, as well as the type of event. Obviously, sufficient environmental data are necessary to detect and evaluate the potential of an extreme event to cause long-term change, and data scarcity is often a problem in the mountains of the western US. We look at the available data for five extreme events affecting the Front Range of the Colorado Rocky Mountains, and find a range of effects, suggesting that Front Range systems are more sensitive to drought than excessive moisture, and to events of longer duration. The events are defined by the surface climatic parameters of snow, rain, or temperature, and characterized by their synoptic atmospheric circulation pattern. Factors assessing the environmental impact include net ecosystem carbon dioxide exchange, alpine lake algal populations and hydrologic residence times, rock glacier temperatures, snowpack, and reservoir storage. The events are the April 15-16, 1921 record U.S. 24-hour snowfall at Silver Lake, CO, the 1981-86 upper elevation cold period in central Colorado and southern Wyoming, an anomalously high April and May 1995 snowfall, the 2002 drought, and the March 17-19, 2003 anomalously high snowfall in the South Platte and Arkansas River basins of Colorado.

  8. Corticosterone enhances the potency of ethanol against hippocampal long-term potentiation via local neurosteroid synthesis

    Directory of Open Access Journals (Sweden)

    Yukitoshi eIzumi

    2015-07-01

    Full Text Available Corticosterone is known to accumulate in brain after various stressors including alcohol intoxication. Just as severe alcohol intoxication is typically required to impair memory formation only high concentrations of ethanol (60mM acutely inhibit long-term potentiation (LTP, a cellular memory mechanism, in naïve hippocampal slices. This LTP inhibition involves synthesis of neurosteroids, including allopregnanolone, and appears to involve a form of cellular stress. In the CA1 region of rat hippocampal slices, we examined whether a lower concentration of ethanol (20 mM inhibits LTP in the presence of corticosterone, a stress-related modulator, and whether corticosterone stimulates local neurosteroid synthesis. Although low micromolar corticosterone alone did not inhibit LTP induction, we found that 20 mM ethanol inhibited LTP in the presence of corticosterone. At 20 mM, ethanol alone did not stimulate neurosteroid synthesis or inhibit LTP. LTP inhibition by corticosterone plus ethanol was blocked by finasteride, an inhibitor of 5α-reductase, suggesting a role for neurosteroid synthesis. We also found that corticosterone alone enhanced neurosteroid immunostaining in CA1 pyramidal neurons and that this immunostaining was further augmented by 20 mM ethanol. The enhanced neurosteroid staining was blocked by finasteride and the N-methyl-D-aspartate antagonist, 2-amino-5-phosphonovalerate (APV. These results indicate that corticosterone promotes neurosteroid synthesis in hippocampal pyramidal neurons and can participate in ethanol-mediated synaptic dysfunction even at moderate ethanol levels. These effects may contribute to the influence of stress on alcohol-induced cognitive impairment.

  9. Dual Influence of Endocannabinoids on Long-Term Potentiation of Synaptic Transmission

    Directory of Open Access Journals (Sweden)

    Armando Silva-Cruz

    2017-12-01

    Full Text Available Cannabinoid receptor 1 (CB1R is widely distributed in the central nervous system, in excitatory and inhibitory neurons, and in astrocytes. CB1R agonists impair cognition and prevent long-term potentiation (LTP of synaptic transmission, but the influence of endogenously formed cannabinoids (eCBs on hippocampal LTP remains ambiguous. Based on the knowledge that eCBs are released upon high frequency neuronal firing, we hypothesized that the influence of eCBs upon LTP could change according to the paradigm of LTP induction. We thus tested the influence of eCBs on hippocampal LTP using two θ-burst protocols that induce either a weak or a strong LTP. LTP induced by a weak-θ-burst protocol is facilitated while preventing the endogenous activation of CB1Rs. In contrast, the same procedures lead to inhibition of LTP induced by the strong-θ-burst protocol, suggestive of a facilitatory action of eCBs upon strong LTP. Accordingly, an inhibitor of the metabolism of the predominant eCB in the hippocampus, 2-arachidonoyl-glycerol (2-AG, facilitates strong LTP. The facilitatory action of endogenous CB1R activation does not require the activity of inhibitory A1 adenosine receptors, is not affected by inhibition of astrocytic metabolism, but involves inhibitory GABAergic transmission. The continuous activation of CB1Rs via exogenous cannabinoids, or by drugs known to prevent metabolism of the non-prevalent hippocampal eCB, anandamide, inhibited LTP. We conclude that endogenous activation of CB1Rs by physiologically formed eCBs exerts a fine-tune homeostatic control of LTP in the hippocampus, acting as a high-pass filter, therefore likely reducing the signal-to-noise ratio of synaptic strengthening.

  10. Opposing Actions of Chronic[Deta][superscript 9] Tetrahydrocannabinol and Cannabinoid Antagonists on Hippocampal Long-Term Potentiation

    Science.gov (United States)

    Hoffman, Alexander F.; Oz, Murat; Yang, Ruiqin; Lichtman, Aron H.; Lupica, Carl R.

    2007-01-01

    Memory deficits produced by marijuana arise partly via interaction of the psychoactive component, [Deta][superscript 9]-tetrahydrocannabinol ([Deta][superscript 9]-THC), with cannabinoid receptors in the hippocampus. Although cannabinoids acutely reduce glutamate release and block hippocampal long-term potentiation (LTP), a potential substrate for…

  11. Potentials of short term and long term cryopreserved sperm of the ...

    African Journals Online (AJOL)

    To service the growing demand for male African giant catfish (Clarias gariepinus) broodstock for aquaculture in Nigeria, and to conserve valuable genetic resources, we improved both short-term (in deep freezer at -35°C) and long-term cryopreservation (in liquid nitrogen at -296°C) of catfish sperm. Catfish sperm ...

  12. Worldwide impact of aerosol's time scale on the predicted long-term concentrating solar power potential.

    Science.gov (United States)

    Ruiz-Arias, Jose A; Gueymard, Christian A; Santos-Alamillos, Francisco J; Pozo-Vázquez, David

    2016-08-10

    Concentrating solar technologies, which are fuelled by the direct normal component of solar irradiance (DNI), are among the most promising solar technologies. Currently, the state-of the-art methods for DNI evaluation use datasets of aerosol optical depth (AOD) with only coarse (typically monthly) temporal resolution. Using daily AOD data from both site-specific observations at ground stations as well as gridded model estimates, a methodology is developed to evaluate how the calculated long-term DNI resource is affected by using AOD data averaged over periods from 1 to 30 days. It is demonstrated here that the use of monthly representations of AOD leads to systematic underestimations of the predicted long-term DNI up to 10% in some areas with high solar resource, which may result in detrimental consequences for the bankability of concentrating solar power projects. Recommendations for the use of either daily or monthly AOD data are provided on a geographical basis.

  13. Skilled but unaware of it: Occurrence and potential long-term effects of females' financial underconfidence

    OpenAIRE

    Bannier, Christina E.; Schwarz, Milena

    2017-01-01

    We find strong gender- and education-related differences in the distribution of actual and perceived financial sophistication: Whereas financial literacy rises in formal education, confidence increases in education for men but decreases for women. We show that the financial decisions of highly-educated men benefit strongly from this excess confidence, while the underconfidence of highly-educated women, in contrast, impairs their long-term financial planning.

  14. Long-term no-till and stover retention each decrease the global warming potential of irrigated continuous corn

    Science.gov (United States)

    Over the last 50 years, the most increase in cultivated land area globally has been due to a doubling of irrigated land. Long-term agronomic management impacts on soil organic carbon (SOC) stocks, soil greenhouse gas (GHG) emis-sions, and global warming potential (GWP) in irrigated systems, however,...

  15. Maternal sleep deprivation at different stages of pregnancy impairs the emotional and cognitive functions, and suppresses hippocampal long-term potentiation in the offspring rats.

    Science.gov (United States)

    Peng, Yan; Wang, Wei; Tan, Tao; He, Wenting; Dong, Zhifang; Wang, Yu Tian; Han, Huili

    2016-02-15

    Sleep deprivation during pregnancy is a serious public health problem as it can affect the health of pregnant women and newborns. However, it is not well studied whether sleep deprivation at different stages of pregnancy has similar effects on emotional and cognitive functions of the offspring, and if so, the potential cellular mechanisms also remain poorly understood. In the present study, the pregnant rats were subjected to sleep deprivation for 6 h per day by gentle handling during the first (gestational days 1-7), second (gestational days 8-14) and third trimester (gestational days 15-21) of pregnancy, respectively. The emotional and cognitive functions as well as hippocampal long-term potentiation (LTP) were tested in the offspring rats (postnatal days 42-56). The offspring displayed impaired hippocampal-dependent spatial learning and memory, and increased depressive- and anxiety-like behaviors. Quantification of BrdU-positive cells revealed that adult hippocampal neurogenesis was significantly reduced compared to control. Electrophysiological recording showed that maternal sleep deprivation impaired hippocampal CA1 LTP and reduced basal synaptic transmission, as reflected by a decrease in the frequency and amplitude of miniature excitatory postsynaptic current in the hippocampal CA1 pyramidal neurons. Taken together, these results suggest that maternal sleep deprivation at different stages of pregnancy disrupts the emotional and cognitive functions of the offspring that might be attributable to the suppression of hippocampal LTP and basal synaptic transmission.

  16. A systematic review of potential long-term effects of sport-related concussion

    Science.gov (United States)

    Gardner, Andrew J; Schneider, Kathryn J; Guskiewicz, Kevin M; Bailes, Julian; Cantu, Robert C; Castellani, Rudolph J; Turner, Michael; Jordan, Barry D; Randolph, Christopher; Dvořák, Jiří; Hayden, K. Alix; Tator, Charles H; McCrory, Paul; Iverson, Grant L

    2017-01-01

    Objective Systematic review of possible long-term effects of sports-related concussion in retired athletes. Data sources Ten electronic databases. Study selection Original research; incidence, risk factors or causation related to long-term mental health or neurological problems; individuals who have suffered a concussion; retired athletes as the subjects and possible long-term sequelae defined as >10 years after the injury. Data extraction Study population, exposure/outcome measures, clinical data, neurological examination findings, cognitive assessment, neuroimaging findings and neuropathology results. Risk of bias and level of evidence were evaluated by two authors. Results Following review of 3819 studies, 47 met inclusion criteria. Some former athletes have depression and cognitive deficits later in life, and there is an association between these deficits and multiple prior concussions. Former athletes are not at increased risk for death by suicide (two studies). Former high school American football players do not appear to be at increased risk for later life neurodegenerative diseases (two studies). Some retired professional American football players may be at increased risk for diminishment in cognitive functioning or mild cognitive impairment (several studies), and neurodegenerative diseases (one study). Neuroimaging studies show modest evidence of macrostructural, microstructural, functional and neurochemical changes in some athletes. Conclusion Multiple concussions appear to be a risk factor for cognitive impairment and mental health problems in some individuals. More research is needed to better understand the prevalence of chronic traumatic encephalopathy and other neurological conditions and diseases, and the extent to which they are related to concussions and/or repetitive neurotrauma sustained in sports. PMID:28455362

  17. A systematic review of potential long-term effects of sport-related concussion.

    Science.gov (United States)

    Manley, Geoff; Gardner, Andrew J; Schneider, Kathryn J; Guskiewicz, Kevin M; Bailes, Julian; Cantu, Robert C; Castellani, Rudolph J; Turner, Michael; Jordan, Barry D; Randolph, Christopher; Dvořák, Jiří; Hayden, K Alix; Tator, Charles H; McCrory, Paul; Iverson, Grant L

    2017-06-01

    Systematic review of possible long-term effects of sports-related concussion in retired athletes. Ten electronic databases. Original research; incidence, risk factors or causation related to long-term mental health or neurological problems; individuals who have suffered a concussion; retired athletes as the subjects and possible long-term sequelae defined as >10 years after the injury. Study population, exposure/outcome measures, clinical data, neurological examination findings, cognitive assessment, neuroimaging findings and neuropathology results. Risk of bias and level of evidence were evaluated by two authors. Following review of 3819 studies, 47 met inclusion criteria. Some former athletes have depression and cognitive deficits later in life, and there is an association between these deficits and multiple prior concussions. Former athletes are not at increased risk for death by suicide (two studies). Former high school American football players do not appear to be at increased risk for later life neurodegenerative diseases (two studies). Some retired professional American football players may be at increased risk for diminishment in cognitive functioning or mild cognitive impairment (several studies), and neurodegenerative diseases (one study). Neuroimaging studies show modest evidence of macrostructural, microstructural, functional and neurochemical changes in some athletes. Multiple concussions appear to be a risk factor for cognitive impairment and mental health problems in some individuals. More research is needed to better understand the prevalence of chronic traumatic encephalopathy and other neurological conditions and diseases, and the extent to which they are related to concussions and/or repetitive neurotrauma sustained in sports. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  18. Deletion of CB2 cannabinoid receptors reduces synaptic transmission and long-term potentiation in the mouse hippocampus.

    Science.gov (United States)

    Li, Yong; Kim, Jimok

    2016-03-01

    The effects of cannabinoids are mostly mediated by two types of cannabinoid receptors--CB1 receptors in the nervous system and CB2 receptors in the immune system. However, CB2 cannabinoid receptors have recently been discovered in the brain and also implicated in neurophysiological functions. The deletion of CB2 receptors in mice induces long-term memory deficits and schizophrenia-like behaviors, implying that endogenous activity of CB2 receptors might be involved in neuropsychiatric effects. Little is known about the cellular mechanisms by which physiological activation of CB2 receptors modulates neuronal functions. We aimed to determine how deletion of CB2 receptors in mice affects synaptic transmission and plasticity. Electrophysiological and morphological studies indicated that CB2 receptor knockout resulted in decreases in excitatory synaptic transmission, long-term potentiation, and dendritic spine density in the hippocampus. Our data imply that endogenous activity of CB2 receptors might contribute to the maintenance of synaptic functions and the expression of normal long-term potentiation. This study provides insights into the role of CB2 cannabinoid receptors in regulating cognitive functions such as long-term memory. © 2016 Wiley Periodicals, Inc.

  19. Sex, hormones and neurogenesis in the hippocampus: hormonal modulation of neurogenesis and potential functional implications.

    Science.gov (United States)

    Galea, L A M; Wainwright, S R; Roes, M M; Duarte-Guterman, P; Chow, C; Hamson, D K

    2013-11-01

    The hippocampus is an area of the brain that undergoes dramatic plasticity in response to experience and hormone exposure. The hippocampus retains the ability to produce new neurones in most mammalian species and is a structure that is targeted in a number of neurodegenerative and neuropsychiatric diseases, many of which are influenced by both sex and sex hormone exposure. Intriguingly, gonadal and adrenal hormones affect the structure and function of the hippocampus differently in males and females. Adult neurogenesis in the hippocampus is regulated by both gonadal and adrenal hormones in a sex- and experience-dependent way. Sex differences in the effects of steroid hormones to modulate hippocampal plasticity should not be completely unexpected because the physiology of males and females is different, with the most notable difference being that females gestate and nurse the offspring. Furthermore, reproductive experience (i.e. pregnancy and mothering) results in permanent changes to the maternal brain, including the hippocampus. This review outlines the ability of gonadal and stress hormones to modulate multiple aspects of neurogenesis (cell proliferation and cell survival) in both male and female rodents. The function of adult neurogenesis in the hippocampus is linked to spatial memory and depression, and the present review provides early evidence of the functional links between the hormonal modulation of neurogenesis that may contribute to the regulation of cognition and stress. © 2013 British Society for Neuroendocrinology.

  20. Spectral model for long-term computation of thermodynamics and potential evaporation in shallow wetlands

    Science.gov (United States)

    de la Fuente, Alberto; Meruane, Carolina

    2017-09-01

    Altiplanic wetlands are unique ecosystems located in the elevated plateaus of Chile, Argentina, Peru, and Bolivia. These ecosystems are under threat due to changes in land use, groundwater extractions, and climate change that will modify the water balance through changes in precipitation and evaporation rates. Long-term prediction of the fate of aquatic ecosystems imposes computational constraints that make finding a solution impossible in some cases. In this article, we present a spectral model for long-term simulations of the thermodynamics of shallow wetlands in the limit case when the water depth tends to zero. This spectral model solves for water and sediment temperature, as well as heat, momentum, and mass exchanged with the atmosphere. The parameters of the model (water depth, thermal properties of the sediments, and surface albedo) and the atmospheric downscaling were calibrated using the MODIS product of the land surface temperature. Moreover, the performance of the daily evaporation rates predicted by the model was evaluated against daily pan evaporation data measured between 1964 and 2012. The spectral model was able to correctly represent both seasonal fluctuation and climatic trends observed in daily evaporation rates. It is concluded that the spectral model presented in this article is a suitable tool for assessing the global climate change effects on shallow wetlands whose thermodynamics is forced by heat exchanges with the atmosphere and modulated by the heat-reservoir role of the sediments.

  1. Postfatigue potentiation of the paralyzed soleus muscle: evidence for adaptation with long-term electrical stimulation training

    OpenAIRE

    Shields, Richard K.; Dudley-Javoroski, Shauna; Littmann, Andrew E.

    2006-01-01

    Understanding the torque output behavior of paralyzed muscle has important implications for the use of functional neuromuscular electrical stimulation systems. Postfatigue potentiation is an augmentation of peak muscle torque during repetitive activation after a fatigue protocol. The purposes of this study were 1) to quantify postfatigue potentiation in the acutely and chronically paralyzed soleus and 2) to determine the effect of long-term soleus electrical stimulation training on the potent...

  2. Potentials for energy savings and long term energy demands for Croatian households sector

    DEFF Research Database (Denmark)

    Pukšec, Tomislav; Mathiesen, Brian Vad; Duic, Neven

    2013-01-01

    demand in the future, based on careful and rational energy planning. Different financial, legal and technological mechanisms can lead to significant savings in the households sector which also leads to lesser greenhouse gas emissions and lower Croatian dependence on foreign fossil fuels....... relevant. In order to plan future energy systems it is important to know future possibilities and needs regarding energy demand for different sectors. Through this paper long term energy demand projections for Croatian households sector will be shown with a special emphasis on different mechanisms, both...... financial, legal but also technological that will influence future energy demand scenarios. It is important to see how these mechanisms influence, positive or negative, on future energy demand and which mechanism would be most influential. Energy demand predictions in this paper are based upon bottom...

  3. Potentials for energy savings and long term energy demands for Croatian households sector

    DEFF Research Database (Denmark)

    Pukšec, Tomislav; Mathiesen, Brian Vad; Duic, Neven

    2011-01-01

    demand in the future, based on careful and rational energy planning. Different financial, legal and technological mechanisms can lead to significant savings in the households sector which also leads to lesser greenhouse gas emissions and lower Croatian dependence on foreign fossil fuels....... relevant. In order to plan future energy systems it is important to know future possibilities and needs regarding energy demand for different sectors. Through this paper long term energy demand projections for Croatian households sector will be shown with a special emphasis on different mechanisms, both...... financial, legal but also technological that will influence future energy demand scenarios. It is important to see how these mechanisms influence, positive or negative, on future energy demand and which mechanism would be most influential. Energy demand predictions in this paper are based upon bottom...

  4. Deliberating and communicating the potential of fusion power based on long-term foresight knowledge

    Energy Technology Data Exchange (ETDEWEB)

    Laes, Erik [SCK-CEN - Belgian Nuclear Research Centre, Boeretang 200, 2400 Mol (Belgium)], E-mail: erik.laes@sckcen.be; Bombaerts, Gunter [SCK-CEN - Belgian Nuclear Research Centre, Boeretang 200, 2400 Mol (Belgium); UGent (Ghent University) (Belgium)

    2007-10-15

    The main aim of this contribution is to provide guidance (in terms of quality criteria) for setting up foresight exercises as a platform for discussion and communication of the benefits and drawbacks of fusion with a broad range of stakeholders. At the same time, we explore conditions that might enhance the resonance of such foresight exercises in the policy sphere. In order to address this dual aim, we first introduce a philosophical framework called 'constructivism'. Next, we give a constructivist reading of scientific foresight as a combined scientific-political practice and point out some of the main points of interest regarding the relationship between foresight knowledge and policy. We illustrate these points of interest with practical case-study examples. Finally, we draw upon our theoretical and case-study research to propose some points of particular interest for the fusion community wishing to develop long-term energy scenarios.

  5. Wnt Signaling Is Required for Long-Term Memory Formation

    OpenAIRE

    Tan, Ying; Yu, Dinghui; Busto, Germain U.; Wilson, Curtis; Davis, Ronald L.

    2013-01-01

    Wnt signaling regulates synaptic plasticity and neurogenesis in the adult nervous system, suggesting a potential role in behavioral processes. Here, we probed the requirement for Wnt signaling during olfactory memory formation in Drosophila using an inducible RNA interference approach. Interfering with β-catenin expression in the adult mushroom body neurons specifically impaired long-term memory without altering short-term memory. The impairment was reversible, rescued with expression of a wi...

  6. Net sulfur mineralization potential in Swedish arable soils in relation to long-term treatment history and soil properties

    DEFF Research Database (Denmark)

    Boye, Kristin; Nilsson, S Ingvar; Eriksen, Jørgen

    2009-01-01

    The long-term treatment effect (since 1957-1966) of farmyard manure (FYM) application compared with crop residue incorporation was investigated in five soils (sandy loam to silty clay) with regards to the net sulfur (S) mineralization potential. An open incubation technique was used to determine ...... to SAccMin. Conclusively, different treatment histories influenced the quality (e.g., chemical composition) and cycling rate of the organic S pool, rather than its size...

  7. Long-term persistence and bacterial transformation potential of transplastomic plant DNA in soil.

    Science.gov (United States)

    Pontiroli, Alessandra; Ceccherini, Maria-Teresa; Poté, John; Wildi, Walter; Kay, Elisabeth; Nannipieri, Paolo; Vogel, Timothy M; Simonet, Pascal; Monier, Jean-Michel

    2010-06-01

    The long-term physical persistence and biological activity of transplastomic plant DNA (transgenes contained in the chloroplast genome) either purified and added to soil or naturally released by decaying tobacco leaves in soil was determined. Soil microcosms were amended with transplastomic tobacco leaves or purified plant DNA and incubated for up to 4 years. Total DNA was extracted from soil and the number of transgenes (aadA, which confers resistance to both spectinomycin and streptomycin) was quantified by quantitative PCR. The biological activity of these transgenes was assessed by transformation in the bacterial strain Acinetobacter sp. BD413(pBAB2) in vitro. While the proportion of transgenes recovered increased with the increasing amount of transplastomic DNA added, plant DNA was rapidly degraded over time. The number of transgenes recovered decreased about 10,000 fold within 2 weeks. Data reveal, however, that a small fraction of the plant DNA escaped degradation. Transgene sequences were still detected after 4 years and transformation assays showed that extracted DNA remained biologically active and could still transform competent cells of Acinetobacter sp. BD413(pBAB2). The approach presented here quantified the number of transgenes (based on quantitative PCR of 50% of the gene) released and persisting in the environment over time and provided new insights into the fate of transgenic plant DNA in soil. 2010 Elsevier Masson SAS. All rights reserved.

  8. Sex Differences in Long-Term Potentiation at Temporoammonic-CA1 Synapses: Potential Implications for Memory Consolidation.

    Directory of Open Access Journals (Sweden)

    Xiaoqiang Qi

    Full Text Available Sex differences in spatial memory have long been observed in humans, non-human primates and rodents, but the underlying cellular and molecular mechanisms responsible for these differences remain obscure. In the present study we found that adolescent male rats outperformed female rats in 7 d and 28 d retention probes, but not in learning trials and immediate probes, in the Morris water maze task. Male rats also had larger long-term potentiation (LTP at hippocampal temproammonic-CA1 (TA-CA1 synapses, which have been implicated to play a key role in place field and memory consolidation, when protocols designed to elicit late-stage LTP (LLTP were used. Interestingly, the ratio of evoked AMPA/NMDA currents was found to be smaller at TA-CA1 synapses in male rats compared to female rats. Protein biotinylation experiments showed that male rats expressed more surface GluN1 receptors in hippocampal CA1 stratum lacunosum-moleculare (SLM than female rats, although GluA1 expression was also slightly higher in male rats. Taken together, our results suggest that differences in the expression of AMPA and NMDA receptors may affect LTP expression at TA-CA1 synapses in adolescent male and female rats, and thus possibly contribute to the observed sex difference in spatial memory.

  9. Potential role of plasma myeloperoxidase level in predicting long-term outcome of acute myocardial infarction.

    Science.gov (United States)

    Kaya, Mehmet Gungor; Yalcin, Ridvan; Okyay, Kaan; Poyraz, Fatih; Bayraktar, Nilufer; Pasaoglu, Hatice; Boyaci, Bulent; Cengel, Atiye

    2012-01-01

    We investigated the prognostic importance of plasma myeloperoxidase levels in patients with ST-elevation myocardial infarction (STEMI) at long-term follow-up, and we analyzed the correlations between plasma myeloperoxidase levels and other biochemical values. We evaluated 73 consecutive patients (56 men; mean age, 56 ± 11 yr) diagnosed with acute STEMI and 46 age- and sex-matched healthy control participants. Patients were divided into 2 groups according to the median myeloperoxidase level (Group 1: plasma myeloperoxidase ≤ 68 ng/mL; and Group 2: plasma myeloperoxidase > 68 ng/mL). Patients were monitored for the occurrence of major adverse cardiovascular events (MACE), which were defined as cardiac death; reinfarction; new hospital admission for angina; heart failure; and revascularization procedures. The mean follow-up period was 25 ± 16 months. Plasma myeloperoxidase levels were higher in STEMI patients than in control participants (82 ± 34 vs 20 ± 12 ng/mL; P = 0.001). Composite MACE occurred in 12 patients with high myeloperoxidase levels (33%) and in 4 patients with low myeloperoxidase levels (11%) (P = 0.02). The incidences of nonfatal recurrent myocardial infarction and verified cardiac death were higher in the high-myeloperoxidase group. In multivariate analysis, high plasma myeloperoxidase levels were independent predictors of MACE (odds ratio = 3.843; <95% confidence interval, 1.625-6.563; P = 0.003). High plasma myeloperoxidase levels identify patients with a worse prognosis after acute STEMI at 2-year follow-up. Evaluation of plasma myeloperoxidase levels might be useful in determining patients at high risk of death and MACE who can benefit from further aggressive treatment and closer follow-up.

  10. Elevated NMDA receptor levels and enhanced postsynaptic long-term potentiation induced by prenatal exposure to valproic acid

    DEFF Research Database (Denmark)

    Rinaldi, Tania; Kulangara, Karina; Antoniello, Katia

    2007-01-01

    as the commonly linked kinase calcium/calmodulin-dependent protein kinase II. Synaptic plasticity experiments between pairs of pyramidal neurons revealed an augmented postsynaptic form of long-term potentiation. These results indicate that VPA significantly enhances NMDA receptor-mediated transmission and causes...... increased plasticity in the neocortex. Enhanced plasticity introduces a surprising perspective to the potential molecular and synaptic mechanisms involved in children prenatally exposed to VPA.......Valproic acid (VPA) is a powerful teratogen causing birth defects in humans, including autism spectrum disorder (ASD), if exposure occurs during the first trimester of embryogenesis. Learning and memory alterations are common symptoms of ASD, but underlying molecular and synaptic alterations remain...

  11. Reducing soil phosphorus fertility brings potential long-term environmental gains: A UK analysis

    Science.gov (United States)

    Withers, Paul J. A.; Hodgkinson, Robin A.; Rollett, Alison; Dyer, Chris; Dils, Rachael; Collins, Adrian L.; Bilsborrow, Paul E.; Bailey, Geoff; Sylvester-Bradley, Roger

    2017-05-01

    Soil phosphorus (P) fertility arising from historic P inputs is a major driver of P mobilisation in agricultural runoff and increases the risk of aquatic eutrophication. To determine the environmental benefit of lowering soil P fertility, a meta-analysis of the relationship between soil test P (measured as Olsen-P) and P concentrations in agricultural drainflow and surface runoff in mostly UK soils was undertaken in relation to current eutrophication control targets (30-35 µg P L-1). At agronomic-optimum Olsen P (16-25 mg kg-1), concentrations of soluble reactive P (SRP), total dissolved P (TDP), total P (TP) and sediment-P (SS-P) in runoff were predicted by linear regression analysis to vary between 24 and 183 µg L-1, 38 and 315 µg L-1, 0.2 and 9.6 mg L-1, and 0.31 and 3.2 g kg-1, respectively. Concentrations of SRP and TDP in runoff were much more sensitive to changes in Olsen-P than were TP and SS-P concentrations, which confirms that separate strategies are required for mitigating the mobilisation of dissolved and particulate P forms. As the main driver of eutrophication, SRP concentrations in runoff were reduced on average by 60 µg L-1 (71%) by lowering soil Olsen-P from optimum (25 mg kg-1) to 10 mg kg-1. At Olsen-P concentrations below 12 mg kg-1, dissolved hydrolysable P (largely organic) became the dominant form of soluble P transported. We concluded that maintaining agronomic-optimum Olsen-P could still pose a eutrophication risk, and that a greater research focus on reducing critical soil test P through innovative agro-engineering of soils, crops and fertilisers would give long-term benefits in reducing the endemic eutrophication risk arising from legacy soil P. Soil P testing should become compulsory in priority catchments suffering, or sensitive to, eutrophication to ensure soil P reserves are fully accounted for as part of good fertiliser and manure management.

  12. Ischemic long-term-potentiation (iLTP): perspectives to set the threshold of neural plasticity toward therapy.

    Science.gov (United States)

    Lenz, Maximilian; Vlachos, Andreas; Maggio, Nicola

    2015-10-01

    The precise role of neural plasticity under pathological conditions remains not well understood. It appears to be well accepted, however, that changes in the ability of neurons to express plasticity accompany neurological diseases. Here, we discuss recent experimental evidence, which suggests that synaptic plasticity induced by a pathological stimulus, i.e., ischemic long-term-potentiation (iLTP) of excitatory synapses, could play an important role for post-stroke recovery by influencing the post-lesional reorganization of surviving neuronal networks.

  13. Long-term outcome of primary Papillary Urothelial Neoplasm of Low Malignant Potential (PUNLMP) including PUNLMP with inverted growth.

    Science.gov (United States)

    Maxwell, Jay P; Wang, Cheng; Wiebe, Nicholas; Yilmaz, Asli; Trpkov, Kiril

    2015-03-13

    Few larger studies have evaluated the long-term outcome after a diagnosis of papillary urothelial neoplasm of low malignant potential (PUNLMP), demonstrating a broad range of recurrence and progression rates. Additionally, no study has addressed the outcome of PUNLMP exhibiting inverted growth. We evaluated the long term clinical outcome of primary papillary urothelial neoplasm of low malignant potential (PUNLMP), including PUNLMP with inverted growth in a large single center study. We evaluated 189 primary PUNLMP (177 exophytic, 12 inverted), diagnosed from January 1, 2000 to December 31, 2009, in a centralized uropathology practice. We excluded PUNLMP diagnosed after a previous or with a concurrent urothelial neoplasm. Recurrence was defined as any subsequent urothelial neoplasm, regardless of the grade. Progression was defined as any subsequent higher-grade or invasive urothelial neoplasm. Recurrence and progression were established only if documented on a subsequent biopsy. Descriptive statistical analysis was performed using Microsof Excel software package. The location of PUNLMP included bladder (187) and renal pelvis and ureter (1 each). After a median follow-up of 61 months (range, 9-128 months), 20.1% patients developed a recurrence. Recurrence with PUNLMP only was found in 9% of patients. Subsequent low-grade urothelial carcinoma was documented in 9.5% of patients. Progression to high-grade urothelial carcinoma was found in 1.6% patients (1% with muscle invasion). No patients with recurrent PUNLMP or subsequent low-grade carcinoma demonstrated invasion. All patients with PUNLMP exhibiting an inverted growth had no recurrence or progression on follow-up. In this study, primary PUNLMP recurred primarily either as PUNLMP or low grade urothelial carcinoma. Primary PUNLMP rarely progressed to high grade or invasive carcinoma on long term follow-up. No recurrence or progression was documented on follow-up for PUNLMP that demonstrated exclusively inverted

  14. Regional prediction of long-term landfill gas to energy potential.

    Science.gov (United States)

    Amini, Hamid R; Reinhart, Debra R

    2011-01-01

    Quantifying landfill gas to energy (LFGTE) potential as a source of renewable energy is difficult due to the challenges involved in modeling landfill gas (LFG) generation. In this paper a methodology is presented to estimate LFGTE potential on a regional scale over a 25-year timeframe with consideration of modeling uncertainties. The methodology was demonstrated for the US state of Florida, as a case study, and showed that Florida could increase the annual LFGTE production by more than threefold by 2035 through installation of LFGTE facilities at all landfills. The estimated electricity production potential from Florida LFG is equivalent to removing some 70 million vehicles from highways or replacing over 800 million barrels of oil consumption during the 2010-2035 timeframe. Diverting food waste could significantly reduce fugitive LFG emissions, while having minimal effect on the LFGTE potential; whereas, achieving high diversion goals through increased recycling will result in reduced uncollected LFG and significant loss of energy production potential which may be offset by energy savings from material recovery and reuse. Estimates showed that the power density for Florida LFGTE production could reach as high as 10 Wm(-2) with optimized landfill operation and energy production practices. The environmental benefits from increased lifetime LFG collection efficiencies magnify the value of LFGTE projects. Copyright © 2011 Elsevier Ltd. All rights reserved.

  15. Age-related synaptic dysfunction in Tg2576 mice starts as a failure in early long-term potentiation which develops into a full abolishment of late long-term potentiation.

    Science.gov (United States)

    Fernández-Fernández, Diego; Dorner-Ciossek, Cornelia; Kroker, Katja S; Rosenbrock, Holger

    2016-03-01

    Tg2576 mice are widely used to study amyloid-dependent synaptic dysfunction related to Alzheimer's disease. However, conflicting data have been reported for these mice with regard to basal transmission as well as the in vitro correlate of memory, long-term potentiation (LTP). Some studies show clear impairments, whereas others report no deficiency. The present study uses hippocampal slices from 3-, 10-, and 15-month-old wild-type (WT) and Tg2576 mice to evaluate synaptic function in each group, including experiments to investigate basal synaptic transmission, short- and long-term plasticity by inducing paired-pulse facilitation, and both early and late LTP. We show that synaptic function remains intact in hippocampal slices from Tg2576 mice at 3 months of age. However, both early and late LTP decline progressively during aging in these mice. This deterioration of synaptic plasticity starts affecting early LTP, ultimately leading to the abolishment of both forms of LTP in 15-month-old animals. In comparison, WT littermates display normal synaptic parameters during aging. Additional pharmacological investigation into the involvement of NMDA receptors and L-type voltage-gated calcium channels in LTP suggests a distinct mechanism of induction among age groups, demonstrating that both early and late LTP are differentially affected by these channels in Tg2576 mice during aging. © 2015 Wiley Periodicals, Inc.

  16. Ampakines promote spine actin polymerization, long-term potentiation, and learning in a mouse model of Angelman syndrome.

    Science.gov (United States)

    Baudry, Michel; Kramar, Eniko; Xu, Xiaobo; Zadran, Homera; Moreno, Stephanie; Lynch, Gary; Gall, Christine; Bi, Xiaoning

    2012-08-01

    Angelman syndrome (AS) is a neurodevelopmental disorder largely due to abnormal maternal expression of the UBE3A gene leading to the deletion of E6-associated protein. AS subjects have severe cognitive impairments for which there are no therapeutic interventions. Mouse models (knockouts of the maternal Ube3a gene: 'AS mice') of the disorder have substantial deficits in long-term potentiation (LTP) and learning. Here we report a clinically plausible pharmacological treatment that ameliorates both deficits. AS mice were injected ip twice daily for 5 days with vehicle or the ampakine CX929; drugs of this type enhance fast EPSCs by positively modulating AMPA receptors. Theta burst stimulation (TBS) produced a normal enhancement of field EPSPs in hippocampal slices prepared from vehicle-treated AS mice but LTP decreased steadily to baseline; however, LTP in slices from ampakine-treated AS mice stabilized at levels found in wild-type controls. TBS-induced actin polymerization within dendritic spines, an essential event for stabilizing LTP, was severely impaired in slices from vehicle-treated AS mice but not in those from ampakine-treated AS mice. Long-term memory scores in a fear conditioning paradigm were reduced by 50% in vehicle-treated AS mice but were comparable to values for littermate controls in the ampakine-treated AS mice. We propose that AS is associated with a profound defect in activity-driven spine cytoskeletal reorganization, resulting in a loss of the synaptic plasticity required for the encoding of long-term memory. Notably, the spine abnormality along with the LTP and learning impairments can be reduced by a minimally invasive drug treatment. Copyright © 2012 Elsevier Inc. All rights reserved.

  17. Long-term trend in potential vorticity intrusion events over the Pacific Ocean: Role of global mean temperature rise

    Science.gov (United States)

    Nath, Debashis; Chen, Wen; Lan, Xiaoqing

    2017-10-01

    In this study, we examine a long-term increasing trend in subtropical potential vorticity (PV) intrusion events over the Pacific Ocean in relation to the global mean temperature rise, based on multiple reanalysis datasets. The frequency of the PV intrusions is closely related to the upper-tropospheric equatorial westerly duct and the subtropical jet (STJ). An overall strengthening of the westerly duct and weakening of the STJ are found to be driven by the warming-induced strengthening of Walker circulation and regional changes in Hadley circulation on multi-decadal timescale, leading to an increase in the PV intrusion frequency over the tropics. The results are robust in all datasets. The multi-decadal strengthening in the Pacific Walker circulation is consistent with the global mean temperature rise. In this way, the PV intrusions are correlated with the warming related global mean temperuate rise. When the interannual variability of ENSO is removed from the intrusion time series, the long-term trend in PV intrusions due to external forcing associated with anthropogenic warming (global mean temperature rise) becomes clearer. The link between the global mean temperature rise and intrusion frequency is further verified by performing a correlation analysis between the two. The significant (> 95%) correlation coefficient is 0.85, 0.94, 0.84, 0.83, and 0.84 for ERA-40, ERA-Interim, NCEP-NCAR, JRA-55, and JRA-25, respectively. This unequivocally indicates that the global mean temperature rise can explain around 69%-88% of the variance related to the long-term increase in PV intrusion frequency over the Pacific Ocean.

  18. D-Serine rescues the deficits of hippocampal long-term potentiation and learning and memory induced by sodium fluoroacetate.

    Science.gov (United States)

    Han, Huili; Peng, Yan; Dong, Zhifang

    2015-06-01

    It is well known that bidirectional glia-neuron interactions play important roles in the neurophysiological and neuropathological processes. It is reported that impairing glial functions with sodium fluoroacetate (FAC) impaired hippocampal long-term depression (LTD) and spatial memory retrieval. However, it remains unknown whether FAC impairs hippocampal long-term potentiation (LTP) and learning and/or memory, and if so, whether pharmacological treatment with exogenous d-serine can recuse the impairment. Here, we reported that systemic administration of FAC (3mg/kg, i.p.) before training resulted in dramatic impairments of spatial learning and memory in water maze and fear memory in contextual fear conditioning. Furthermore, the behavioral deficits were accompanied by impaired LTP induction in the hippocampal CA1 area of brain slices. More importantly, exogenous d-serine treatment succeeded in recusing the deficits of hippocampal LTP and learning and memory induced by FAC. Together, these results suggest that astrocytic d-serine may be essential for hippocampal synaptic plasticity and memory, and that alteration of its levels may be relevant to the induction and potentially treatment of psychiatric and neurological disorders. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Chronic treatment with ginsenoside Rg1 promotes memory and hippocampal long-term potentiation in middle-aged mice.

    Science.gov (United States)

    Zhu, G; Wang, Y; Li, J; Wang, J

    2015-04-30

    Ginseng serves as a potential candidate for the treatment of aging-related memory decline or memory loss. However, the related mechanism is not fully understood. In this study, we applied an intraperitoneal injection of ginsenoside Rg1, an active compound from ginseng in middle-aged mice and detected memory improvement and the underlying mechanisms. Our results showed that a period of 30-day administration of ginsenoside Rg1 enhanced long-term memory in the middle-aged animals. Consistent with the memory improvement, ginsenoside Rg1 administration facilitated weak theta-burst stimulation (TBS)-induced long-term potentiation (LTP) in acute hippocampal slices from middle-aged animals. Ginsenoside Rg1 administration increased the dendritic apical spine numbers and area in the CA1 region. In addition, ginsenoside Rg1 administration up-regulated the expression of hippocampal p-AKT, brain-derived neurotrophic factor (BDNF), proBDNF and glutamate receptor 1 (GluR1), but not p-ERK. Interestingly, the phosphatase and tensin homolog deleted on chromosome ten (PTEN) inhibitor (bpV) mimicked the ginsenoside Rg1 effects, including increasing p-AKT expression, promoting hippocampal basal synaptic transmission, LTP and memory. Taken together, our data suggest that ginsenoside Rg1 treatment improves memory in middle-aged mice possibly through regulating the PI3K/AKT pathway, altering apical spines and facilitating hippocampal LTP. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  20. Long Term Corrosion Potential and Corrosion Rate of Creviced Alloy 22 in Chloride Plus Nitrate Brines

    Energy Technology Data Exchange (ETDEWEB)

    Evans, K J; Stuart, M L; Etien, R A; Hust, G A; Estill, J C; Rebak, R B

    2005-11-05

    Alloy 22 is a nickel base alloy highly resistant to all forms of corrosion. In conditions where tight crevices exist in hot chloride containing solutions and at anodic potentials, Alloy 22 may suffer crevice corrosion, a form of localized attack. The occurrence (or not) of crevice corrosion in a given environment (e.g. salt concentration and temperature), is governed by the values of the critical potential (E{sub crit}) for crevice corrosion and the corrosion potential (E{sub corr}) that the alloy may establish in the studied environment. If E{sub corr} is equal or higher than E{sub crit}, crevice corrosion may be expected. In addition, it is generally accepted that as Alloy 22 becomes passive in a certain environment, its E{sub corr} increases and its corrosion rate (CR) decreases. This paper discusses the evolution of E{sub corr} and corrosion rate (CR) of creviced Alloy 22 specimens in six different mixtures of sodium chloride (NaCl) and potassium nitrate (KNO{sub 3}) at 100 C. The effect of immersion time on the value of E{sub crit} was also determined. Two types of specimens were used, polished as-welded (ASW) and as-welded plus solution heat-treated (ASW+SHT). The latter contained the black annealing oxide film on the surface. Results show that, as the immersion time increases, E{sub corr} increased and the CR decreased. Even for highly concentrated brine solutions at 100 C the CR was < 30 nm/year after more than 250 days immersion. Some of the exposed specimens (mainly the SHT specimens) suffered crevice corrosion at the open circuit potential in the naturally aerated brines. Immersion times of over 250 days did not reduce the resistance of Alloy 22 to localized corrosion.

  1. Long-term potentiation in hippocampal oriens interneurons: postsynaptic induction, presynaptic expression and evaluation of candidate retrograde factors

    Science.gov (United States)

    Nicholson, Elizabeth; Kullmann, Dimitri M.

    2014-01-01

    Several types of hippocampal interneurons exhibit a form of long-term potentiation (LTP) that depends on Ca2+-permeable AMPA receptors and group I metabotropic glutamate receptors. Several sources of evidence point to a presynaptic locus of LTP maintenance. The retrograde factor that triggers the expression of LTP remains unidentified. Here, we show that trains of action potentials in putative oriens-lacunosum-moleculare interneurons of the mouse CA1 region can induce long-lasting potentiation of stimulus-evoked excitatory postsynaptic currents that mimics LTP elicited by high-frequency afferent stimulation. We further report that blockers of nitric oxide production or TRPV1 receptors failed to prevent LTP induction. The present results add to the evidence that retrograde signalling underlies N-methyl-d-aspartate (NMDA) receptor-independent LTP in oriens interneurons, mediated by an unidentified factor. PMID:24298136

  2. [Potential analysis for research on Advanced Practice Nursing (APN) for persons with dementia living in long-term care facilities].

    Science.gov (United States)

    Koch, Sabine; Fleischer, Steffen

    2014-01-01

    The nursing Minimum Data Set 3.0 (MDS 3.0) and other nursing quality indices summarise relevant health and nursing outcomes for long-term care that are recommended as quality measures. These are measures like "Percent of High-Risk Residents with Pressure Ulcers", "Percent of Low-Risk Residents Who Lose Control of Their Bowels or Bladder", "Percent of Residents Experiencing One or More Falls with Major Injury", "Percent of Residents Who Lose Too Much Weight" etc. Analyses of healthcare data in Germany showed a substantial higher risk for negative outcomes in the long-term care setting in persons with dementia compared to persons without dementia. There already exist evidence-based guidelines and recommendations for most of the quality measures and underlying health problems (e.g., the German "Expertenstandards in der Pflege"). Implementation and translation of evidence have not been systematically researched yet, and there is uncertainty about structures and processes that support implementation and eventually lead to improved nursing outcomes in people with dementia in long-term care. Studies showed a potential benefit of master-level geriatric advanced practice nurses (GAPNs) concerning the implementation of evidence-based guidelines. This corresponds to the expectation that academic nursing staff positively influences research utilisation in practice. A systematic review identified four controlled trials that evaluated the effectiveness of GAPN on select quality measures. Both the internal and external validity of the trials require a thorough investigation into the intervention before translation and effectiveness research in Germany can be recommended. In accordance with national and international recommendations on the development and clinical evaluation of complex interventions, we recommend a multistage model. Such a model comprises the conceptualisation and adaptation of the original intervention. In this way, the original concept of a GAPN has to be

  3. Human Onchocerciasis: Modelling the Potential Long-term Consequences of a Vaccination Programme.

    Directory of Open Access Journals (Sweden)

    Hugo C Turner

    Full Text Available Currently, the predominant onchocerciasis control strategy in Africa is annual mass drug administration (MDA with ivermectin. However, there is a consensus among the global health community, supported by mathematical modelling, that onchocerciasis in Africa will not be eliminated within proposed time frameworks in all endemic foci with only annual MDA, and novel and alternative strategies are urgently needed. Furthermore, use of MDA with ivermectin is already compromised in large areas of central Africa co-endemic with Loa loa, and there are areas where suboptimal or atypical responses to ivermectin have been documented. An onchocerciasis vaccine would be highly advantageous in these areas.We used a previously developed onchocerciasis transmission model (EPIONCHO to investigate the impact of vaccination in areas where loiasis and onchocerciasis are co-endemic and ivermectin is contraindicated. We also explore the potential influence of a vaccination programme on infection resurgence in areas where local elimination has been successfully achieved. Based on the age range included in the Expanded Programme on Immunization (EPI, the vaccine was assumed to target 1 to 5 year olds. Our modelling results indicate that the deployment of an onchocerciasis vaccine would have a beneficial impact in onchocerciasis-loiasis co-endemic areas, markedly reducing microfilarial load in the young (under 20 yr age groups.An onchocerciasis prophylactic vaccine would reduce the onchocerciasis disease burden in populations where ivermectin cannot be administered safely. Moreover, a vaccine could substantially decrease the chance of re-emergence of Onchocerca volvulus infection in areas where it is deemed that MDA with ivermectin can be stopped. Therefore, a vaccine would protect the substantial investments made by present and past onchocerciasis control programmes, decreasing the chance of disease recrudescence and offering an important additional tool to mitigate the

  4. Analyzing long-term correlated stochastic processes by means of recurrence networks: potentials and pitfalls.

    Science.gov (United States)

    Zou, Yong; Donner, Reik V; Kurths, Jürgen

    2015-02-01

    Long-range correlated processes are ubiquitous, ranging from climate variables to financial time series. One paradigmatic example for such processes is fractional Brownian motion (fBm). In this work, we highlight the potentials and conceptual as well as practical limitations when applying the recently proposed recurrence network (RN) approach to fBm and related stochastic processes. In particular, we demonstrate that the results of a previous application of RN analysis to fBm [Liu et al. Phys. Rev. E 89, 032814 (2014)] are mainly due to an inappropriate treatment disregarding the intrinsic nonstationarity of such processes. Complementarily, we analyze some RN properties of the closely related stationary fractional Gaussian noise (fGn) processes and find that the resulting network properties are well-defined and behave as one would expect from basic conceptual considerations. Our results demonstrate that RN analysis can indeed provide meaningful results for stationary stochastic processes, given a proper selection of its intrinsic methodological parameters, whereas it is prone to fail to uniquely retrieve RN properties for nonstationary stochastic processes like fBm.

  5. Potential long-term consequences of fad diets on health, cancer, and longevity: lessons learned from model organism studies.

    Science.gov (United States)

    Ruden, Douglas M; Rasouli, Parsa; Lu, Xiangyi

    2007-06-01

    While much of the third world starves, many in the first world are undergoing an obesity epidemic, and the related epidemics of type II diabetes, heart disease, and other diseases associated with obesity. The amount of economic wealth being directly related to a decline in health by obesity is ironic because rich countries contribute billions of dollars to improve the health of their citizens. Nevertheless, nutritional experiments in model organisms such as yeast, C. elegans, Drosophila, and mice confirm that "caloric restriction" (CR), which is defined generally as a 30-40% decrease in caloric intake, a famine-like condition for humans seen only in the poorest of countries, promotes good health and increases longevity in model organisms. Because caloric restriction, and dieting in general, requires a great deal of will power to deal with the feelings of deprivation, many fad diets, such as the Atkins, South Beach, and Protein Power, have been developed which allow people to lose weight purportedly without the severe feelings of deprivation. However, the long-term effects of such fad diets are not known and few experiments have been performed in the laboratory to investigate possible side affects and adverse consequences. In this paper, we review studies with fad-like dietary conditions in humans and model organisms, and we propose a "Dietary Ames Test" to rapidly screen fad diets, dietary supplements, and drugs for potential long-term health consequences in model organisms.

  6. Targeting Nicotinamide Phosphoribosyltransferase as a Potential Therapeutic Strategy to Restore Adult Neurogenesis.

    Science.gov (United States)

    Wang, Shu-Na; Xu, Tian-Ying; Li, Wen-Lin; Miao, Chao-Yu

    2016-06-01

    Adult neurogenesis is the process of generating new neurons throughout life in the olfactory bulb and hippocampus of most mammalian species, which is closely related to aging and disease. Nicotinamide phosphoribosyltransferase (NAMPT), also an adipokine known as visfatin, is the rate-limiting enzyme for mammalian nicotinamide adenine dinucleotide (NAD) salvage synthesis by generating nicotinamide mononucleotide (NMN) from nicotinamide. Recent findings from our laboratory and other laboratories have provided much evidence that NAMPT might serve as a therapeutic target to restore adult neurogenesis. NAMPT-mediated NAD biosynthesis in neural stem/progenitor cells is important for their proliferation, self-renewal, and formation of oligodendrocytes in vivo and in vitro. Therapeutic interventions by the administration of NMN, NAD, or recombinant NAMPT are effective for restoring adult neurogenesis in several neurological diseases. We summarize adult neurogenesis in aging, ischemic stroke, traumatic brain injury, and neurodegenerative disease and review the advances of targeting NAMPT in restoring neurogenesis. Specifically, we provide emphasis on the P7C3 family, a class of proneurogenic compounds that are potential NAMPT activators, which might shed light on future drug development in neurogenesis restoration. © 2016 John Wiley & Sons Ltd.

  7. The global economic long-term potential of modern biomass in a climate-constrained world

    Science.gov (United States)

    Klein, David; Humpenöder, Florian; Bauer, Nico; Dietrich, Jan Philipp; Popp, Alexander; Bodirsky, Benjamin Leon; Bonsch, Markus; Lotze-Campen, Hermann

    2014-07-01

    Low-stabilization scenarios consistent with the 2 °C target project large-scale deployment of purpose-grown lignocellulosic biomass. In case a GHG price regime integrates emissions from energy conversion and from land-use/land-use change, the strong demand for bioenergy and the pricing of terrestrial emissions are likely to coincide. We explore the global potential of purpose-grown lignocellulosic biomass and ask the question how the supply prices of biomass depend on prices for greenhouse gas (GHG) emissions from the land-use sector. Using the spatially explicit global land-use optimization model MAgPIE, we construct bioenergy supply curves for ten world regions and a global aggregate in two scenarios, with and without a GHG tax. We find that the implementation of GHG taxes is crucial for the slope of the supply function and the GHG emissions from the land-use sector. Global supply prices start at 5 GJ-1 and increase almost linearly, doubling at 150 EJ (in 2055 and 2095). The GHG tax increases bioenergy prices by 5 GJ-1 in 2055 and by 10 GJ-1 in 2095, since it effectively stops deforestation and thus excludes large amounts of high-productivity land. Prices additionally increase due to costs for N2O emissions from fertilizer use. The GHG tax decreases global land-use change emissions by one-third. However, the carbon emissions due to bioenergy production increase by more than 50% from conversion of land that is not under emission control. Average yields required to produce 240 EJ in 2095 are roughly 600 GJ ha-1 yr-1 with and without tax.

  8. The Greenville Fault: preliminary estimates of its long-term creep rate and seismic potential

    Science.gov (United States)

    Lienkaemper, James J.; Barry, Robert G.; Smith, Forrest E.; Mello, Joseph D.; McFarland, Forrest S.

    2013-01-01

    Once assumed locked, we show that the northern third of the Greenville fault (GF) creeps at 2 mm/yr, based on 47 yr of trilateration net data. This northern GF creep rate equals its 11-ka slip rate, suggesting a low strain accumulation rate. In 1980, the GF, easternmost strand of the San Andreas fault system east of San Francisco Bay, produced a Mw5.8 earthquake with a 6-km surface rupture and dextral slip growing to ≥2 cm on cracks over a few weeks. Trilateration shows a 10-cm post-1980 transient slip ending in 1984. Analysis of 2000-2012 crustal velocities on continuous global positioning system stations, allows creep rates of ~2 mm/yr on the northern GF, 0-1 mm/yr on the central GF, and ~0 mm/yr on its southern third. Modeled depth ranges of creep along the GF allow 5-25% aseismic release. Greater locking in the southern two thirds of the GF is consistent with paleoseismic evidence there for large late Holocene ruptures. Because the GF lacks large (>1 km) discontinuities likely to arrest higher (~1 m) slip ruptures, we expect full-length (54-km) ruptures to occur that include the northern creeping zone. We estimate sufficient strain accumulation on the entire GF to produce Mw6.9 earthquakes with a mean recurrence of ~575 yr. While the creeping 16-km northern part has the potential to produce a Mw6.2 event in 240 yr, it may rupture in both moderate (1980) and large events. These two-dimensional-model estimates of creep rate along the southern GF need verification with small aperture surveys.

  9. Ginsenoside Rg1 ameliorates hippocampal long-term potentiation and memory in an Alzheimer's disease model.

    Science.gov (United States)

    Li, Fengling; Wu, Xiqing; Li, Jing; Niu, Qingliang

    2016-06-01

    The complex etiopathogenesis of Alzheimer's disease (AD) has limited progression in the identification of effective therapeutic agents. Amyloid precursor protein (APP) and presenilin‑1 (PS1) are always overexpressed in AD, and are considered to be the initiators of the formation of β‑amyloid plaques and the symptoms of AD. In the present study, a transgenic AD model, constructed via the overexpression of APP and PS1, was used to verify the protective effects of ginsenoside Rg1 on memory performance and synaptic plasticity. AD mice (6‑month‑old) were treated via intraperitoneal injection of 0.1‑10 mg/kg ginsenoside Rg1. Long‑term memory, synaptic plasticity, and the levels of AD‑associated and synaptic plasticity‑associated proteins were measured following treatment. Memory was measured using a fear conditioning task and protein expression levels were investigated using western blotting. All the data was analyzed by one-way analysis of variance or t‑test. Following 30 days of consecutive treatment, memory in the AD mouse model was ameliorated in the 10 mg/kg ginsenoside Rg1 treatment group. As demonstrated by biochemical experiments, ginsenoside Rg1 treatment reduced the accumulations of β‑amyloid 1‑42 and phosphorylated (p)‑Tau in the AD model. Additionally, brain-derived neurotrophic factor (BDNF) and p‑TrkB synaptic plasticity‑associated proteins were upregulated following ginsenoside Rg1 application. Correspondingly, long‑term potentiation (LTP) was restored following ginsenoside Rg1 application in the AD mice model. Taken together, ginsenoside Rg1 repaired hippocampal LTP and memory, likely through facilitating the clearance of AD‑associated proteins and through activation of the BDNF‑TrkB pathway. Therefore, ginsenoside Rg1 may be a candidate drug for the treatment of AD.

  10. Long-Term Warming Alters Carbohydrate Degradation Potential in Temperate Forest Soils.

    Science.gov (United States)

    Pold, Grace; Billings, Andrew F; Blanchard, Jeff L; Burkhardt, Daniel B; Frey, Serita D; Melillo, Jerry M; Schnabel, Julia; van Diepen, Linda T A; DeAngelis, Kristen M

    2016-11-15

    As Earth's climate warms, soil carbon pools and the microbial communities that process them may change, altering the way in which carbon is recycled in soil. In this study, we used a combination of metagenomics and bacterial cultivation to evaluate the hypothesis that experimentally raising soil temperatures by 5°C for 5, 8, or 20 years increased the potential for temperate forest soil microbial communities to degrade carbohydrates. Warming decreased the proportion of carbohydrate-degrading genes in the organic horizon derived from eukaryotes and increased the fraction of genes in the mineral soil associated with Actinobacteria in all studies. Genes associated with carbohydrate degradation increased in the organic horizon after 5 years of warming but had decreased in the organic horizon after warming the soil continuously for 20 years. However, a greater proportion of the 295 bacteria from 6 phyla (10 classes, 14 orders, and 34 families) isolated from heated plots in the 20-year experiment were able to depolymerize cellulose and xylan than bacterial isolates from control soils. Together, these findings indicate that the enrichment of bacteria capable of degrading carbohydrates could be important for accelerated carbon cycling in a warmer world. The massive carbon stocks currently held in soils have been built up over millennia, and while numerous lines of evidence indicate that climate change will accelerate the processing of this carbon, it is unclear whether the genetic repertoire of the microbes responsible for this elevated activity will also change. In this study, we showed that bacteria isolated from plots subject to 20 years of 5°C of warming were more likely to depolymerize the plant polymers xylan and cellulose, but that carbohydrate degradation capacity is not uniformly enriched by warming treatment in the metagenomes of soil microbial communities. This study illustrates the utility of combining culture-dependent and culture-independent surveys of

  11. Decellularized allogeneic heart valves demonstrate self-regeneration potential after a long-term preclinical evaluation.

    Directory of Open Access Journals (Sweden)

    Laura Iop

    Full Text Available Tissue-engineered heart valves are proposed as novel viable replacements granting longer durability and growth potential. However, they require extensive in vitro cell-conditioning in bioreactor before implantation. Here, the propensity of non-preconditioned decellularized heart valves to spontaneous in body self-regeneration was investigated in a large animal model. Decellularized porcine aortic valves were evaluated for right ventricular outflow tract (RVOT reconstruction in Vietnamese Pigs (n = 11 with 6 (n = 5 and 15 (n = 6 follow-up months. Repositioned native valves (n = 2 for each time were considered as control. Tissue and cell components from explanted valves were investigated by histology, immunohistochemistry, electron microscopy, and gene expression. Most substitutes constantly demonstrated in vivo adequate hemodynamic performances and ex vivo progressive repopulation during the 15 implantation months without signs of calcifications, fibrosis and/or thrombosis, as revealed by histological, immunohistochemical, ultrastructural, metabolic and transcriptomic profiles. Colonizing cells displayed native-like phenotypes and actively synthesized novel extracellular matrix elements, as collagen and elastin fibers. New mature blood vessels, i.e. capillaries and vasa vasorum, were identified in repopulated valves especially in the medial and adventitial tunicae of regenerated arterial walls. Such findings correlated to the up-regulated vascular gene transcription. Neoinnervation hallmarks were appreciated at histological and ultrastructural levels. Macrophage populations with reparative M2 phenotype were highly represented in repopulated valves. Indeed, no aspects of adverse/immune reaction were revealed in immunohistochemical and transcriptomic patterns. Among differentiated elements, several cells were identified expressing typical stem cell markers of embryonic, hematopoietic, neural and mesenchymal lineages in significantly

  12. Postfatigue potentiation of the paralyzed soleus muscle: evidence for adaptation with long-term electrical stimulation training.

    Science.gov (United States)

    Shields, Richard K; Dudley-Javoroski, Shauna; Littmann, Andrew E

    2006-08-01

    Understanding the torque output behavior of paralyzed muscle has important implications for the use of functional neuromuscular electrical stimulation systems. Postfatigue potentiation is an augmentation of peak muscle torque during repetitive activation after a fatigue protocol. The purposes of this study were 1) to quantify postfatigue potentiation in the acutely and chronically paralyzed soleus and 2) to determine the effect of long-term soleus electrical stimulation training on the potentiation characteristics of recently paralyzed soleus muscle. Five subjects with chronic paralysis (>2 yr) demonstrated significant postfatigue potentiation during a repetitive soleus activation protocol that induced low-frequency fatigue. Ten subjects with acute paralysis (stimulation. Seven of these acute subjects completed 2 yr of home-based isometric soleus electrical stimulation training of one limb (compliance = 83%; 8,300 contractions/wk). With the early implementation of electrically stimulated training, potentiation characteristics of trained soleus muscles were preserved as in the acute postinjury state. In contrast, untrained limbs showed marked postfatigue potentiation at 2 yr after spinal cord injury (SCI). A single acute SCI subject who was followed longitudinally developed potentiation characteristics very similar to the untrained limbs of the training subjects. The results of the present investigation support that postfatigue potentiation is a characteristic of fast-fatigable muscle and can be prevented by timely neuromuscular electrical stimulation training. Potentiation is an important consideration in the design of functional electrical stimulation control systems for people with SCI.

  13. Long-term potentiation in bone – a role for glutamate in strain-induced cellular memory?

    Directory of Open Access Journals (Sweden)

    Genever Paul G

    2003-07-01

    Full Text Available Abstract Background The adaptive response of bone cells to mechanical strain is a primary determinant of skeletal architecture and bone mass. In vivo mechanical loading induces new bone formation and increases bone mineral density whereas disuse, immobilisation and weightlessness induce bone loss. The potency of mechanical strain is such that a single brief period of loading at physiological strain magnitude is able to induce a long-lasting osteogenic response that lasts for days. Although the process of mechanotransduction in bone is incompletely understood, observations that responses to mechanical strain outlast the duration of stimulation necessitate the existence of a form of cellular memory through which transient strain episodes are recorded, interpreted and remembered by bone cells. Recent evidence supports the existence of a complex multicellular glutamate-signalling network in bone that shares functional similarities to glutamatergic neurotransmission in the central nervous system. In neurones, these signalling molecules coordinate synaptic communication required to support learning and memory formation, through a complex process of long-term potentiation. Presentation of the hypothesis We hypothesise that osteoblasts use a cellular mechanism similar or identical to neuronal long-term potentiation in the central nervous system to mediate long-lasting changes in osteogenesis following brief periods of mechanical strain. Testing the hypothesis N-methyl-D-aspartate (NMDA receptor antagonism should inhibit the saturating response of mechanical strain and reduce the enhanced osteogenicity of segregated loading to that of an equivalent period of uninterrupted loading. Changes in α-amino-3-hydroxy-5-methyl-isoxazole propionate (AMPA receptor expression, localisation and electrophysiological responses should be induced by mechanical strain and inhibited by modulators of neuronal long-term potentiation. Implications of the hypothesis If true

  14. Synaptic long-term potentiation realized in Pavlov's dog model based on a NiOx-based memristor

    Science.gov (United States)

    Hu, S. G.; Liu, Y.; Liu, Z.; Chen, T. P.; Yu, Q.; Deng, L. J.; Yin, Y.; Hosaka, Sumio

    2014-12-01

    Synaptic Long-Term Potentiation (LTP), which is a long-lasting enhancement in signal transmission between neurons, is widely considered as the major cellular mechanism during learning and memorization. In this work, a NiOx-based memristor is found to be able to emulate the synaptic LTP. Electrical conductance of the memristor is increased by electrical pulse stimulation and then spontaneously decays towards its initial state, which resembles the synaptic LTP. The lasting time of the LTP in the memristor can be estimated with the relaxation equation, which well describes the conductance decay behavior. The LTP effect of the memristor has a dependence on the stimulation parameters, including pulse height, width, interval, and number of pulses. An artificial network consisting of three neurons and two synapses is constructed to demonstrate the associative learning and LTP behavior in extinction of association in Pavlov's dog experiment.

  15. Postsynaptic GABABRs Inhibit L-Type Calcium Channels and Abolish Long-Term Potentiation in Hippocampal Somatostatin Interneurons.

    Science.gov (United States)

    Booker, Sam A; Loreth, Desiree; Gee, Annabelle L; Watanabe, Masahiko; Kind, Peter C; Wyllie, David J A; Kulik, Ákos; Vida, Imre

    2018-01-02

    Inhibition provided by local GABAergic interneurons (INs) activates ionotropic GABAA and metabotropic GABAB receptors (GABABRs). Despite GABABRs representing a major source of inhibition, little is known of their function in distinct IN subtypes. Here, we show that, while the archetypal dendritic-inhibitory somatostatin-expressing INs (SOM-INs) possess high levels of GABABR on their somato-dendritic surface, they fail to produce significant postsynaptic inhibitory currents. Instead, GABABRs selectively inhibit dendritic CaV1.2 (L-type) Ca2+ channels on SOM-IN dendrites, leading to reduced calcium influx and loss of long-term potentiation at excitatory input synapses onto these INs. These data provide a mechanism by which GABABRs can contribute to disinhibition and control the efficacy of extrinsic inputs to hippocampal networks. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  16. Long-term effects of cropping system on N2O emission potential

    DEFF Research Database (Denmark)

    Petersen, Søren O.; Ambus, Per; Elsgaard, Lars

    2013-01-01

    The potential for N2O emissions outside the main growing season may be influenced by long-term effects of cropping system. This was investigated by collecting intact soil cores (100 cm3, 0-4 cm depth) under winter wheat in three organic cropping systems and a conventional reference within a long......Pa and amended with excess 15NO3- prior to freezing and thawing. Denitrification was the main source of N2O during a 72-h incubation at 22 °C, as judged from N2O and total 15N evolution. Although the input of C in the conventionally managed cropping system was significantly less than in the organic cropping...

  17. Acupuncture Attenuated Vascular Dementia-Induced Hippocampal Long-Term Potentiation Impairments via Activation of D1/D5 Receptors.

    Science.gov (United States)

    Ye, Yang; Li, Hui; Yang, Jing-Wen; Wang, Xue-Rui; Shi, Guang-Xia; Yan, Chao-Qun; Ma, Si-Ming; Zhu, Wen; Li, Qian-Qian; Li, Tian-Ran; Xiao, Ling-Yong; Liu, Cun-Zhi

    2017-04-01

    Emerging evidence suggests that acupuncture could improve cognitive impairment in vascular dementia by enhancing synaptic plasticity in the hippocampus. The purpose of this study is to investigate whether dopamine, a key mediator of synaptic plasticity, is involved in this cognitive improvement. Vascular dementia model was established by bilateral common carotid arteries occlusion in male Wistar rats. Three days after the operation, animals received acupuncture treatment for 2 weeks, once daily. The D1/D5 receptors antagonist SCH23390 was administered intraperitoneally 15 minutes before each acupuncture treatment. Morris water maze was examined after acupuncture. Long-term potentiation was studied by an electrophysiological technique. Dopamine and metabolites levels were detected by microdialysis and high-performance liquid chromatography from brain tissue. The expression of D1R and D5R was analyzed by immunofluorescence. Acupuncture remarkably reversed cognitive deficits in 2-vessel occlusion model (2VO) rats, and the acupuncture points Zusanli (ST36) and Baihui (GV20) were confirmed to be the most effective combination. Electrophysiological recording data showed that 2VO-induced impairments of long-term potentiation were prevented by acupuncture. In addition, acupuncture promoted the release of dopamine and its major metabolites in the hippocampus of 2VO rats. The immunofluorescence experiment showed that the decrease of D1R and D5R in hippocampal dentate gyrus region of 2VO rats was reversed by acupuncture. Furthermore, we found that the effects of acupuncture against 2VO-induced impairments in cognition and synaptic plasticity were abolished by SCH23390. Improvement in cognition and hippocampal synaptic plasticity induced by acupuncture was achieved via activation of D1/D5 receptors in 2VO rats. © 2017 American Heart Association, Inc.

  18. Amyloid-β Peptide Is Needed for cGMP-Induced Long-Term Potentiation and Memory.

    Science.gov (United States)

    Palmeri, Agostino; Ricciarelli, Roberta; Gulisano, Walter; Rivera, Daniela; Rebosio, Claudia; Calcagno, Elisa; Tropea, Maria Rosaria; Conti, Silvia; Das, Utpal; Roy, Subhojit; Pronzato, Maria Adelaide; Arancio, Ottavio; Fedele, Ernesto; Puzzo, Daniela

    2017-07-19

    High levels of amyloid-β peptide (Aβ) have been related to Alzheimer's disease pathogenesis. However, in the healthy brain, low physiologically relevant concentrations of Aβ are necessary for long-term potentiation (LTP) and memory. Because cGMP plays a key role in these processes, here we investigated whether the cyclic nucleotide cGMP influences Aβ levels and function during LTP and memory. We demonstrate that the increase of cGMP levels by the phosphodiesterase-5 inhibitors sildenafil and vardenafil induces a parallel release of Aβ due to a change in the approximation of amyloid precursor protein (APP) and the β-site APP cleaving enzyme 1. Moreover, electrophysiological and behavioral studies performed on animals of both sexes showed that blocking Aβ function, by using anti-murine Aβ antibodies or APP knock-out mice, prevents the cGMP-dependent enhancement of LTP and memory. Our data suggest that cGMP positively regulates Aβ levels in the healthy brain which, in turn, boosts synaptic plasticity and memory.SIGNIFICANCE STATEMENT Amyloid-β (Aβ) is a key pathogenetic factor in Alzheimer's disease. However, low concentrations of endogenous Aβ, mimicking levels of the peptide in the healthy brain, enhance hippocampal long-term potentiation (LTP) and memory. Because the second messenger cGMP exerts a central role in LTP mechanisms, here we studied whether cGMP affects Aβ levels and function during LTP. We show that cGMP enhances Aβ production by increasing the APP/BACE-1 convergence in endolysosomal compartments. Moreover, the cGMP-induced enhancement of LTP and memory was disrupted by blockade of Aβ, suggesting that the physiological effect of the cyclic nucleotide on LTP and memory is dependent upon Aβ. Copyright © 2017 the authors 0270-6474/17/376926-12$15.00/0.

  19. Long-term no-till and stover retention each decrease the global warming potential of irrigated continuous corn.

    Science.gov (United States)

    Jin, Virginia L; Schmer, Marty R; Stewart, Catherine E; Sindelar, Aaron J; Varvel, Gary E; Wienhold, Brian J

    2017-07-01

    Over the last 50 years, the most increase in cultivated land area globally has been due to a doubling of irrigated land. Long-term agronomic management impacts on soil organic carbon (SOC) stocks, soil greenhouse gas (GHG) emissions, and global warming potential (GWP) in irrigated systems, however, remain relatively unknown. Here, residue and tillage management effects were quantified by measuring soil nitrous oxide (N 2 O) and methane (CH 4 ) fluxes and SOC changes (ΔSOC) at a long-term, irrigated continuous corn (Zea mays L.) system in eastern Nebraska, United States. Management treatments began in 2002, and measured treatments included no or high stover removal (0 or 6.8 Mg DM ha -1  yr -1 , respectively) under no-till (NT) or conventional disk tillage (CT) with full irrigation (n = 4). Soil N 2 O and CH 4 fluxes were measured for five crop-years (2011-2015), and ΔSOC was determined on an equivalent mass basis to ~30 cm soil depth. Both area- and yield-scaled soil N 2 O emissions were greater with stover retention compared to removal and for CT compared to NT, with no interaction between stover and tillage practices. Methane comprised <1% of total emissions, with NT being CH 4 neutral and CT a CH 4 source. Surface SOC decreased with stover removal and with CT after 14 years of management. When ΔSOC, soil GHG emissions, and agronomic energy usage were used to calculate system GWP, all management systems were net GHG sources. Conservation practices (NT, stover retention) each decreased system GWP compared to conventional practices (CT, stover removal), but pairing conservation practices conferred no additional mitigation benefit. Although cropping system, management equipment/timing/history, soil type, location, weather, and the depth to which ΔSOC is measured affect the GWP outcomes of irrigated systems at large, this long-term irrigated study provides valuable empirical evidence of how management decisions can impact soil GHG emissions and surface

  20. Potential effect of conservation tillage on sustainable land use : a review of global long-term studies

    NARCIS (Netherlands)

    Wang Xiaobin,; Cai, D.; Hoogmoed, W.B.; Oenema, O.; Perdok, U.D.

    2006-01-01

    Although understood differently in different parts of the world, conservation tillage usually includes leaving crop residues on the soil surface to reduce tillage. Through a global review of long-term conservation tillage research, this paper discusses the long-term effect of conservation tillage on

  1. Spatial, contextual and working memory are not affected by the absence of mossy fiber long-term potentiation and depression

    NARCIS (Netherlands)

    Hensbroek, R.A.; Kamal, A.; Baars, A.M.; Verhage, M.; Spruijt, B.M.

    2003-01-01

    The mossy fibers of the hippocampus display NMDA-receptor independent long-term plasticity. A number of studies addressed the role of mossy fiber long-term plasticity in memory, but have provided contrasting results. Here, we have exploited a genetic model, the rab3A null-mutant, which is

  2. Drivers, trends, and potential impacts of long-term coastal reclamation in China from 1985 to 2010

    Science.gov (United States)

    Tian, Bo; Wu, Wenting; Yang, Zhaoqing; Zhou, Yunxuan

    2016-03-01

    The reclamation of coastal land for agricultural, industrial, and urban land use-a common worldwide practice-has occurred extensively in the coastal region of China. In recent decades, all coastal provinces and metropolises in China have experienced severe coastal reclamation related to land scarcity caused by rapid economic growth and urbanization. However, the value of coastal wetlands and ecosystems has not been well understood and appreciated until recent development of advantageous methods of restoring reclaimed land to coastal wetlands in many developed countries. The overall objective of this study is to provide detailed spatial and temporal distributions of coastal reclamation; analyze drivers such as coastal economy, population growth, and urbanization; and understand the relationships among the drivers and land reclamation. We used long-term Landsat image time series from 1985 to 2010 in 5-year intervals, in combination with remotely sensed image interpretation and spatial analysis, to map the reclamation status and changes across the coastal region of China. The Landsat images time-series analysis was also conducted to evaluate the effects of the economy, population, and urbanization drivers on coastal reclamation. The analysis results indicated that 754,697 ha of coastal wetlands have been reclaimed across all coastal provinces and metropolises from 1985 to 2010, and the trend increased sharply after 2005. High-intensity coastal reclamation was mainly driven by the booming economy, especially after 2000, associated with urbanization and industrial development in China's coastal region; this was closely correlated with the gross domestic product (GDP) per capita. The continuous large-scale coastal reclamation of its coastal region now means China is facing a great challenge, including the enormous loss of vegetated coastal wetlands, negative environmental effects, and potential disaster risks related to coastal flooding under future change climate

  3. Acid Mine Drainage Passive Remediation: Potential Use of Alkaline Clay, Optimal Mixing Ratio and Long Term Impacts

    Science.gov (United States)

    Plaza, F.; Liang, X.; Wen, Y.; Perone, H.

    2015-12-01

    Acid mine drainage (AMD) is one of the most adverse environmental problems of the mine industry. Surface water and ground water affected by this pollution are characterized by their acidity and the high content of sulfates and heavy metals. In this study, alkaline clay, an industrial waste with a high pH, which is utilized in the alumina refining process, was used as the remediation material to inhibit pyrite oxidation. Through a series of batch and column experiments, complemented with field measurements and geochemical modeling, three important issues associated with this passive and auto sustainable acid mine drainage remediation method were investigated: 1) the potential use of alkaline clay as an AMD remediation material, 2) the adequate alkaline clay/coal refuse mixing ratio (AC/CR) to ensure pH values near to neutral conditions, and, 3) the prediction of long term impacts, in terms of the trends of the main parameters involved in this process such as pH, concentrations of sulfate, iron and other dissolved contaminants. Both field measurements and the samples used for the experiments came from a coal waste site located in Mather, Pennsylvania. Alkaline clay proved to be an effective remediation material for AMD. It was found that 10% AC/CR is an adequate mixing ratio (i.e. the upper limit), which has been also indicated by field measurements. The concentrations of some contaminants such as iron, manganese or sulfate are significantly reduced with the remediation approach, compared to those representative concentrations found in mine tailings. Moreover, results suggest a very reliable long-term stability of the remediation (i.e. neutral pH conditions are maintained), thus enhancing the generation of iron precipitates that could produce pyrite grain coating and hardpan (i.e. cemented layer) on the surface. These processes also made the amended layer less porous, thus increasing water retention and hindering oxygen diffusion.

  4. Enhanced decomposition of stable soil organic carbon and microbial catabolic potentials by long-term field warming.

    Science.gov (United States)

    Feng, Wenting; Liang, Junyi; Hale, Lauren E; Jung, Chang Gyo; Chen, Ji; Zhou, Jizhong; Xu, Minggang; Yuan, Mengting; Wu, Liyou; Bracho, Rosvel; Pegoraro, Elaine; Schuur, Edward A G; Luo, Yiqi

    2017-11-01

    Quantifying soil organic carbon (SOC) decomposition under warming is critical to predict carbon-climate feedbacks. According to the substrate regulating principle, SOC decomposition would decrease as labile SOC declines under field warming, but observations of SOC decomposition under warming do not always support this prediction. This discrepancy could result from varying changes in SOC components and soil microbial communities under warming. This study aimed to determine the decomposition of SOC components with different turnover times after subjected to long-term field warming and/or root exclusion to limit C input, and to test whether SOC decomposition is driven by substrate lability under warming. Taking advantage of a 12-year field warming experiment in a prairie, we assessed the decomposition of SOC components by incubating soils from control and warmed plots, with and without root exclusion for 3 years. We assayed SOC decomposition from these incubations by combining inverse modeling and microbial functional genes during decomposition with a metagenomic technique (GeoChip). The decomposition of SOC components with turnover times of years and decades, which contributed to 95% of total cumulative CO 2 respiration, was greater in soils from warmed plots. But the decomposition of labile SOC was similar in warmed plots compared to the control. The diversity of C-degradation microbial genes generally declined with time during the incubation in all treatments, suggesting shifts of microbial functional groups as substrate composition was changing. Compared to the control, soils from warmed plots showed significant increase in the signal intensities of microbial genes involved in degrading complex organic compounds, implying enhanced potential abilities of microbial catabolism. These are likely responsible for accelerated decomposition of SOC components with slow turnover rates. Overall, the shifted microbial community induced by long-term warming accelerates the

  5. The striatal-enriched protein tyrosine phosphatase gates long-term potentiation and fear memory in the lateral amygdala.

    Science.gov (United States)

    Paul, Surojit; Olausson, Peter; Venkitaramani, Deepa V; Ruchkina, Irina; Moran, Timothy D; Tronson, Natalie; Mills, Evan; Hakim, Shawn; Salter, Michael W; Taylor, Jane R; Lombroso, Paul J

    2007-05-01

    Formation of long-term memories is critically dependent on extracellular-regulated kinase (ERK) signaling. Activation of the ERK pathway by the sequential recruitment of mitogen-activated protein kinases is well understood. In contrast, the proteins that inactivate this pathway are not as well characterized. Here we tested the hypothesis that the brain-specific striatal-enriched protein tyrosine phosphatase (STEP) plays a key role in neuroplasticity and fear memory formation by its ability to regulate ERK1/2 activation. STEP co-localizes with the ERKs within neurons of the lateral amygdala. A substrate-trapping STEP protein binds to the ERKs and prevents their nuclear translocation after glutamate stimulation in primary cell cultures. Administration of TAT-STEP into the lateral amygdala (LA) disrupts long-term potentiation (LTP) and selectively disrupts fear memory consolidation. Fear conditioning induces a biphasic activation of ERK1/2 in the LA with an initial activation within 5 minutes of training, a return to baseline levels by 15 minutes, and an increase again at 1 hour. In addition, fear conditioning results in the de novo translation of STEP. Inhibitors of ERK1/2 activation or of protein translation block the synthesis of STEP within the LA after fear conditioning. Together, these data imply a role for STEP in experience-dependent plasticity and suggest that STEP modulates the activation of ERK1/2 during amygdala-dependent memory formation. The regulation of emotional memory by modulating STEP activity may represent a target for the treatment of psychiatric disorders such as posttraumatic stress disorder (PTSD), panic, and anxiety disorders.

  6. The Protein Tyrosine Phosphatase STEP Gates Long-term Potentiation and Fear Memory in the Lateral Amygdala

    Science.gov (United States)

    Paul, Surojit; Olausson, Peter; Venkitaramani, Deepa V.; Ruchkina, Irina; Moran, Timothy D; Tronson, Natalie; Mills, Evan; Hakim, Shawn; Salter, Michael W; Taylor, Jane R.; Lombroso, Paul J

    2006-01-01

    Background Formation of long-term memories is critically dependent on extracellular-regulated kinase (ERK) signaling. Activation of the ERK pathway by the sequential recruitment of mitogen-activated protein kinases is well understood. In contrast, the proteins that inactivate this pathway are not as well characterized. Methods Here we tested the hypothesis that the brain-specific protein tyrosine phosphatase STEP plays a key role in neuroplasticity and fear memory formation by its ability to regulate ERK1/2 activation. Results STEP co-localizes with the ERKs within neurons of the lateral amygdala. A substrate-trapping STEP protein (TAT-STEP) binds to the ERKs and prevents their nuclear translocation after glutamate stimulation in primary cell cultures. Administration of TAT-STEP into the lateral amygdala disrupts long-term potentiation (LTP) and selectively disrupts fear memory consolidation. Fear conditioning induces a bi-phasic activation of ERK1/2 in the lateral amygdala (LA) with an initial activation within 5 minutes of training, a return to baseline levels by 15 minutes, and an increase again at 1 hour. In addition, fear conditioning results in the de novo translation of STEP. Inhibitors of ERK1/2 activation or of protein translation block the synthesis of STEP within the LA after fear conditioning. Conclusions Together, these data imply a role for STEP in experience-dependent plasticity, and suggest that STEP modulates the activation of ERK1/2 during amygdala–dependent memory formation. The regulation of emotional memory by modulating STEP activity may represent a target for the treatment of psychiatric disorders such as PTSD, panic, and anxiety disorders. PMID:17081505

  7. Long-Term Expansion, Enhanced Chondrogenic Potential, and Suppression of Endochondral Ossification of Adult Human MSCs via WNT Signaling Modulation

    Directory of Open Access Journals (Sweden)

    Roberto Narcisi

    2015-03-01

    Full Text Available Mesenchymal stem cells (MSCs are a potential source of chondrogenic cells for the treatment of cartilage disorders, but loss of chondrogenic potential during in vitro expansion and the propensity of cartilage to undergo hypertrophic maturation impede their therapeutic application. Here we report that the signaling protein WNT3A, in combination with FGF2, supports long-term expansion of human bone marrow-derived MSCs. The cells retained their chondrogenic potential and other phenotypic and functional properties of multipotent MSCs, which were gradually lost in the absence of WNT3A. Moreover, we discovered that endogenous WNT signals are the main drivers of the hypertrophic maturation that follows chondrogenic differentiation. Inhibition of WNT signals during differentiation prevented calcification and maintained cartilage properties following implantation in a mouse model. By maintaining potency during expansion and preventing hypertrophic maturation following differentiation, the modulation of WNT signaling removes two major obstacles that impede the clinical application of MSCs in cartilage repair.

  8. Long-term Water Table Monitoring of Rio Grande Riparian Ecosystems for Restoration Potential Amid Hydroclimatic Challenges.

    Science.gov (United States)

    Thibault, James R; Cleverly, James R; Dahm, Clifford N

    2017-12-01

    Hydrological processes drive the ecological functioning and sustainability of cottonwood-dominated riparian ecosystems in the arid southwestern USA. Snowmelt runoff elevates groundwater levels and inundates floodplains, which promotes cottonwood germination. Once established, these phreatophytes rely on accessible water tables (WTs). In New Mexico's Middle Rio Grande corridor diminished flooding and deepening WTs threaten native riparian communities. We monitored surface flows and riparian WTs for up to 14 years, which revealed that WTs and surface flows, including peak snowmelt discharge, respond to basin climate conditions and resource management. WT hydrographs influence the composition of riparian communities and can be used to assess if potential restoration sites meet native vegetation tolerances for WT depths, rates of recession, and variability throughout their life stages. WTs were highly variable in some sites, which can preclude native vegetation less adapted to deep drawdowns during extended droughts. Rates of WT recession varied between sites and should be assessed in regard to recruitment potential. Locations with relatively shallow WTs and limited variability are likely to be more viable for successful restoration. Suitable sites have diminished greatly as the once meandering Rio Grande has been constrained and depleted. Increasing demands on water and the presence of invasive vegetation better adapted to the altered hydrologic regime further impact native riparian communities. Long-term monitoring over a range of sites and hydroclimatic extremes reveals attributes that can be evaluated for restoration potential.

  9. Long-term Water Table Monitoring of Rio Grande Riparian Ecosystems for Restoration Potential Amid Hydroclimatic Challenges

    Science.gov (United States)

    Thibault, James R.; Cleverly, James R.; Dahm, Clifford N.

    2017-12-01

    Hydrological processes drive the ecological functioning and sustainability of cottonwood-dominated riparian ecosystems in the arid southwestern USA. Snowmelt runoff elevates groundwater levels and inundates floodplains, which promotes cottonwood germination. Once established, these phreatophytes rely on accessible water tables (WTs). In New Mexico's Middle Rio Grande corridor diminished flooding and deepening WTs threaten native riparian communities. We monitored surface flows and riparian WTs for up to 14 years, which revealed that WTs and surface flows, including peak snowmelt discharge, respond to basin climate conditions and resource management. WT hydrographs influence the composition of riparian communities and can be used to assess if potential restoration sites meet native vegetation tolerances for WT depths, rates of recession, and variability throughout their life stages. WTs were highly variable in some sites, which can preclude native vegetation less adapted to deep drawdowns during extended droughts. Rates of WT recession varied between sites and should be assessed in regard to recruitment potential. Locations with relatively shallow WTs and limited variability are likely to be more viable for successful restoration. Suitable sites have diminished greatly as the once meandering Rio Grande has been constrained and depleted. Increasing demands on water and the presence of invasive vegetation better adapted to the altered hydrologic regime further impact native riparian communities. Long-term monitoring over a range of sites and hydroclimatic extremes reveals attributes that can be evaluated for restoration potential.

  10. X11beta rescues memory and long-term potentiation deficits in Alzheimer's disease APPswe Tg2576 mice.

    LENUS (Irish Health Repository)

    Mitchell, Jacqueline C

    2009-12-01

    Increased production and deposition of amyloid beta-protein (Abeta) are believed to be key pathogenic events in Alzheimer\\'s disease. As such, routes for lowering cerebral Abeta levels represent potential therapeutic targets for Alzheimer\\'s disease. X11beta is a neuronal adaptor protein that binds to the intracellular domain of the amyloid precursor protein (APP). Overexpression of X11beta inhibits Abeta production in a number of experimental systems. However, whether these changes to APP processing and Abeta production induced by X11beta overexpression also induce beneficial effects to memory and synaptic plasticity are not known. We report here that X11beta-mediated reduction in cerebral Abeta is associated with normalization of both cognition and in vivo long-term potentiation in aged APPswe Tg2576 transgenic mice that model the amyloid pathology of Alzheimer\\'s disease. Overexpression of X11beta itself has no detectable adverse effects upon mouse behaviour. These findings support the notion that modulation of X11beta function represents a therapeutic target for Abeta-mediated neuronal dysfunction in Alzheimer\\'s disease.

  11. HIPPOCAMPAL ADULT NEUROGENESIS: ITS REGULATION AND POTENTIAL ROLE IN SPATIAL LEARNING AND MEMORY

    Science.gov (United States)

    Lieberwirth, Claudia; Pan, Yongliang; Liu, Yan; Zhang, Zhibin; Wang, Zuoxin

    2016-01-01

    Adult neurogenesis, defined here as progenitor cell division generating functionally integrated neurons in the adult brain, occurs within the hippocampus of numerous mammalian species including humans. The present review details various endogenous (e.g., neurotransmitters) and environmental (e.g., physical exercise) factors that have been shown to influence hippocampal adult neurogenesis. In addition, the potential involvement of adult-generated neurons in naturally-occurring spatial learning behavior is discussed by summarizing the literature focusing on traditional animal models (e.g., rats and mice), non-traditional animal models (e.g., tree shrews), as well as natural populations (e.g., chickadees and Siberian chipmunk). PMID:27174001

  12. Effects of inhaled anesthetic isoflurane on long-term potentiation of CA3 pyramidal cell afferents in vivo

    Directory of Open Access Journals (Sweden)

    Ballesteros KA

    2012-11-01

    Full Text Available Kristen A Ballesteros,1 Angela Sikorski,2 James E Orfila,3 Joe L Martinez Jr41Department of Biology, The University of Texas at San Antonio, San Antonio, TX, USA; 2Texas A&M University Texarkana, Texarkana, TX, USA; 3University of Colorado in Denver, Denver, CO, USA; 4University of Illinois in Chicago, Chicago, IL, USAAbstract: Isoflurane is a preferred anesthetic, due to its properties that allow a precise concentration to be delivered continually during in vivo experimentation. The major mechanism of action of isoflurane is modulation of the γ-amino butyric acid (GABAA receptor-chloride channel, mediating inhibitory synaptic transmission. Animal studies have shown that isoflurane does not cause cell death, but it does inhibit cell growth and causes long-term hippocampal learning deficits. As there are no studies characterizing the effects of isoflurane on electrophysiological aspects of long-term potentiation (LTP in the hippocampus, it is important to determine whether isoflurane alters the characteristic responses of hippocampal afferents to cornu ammonis region 3 (CA3. We investigated the effects of isoflurane on adult male rats during in vivo induction of LTP, using the mossy fiber pathway, the lateral perforant pathway, the medial perforant pathway, and the commissural CA3 (cCA3 to CA3, with intracranial administration of Ringer’s solution, naloxone, RS-aminoindan-1, 5-dicarboxylic acid (AIDA, or 3-[(R-2-carboxypiperazin-4-yl]-propo-2-enyl-1-phosphonic acid (CPP. Then, we compared these responses to published electrophysiological data, using sodium pentobarbital as an anesthetic, under similar experimental conditions. Our results showed that LTP was exhibited in animals anesthetized with isoflurane under vehicle conditions. With the exception of AIDA in the lateral perforant pathway, the defining characteristics of the four pathways appeared to remain intact, except for the observation that LTP was markedly reduced in animals

  13. The Down syndrome critical region protein RCAN1 regulates long-term potentiation and memory via inhibition of phosphatase signaling.

    Science.gov (United States)

    Hoeffer, Charles A; Dey, Asim; Sachan, Nita; Wong, Helen; Patterson, Richard J; Shelton, John M; Richardson, James A; Klann, Eric; Rothermel, Beverly A

    2007-11-28

    Regulator of calcineurin 1 (RCAN1/MCIP1/DSCR1) regulates the calmodulin-dependent phosphatase calcineurin. Because it is located on human chromosome 21, RCAN1 has been postulated to contribute to mental retardation in Down syndrome and has been reported to be associated with neuronal degeneration in Alzheimer's disease. The studies herein are the first to assess the role of RCAN1 in memory and synaptic plasticity by examining the behavioral and electrophysiological properties of RCAN1 knock-out mice. These mice exhibit deficits in spatial learning and memory, reduced associative cued memory, and impaired late-phase long-term potentiation (L-LTP), phenotypes similar to those of transgenic mice with increased calcineurin activity. Consistent with this, the RCAN1 knock-out mice display increased enzymatic calcineurin activity, increased abundance of a cleaved calcineurin fragment, and decreased phosphorylation of the calcineurin substrate dopamine and cAMP-regulated phosphoprotein-32. We propose a model in which RCAN1 plays a positive role in L-LTP and memory by constraining phosphatase signaling.

  14. Neuraminidase Inhibition Primes Short-Term Depression and Suppresses Long-Term Potentiation of Synaptic Transmission in the Rat Hippocampus

    Directory of Open Access Journals (Sweden)

    Alina Savotchenko

    2015-01-01

    Full Text Available Neuraminidase (NEU is a key enzyme that cleaves negatively charged sialic acid residues from membrane proteins and lipids. Clinical and basic science studies have shown that an imbalance in NEU metabolism or changes in NEU activity due to various pathological conditions parallel with behavior and cognitive impairment. It has been suggested that the decreases of NEU activity could cause serious neurological consequences. However, there is a lack of direct evidences that modulation of endogenous NEU activity can impair neuronal function. Using combined rat entorhinal cortex/hippocampal slices and a specific inhibitor of NEU, 2-deoxy-2,3-dehydro-N-acetylneuraminic acid (NADNA, we examined the effect of downregulation of NEU activity on different forms of synaptic plasticity in the hippocampal CA3-to-CA1 network. We show that NEU inhibition results in a significant decrease in long-term potentiation (LTP and an increase in short-term depression. Synaptic depotentiation restores LTP in NADNA-pretreated slices to the control level. These data suggest that short-term NEU inhibition produces the LTP-like effect on neuronal network, which results in damping of further LTP induction. Our findings demonstrate that downregulation of NEU activity could have a major impact on synaptic plasticity and provide a new insight into the cellular mechanism underlying behavioral and cognitive impairment associated with abnormal metabolism of NEU.

  15. Enhanced deficits in long-term potentiation in the adult dentate gyrus with 2nd trimester ethanol consumption.

    Directory of Open Access Journals (Sweden)

    Jennifer L Helfer

    Full Text Available Ethanol exposure during pregnancy can cause structural and functional changes in the brain that can impair cognitive capacity. The hippocampal formation, an area of the brain strongly linked with learning and memory, is particularly vulnerable to the teratogenic effects of ethanol. In the present experiments we sought to determine if the functional effects of developmental ethanol exposure could be linked to ethanol exposure during any single trimester-equivalent. Ethanol exposure during the 1(st or 3(rd trimester-equivalent produced only minor changes in synaptic plasticity in adult offspring. In contrast, ethanol exposure during the 2(nd trimester equivalent resulted in a pronounced decrease in long-term potentiation, indicating that the timing of exposure influences the severity of the deficit. Together, the results from these experiments demonstrate long-lasting alterations in synaptic plasticity as the result of developmental ethanol exposure and dependent on the timing of exposure. Furthermore, these results allude to neural circuit malfunction within the hippocampal formation, perhaps relating to the learning and memory deficits observed in individuals with fetal alcohol spectrum disorders.

  16. Long-term potentiation at C-fibre synapses by low-level presynaptic activity in vivo

    Directory of Open Access Journals (Sweden)

    Sandkühler Jürgen

    2008-05-01

    Full Text Available Abstract Inflammation, trauma or nerve injury trigger low-level activity in C-fibres and may cause long-lasting hyperalgesia. Long-term potentiation (LTP at synapses of primary afferent C-fibres is considered to underlie some forms of hyperalgesia. In previous studies, high- but not low-frequency conditioning stimulation of C-fibres has, however, been used to induce LTP in pain pathways. Recently we could show that also conditioning low-frequency stimulation (LFS at C-fibre intensity induces LTP in vitro as well as in the intact animal, i.e. with tonic descending inhibition fully active. In the slice preparation, this form of LTP requires a rise in postsynaptic Ca2+-concentration and activation of Ca2+-dependent signalling pathways. Here, we investigated the signalling mechanisms underlying this novel form of LTP in vivo. We found that the signal transduction pathways causing LFS-induced LTP in vivo include activation of neurokinin 1 and N-methyl-D-aspartate receptors, rise of [Ca2+]i from intracellular stores and via T-type voltage-dependent Ca2+ channels, activation of phospholipase C, protein kinase C and Ca2+-calmodulin dependent kinase II. These pathways match those leading to hyperalgesia in behaving animals and humans. We thus propose that LTP induced by low-level activity in C-fibres may underlie some forms of hyperalgesia.

  17. Chronic Fluoxetine Treatment Induces Brain Region-Specific Upregulation of Genes Associated with BDNF-Induced Long-Term Potentiation

    Directory of Open Access Journals (Sweden)

    Maria Nordheim Alme

    2007-01-01

    Full Text Available Several lines of evidence implicate BDNF in the pathogenesis of stress-induced depression and the delayed efficacy of antidepressant drugs. Antidepressant-induced upregulation of BDNF signaling is thought to promote adaptive neuronal plasticity through effects on gene expression, but the effector genes downstream of BDNF has not been identified. Local infusion of BDNF into the dentate gyrus induces a long-term potentiation (BDNF-LTP of synaptic transmission that requires upregulation of the immediate early gene Arc. Recently, we identified five genes (neuritin, Narp, TIEG1, Carp, and Arl4d that are coupregulated with Arc during BDNF-LTP. Here, we examined the expression of these genes in the dentate gyrus, hippocampus proper, and prefrontal cortex after antidepressant treatment. We show that chronic, but not acute, fluoxetine administration leads to upregulation of these BDNF-LTP-associated genes in a brain region-specific pattern. These findings link chronic effects of antidepressant treatment to molecular mechanisms underlying BDNF-induced synaptic plasticity.

  18. Despair-associated memory requires a slow-onset CA1 long-term potentiation with unique underlying mechanisms.

    Science.gov (United States)

    Jing, Liang; Duan, Ting-Ting; Tian, Meng; Yuan, Qiang; Tan, Ji-Wei; Zhu, Yong-Yong; Ding, Ze-Yang; Cao, Jun; Yang, Yue-Xiong; Zhang, Xia; Mao, Rong-Rong; Richter-Levin, Gal; Zhou, Qi-Xin; Xu, Lin

    2015-10-09

    The emotion of despair that occurs with uncontrollable stressful event is probably retained by memory, termed despair-associated memory, although little is known about the underlying mechanisms. Here, we report that forced swimming (FS) with no hope to escape, but not hopefully escapable swimming (ES), enhances hippocampal α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)-dependent GluA1 Ser831 phosphorylation (S831-P), induces a slow-onset CA1 long-term potentiation (LTP) in freely moving rats and leads to increased test immobility 24-h later. Before FS application of the antagonists to block S831-P or N-methyl-D-aspartic acid receptor (NMDAR) or glucocorticoid receptor (GR) disrupts LTP and reduces test immobility, to levels similar to those of the ES group. Because these mechanisms are specifically linked with the hopeless of escape from FS, we suggest that despair-associated memory occurs with an endogenous CA1 LTP that is intriguingly mediated by a unique combination of rapid S831-P with NMDAR and GR activation to shape subsequent behavioral despair.

  19. Impaired induction of long-term potentiation-like plasticity in patients with high-functioning autism and Asperger syndrome.

    Science.gov (United States)

    Jung, Nikolai H; Janzarik, Wibke G; Delvendahl, Igor; Münchau, Alexander; Biscaldi, Monica; Mainberger, Florian; Bäumer, Tobias; Rauh, Reinhold; Mall, Volker

    2013-01-01

    We aimed to investigate the induction of long-term potentiation (LTP)-like plasticity by paired associative stimulation (PAS) in patients with high-functioning autism and Asperger syndrome (HFA/AS). PAS with an interstimulus interval between electrical and transcranial magnetic stimulation of 25 ms (PAS(25)) was performed in patients with HFA/AS (n=9; eight males, one female; mean age 17 y 11 mo, SD 4 y 5 mo) and in typically developing age-matched volunteers (n=9; five males, four females; mean age 22 y 4 mo, SD 5 y 2 mo). The amplitude of motor-evoked potentials was measured before PAS(25), immediately after stimulation, and 30 minutes and 60 minutes later. A PAS protocol adapted to individual N20 latency (PAS(N20+2)) was performed in six additional patients with HFA/AS. Short-interval intracortical inhibition was measured using paired-pulse stimulation. In contrast to the typically developing participants, the patients with HFA/AS did not show a significant increase in motor-evoked potentials after PAS(25). This finding could also be demonstrated after adaptation for N20 latency. Short-interval intracortical inhibition of patients with HFA/AS was normal compared with the comparison group and did not correlate with PAS effect. Our results show a significant impairment of LTP-like plasticity induced by PAS in individuals with HFA/AS compared with typically developing participants. This finding is in accordance with results from animal studies as well as human studies. Impaired LTP-like plasticity in patients with HFA/AS points towards reduced excitatory synaptic connectivity and deficits in sensory-motor integration in these patients. © The Authors. Developmental Medicine & Child Neurology © 2012 Mac Keith Press.

  20. The effect of age on the homotopic motor cortical long-term potentiation-like effect induced by quadripulse stimulation.

    Science.gov (United States)

    Hanajima, Ritsuko; Tanaka, Nobuyuki; Tsutsumi, Ryosuke; Enomoto, Hiroyuki; Abe, Mitsunari; Nakamura, Koichiro; Kobayashi, Shunsuke; Hamada, Masashi; Shimizu, Takahiro; Terao, Yasuo; Ugawa, Yoshikazu

    2017-07-01

    The reduction of plasticity with age has been shown by many previous papers in animal experiments. This issue can be studied in humans because several non-invasive brain stimulation techniques induce synaptic plasticity in the human brain. We investigated the influence of individuals' age on the responder rate of the long-term potentiation (LTP)-like effect induced by quadripulse magnetic stimulation (QPS). The participants were 107 healthy volunteers: 53 older participants (Mean ± SD 65.0 ± 1.5 years) and 54 younger participants (37.2 ± 8.7). The quadripulse stimulation with 5-ms inter-pulse interval (QPS5) was applied over the primary motor cortex (M1). We measured motor evoked potentials (MEPs) before QPS, and at five time points after QPS for up to 25 min. In each participant, average MEP amplitude (size) ratios were quantified. We first classified participants as responders and non-responders simply by comparing the size ratio with 1.0 for consistency with previous studies, then as "significant responders", "non-responders", and "opposite responders" for more detailed analysis by comparing the size ratio with the mean and standard deviation of the MEP size ratios of the sham condition. The degree of LTP-like effects induced by QPS5 was significantly smaller in the older group compared to the younger group. Also, the rates of responders and significant responders were lower in the older group (58 and 47%, respectively) compared to the younger group (80 and 76%, respectively). The age of the participants significantly affected the LTP-like effect induced by QPS5, which suggests that brain plasticity decreases with age.

  1. Wnt-5a prevents Aβ-induced deficits in long-term potentiation and spatial memory in rats.

    Science.gov (United States)

    Zhang, Gui-Li; Zhang, Jun; Li, Shao-Feng; Lei, Liu; Xie, Hong-Yan; Deng, Fang; Feng, Jia-Chun; Qi, Jin-Shun

    2015-10-01

    Although the neurotoxicity of amyloid β (Aβ) protein in Alzheimer's disease (AD) has been reported widely, the exact molecular mechanism underlying the Aβ-induced synaptic dysfunction and memory impairment remains largely unclear. Growing evidence indicates that wingless-type (Wnt) signaling plays an important role in neuronal development, synapse formation and synaptic plasticity. In the present study, we investigated the neuroprotective action of Wnt-5a against the synaptic damage and memory deficit induced by Aβ25-35 by using in vivo electrophysiological recording and Morris water maze (MWM) test. We found that intracerebroventricular (i.c.v.) injection of Aβ25-35 alone did not affect the baseline field excitatory postsynaptic potentials (fEPSPs) and the paired-pulse facilitation (PPF) in the hippocampal CA1 region of rats, but significantly suppressed high frequency stimulation (HFS) induced long-term potentiation (LTP); pretreatment with Wnt-5a prevented the Aβ25-35-induced suppression of hippocampal LTP in a dose-dependent manner; soluble Frizzled-related protein (sFRP), a specific Wnt antagonist, effectively attenuated the protective effects of Wnt-5a. In MWM test, Aβ25-35 alone significantly disrupted spatial learning and memory ability of rats, while pretreatment with Wnt-5a effectively prevented the impairments induced by Aβ25-35. These results in the present study demonstrated for the first time the neuroprotective effects of Wnt-5a against Aβ-induced in vivo synaptic plasticity impairment and memory disorder, suggesting that Wnt signaling pathway is one of the important targets of Aβ neurotoxicity and Wnt-5a might be used as one of the putative candidates for the therapeutic intervention of AD. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Harmful potential toxic elements in greenhouse soils under long-term cultivation in Almería (Spain)

    Science.gov (United States)

    Joaquin Ramos-Miras, Jose; Rodríguez Martín, Jose Antonio; Boluda, Rafael; Bech, Jaume; Gil, Carlos

    2014-05-01

    Heavy metals (HM) are considered highly significant environmental contaminants and are the object of many scientific research works into the soil environment. Activities like agriculture or industry can increase the concentration of these contaminants in soils and waters, which can affect the food chain. Intensification of certain agricultural practices, constant and excessive use of fertilizers and phytosanitary products, and using machinery, increase the HM content in agricultural soils. Many studies have dealt with HM accumulation over time. Despite these works, the influence of long periods of time on these contents, the dynamics and evolution of these elements in agricultural soils, especially soils used for intensive farming purposes under greenhouse conditions, remain unknown to a certain extent. The western Almería region (Spain) is a very important area from both the socio-economic and agricultural viewpoints. A common practice in greenhouse agriculture is the addition of agrochemicals to soils and crops to improve nutrient supply or crop protection and disease control. Such intense agricultural activity has a strong impact, which may have negative repercussions on both these greenhouse soils and the environment. A research has been carried out to determine the total and available levels of six harmful potentially toxic elements (Cd, Cu, Pb, Ni, Zn and Co), and to assess long-term variations in the greenhouse soils of western Almeria. The results indicate that managing soils in the greenhouse preparation stage determines major changes in total and available HM contents. Furthermore, Cd, Cu and Pb enrichment in soil was observed depending on the element and years of growth.

  3. Daily acclimation handling does not affect hippocampal long-term potentiation or cause chronic sleep deprivation in mice.

    Science.gov (United States)

    Vecsey, Christopher G; Wimmer, Mathieu E J; Havekes, Robbert; Park, Alan J; Perron, Isaac J; Meerlo, Peter; Abel, Ted

    2013-04-01

    Gentle handling is commonly used to perform brief sleep deprivation in rodents. It was recently reported that daily acclimation handling, which is often used before behavioral assays, causes alterations in sleep, stress, and levels of N-methyl-D-aspartate receptor subunits prior to the actual period of sleep deprivation. It was therefore suggested that acclimation handling could mediate some of the observed effects of subsequent sleep deprivation. Here, we examine whether acclimation handling, performed as in our sleep deprivation studies, alters sleep/wake behavior, stress, or forms of hippocampal synaptic plasticity that are impaired by sleep deprivation. Adult C57BL/6J mice were either handled daily for 6 days or were left undisturbed in their home cages. On the day after the 6(th) day of handling, long-term potentiation (LTP) was induced in hippocampal slices with spaced four-train stimulation, which we previously demonstrated to be impaired by brief sleep deprivation. Basal synaptic properties were also assessed. In three other sets of animals, activity monitoring, polysomnography, and stress hormone measurements were performed during the 6 days of handling. Daily gentle handling alone does not alter LTP, rest/activity patterns, or sleep/wake architecture. Handling initially induces a minimal stress response, but by the 6(th) day, stress hormone levels are unaltered by handling. It is possible to handle mice daily to accustom them to the researcher without causing alterations in sleep, stress, or synaptic plasticity in the hippocampus. Therefore, effects of acclimation handling cannot explain the impairments in signaling mechanisms, synaptic plasticity, and memory that result from brief sleep deprivation.

  4. Preventive effect of theanine intake on stress-induced impairments of hippocamapal long-term potentiation and recognition memory.

    Science.gov (United States)

    Tamano, Haruna; Fukura, Kotaro; Suzuki, Miki; Sakamoto, Kazuhiro; Yokogoshi, Hidehiko; Takeda, Atsushi

    2013-06-01

    Theanine, γ-glutamylethylamide, is one of the major amino acid components in green tea. On the basis of the preventive effect of theanine intake after birth on mild stress-induced attenuation of hippocamapal CA1 long-term potentiation (LTP), the present study evaluated the effect of theanine intake after weaning on stress-induced impairments of LTP and recognition memory. Young rats were fed water containing 0.3% theanine for 3 weeks after weaning and subjected to water immersion stress for 30min, which was more severe than tail suspension stress for 30s used previously. Serum corticosterone levels were lower in theanine-administered rats than in the control rats even after exposure to stress. CA1 LTP induced by a 100-Hz tetanus for 1s was inhibited in the presence of 2-amino-5-phosphonovalerate (APV), an N-methyl-d-aspartate (NMDA) receptor antagonist, in hippocampal slices from the control rats and was attenuated by water immersion stress. In contrast, CA1 LTP was not significantly inhibited in the presence of APV in hippocampal slices from theanine-administered rats and was not attenuated by the stress. Furthermore, object recognition memory was impaired in the control rats, but not in theanine-administered rats. The present study indicates the preventive effect of theanine intake after weaning on stress-induced impairments of hippocampal LTP and recognition memory. It is likely that the modification of corticosterone secretion after theanine intake is involved in the preventive effect. Copyright © 2013 Elsevier Inc. All rights reserved.

  5. Social Isolation During Adolescence Strengthens Retention of Fear Memories and Facilitates Induction of Late-Phase Long-Term Potentiation.

    Science.gov (United States)

    Liu, Ji-Hong; You, Qiang-Long; Wei, Mei-Dan; Wang, Qian; Luo, Zheng-Yi; Lin, Song; Huang, Lang; Li, Shu-Ji; Li, Xiao-Wen; Gao, Tian-Ming

    2015-12-01

    Social isolation during the vulnerable period of adolescence produces emotional dysregulation that often manifests as abnormal behavior in adulthood. The enduring consequence of isolation might be caused by a weakened ability to forget unpleasant memories. However, it remains unclear whether isolation affects unpleasant memories. To address this, we used a model of associative learning to induce the fear memories and evaluated the influence of isolation mice during adolescence on the subsequent retention of fear memories and its underlying cellular mechanisms. Following adolescent social isolation, we found that mice decreased their social interaction time and had an increase in anxiety-related behavior. Interestingly, when we assessed memory retention, we found that isolated mice were unable to forget aversive memories when tested 4 weeks after the original event. Consistent with this, we observed that a single train of high-frequency stimulation (HFS) enabled a late-phase long-term potentiation (L-LTP) in the hippocampal CA1 region of isolated mice, whereas only an early-phase LTP was observed with the same stimulation in the control mice. Social isolation during adolescence also increased brain-derived neurotrophic factor (BDNF) expression in the hippocampus, and application of a tropomyosin-related kinase B (TrkB) receptor inhibitor ameliorated the facilitated L-LTP seen after isolation. Together, our results suggest that adolescent isolation may result in mental disorders during adulthood and that this may stem from an inability to forget the unpleasant memories via BDNF-mediated synaptic plasticity. These findings may give us a new strategy to prevent mental disorders caused by persistent unpleasant memories.

  6. Mechanistic target of rapamycin is necessary for changes in dendritic spine morphology associated with long-term potentiation.

    Science.gov (United States)

    Henry, Fredrick E; Hockeimer, William; Chen, Alex; Mysore, Shreesh P; Sutton, Michael A

    2017-10-30

    Alterations in the strength of excitatory synapses in the hippocampus is believed to serve a vital function in the storage and recall of new information in the mammalian brain. These alterations involve the regulation of both functional and morphological features of dendritic spines, the principal sites of excitatory synaptic contact. New protein synthesis has been implicated extensively in the functional changes observed following long-term potentiation (LTP), and changes to spine morphology have similarly been documented extensively following synaptic potentiation. However, mechanistic links between de novo translation and the structural changes of potentiated spines are less clear. Here, we assess explicitly the potential contribution of new protein translation under control of the mechanistic target of rapamycin (mTOR) to LTP-associated changes in spine morphology. Utilizing genetic and pharmacological manipulations of mTORC1 function in combination with confocal microscopy in live dissociated hippocampal cultures, we demonstrate that chemically-induced LTP (cLTP) requires do novo protein synthesis and intact mTORC1 signaling. We observed a striking diversity in response properties across morphological classes, with mushroom spines displaying a particular sensitivity to altered mTORC1 signaling across varied levels of synaptic activity. Notably, while pharmacological inhibition of mTORC1 signaling significantly diminished glycine-induced changes in spine morphology, transient genetic upregulation of mTORC1 signaling was insufficient to produce spine enlargements on its own. In contrast, genetic upregulation of mTORC1 signaling promoted rapid expansion in spine head diameter when combined with otherwise sub-threshold synaptic stimulation. These results suggest that synaptic activity-derived signaling pathways act in combination with mTORC1-dependent translational control mechanisms to ultimately regulate changes in spine morphology. As several monogenic

  7. Congenital Heart Disease With and Without Cyanotic Potential and the Long-term Risk of Diabetes Mellitus

    DEFF Research Database (Denmark)

    Madsen, Nicolas L; Marino, Bradley S; Woo, Jessica G

    2016-01-01

    BACKGROUND: Long-term survival for persons born with congenital heart disease (CHD) is improved, but limited knowledge exists of this growing population's acquired cardiovascular risk profile. This study's purpose was to assess CHD survivors' risk for type 2 diabetes mellitus (T2DM) with attention...

  8. A Review of Potential Adverse Effects of Long-Term Opioid Therapy: A Practitioner’s Guide

    OpenAIRE

    Baldini, AnGee; Von Korff, Michael; Lin, Elizabeth H. B.

    2012-01-01

    Objective:Review, synthesize, and summarize recent evidence on adverse effects of long-term opioid treatment for noncancer pain and present an organ system–based guide for primary care physicians in initiating and monitoring patients receiving chronic opioid therapy.

  9. Long-Term Mechanical Ventilation.

    Science.gov (United States)

    Sahetya, Sarina; Allgood, Sarah; Gay, Peter C; Lechtzin, Noah

    2016-12-01

    Although precise numbers are difficult to obtain, the population of patients receiving long-term ventilation has increased over the last 20 years, and includes patients with chronic lung diseases, neuromuscular diseases, spinal cord injury, and children with complex disorders. This article reviews the equipment and logistics involved with ventilation outside of the hospital. Discussed are common locations for long-term ventilation, airway and secretion management, and many of the potential challenges faced by individuals on long-term ventilation. Published by Elsevier Inc.

  10. Worldwide impact of aerosol’s time scale on the predicted long-term concentrating solar power potential

    Science.gov (United States)

    Ruiz-Arias, Jose A.; Gueymard, Christian A.; Santos-Alamillos, Francisco J.; Pozo-Vázquez, David

    2016-08-01

    Concentrating solar technologies, which are fuelled by the direct normal component of solar irradiance (DNI), are among the most promising solar technologies. Currently, the state-of the-art methods for DNI evaluation use datasets of aerosol optical depth (AOD) with only coarse (typically monthly) temporal resolution. Using daily AOD data from both site-specific observations at ground stations as well as gridded model estimates, a methodology is developed to evaluate how the calculated long-term DNI resource is affected by using AOD data averaged over periods from 1 to 30 days. It is demonstrated here that the use of monthly representations of AOD leads to systematic underestimations of the predicted long-term DNI up to 10% in some areas with high solar resource, which may result in detrimental consequences for the bankability of concentrating solar power projects. Recommendations for the use of either daily or monthly AOD data are provided on a geographical basis.

  11. VIRTEx project aims to promote long term health and improve social care. Virtual extra care project develops the potential of telehealthcare to provide community-based care.

    Science.gov (United States)

    Sadler, Steve

    2009-03-01

    Funded by the Technology Strategy Boards Assisted Living Innovation Platform, the VIRTEx project aims to develop the potential of telehealthcare to provide community-based care and increased social activity, inclusion and support for the growing number of people with long-term needs.

  12. Emotional and Cognitive Information Processing: Relations to Behavioral Performance and Hippocampal Long-Term Potentiation In Vivo during a Spatial Water Maze Training in Rats

    Science.gov (United States)

    Schulz, Kristina; Korz, Volker

    2010-01-01

    Emotionality as well as cognitive abilities contribute to the acquisition and retrieval of memories as well as to the consolidation of long-term potentiation (LTP), a cellular model of memory formation. However, little is known about the timescale and relative contribution of these processes. Therefore, we tested the effects of weak water maze…

  13. Assessing Potential Implications of Climate Change for Long-Term Water Resources Planning in the Colorado River Basin, Texas

    Science.gov (United States)

    Munevar, A.; Butler, S.; Anderson, R.; Rippole, J.

    2008-12-01

    exploring climate change projections and methods to assess potential impacts over the project's expected life. Following an initial qualitative risk assessment, quantitative climate scenarios were developed based on multiple coupled atmosphere-ocean general circulation model (AOGCM) simulations under a range of global emission scenarios. Projected temperature and precipitation changes were evaluated from 112 downscaled AOGCM projections. A Four scenarios were selected for detailed hydrologic evaluations using the Variable Infiltration Capacity (VIC) macroscale model. A quantile mapping procedure was applied to map future climatological period change statistics onto the long-term natural climate variability in the observed record. Simulated changes in runoff, river flow, evaporation, and evapotranspiration are used to generate adjustments to historical hydrology for assessment of potential changes to surface water availability, river water quality, riverine habitat, and Bay health. Projected temperature, precipitation, and atmospheric CO2 concentrations are used to estimate changes in agricultural demand. Sea level rise scenarios that include trends in Gulf Coast shelf subsidence are combined with changes in inflows to evaluate increased coastal erosion, upland migration of the estuary, and changes to the salinity regime. Results of the scenario-based analyses are being considered in the development of adaptive management strategies for future operations of the system and the proposed project.

  14. Identifying flood deposits in lake sediments: Changing frequencies and potential links to long-term climate change

    Energy Technology Data Exchange (ETDEWEB)

    Stoeren, Eivind Wilhelm Nagel

    2011-05-15

    ,000 years, including floods that have also been recorded by instrumental and historical data. The minimum number of individual floods recorded for this period is c. 100. On centennial timescales significant change in flood frequency is observed that arguably can be attributed to large-scale climatic changes such as the varying amount of winter precipitation and number of summer rainstorms. The flood frequency was low during the early Holocene (9770-7700 cal. years BP), and was even lower for the period that followed, lasting until 5500 cal. years BP. For the next 2500 years, a modest increase in flood activity followed. This trend was truncated at 2500 cal. years BP by a sudden shift towards increased flooding frequency. With the exception of a short interval around 1000 cal. years BP, when the number of floods was again low, this tendency of increased flood activity prevailed until the present day; including Stor-Ofsen, a large flood that occurred in AD 1789, and also three other historically documented river floods. In Parer III we compared the record from Jotunheimen to a second continuous, high resolution palaeo flood record from Butjoenna (62' N 10' E) and found that both the frequency and distribution of flood events over southern Norway has changed significantly during the Holocene. The present regional-discharge regime is dominated by spring-summer snow melt, and results indicate that the changing flood frequency cannot be explained by local conditions associated with the respective catchment of the two lakes, but rather by long-term variations of solid winter precipitation and related snow melt. Applying available instrumental winter precipitation data and associated sea-level pressure re-analysis data as a modern analogue, we document that atmospheric-circulation anomalies, significantly different from the North Atlantic Oscillation (NAO), have some potential in explaining the variability of the two different palaeo flood records. Centennial

  15. Potentials, Limitations and Applications of long-term and mobile ad-hoc Wireless Sensor Networks for Environmental Monitoring

    Science.gov (United States)

    Bumberger, Jan; Mollenhauer, Hannes; Lapteva, Yulia; Hutschenreuther, Tino; Toepfer, Hannes; Dietrich, Peter

    2014-05-01

    To characterize environmental systems it is necessary to identify and describe processes with suitable methods. Environmental systems are often characterized by their high heterogeneity, so individual measurements for their complete representation are often not sufficient. The application of wireless sensor networks in terrestrial and aquatic ecosystems offer significant benefits as a better consideration of the local test conditions becomes possible. This can be essential for the monitoring of heterogeneous environmental systems. Significant advantages in the application of mobile ad-hoc wireless sensor networks are their self-organizing behavior, resulting in a major reduction in installation and operation costs and time. In addition, a point measurement with a sensor is significantly improved by measuring at several points. It is also possible to perform analog and digital signal processing and computation on the basis of the measured data close to the sensor. Hence, a significant reduction of the data to be transmitted can be achieved which leads to a better energy management of sensor nodes. Furthermore, their localization via satellite, the miniaturization of the nodes and long-term energy self-sufficiency are current topics under investigation. The possibilities and limitations of the applicability of wireless sensor networks for long-term and mobile environmental monitoring are presented. A concepts and realization example are given in the field of micrometeorology and soil parameters for the interaction of biotic and abiotic processes .This long term monitoring is part of the Global Change Experimental Facility (GCEF), a large field-based experimental platform to assess the effects of climate change on ecosystem functions and processes under different land-use scenarios. Furthermore a mobile ad-hoc sensor network is presented for the monitoring of water induced mass wasting processes.

  16. Long term-cultured and cryopreserved primordial germ cells from various chicken breeds retain high proliferative potential and gonadal colonisation competency.

    Science.gov (United States)

    Tonus, Céline; Cloquette, Karine; Ectors, Fabien; Piret, Joëlle; Gillet, Laurent; Antoine, Nadine; Desmecht, Daniel; Vanderplasschen, Alain; Waroux, Olivier; Grobet, Luc

    2016-04-01

    When derived from chicken embryos, avian primordial germ cells (PGCs) have been reported to keep their germline-specific properties and proliferative potential even after long-term culture and genetic modifications. Few teams to date have reported such long-term expansion and engineering without differentiation of primary avian PGCs' cultures. We have developed original and robust methods that allow more than 1 year culture, expansion and cryobanking of primary cultures of PGCs without obvious effects on their biological properties, including their ability to colonise the genital ridges. Overall, 38% of embryonic samples gave rise to PGCs lines derived from three commercial layers and two Belgian endangered breeds. The lines kept their proliferative potential and their characteristic PGCs phenotype after 20 months in culture, whether or not interrupted by a cryopreservation step. All the resulting lines appeared devoid of female cells, although initially pooled from male and female embryos. Labelled PGCs from 12 long-term cultured lines colonised the genital ridges of recipient embryos. Thus, this procedure allows derivation, long-term expansion and cryobanking of primary cultures of PGCs without obvious changes to their original characteristics, providing an alternative access to applications in avian biotechnology and preservation of genetic resources.

  17. Forever Young(er: Potential Age-defying Effects of Long-term Meditation on Gray Matter Atrophy

    Directory of Open Access Journals (Sweden)

    Eileen eLuders

    2015-01-01

    Full Text Available While overall life expectancy has been increasing, the human brain still begins deteriorating after the first two decades of life and continues degrading further with increasing age. Thus, techniques that diminish the negative impact of aging on the brain are desirable. Existing research, although scarce, suggests meditation to be an attractive candidate in the quest for an accessible and inexpensive, efficacious remedy. Here, we examined the link between age and cerebral gray matter re-analyzing a large sample (n=100 of long-term meditators and control subjects aged between 24 and 77 years. When correlating global and local gray matter with age, we detected negative correlations within both controls and meditators, suggesting a decline over time. However, the slopes of the regression lines were steeper and the correlation coefficients were stronger in controls than in meditators. Moreover, the age-affected brain regions were much more extended in controls than in meditators, with significant group-by-age interactions in numerous clusters throughout the brain. Altogether, these findings seem to suggest less age-related gray matter atrophy in long-term meditation practitioners.

  18. Predictive Potential of Preoperative Nutritional Status in Long-Term Outcome Projections for Patients with Gastric Cancer.

    Science.gov (United States)

    Sakurai, Katsunobu; Ohira, Masaichi; Tamura, Tatsuro; Toyokawa, Takahiro; Amano, Ryosuke; Kubo, Naoshi; Tanaka, Hiroaki; Muguruma, Kazuya; Yashiro, Masakazu; Maeda, Kiyoshi; Hirakawa, Kosei

    2016-02-01

    Preoperative nutritional status not only correlates with the incidence of postoperative complications but also may be indicative of long-term outcomes for patients with cancer. The impact of preoperative nutritional status on outcomes for patients undergoing gastrectomy for gastric cancer (GC) was investigated. The study reviewed 594 patients treated for GC by gastrectomy at the authors' hospital between January, 2004 and December, 2010. Onodera's prognostic nutritional index (PNI) was invoked, using an optimal cut point to group patients as having high (PNI > 45; n = 449) or low (PNI ≤ 45; n = 145) nutritional status. Clinicopathologic features, perioperative results, and long-term outcomes, including cause of death, were compared. Multivariate analysis of 5-year overall survival (OS) and disease-specific survival (DSS) indicated that low PNI was independently associated with unfavorable outcomes for patients with GC. In subgroup analysis, the 5-year OS and DSS rates for patients with GC at stages 1 and 2 were significantly worse in the low PNI group than in the high PNI group. Although wound and extrasurgical field infections also tended to be more frequent in the low PNI group, postoperative intraabdominal infections did not differ significantly by group. Preoperative PNI may have merit as a gauge of prognosis for patients with GC at stages 1 and 2, but PNI and postoperative morbidity showed no correlation in this setting.

  19. The effect of extensive reading and paired-associate learning on long-term vocabulary retention: an event-related potential study.

    Science.gov (United States)

    Chun, Eunjin; Choi, Sungmook; Kim, Junsoo

    2012-07-19

    We investigated the relative efficacy of extensive reading (ER) and paired-associate learning (PAL) in the ability of second language (L2) learners to retain new vocabulary words. To that end, we combined behavioral measures (i.e., vocabulary tests) and an event-related potential (ERP) investigation with a focus on the N400 ERP component to track short- and long-term vocabulary retention as a consequence of the two different approaches. Behavioral results indicated that both ER and PAL led to substantial short-term retention of the target words. In contrast, on a long-term basis, ER was more effective than PAL to a considerable degree as indicated by a large-size effect (d=1.35). Evidence from the N400 effects (d=1.70) observed in the parietal electrode group (P3, Pz, P4) provided further support for the superior effects of ER over PAL on long-term vocabulary retention. The converging evidence challenges the assumptions of some L2 researchers and makes a significant contribution to the literature of vocabulary acquisition, because it provides the first ERP evidence that ER is more conducive to long-term vocabulary retention than PAL. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  20. Brevican-deficient mice display impaired hippocampal CA1 long-term potentiation but show no obvious deficits in learning and memory

    DEFF Research Database (Denmark)

    Brakebusch, Cord; Seidenbecher, Constanze I; Asztely, Fredrik

    2002-01-01

    to be less prominent in mutant than in wild-type mice. Brevican-deficient mice showed significant deficits in the maintenance of hippocampal long-term potentiation (LTP). However, no obvious impairment of excitatory and inhibitory synaptic transmission was found, suggesting a complex cause for the LTP defect....... Detailed behavioral analysis revealed no statistically significant deficits in learning and memory. These data indicate that brevican is not crucial for brain development but has restricted structural and functional roles....

  1. Long-term collections

    CERN Multimedia

    Collectes à long terme

    2007-01-01

    The Committee of the Long Term Collections (CLT) asks for your attention for the following message from a young Peruvian scientist, following the earthquake which devastated part of her country a month ago.

  2. Impact of long-term treatment of onchocerciasis with ivermectin in Ecuador: potential for elimination of infection

    Directory of Open Access Journals (Sweden)

    Proaño Roberto

    2007-05-01

    Full Text Available Abstract Background Onchocerciasis is a leading cause of blindness worldwide, hence elimination of the infection is an important health priority. Community-based treatment programs with ivermectin form the basis of control programs for the disease in Latin America. The long-term administration of ivermectin could eliminate Onchocerca volvulus infection from endemic areas in Latin America. Methods A strategy of annual to twice-annual treatments with ivermectin has been used for onchocerciasis in endemic communities in Ecuador for up to 14 years. The impact of ivermectin treatment on ocular morbidity, and O. volvulus infection and transmission was monitored in seven sentinel communities. Results Over the period 1990–2003, high rates of treatment coverage of the eligible population were maintained in endemic communities (mean 85.2% per treatment round. Ivermectin reduced the prevalence of anterior segment disease of the eye to 0% in sentinel communities and had a major impact on the prevalence and transmission of infection, with possible elimination of infection in some foci. Conclusion The distribution of ivermectin in endemic communities in Ecuador might have eliminated ocular morbidity and significant progress has been made towards elimination of the infection. A strategy of more frequent treatments with ivermectin may be required in communities where the infection persists to achieve the objective of elimination of the infection from Ecuador. The elimination of the infection from an endemic country in Latin America would be a major public health achievement and could stimulate the implementation of elimination strategies in other endemic countries.

  3. Congenital Heart Disease With and Without Cyanotic Potential and the Long-term Risk of Diabetes Mellitus

    DEFF Research Database (Denmark)

    Madsen, Nicolas L; Marino, Bradley S; Woo, Jessica G

    2016-01-01

    BACKGROUND: Long-term survival for persons born with congenital heart disease (CHD) is improved, but limited knowledge exists of this growing population's acquired cardiovascular risk profile. This study's purpose was to assess CHD survivors' risk for type 2 diabetes mellitus (T2DM) with attention...... population. After adjusting for CHD severity, as well as age, sex, preterm birth, and extracardiac defects, we analyzed the impact of cyanotic compared with acyanotic CHD. By age 45 years, the cumulative incidence of T2DM after age 30 was 4% among subjects with CHD. Subjects with CHD were more likely...... to develop T2DM than the general population (hazard raio 1.4, 95% CI 1.1-1.6). Subjects CHD who had cyanotic defects were more likely to develop T2DM than were subjects with acyanotic CHD (hazard ratio 1.9, 95% CI 1.1-3.3). CONCLUSIONS: CHD survivors had an increased risk of developing T2DM after age 30...

  4. p-Coumaric acid enhances long-term potentiation and recovers scopolamine-induced learning and memory impairments.

    Science.gov (United States)

    Kim, Hyun-Bum; Lee, Seok; Hwang, Eun-Sang; Maeng, Sungho; Park, Ji-Ho

    2017-10-21

    Due to the improvement of medical level, life expectancy increased. But the increased incidence of cognitive disorders is an emerging social problem. Current drugs for dementia treatment can only delay the progress rather than cure. p-Coumaric acid is a phenylpropanoic acid derived from aromatic amino acids and known as a precursor for flavonoids such as resveratrol and naringenin. It was shown to reduce oxidative stress, inhibit genotoxicity and exert neuroprotection. Based on these findings, we evaluated whether p-coumaric acid can protect scopolamine induced learning and memory impairment by measuring LTP in organotypic hippocampal slice and cognitive behaviors in rats. p-Coumaric acid dose-dependently increased the total activity of fEPSP after high frequency stimulation and attenuated scopolamine-induced blockade of fEPSP in the hippocampal CA1 area. In addition, while scopolamine shortened the step-through latency in the passive avoidance test and prolonged the latency as well as reduced the latency in the target quadrant in the Morris water maze test, co-treatment of p-coumaric acid improved avoidance memory and long-term retention of spatial memory in behavioral tests. Since p-coumaric acid improved electrophysiological and cognitive functional deterioration by scopolamine, it may have regulatory effects on central cholinergic synapses and is expected to improve cognitive problems caused by abnormality of the cholinergic nervous system. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. A substrate trapping mutant form of striatal-enriched protein tyrosine phosphatase prevents amphetamine-induced stereotypies and long-term potentiation in the striatum.

    Science.gov (United States)

    Tashev, Roman; Moura, Paula J; Venkitaramani, Deepa V; Prosperetti, Chiara; Centonze, Diego; Paul, Surojit; Lombroso, Paul J

    2009-04-15

    Chronic, intermittent exposure to psychostimulant drugs results in striatal neuroadaptations leading to an increase in an array of behavioral responses on subsequent challenge days. A brain-specific striatal-enriched tyrosine phosphatase (STEP) regulates synaptic strengthening by dephosphorylating and inactivating several key synaptic proteins. This study tests the hypothesis that a substrate-trapping form of STEP will prevent the development of amphetamine-induced stereotypies. A substrate-trapping STEP protein, TAT-STEP (C-S), was infused into the ventrolateral striatum on each of 5 consecutive exposure days and 1 hour before amphetamine injection. Animals were challenged to see whether sensitization to the stereotypy-producing effects of amphetamine developed. The same TAT-STEP (C-S) protein was used on acute striatal slices to determine the impact on long-term potentiation and depression. Infusion of TAT-STEP (C-S) blocks the increase of amphetamine-induced stereotypies when given during the 5-day period of sensitization. The TAT-STEP (C-S) has no effect if only infused on the challenge day. Treatment of acute striatal slices with TAT-STEP (C-S) blocks the induction of long-term potentiation and potentates long-term depression. A substrate trapping form of STEP blocks the induction of amphetamine-induced neuroplasticity within the ventrolateral striatum and supports the hypothesis that STEP functions as a tonic break on synaptic strengthening.

  6. Drivers, trends, and potential impacts of long-term coastal reclamation in China from 1985 to 2010

    Energy Technology Data Exchange (ETDEWEB)

    Tian, Bo; Wu, Wenting; Yang, Zhaoqing; Zhou, Yunxuan

    2016-03-01

    Driven by rapid economic development, population growth, and urbanization, China has experienced severe coastal land reclamation over the last decades, which resulted in significant loss of coastal wetland and wildlife habitat, and degradation of marine ecosystems. This study used advanced remote-sensing techniques to analyze the spatial and temporal distributions of coastal reclamation in China and investigated the relationships between coastal land reclamation and coastal economy, population growth, and urbanization. Analysis of long-term Landsat images time series from 1985 to 2010 in 5-year intervals, in combination with remotely sensed image techniques, indicated a sharp increasing trend of land reclamation after 2005, which accounted for over 35% of China’s total reclamation during the 25-year period since 1985. High-intensity coastal reclamation in China was mainly driven by the booming economy associated with urbanization and industrial development in the coastal region. Analysis indicated that coastal land reclamation is closely correlated with the GDP per capita in China. Study results of Landsat images showed that 754,697 ha of coastal wetlands have been reclaimed across all coastal provinces and metropolises from 1985 to 2010, at an annual rate of 5.9%. Coastal areas within the three major economic zones (Bohai Bay, Yangtze River Delta, and Pearl River Delta) were found to generally have higher reclamation rates. For example, the built-up area in Shanghai, which is located in the Yangtze River Delta, increased more than five times from 1985 to 2010. Approximately 35% of the reclamation occurred in Bohai Bay, in which the CRI between 2005 and 2010 was three times higher than the average CRI over the 25-year period.

  7. Evaluation of differentiated neurotherapy programs for a patient after severe TBI and long term coma using event-related potentials.

    Science.gov (United States)

    Pachalska, Maria; Łukowicz, Małgorzata; Kropotov, Juri D; Herman-Sucharska, Izabela; Talar, Jan

    2011-10-01

    This article examines the effectiveness of differentiated rehabilitation programs for a patient with frontal syndrome after severe TBI and long-term coma. We hypothesized that there would be a small response to relative beta training, and a good response to rTMS, applied to regulate the dynamics of brain function. M. L-S, age 26, suffered from anosognosia, executive dysfunction, and behavioral changes, after a skiing accident and prolonged coma, rendering him unable to function independently in many situations of everyday life. Only slight progress was made after traditional rehabilitation. The patient took part in 20 sessions of relative beta training (program A) and later in 20 sessions of rTMS (program B); both programs were combined with behavioral training. We used standardized neuropsychological testing, as well as ERPs before the experiment, after the completion of program A, and again after the completion of program B. As hypothesized, patient M.L-S showed small improvements in executive dysfunction and behavioral disorders after the conclusion of program A, and major improvement after program B. Similarly, in physiological changes the patient showed small improvement after relative beta training and a significant improvement of the P300 NOGO component after the rTMS program. The rTMS program produced larger physiological and behavioral changes than did relative beta training. A combination of different neurotherapeutical approaches (such as neurofeedback, rTMS, tDCS) can be suggested for similar severe cases of TBI. ERPs can be used to assess functional brain changes induced by neurotherapeutical programs.

  8. Burn injury during long-term oxygen therapy in Denmark and Sweden: the potential role of smoking.

    Science.gov (United States)

    Tanash, Hanan A; Ringbaek, Thomas; Huss, Fredrik; Ekström, Magnus

    2017-01-01

    Long-term oxygen therapy (LTOT) increases life expectancy in patients with COPD and severe hypoxemia. Smoking is the main cause of burn injury during LTOT. Policy regarding smoking while on LTOT varies between countries. In this study, we compare the incidence of burn injury that required contact with a health care specialist, between Sweden (a country with a strict policy regarding smoking while on LTOT) and Denmark (a country with less strict smoking policy). This was a population-based, cohort study of patients initiating LTOT due to any cause in Sweden and Denmark. Data on diagnoses, external causes, and procedures were obtained from the Swedish and Danish National Patient Registers for inpatient and outpatient care. Patients were followed from January 1, 2000, until the first of the following: LTOT withdrawal, death, or study end (December 31, 2009). The primary end point was burn injury during LTOT. A total of 23,741 patients received LTOT in Denmark and 7,754 patients in Sweden. Most patients started LTOT due to COPD, both in Sweden (74%) and in Denmark (62%). The rate of burn injury while on LTOT was higher in Denmark than in Sweden; 170 (95% confidence interval [CI], 126-225) vs 85 (95% CI, 44-148) per 100,000 person-years; rate ratio 2.0 (95% CI, 1.0-4.1). The risk remained higher after adjustment for gender, age, and diagnosis in multivariate Cox regression, hazard ratio 1.8 (95% CI, 1.0-3.5). Thirty-day mortality after burn injury was 8% in both countries. Compared to Sweden, the rate of burn injury was twice as high in Denmark where smoking is not a contraindication for prescribing LTOT.

  9. Global climate change in large European rivers: long-term effects on macroinvertebrate communities and potential local confounding factors.

    Science.gov (United States)

    Floury, Mathieu; Usseglio-Polatera, Philippe; Ferreol, Martial; Delattre, Cecile; Souchon, Yves

    2013-04-01

    Aquatic species living in running waters are widely acknowledged to be vulnerable to climate-induced, thermal and hydrological fluctuations. Climate changes can interact with other environmental changes to determine structural and functional attributes of communities. Although such complex interactions are most likely to occur in a multiple-stressor context as frequently encountered in large rivers, they have received little attention in such ecosystems. In this study, we aimed at specifically addressing the issue of relative long-term effects of global and local changes on benthic macroinvertebrate communities in multistressed large rivers. We assessed effects of hydroclimatic vs. water quality factors on invertebrate community structure and composition over 30 years (1979-2008) in the Middle Loire River, France. As observed in other large European rivers, water warming over the three decades (+0.9 °C between 1979-1988 and 1999-2008) and to a lesser extent discharge reduction (-80 m(3) s(-1) ) were significantly involved in the disappearance or decrease in taxa typical from fast running, cold waters (e.g. Chloroperlidae and Potamanthidae). They explained also a major part of the appearance and increase of taxa typical from slow flowing or standing waters and warmer temperatures, including invasive species (e.g. Corbicula sp. and Atyaephyra desmarestii). However, this shift towards a generalist and pollution tolerant assemblage was partially confounded by local improvement in water quality (i.e. phosphate input reduction by about two thirds and eutrophication limitation by almost one half), explaining a significant part of the settlement of new pollution-sensitive taxa (e.g. the caddisfly Brachycentridae and Philopotamidae families) during the last years of the study period. The regain in such taxa allowed maintaining a certain level of specialization in the invertebrate community despite climate change effects. © 2012 Blackwell Publishing Ltd.

  10. Long-term decoding stability of local field potentials from silicon arrays in primate motor cortex during a 2D center out task

    Science.gov (United States)

    Wang, Dong; Zhang, Qiaosheng; Li, Yue; Wang, Yiwen; Zhu, Junming; Zhang, Shaomin; Zheng, Xiaoxiang

    2014-06-01

    Objective. Many serious concerns exist in the long-term stability of brain-machine interfaces (BMIs) based on spike signals (single unit activity, SUA; multi unit activity, MUA). Some studies showed local field potentials (LFPs) could offer a stable decoding performance. However, the decoding stability of LFPs was examined only when high quality spike signals were recorded. Here we aim to examine the long-term decoding stability of LFPs over a larger time scale when the quality of spike signals was from good to poor or even no spike was recorded. Approach. Neural signals were collected from motor cortex of three monkeys via silicon arrays over 230, 290 and 690 days post-implantation when they performed 2D center out task. To compare long-term stability between LFPs and spike signals, we examined them in neural signals characteristics, directional tuning properties and offline decoding performance, respectively. Main results. We observed slow decreasing trends in the number of LFP channels recorded and mean LFP power in different frequency bands when spike signals quality decayed over time. The number of significantly directional tuning LFP channels decreased more slowly than that of tuning SUA and MUA. The variable preferred directions for the same signal features across sessions indicated non-stationarity of neural activity. We also found that LFPs achieved better decoding performance than SUA and MUA in retrained decoder when the quality of spike signals seriously decayed. Especially, when no spike was recorded in one monkey after 671 days post-implantation, LFPs still provided some kinematic information. In addition, LFPs outperformed MUA in long-term decoding stability in a static decoder. Significance. Our results suggested that LFPs were more durable and could provide better decoding performance when spike signals quality seriously decayed. It might be due to their resistance to recording degradation and their high redundancy among channels.

  11. Encapsulated living choroid plexus cells: potential long-term treatments for central nervous system disease and trauma

    Science.gov (United States)

    Skinner, S. J. M.; Geaney, M. S.; Lin, H.; Muzina, M.; Anal, A. K.; Elliott, R. B.; Tan, P. L. J.

    2009-12-01

    . Previously reported evidence demonstrated that CP cells support the survival and differentiation of neuronal cells in vitro and effectively treat acute brain injury and disease in rodents and non-human primates in vivo. The accumulated preclinical data together with the long-term survival of implanted encapsulated cells in vivo provide a sound base for the investigation of these treatments for chronic inherited and established neurodegenerative conditions.

  12. Long-term exposure to estrogen enhances chemotherapeutic efficacy potentially through epigenetic mechanism in human breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Yu-Wei Chang

    Full Text Available Chemotherapy is the most common clinical option for treatment of breast cancer. However, the efficacy of chemotherapy depends on the age of breast cancer patients. Breast tissues are estrogen responsive and the levels of ovarian estrogen vary among the breast cancer patients primarily between pre- and post-menopausal age. Whether this age-dependent variation in estrogen levels influences the chemotherapeutic efficacy in breast cancer patients is not known. Therefore, the objective of this study was to evaluate the effects of natural estrogen 17 beta-estradiol (E2 on the efficacy of chemotherapeutic drugs in breast cancer cells. Estrogen responsive MCF-7 and T47D breast cancer cells were long-term exposed to 100 pg/ml estrogen, and using these cells the efficacy of chemotherapeutic drugs doxorubicin and cisplatin were determined. The result of cell viability and cell cycle analysis revealed increased sensitivities of doxorubicin and cisplatin in estrogen-exposed MCF-7 and T47D cells as compared to their respective control cells. Gene expression analysis of cell cycle, anti-apoptosis, DNA repair, and drug transporter genes further confirmed the increased efficacy of chemotherapeutic drugs in estrogen-exposed cells at molecular level. To further understand the role of epigenetic mechanism in enhanced chemotherapeutic efficacy by estrogen, cells were pre-treated with epigenetic drugs, 5-aza-2-deoxycytidine and Trichostatin A prior to doxorubicin and cisplatin treatments. The 5-aza-2 deoxycytidine pre-treatment significantly decreased the estrogen-induced efficacy of doxorubicin and cisplatin, suggesting the role of estrogen-induced hypermethylation in enhanced sensitivity of these drugs in estrogen-exposed cells. In summary, the results of this study revealed that sensitivity to chemotherapy depends on the levels of estrogen in breast cancer cells. Findings of this study will have clinical implications in selecting the chemotherapy strategies for

  13. Monitoring the long-term molecular epidemiology of the pneumococcus and detection of potential 'vaccine escape' strains.

    Directory of Open Access Journals (Sweden)

    Gagan A Pandya

    2011-01-01

    Full Text Available While the pneumococcal protein conjugate vaccines reduce the incidence in invasive pneumococcal disease (IPD, serotype replacement remains a major concern. Thus, serotype-independent protection with vaccines targeting virulence genes, such as PspA, have been pursued. PspA is comprised of diverse clades that arose through recombination. Therefore, multi-locus sequence typing (MLST-defined clones could conceivably include strains from multiple PspA clades. As a result, a method is needed which can both monitor the long-term epidemiology of the pneumococcus among a large number of isolates, and analyze vaccine-candidate genes, such as pspA, for mutations and recombination events that could result in 'vaccine escape' strains.We developed a resequencing array consisting of five conserved and six variable genes to characterize 72 pneumococcal strains. The phylogenetic analysis of the 11 concatenated genes was performed with the MrBayes program, the single nucleotide polymorphism (SNP analysis with the DNA Sequence Polymorphism program (DnaSP, and the recombination event analysis with the recombination detection package (RDP.The phylogenetic analysis correlated with MLST, and identified clonal strains with unique PspA clades. The DnaSP analysis correlated with the serotype-specific diversity detected using MLST. Serotypes associated with more than one ST complex had a larger degree of sequence polymorphism than a serotype associated with one ST complex. The RDP analysis confirmed the high frequency of recombination events in the pspA gene.The phylogenetic tree correlated with MLST, and detected multiple PspA clades among clonal strains. The genetic diversity of the strains and the frequency of recombination events in the mosaic gene, pspA were accurately assessed using the DnaSP and RDP programs, respectively. These data provide proof-of-concept that resequencing arrays could play an important role within research and clinical laboratories in both

  14. Long-Term Collections

    CERN Multimedia

    Comité des collectes à long terme

    2011-01-01

    It is the time of the year when our fireman colleagues go around the laboratory for their traditional calendars sale. A part of the money of the sales will be donated in favour of the long-term collections. We hope that you will welcome them warmly.

  15. Wnt Signaling Is Required for Long-Term Memory Formation

    Directory of Open Access Journals (Sweden)

    Ying Tan

    2013-09-01

    Full Text Available Wnt signaling regulates synaptic plasticity and neurogenesis in the adult nervous system, suggesting a potential role in behavioral processes. Here, we probed the requirement for Wnt signaling during olfactory memory formation in Drosophila using an inducible RNAi approach. Interfering with β-catenin expression in adult mushroom body neurons specifically impaired long-term memory (LTM without altering short-term memory. The impairment was reversible, being rescued by expression of a wild-type β-catenin transgene, and correlated with disruption of a cellular LTM trace. Inhibition of wingless, a Wnt ligand, and arrow, a Wnt coreceptor, also impaired LTM. Wingless expression in wild-type flies was transiently elevated in the brain after LTM conditioning. Thus, inhibiting three key components of the Wnt signaling pathway in adult mushroom bodies impairs LTM, indicating that this pathway mechanistically underlies this specific form of memory.

  16. Insulin-Like Growth Factor I Produces an Antidepressant-Like Effect and Elicits N-Methyl-D-Aspartate Receptor Independent Long-Term Potentiation of Synaptic Transmission in Medial Prefrontal Cortex and Hippocampus.

    Science.gov (United States)

    Burgdorf, Jeffrey; Zhang, Xiao-lei; Colechio, Elizabeth M; Ghoreishi-Haack, Nayereh; Gross, Amanda; Kroes, Roger A; Stanton, Patric K; Moskal, Joseph R

    2015-09-15

    Growth factors play an important role in regulating neurogenesis and synapse formation and may be involved in regulating the antidepressant response to conventional antidepressants. To date, Insulin-like growth factor I (IGFI) is the only growth factor that has shown antidepressant properties in human clinical trials. However, its mechanism of action remains unclear. The antidepressant-like effect of a single IV dose of IGFI was determined using a chronic unpredictable stress paradigm in the rat Porsolt, sucrose preference, novelty-induced hypophagia, and ultrasonic vocalization models. The dependence of the medial prefrontal cortex for these effects was determined by direct medial prefrontal cortex injection followed by Porsolt testing as well as IGFI receptor activation in the medial prefrontal cortex following an optimal IV antidepressant-like dose of IGFI. The effect of IGFI on synaptic transmission and long-term potentiation (LTP) of synaptic strength was assessed in the hippocampus and medial prefrontal cortex. The dependence of these effects on IGFI and AMPA receptor activation and protein synthesis were also determined. IGFI produced a rapid-acting and long-lasting antidepressant-like effect in each of the depression models. These effects were blocked by IGFI and AMPA receptor antagonists, and medial prefrontal cortex was localized. IGFI robustly increased synaptic strength in the hippocampus and medial prefrontal cortex and these effects were IGFI receptor and protein synthesis-dependent but N-methyl-d-aspartate receptor independent. IGFI also robustly facilitated hippocampal metaplasticity 24 hours postdosing. These data support the conclusion that the antidepressant-like effects of IGFI are mediated by a persistent, LTP-like enhancement of synaptic strength requiring both IGFIR activation and ongoing protein synthesis. © The Author 2015. Published by Oxford University Press on behalf of CINP.

  17. In vitro field potential monitoring on a multi-microelectrode array for the electrophysiological long-term screening of neural stem cell maturation.

    Science.gov (United States)

    Seidel, Diana; Jahnke, Heinz-Georg; Englich, Beate; Girard, Mathilde; Robitzki, Andrea A

    2017-05-30

    Due to the lack of appropriate cell models as well as automated electrophysiology monitoring technologies, the standardized identification of neurotoxic or protective effects in vitro remains a major problem in today's pharmaceutical ingredient development. Over the past few years, in vivo-like human pluripotent stem cell-derived neuronal networks have turned out to be a promising physiological cell source, if the establishment of robust and time-saving functional maturation strategies based on stable and expandable neural progenitor populations can be achieved. Here, we describe a multi-microelectrode array (MMEA)-based bioelectronics platform that was optimized for long-term electrophysiological activity monitoring of neuronal networks via field potential measurements. Differentiation of small molecule-based neuronal progenitors on MMEAs led to functional neurons within 15 days. More strikingly, these functional neuronal cultures could remain electrophysiologically stable on the MMEAs for more than four weeks. The observed electrophysiological properties correlated with the expression of typical neuron subtype markers and were further validated by specific neurotransmitter applications. With our established monitoring platform, we could show for the first time the long-term stability of the neural stem cell-like progenitor population to differentiate to electrophysiologically active dopaminergic neuronal networks for more than 80 passages. In conclusion, we provide a comprehensive long-term stable field potential monitoring platform based on stem cell-derived human neuronal networks that can be automated and up-scaled for standardized high-content screening applications e.g. in the field of neurotoxic and neuroprotective therapeutics identification.

  18. The impact of cocaine on adult hippocampal neurogenesis: Potential neurobiological mechanisms and contributions to maladaptive cognition in cocaine addiction disorder.

    Science.gov (United States)

    Castilla-Ortega, Estela; Ladrón de Guevara-Miranda, David; Serrano, Antonia; Pavón, Francisco J; Suárez, Juan; Rodríguez de Fonseca, Fernando; Santín, Luis J

    2017-10-01

    After discovering that addictive drugs alter adult neurogenesis, the potential role of adult-born hippocampal neurons in drug addiction has become a promising research field, in which cocaine is the most frequently investigated drug. Although a substantial amount of pre-clinical evidence has accumulated, additional studies are required to reveal the mechanisms by which cocaine modulates adult hippocampal neurogenesis (AHN) and determine whether these adult-born neurons have a role in cocaine-related behaviors, such as cocaine-mediated cognitive symptoms. First, this review will summarize the cocaine-induced alterations in a number of neurobiological factors (neurotransmitters, neurotrophins, glucocorticoids, inflammatory mediators) that likely regulate both hippocampal-dependent learning and adult hippocampal neurogenesis after cocaine exposure. A separate section will provide a detailed review of the available literature that challenges the common view that cocaine reduces adult hippocampal neurogenesis. In fact, cocaine has a short-term anti-proliferative role, but the young adult-born neurons are apparently spared, or even enhanced, following certain cocaine protocols. Thus, we will try to reconcile this evidence with the hippocampal-dependent cognitive symptoms that are typically observed in cocaine addicts, and we will propose new directions for future studies to test the relevant hypothesis. Based on the evidence presented here, the regulation of adult hippocampal neurogenesis might be one of the many mechanisms by which cocaine sculpts hippocampus-dependent learning. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Long-Term Acid-Generating and Metal Leaching Potential of a Sub-Arctic Oil Shale

    Directory of Open Access Journals (Sweden)

    Kathryn A. Mumford

    2014-04-01

    Full Text Available Shales are increasingly being exploited for oil and unconventional gas. Exploitation of sub-arctic oil shales requires the creation of gravel pads to elevate workings above the heaving effects of ground ice. These gravel pads can potentially generate acidic leachate, which can enhance the mobility of metals from the shale. To examine this potential, pyrite-bearing shale originating from sub-Arctic gravel pad sites were subjected to leaching tests for 600 days at initial pH values ranging from 2 to 5, to simulate potential real world conditions. At set times over the 600 day experiment, pH, oxidation reduction potential (ORP, dissolved oxygen and temperature were recorded and small liquid samples withdrawn and analysed for elemental concentrations using total reflection X-ray fluorescence spectrometry (TRXRF. Six of eight shale samples were found to be acid generating, with pH declining and ORP becoming increasingly positive after 100 days. Two of the eight shale samples produced increasingly alkaline leachate conditions with relatively low ORP after 100 days, indicating an inbuilt buffering capacity. By 600 days the buffering capacity of all samples had been consumed and all leachate samples were acidic. TRXRF analyses demonstrated significant potential for the leaching of S, Fe, Ni, Cu, Zn and Mn with greatest concentrations found in reaction vessels with most acidic pH and highest ORP.

  20. Virtual Models of Long-Term Care

    Science.gov (United States)

    Phenice, Lillian A.; Griffore, Robert J.

    2012-01-01

    Nursing homes, assisted living facilities and home-care organizations, use web sites to describe their services to potential consumers. This virtual ethnographic study developed models representing how potential consumers may understand this information using data from web sites of 69 long-term-care providers. The content of long-term-care web…

  1. Free Radicals Accelerate the Decay of Long-Term Potentiation in Field CA1 of Guinea-Pig Hippocampus

    Science.gov (United States)

    1991-01-01

    pathological conditions To evaloare the neuroprysiologicall consequences of free radical exposure, slices of hippocampus isolated from guinea-igs % sere ...equation for the sum of t a kely to correspond to what McNaughton" called exponentiahs potentiation, which has a time constant around I 5 mm in vivo

  2. Neo-synthesis of estrogenic or androgenic neurosteroids determine whether long-term potentiation or depression is induced in hippocampus of male rat

    Directory of Open Access Journals (Sweden)

    Michela eDi Mauro

    2015-10-01

    Full Text Available Estrogenic and androgenic steroids synthesized in the brain may rapidly modulate synaptic plasticity interacting with specific membrane receptors. We explored by electrophysiological recordings in hippocampal slices of male rat the influence of 17b-estradiol (E2 and 5a-dihydrotestosterone (DHT neo-synthesis on the synaptic changes induced in the CA1 region. Induction of long-term depression (LTD and depotentiation (DP by low frequency stimulation (LFS, 15 min-1 Hz and of long-term potentiation (LTP by high (HFS, 1 s-100 Hz, medium (MFS, 1 s-50 Hz, or weak (WFS, 1 s-25 Hz frequency stimulation was assayed under inhibitors of enzymes converting testosterone (T into DHT (5a-reductase and T into E2 (P450-aromatase. We found that LFS-LTD depends on DHT synthesis, since it was fully prevented under finasteride, an inhibitor of DHT synthesis, and rescued by exogenous DHT, while the E2 synthesis was not involved. Conversely, the full development of HFS-LTP requires the synthesis of E2, as demonstrated by the LTP reduction observed under letrozole, an inhibitor of E2 synthesis, and its full rescue by exogenous E2. For intermediate stimulation protocols DHT, but not E2 synthesis, was involved in the production of a small LTP induced by WFS, while the E2 synthesis was required for the MFS-dependent LTP. Under the combined block of DHT and E2 synthesis all stimulation frequencies induced partial LTP. Overall, these results indicate that DHT is required for converting the partial LTP into LTD whereas E2 is needed for the full expression of LTP, evidencing a key role of the neo-synthesis of sex neurosteroids in determining the direction of synaptic long-term effects.

  3. Distinct Roles of PKCι/λ and PKMζ in the Initiation and Maintenance of Hippocampal Long-Term Potentiation and Memory.

    Science.gov (United States)

    Wang, Shaoli; Sheng, Tao; Ren, Siqiang; Tian, Tian; Lu, Wei

    2016-08-16

    PKMζ has been proposed to be essential for maintenance of long-term potentiation (LTP) and long-term memory (LTM). However, recent data from PKMζ-knockout mice has called this role into question. Instead, the other atypical isoform, protein kinase C iota/lambda (PKCι/λ), has emerged as a potential alternative player. Therefore, the nature of the "memory molecule" maintaining learned information remains uncertain. Here, we report knockdown (KD) of PKCι/λ and PKMζ in the dorsal hippocampus and find deficits in early expression and late maintenance, respectively, during both LTP and hippocampus-dependent LTM. Sequential increases in the active form of PKCι/λ and PKMζ are detected during LTP or fear conditioning. Importantly, PKMζ, but not PKCι/λ, KD disrupts previously established LTM. Thus, PKCι/λ and PKMζ have distinct functions in LTP and memory, with PKMζ playing a specific role in memory maintenance. This relaying pattern may represent a precise molecular mechanism by which atypical PKCs regulate the different stages of memory. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  4. Leptin attenuates the detrimental effects of β-amyloid on spatial memory and hippocampal later-phase long term potentiation in rats.

    Science.gov (United States)

    Tong, Jia-Qing; Zhang, Jun; Hao, Ming; Yang, Ju; Han, Yu-Fei; Liu, Xiao-Jie; Shi, Hui; Wu, Mei-Na; Liu, Qing-Song; Qi, Jin-Shun

    2015-07-01

    β-Amyloid (Aβ) is the main component of amyloid plaques developed in the brain of patients with Alzheimer's disease (AD). The increasing burden of Aβ in the cortex and hippocampus is closely correlated with memory loss and cognition deficits in AD. Recently, leptin, a 16kD peptide derived mainly from white adipocyte tissue, has been appreciated for its neuroprotective function, although less is known about the effects of leptin on spatial memory and synaptic plasticity. The present study investigated the neuroprotective effects of leptin against Aβ-induced deficits in spatial memory and in vivo hippocampal late-phase long-term potentiation (L-LTP) in rats. Y maze spontaneous alternation was used to assess short term working memory, and the Morris water maze task was used to assess long term reference memory. Hippocampal field potential recordings were performed to observe changes in L-LTP. We found that chronically intracerebroventricular injection of leptin (1μg) effectively alleviated Aβ1-42 (20μg)-induced spatial memory impairments of Y maze spontaneous alternation and Morris water maze. In addition, chronic administration of leptin also reversed Aβ1-42-induced suppression of in vivo hippocampal L-LTP in rats. Together, these results suggest that chronic leptin treatments reversed Aβ-induced deficits in learning and memory and the maintenance of L-LTP. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Long term sugarcane crop residue retention offers limited potential to reduce nitrogen fertilizer rates in Australian wet tropical environments

    Directory of Open Access Journals (Sweden)

    Elizabeth Anne Meier

    2016-07-01

    Full Text Available The warming of world climate systems is driving interest in the mitigation of greenhouse gas (GHG emissions. In the agricultural sector, practices that mitigate GHG emissions include those that (1 reduce emissions (e.g. those that reduce nitrous oxide (N2O emissions by avoiding excess nitrogen (N fertilizer application, and (2 increase soil organic carbon (SOC stocks (e.g. by retaining instead of burning crop residues. Sugarcane is a globally important crop that can have substantial inputs of N fertilizer and which produces large amounts of crop residues (‘trash’. Management of N fertilizer and trash affects soil carbon and nitrogen cycling, and hence GHG emissions. Trash has historically been burned at harvest, but increasingly is being retained on the soil surface as a ‘trash blanket’ in many countries. The potential for trash retention to alter N fertilizer requirements and sequester SOC was investigated in this study. The APSIM model was calibrated with data from field and laboratory studies of trash decomposition in the wet tropics of northern Australia. APSIM was then validated against four independent data sets, before simulating location  soil  fertilizer  trash management scenarios. Soil carbon increased in trash blanketed soils relative to SOC in soils with burnt trash. However, further increases in SOC for the study region may be limited because the SOC in trash blanketed soils could be approaching equilibrium; future GHG mitigation efforts in this region should therefore focus on N fertilizer management. Simulated N fertilizer rates were able to be reduced from conventional rates regardless of trash management, because of low yield potential in the wet tropics. For crops subjected to continuous trash blanketing, there was substantial immobilization of N in decomposing trash so conventional N fertilizer rates were required for up to 24 yr after trash blanketing commenced. After this period, there was potential to

  6. The potential to mitigate global warming with no-tillage management is only realized when practised in the long term

    OpenAIRE

    Six, J; Ogle, S M; Breidt, F J; Conant, R T; Mosier, A R; Paustian, K

    2004-01-01

    No-tillage (NT) management has been promoted as a practice capable of offsetting greenhouse gas (GHG) emissions because of its ability to sequester carbon in soils. However, true mitigation is only possible if the overall impact of NT adoption reduces the net global warming potential (GWP) determined by fluxes of the three major biogenic GHGs (i.e. CO2, N2O, and CH4). We compiled all available data of soil-derived GHG emission comparisons between conventional tilled (CT) and NT systems for hu...

  7. Japan's long-term energy outlook to 2050: Estimation for the potential of massive CO2 mitigation

    Energy Technology Data Exchange (ETDEWEB)

    Komiyama, Ryoichi

    2010-09-15

    This paper analyzes Japan's energy outlook and CO2 emissions to 2050. Scenario analysis reveals that Japan's CO2 emissions in 2050 could be potentially reduced by 58% from the emissions in 2005. For achieving this massive mitigation, it is required to reduce primary energy supply per GDP by 60% in 2050 from the 2005 level and to expand the share of non-fossil fuel in total supply to 50% by 2050. Concerning power generation mix, nuclear will account for 60%, renewable for 30% in 2050. For massive CO2 abatement, Japan should tackle technological and economic challenges for large-scale deployment of advanced technologies.

  8. Long-term use of biosolids as organic fertilizers in agricultural soils: potentially toxic elements occurrence and mobility.

    Science.gov (United States)

    Marguí, E; Iglesias, M; Camps, F; Sala, L; Hidalgo, M

    2016-03-01

    The presence of potentially toxic elements (PTEs) may hinder a more widespread application of biosolids in agriculture. At present, the European Directive 86/278/CEE limit the total concentrations of seven metals (Cu, Cr, Ni, Pb, Zn, Cd and Hg) in agricultural soils and in sewage sludges used as fertilizers but it has not taken into consideration the potential impacts of other emerging micropollutants that may be present in the biosolids as well as their mobility. The aim of this study was to evaluate the accumulation and mobility of 13 elements (including regulated metals and other inorganic species) in agricultural soils repeatedly amended with biosolids for 15 years. Firstly, three digestions programs using different acid mixtures were tested to evaluate the most accurate and efficient method for analysis of soil and sludge. Results demonstrated that sewage sludge application increased concentrations of Pb and Hg in soil, but values did not exceed the quality standard established by legislation. In addition, other elements (As, Co, Sb, Ag, Se and Mn) that at present are not regulated by the Spanish and European directives were identified in the sewage sludge, and significant differences were found between Ag content in soils amended with biosolids in comparison with control soils. This fact can be related to the increasing use of silver nanoparticles in consumer products due to their antibacterial properties. Results from the leaching tests show up that, in general, the mobility degree for both regulated and non-regulated elements in soils amended with biosolids was quite low (<10 %).

  9. A greener Greenland? Climatic potential and long-term constraints on future expansions of trees and shrubs

    Science.gov (United States)

    Normand, Signe; Randin, Christophe; Ohlemüller, Ralf; Bay, Christian; Høye, Toke T.; Kjær, Erik D.; Körner, Christian; Lischke, Heike; Maiorano, Luigi; Paulsen, Jens; Pearman, Peter B.; Psomas, Achilleas; Treier, Urs A.; Zimmermann, Niklaus E.; Svenning, Jens-Christian

    2013-01-01

    Warming-induced expansion of trees and shrubs into tundra vegetation will strongly impact Arctic ecosystems. Today, a small subset of the boreal woody flora found during certain Plio-Pleistocene warm periods inhabits Greenland. Whether the twenty-first century warming will induce a re-colonization of a rich woody flora depends on the roles of climate and migration limitations in shaping species ranges. Using potential treeline and climatic niche modelling, we project shifts in areas climatically suitable for tree growth and 56 Greenlandic, North American and European tree and shrub species from the Last Glacial Maximum through the present and into the future. In combination with observed tree plantings, our modelling highlights that a majority of the non-native species find climatically suitable conditions in certain parts of Greenland today, even in areas harbouring no native trees. Analyses of analogous climates indicate that these conditions are widespread outside Greenland, thus increasing the likelihood of woody invasions. Nonetheless, we find a substantial migration lag for Greenland's current and future woody flora. In conclusion, the projected climatic scope for future expansions is strongly limited by dispersal, soil development and other disequilibrium dynamics, with plantings and unintentional seed dispersal by humans having potentially large impacts on spread rates. PMID:23836785

  10. Synaptic long-term potentiation and depression in the rat medial vestibular nuclei depend on neural activation of estrogenic and androgenic signals.

    Directory of Open Access Journals (Sweden)

    Mariangela Scarduzio

    Full Text Available Estrogenic and androgenic steroids can be synthesised in the brain and rapidly modulate synaptic transmission and plasticity through direct interaction with membrane receptors for estrogens (ERs and androgens (ARs. We used whole cell patch clamp recordings in brainstem slices of male rats to explore the influence of ER and AR activation and local synthesis of 17β-estradiol (E2 and 5α-dihydrotestosterone (DHT on the long-term synaptic changes induced in the neurons of the medial vestibular nucleus (MVN. Long-term depression (LTD and long-term potentiation (LTP caused by different patterns of high frequency stimulation (HFS of the primary vestibular afferents were assayed under the blockade of ARs and ERs or in the presence of inhibitors for enzymes synthesizing DHT (5α-reductase and E2 (P450-aromatase from testosterone (T. We found that LTD is mediated by interaction of locally produced androgens with ARs and LTP by interaction of locally synthesized E2 with ERs. In fact, the AR block with flutamide prevented LTD while did not affect LTP, and the blockade of ERs with ICI 182,780 abolished LTP without influencing LTD. Moreover, the block of P450-aromatase with letrozole not only prevented the LTP induction, but inverted LTP into LTD. This LTD is likely due to the local activation of androgens, since it was abolished under blockade of ARs. Conversely, LTD was still induced in the presence of finasteride the inhibitor of 5α-reductase demonstrating that T is able to activate ARs and induce LTD even when DHT is not synthesized. This study demonstrates a key and opposite role of sex neurosteroids in the long-term synaptic changes of the MVN with a specific role of T-DHT for LTD and of E2 for LTP. Moreover, it suggests that different stimulation patterns can lead to LTD or LTP by specifically activating the enzymes involved in the synthesis of androgenic or estrogenic neurosteroids.

  11. [Biographical work in inpatient long-term care for people with dementia: potential of the DEMIAN nursing concept].

    Science.gov (United States)

    Berendonk, C; Stanek, S; Schönit, M; Kaspar, R; Bär, M; Kruse, A

    2011-02-01

    In nursing care for people with dementia, biographical work is a popular concept. In the literature and practice, many different viewpoints of the way biographical work can/should be promoted exist. In the DEMIAN concept, a nursing concept to promote emotional well-being for people with dementia, it is also of major significance. This article gives an overview of the importance of biographical work in caring for people with dementia. In particular, the role and arrangement of biographical work in the DEMIAN concept are described. Within the anamnesis of the DEMIAN concept, meaningful themes are identified in conversations with different participants (person with dementia, reference persons, and care workers) and through observations. From these findings, specific interventions, aimed at supporting emotional well-being of people with dementia, are derived and integrated into everyday nursing care to promote emotional well-being. The potential of the DEMIAN nursing concept are discussed and further possibilities are highlighted.

  12. Premature loss of primary anterior teeth due to trauma--potential short- and long-term sequelae.

    Science.gov (United States)

    Holan, Gideon; Needleman, Howard L

    2014-04-01

    Traumatic dental injuries (TDIs) can result in the premature loss of primary anterior teeth due to an immediate avulsion, extraction later after the injury because of poor prognosis or late complications, or early exfoliation. There are a number of potential considerations or sequelae as a result of this premature loss that have been cited in the dental literature, which include esthetics, quality of life, eating, speech development, arch integrity (space loss), development and eruption of the permanent successors, and development of oral habits. This article provides a comprehensive review of the dental literature on the possible consequences of premature loss of maxillary primary incisors following TDI. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Life History theory hypotheses on child growth: Potential implications for short and long-term child growth, development and health.

    Science.gov (United States)

    Said-Mohamed, Rihlat; Pettifor, John M; Norris, Shane A

    2018-01-01

    Life history theory integrates ecological, physiological, and molecular layers within an evolutionary framework to understand organisms' strategies to optimize survival and reproduction. Two life history hypotheses and their implications for child growth, development, and health (illustrated in the South African context) are reviewed here. One hypothesis suggests that there is an energy trade-off between linear growth and brain growth. Undernutrition in infancy and childhood may trigger adaptive physiological mechanisms prioritizing the brain at the expense of body growth. Another hypothesis is that the period from conception to infancy is a critical window of developmental plasticity of linear growth, the duration of which may vary between and within populations. The transition from infancy to childhood may mark the end of a critical window of opportunity for improving child growth. Both hypotheses emphasize the developmental plasticity of linear growth and the potential determinants of growth variability (including the role of parent-offspring conflict in maternal resources allocation). Implications of these hypotheses in populations with high burdens of undernutrition and infections are discussed. In South Africa, HIV/AIDS during pregnancy (associated with adverse birth outcomes, short duration of breastfeeding, and social consequences) may lead to a shortened window of developmental plasticity of growth. Furthermore, undernutrition and infectious diseases in children living in South Africa, a country undergoing a rapid nutrition transition, may have adverse consequences on individuals' cognitive abilities and risks of cardio-metabolic diseases. Studies are needed to identify physiological mechanisms underlying energy allocation between biological functions and their potential impacts on health. © 2017 Wiley Periodicals, Inc.

  14. Long-term implications of sustained wind power growth in the United States: Potential benefits and secondary impacts

    Energy Technology Data Exchange (ETDEWEB)

    Wiser, Ryan; Bolinger, Mark; Heath, Garvin; Keyser, David; Lantz, Eric; Macknick, Jordan; Mai, Trieu; Millstein, Dev

    2016-10-01

    We model scenarios of the U.S. electric sector in which wind generation reaches 10% of end-use electricity demand in 2020, 20% in 2030, and 35% in 2050. As shown in a companion paper, achieving these penetration levels would have significant implications for the wind industry and the broader electric sector. Compared to a baseline that assumes no new wind deployment, under the primary scenario modeled, achieving these penetrations imposes an incremental cost to electricity consumers of less than 1% through 2030. These cost implications, however, should be balanced against the variety of environmental and social implications of such a scenario. Relative to a baseline that assumes no new wind deployment, our analysis shows that the high-penetration wind scenario yields potential greenhouse-gas benefits of $85-$1,230 billion in present-value terms, with a central estimate of $400 billion. Air-pollution-related health benefits are estimated at $52-$272 billion, while annual electric-sector water withdrawals and consumption are lower by 15% and 23% in 2050, respectively. We also find that a high-wind-energy future would have implications for the diversity and risk of energy supply, local economic development, and land use and related local impacts on communities and ecosystems; however, these additional impacts may not greatly affect aggregate social welfare owing to their nature, in part, as resource transfers.

  15. Paired-Associative Stimulation-Induced Long-term Potentiation-Like Motor Cortex Plasticity in Healthy Adolescents

    Directory of Open Access Journals (Sweden)

    Jonathan C. Lee

    2017-05-01

    Full Text Available ObjectiveThe objective of this study was to evaluate the feasibility of using paired-associative stimulation (PAS to study excitatory and inhibitory plasticity in adolescents while examining variables that may moderate plasticity (such as sex and environment.MethodsWe recruited 34 healthy adolescents (aged 13–19, 13 males, 21 females. To evaluate excitatory plasticity, we compared mean motor-evoked potentials (MEPs elicited by single-pulse transcranial magnetic stimulation (TMS before and after PAS at 0, 15, and 30 min. To evaluate inhibitory plasticity, we evaluated the cortical silent period (CSP elicited by single-pulse TMS in the contracted hand before and after PAS at 0, 15, and 30 min.ResultsAll participants completed PAS procedures. No adverse events occurred. PAS was well tolerated. PAS-induced significant increases in the ratio of post-PAS MEP to pre-PAS MEP amplitudes (p < 0.01 at all post-PAS intervals. Neither socioeconomic status nor sex was associated with post-PAS MEP changes. PAS induced significant CSP lengthening in males but not females.ConclusionPAS is a feasible, safe, and well-tolerated index of adolescent motor cortical plasticity. Gender may influence PAS-induced changes in cortical inhibition. PAS is safe and well tolerated by healthy adolescents and may be a novel tool with which to study adolescent neuroplasticity.

  16. Long-Term Task- and Dopamine-Dependent Dynamics of Subthalamic Local Field Potentials in Parkinson's Disease.

    Science.gov (United States)

    Hanrahan, Sara J; Nedrud, Joshua J; Davidson, Bradley S; Farris, Sierra; Giroux, Monique; Haug, Aaron; Mahoor, Mohammad H; Silverman, Anne K; Zhang, Jun Jason; Hebb, Adam Olding

    2016-11-29

    Subthalamic nucleus (STN) local field potentials (LFP) are neural signals that have been shown to reveal motor and language behavior, as well as pathological parkinsonian states. We use a research-grade implantable neurostimulator (INS) with data collection capabilities to record STN-LFP outside the operating room to determine the reliability of the signals over time and assess their dynamics with respect to behavior and dopaminergic medication. Seven subjects were implanted with the recording augmented deep brain stimulation (DBS) system, and bilateral STN-LFP recordings were collected in the clinic over twelve months. Subjects were cued to perform voluntary motor and language behaviors in on and off medication states. The STN-LFP recorded with the INS demonstrated behavior-modulated desynchronization of beta frequency (13-30 Hz) and synchronization of low gamma frequency (35-70 Hz) oscillations. Dopaminergic medication did not diminish the relative beta frequency oscillatory desynchronization with movement. However, movement-related gamma frequency oscillatory synchronization was only observed in the medication on state. We observed significant inter-subject variability, but observed consistent STN-LFP activity across recording systems and over a one-year period for each subject. These findings demonstrate that an INS system can provide robust STN-LFP recordings in ambulatory patients, allowing for these signals to be recorded in settings that better represent natural environments in which patients are in a variety of medication states.

  17. The effect of long-term Cd and Ni exposure on seed endophytes of Agrostis capillaris and their potential application in phytoremediation of metal-contaminated soils.

    Science.gov (United States)

    Truyens, S; Jambon, I; Croes, S; Janssen, J; Weyens, N; Mench, M; Carleer, R; Cuypers, A; Vangronsveld, J

    2014-01-01

    We examined whether long-term Cd exposure leads to beneficial changes in the cultivable endophytic bacteria present in the seeds of Agrostis capillaris. Therefore the cultivable seed endophytes of Agrostis capillaris growing on a long-term Cd/Ni-contaminated plot (Cd/Ni seeds) were compared with those originating from a non-contaminated plot (control seeds). We observed plant- and contaminant-dependent effects on the population composition between control and Cd/Ni seeds. Also differences in phenotypic characteristics were found: endophytes from Cd/Ni seeds exhibited more ACC deaminase activity and production of siderophores and IAA, while endophytes from control seeds, very surprisingly, showed more metal tolerance. Finally, the 3 most promising seed endophytes were selected based on their metal tolerance and plant growth promoting potential, and inoculated in Agrostis capillaris seedlings. In case of non-exposed plants, inoculation resulted in a significantly improved plant growth; after inoculation of Cd-exposed plants an increased Cd uptake was achieved without affecting plant growth. This indicates that inoculation of Agrostis with its seed endophytes might be beneficial for its establishment during phytoextraction and phytostabilisation of Cd-contaminated soils.

  18. 5-HT4-receptors modulate induction of long-term depression but not potentiation at hippocampal output synapses in acute rat brain slices.

    Directory of Open Access Journals (Sweden)

    Matthias Wawra

    Full Text Available The subiculum is the principal target of CA1 pyramidal cells and mediates hippocampal output to various cortical and subcortical regions of the brain. The majority of subicular pyramidal cells are burst-spiking neurons. Previous studies indicated that high frequency stimulation in subicular burst-spiking cells causes presynaptic NMDA-receptor dependent long-term potentiation (LTP whereas low frequency stimulation induces postsynaptic NMDA-receptor-dependent long-term depression (LTD. In the present study, we investigate the effect of 5-hydroxytryptamine type 4 (5-HT4 receptor activation and blockade on both forms of synaptic plasticity in burst-spiking cells. We demonstrate that neither activation nor block of 5-HT4 receptors modulate the induction or expression of LTP. In contrast, activation of 5-HT4 receptors facilitates expression of LTD, and block of the 5-HT4 receptor prevents induction of short-term depression and LTD. As 5-HT4 receptors are positively coupled to adenylate cyclase 1 (AC1, 5-HT4 receptors might modulate PKA activity through AC1. Since LTD is blocked in the presence of 5-HT4 receptor antagonists, our data are consistent with 5-HT4 receptor activation by ambient serotonin or intrinsically active 5-HT4 receptors. Our findings provide new insight into aminergic modulation of hippocampal output.

  19. Chelation of hippocampal zinc enhances long-term potentiation and synaptic tagging/capture in CA1 pyramidal neurons of aged rats: implications to aging and memory.

    Science.gov (United States)

    Shetty, Mahesh Shivarama; Sharma, Mahima; Sajikumar, Sreedharan

    2017-02-01

    Aging is associated with decline in cognitive functions, prominently in the memory consolidation and association capabilities. Hippocampus plays a crucial role in the formation and maintenance of long-term associative memories, and a significant body of evidence shows that impairments in hippocampal function correlate with aging-related memory loss. A number of studies have implicated alterations in hippocampal synaptic plasticity, such as long-term potentiation (LTP), in age-related cognitive decline although exact mechanisms underlying are not completely clear. Zinc deficiency and the resultant adverse effects on cognition have been well studied. However, the role of excess of zinc in synaptic plasticity, especially in aging, is not addressed well. Here, we have investigated the hippocampal zinc levels and the impairments in synaptic plasticity, such as LTP and synaptic tagging and capture (STC), in the CA1 region of acute hippocampal slices from 82- to 84-week-old male Wistar rats. We report increased zinc levels in the hippocampus of aged rats and also deficits in the tetani-induced and dopaminergic agonist-induced late-LTP and STC. The observed deficits in synaptic plasticity were restored upon chelation of zinc using a cell-permeable chelator. These data suggest that functional plasticity and associativity can be successfully established in aged neural networks by chelating zinc with cell-permeable chelating agents. © 2016 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  20. Endogenous 17ß-estradiol is required for activity-dependent long-term potentiation in the striatum: interaction with the dopaminergic system

    Directory of Open Access Journals (Sweden)

    Alessandro eTozzi

    2015-05-01

    Full Text Available 17β-estradiol (E2, a neurosteroid synthesized by P450-aromatase (ARO, modulates various brain functions. We characterized the role of the locally synthesized E2 on striatal long-term synaptic plasticity and explored possible interactions between E2 receptors (ERs and dopamine (DA receptors in the dorsal striatum of adult male rats. Inhibition of E2 synthesis or antagonism of ERs prevented the induction of long-term potentiation (LTP in both medium spiny neurons (MSNs and cholinergic interneurons (ChIs. Activation of a D1-like DA receptor/cAMP/PKA-dependent pathway restored LTP. In MSNs exogenous E2 reversed the effect of ARO inhibition. Also antagonism of M1 muscarinic receptors prevented the D1-like receptor-mediated restoration of LTP confirming a role for ChIs in controlling the E2-mediated LTP of MSNs. A novel striatal interaction, occurring between ERs and D1-like receptors in both MSNs and ChIs, might be critical to regulate basal ganglia physiology and to compensate synaptic alterations in Parkinson's disease.

  1. Potential for long-term transfer of dissolved organic carbon from riparian zones to streams in boreal catchments.

    Science.gov (United States)

    Ledesma, José L J; Grabs, Thomas; Bishop, Kevin H; Schiff, Sherry L; Köhler, Stephan J

    2015-08-01

    Boreal regions store most of the global terrestrial carbon, which can be transferred as dissolved organic carbon (DOC) to inland waters with implications for both aquatic ecology and carbon budgets. Headwater riparian zones (RZ) are important sources of DOC, and often just a narrow 'dominant source layer' (DSL) within the riparian profile is responsible for most of the DOC export. Two important questions arise: how long boreal RZ could sustain lateral DOC fluxes as the sole source of exported carbon and how its hydromorphological variability influences this role. We estimate theoretical turnover times by comparing carbon pools and lateral exports in the DSL of 13 riparian profiles distributed over a 69 km(2) catchment in northern Sweden. The thickness of the DSL was 36 ± 18 (average ± SD) cm. Thus, only about one-third of the 1-m-deep riparian profile contributed 90% of the lateral DOC flux. The 13 RZ exported 8.7 ± 6.5 g C m(-2) year(-1) , covering the whole range of boreal stream DOC exports. The variation could be explained by local hydromorphological characteristics including RZ width (R(2) = 0.90). The estimated theoretical turnover times were hundreds to a few thousands of years, that is there is a potential long-lasting supply of DOC. Estimates of net ecosystem production in the RZ suggest that lateral fluxes, including both organic and inorganic C, could be maintained without drawing down the riparian pools. This was supported by measurements of stream DO(14) C that indicated modern carbon as the predominant fraction exported, including streams disturbed by ditching. The transfer of DOC into boreal inland waters from new and old carbon sources has a major influence on surface water quality and global carbon balances. This study highlights the importance of local variations in RZ hydromorphology and DSL extent for future DOC fluxes under a changing climate. © 2015 The Authors. Global Change Biology Published by John Wiley & Sons Ltd.

  2. The effects of prolonged administration of norepinephrine reuptake inhibitors on long-term potentiation in dentate gyrus, and on tests of spatial and object recognition memory in rats.

    Science.gov (United States)

    Walling, Susan G; Milway, J Stephen; Ingram, Matthew; Lau, Catherine; Morrison, Gillian; Martin, Gerard M

    2016-02-01

    Phasic norepinephrine (NE) release events are involved in arousal, novelty detection and in plasticity processes underlying learning and memory in mammalian systems. Although the effects of phasic NE release events on plasticity and memory are prevalently documented, it is less understood what effects chronic NE reuptake inhibition and sustained increases in noradrenergic tone, might have on plasticity and cognitive processes in rodent models of learning and memory. This study investigates the effects of chronic NE reuptake inhibition on hippocampal plasticity and memory in rats. Rats were administered NE reuptake inhibitors (NRIs) desipramine (DMI; 0, 3, or 7.5mg/kg/day) or nortriptyline (NTP; 0, 10 or 20mg/kg/day) in drinking water. Long-term potentiation (LTP; 200 Hz) of the perforant path-dentate gyrus evoked potential was examined in urethane anesthetized rats after 30-32 days of DMI treatment. Short- (4-h) and long-term (24-h) spatial memory was tested in separate rats administered 0 or 7.5mg/kg/day DMI (25-30 days) using a two-trial spatial memory test. Additionally, the effects of chronically administered DMI and NTP were tested in rats using a two-trial, Object Recognition Test (ORT) at 2- and 24-h after 45 and 60 days of drug administration. Rats administered 3 or 7.5mg/kg/day DMI had attenuated LTP of the EPSP slope but not the population spike at the perforant path-dentate gyrus synapse. Short- and long-term memory for objects is differentially disrupted in rats after prolonged administration of DMI and NTP. Rats that were administered 7.5mg/kg/day DMI showed decreased memory for a two-trial spatial task when tested at 4-h. In the novel ORT, rats receiving 0 or 7.5mg/kg/day DMI showed a preference for the arm containing a Novel object when tested at both 2- and 24-h demonstrating both short- and long-term memory retention of the Familiar object. Rats that received either dose of NTP or 3mg/kg/day DMI showed impaired memory at 2-h, however this

  3. Calcitonin gene-related peptide erases the fear memory and facilitates long-term potentiation in the central nucleus of the amygdala in rats.

    Science.gov (United States)

    Wu, Xin; Zhang, Jie-Ting; Liu, Jue; Yang, Si; Chen, Tao; Chen, Jian-Guo; Wang, Fang

    2015-11-01

    Calcitonin gene-related peptide (CGRP) is a 37 amino acid neuropeptide, which plays a critical role in the central nervous system. CGRP binds to G protein-coupled receptors, including CGRP1, which couples positively to adenylyl cyclase (AC) and protein kinase A (PKA) activation. CGRP and CGRP1 receptors are enriched in central nucleus of the amygdala (CeA), the main part of the amygdala, which regulates conditioned fear memories. Here, we reported the importance of CGRP and CGRP1 receptor for synaptic plasticity in the CeA and the extinction of fear memory in rats. Our electrophysiological and behavioral in vitro and in vivo results showed exogenous application of CGRP induced an immediate and lasting long-term potentiation in the basolateral nucleus of amygdala-CeA pathway, but not in the lateral nucleus of amygdala-CeA pathway, while bilateral intra-CeA infusion CGRP (0, 5, 13 and 21 μM/side) dose dependently enhanced fear memory extinction. The effects were blocked by CGRP1 receptor antagonist (CGRP8-37 ), N-methyl-d-aspartate receptors antagonist MK801 and PKA inhibitor H89. These results demonstrate that CGRP can lead to long-term potentiation of basolateral nucleus of amygdala-CeA pathway through a PKA-dependent postsynaptic mechanism that involved N-methyl-d-aspartate receptors and enhance the extinction of fear memory in rats. Together, the results strongly support a pivotal role of CGRP in the synaptic plasticity of CeA and extinction of fear memory. Calcitonin gene-related peptide (CGRP) plays an essential role in synaptic plasticity in the amygdala and fear memory. We found that CGRP-induced chemical long-term potentiation (LTP) in a dose-dependent way in the BLA-CeA (basolateral and central nucleus of amygdala, respectively) pathway and enhanced fear memory extinction in rats through a protein kinase A (PKA)-dependent postsynaptic mechanism that involved NMDA receptors. These results support a pivotal role of CGRP in amygdala. © 2015 International

  4. Electroconvulsive stimulation results in long-term survival of newly generated hippocampal neurons in rats

    DEFF Research Database (Denmark)

    Olesen, Mikkel Vestergaard; Wörtwein, Gitta; Folke, Jonas

    2017-01-01

    of the previous work aiming to test the hypothesis that rats subjected to ECS in combination with chronic restraint stress (CRS) display increased formation of new hippocampal neurons, which have a potential for long-term survival. Furthermore, using mediation analysis, we tested if an ECS-induced increase......U-positive neurons showed time-dependent attrition of ∼40% from day 1 to 3 months, with no further decline between 3 and 12 months. ECS did not affect the number of pre-existing dentate granule neurons or the volume of the dentate granule cell layer, suggesting no damaging effect of the treatment. Finally, we found...... that, while ECS increases neurogenesis, this formation of new neurons was not associated to ameliorated immobility in the FST. This implies that other ECS-induced effects than neurogenesis must be part of mediating the antidepressant action of ECS. Taken together, the results of the present study...

  5. The potential role of pain-related SSEPs in the early prognostication of long-term functional outcome in post-anoxic coma.

    Science.gov (United States)

    Del Felice, Alessandra; Bargellesi, Stefano; Linassi, Federico; Scarpa, Bruno; Formaggio, Emanuela; Boldrini, Paolo; Masiero, Stefano; Zanatta, Paolo

    2017-05-12

    Cardiac arrest (CA) is a common cause of disability. Multimodal evaluation has improved prognosis but precocious biomarkers are not appropriate in determining long-term functional outcome. to identify early prognostication markers of long-term functional outcome in post-anoxic coma. retrospective assessment of outcomes. Individuals older than 18 years with post-anoxic coma hospitalized in intensive care units after cardiac arrest (CA) regardless of cause (cardiac or non-cardiac) and location of event (in or out-of-hospital). Clinical, biological and neurophysiological data were collected within 48 hours from CA. Clinical data included time of no and low flow, CA rhythm, pupillary reflex, Glasgow motor score at admission and hyperthermia. Biological marker was the highest creatinine level. Neurophysiological parameters included EEG pattern and reactivity, Somatosensory Evoked Potential (SSEP), and Middle-Latency (ML) SSEP evoked at low (10 mA) and high (50 mA) intensity stimulation. A LASSO multiple regression analysis was fitted to data to investigate the best predictors of LCF, DRS and CRS-R. In-sample prediction was obtained to verify the quality of fitting, and accuracy indices (i.e. total error rate) produced. presence of short and medium latency SSEPs with low and high stimulation intensity were identified as prognostic predictors of outcome for all the scales. Error rate was 4.5% for CRS and LCF, and 9.1% for DRS. Middle latency somatosensory evoked potentials associated with short latency somatosensory evoked potentials during the first 48 hours after a cardiac arrest are strong predictors of functional outcome at 12 months from the event. Replication on larger cohorts is needed to support their routine use as prognostic markers. These markers could inform more appropriate allocation of resources, provide a basis for realistic goal-setting, and help the family to adjust its' expectations.

  6. Potential Use of Deep-ocean Bottom Temperatures Measured by NOAA's Operational DART Systems in Identifying Long-term Climate Trends

    Science.gov (United States)

    Eble, M. C.; Mungov, G.

    2016-12-01

    The National Oceanic and Atmospheric Administration holds more than 3200 months of ocean bottom temperature time series recorded by the network of Deep-ocean Assessment and Reporting of Tsunami (DART) developed for reporting bottom pressure in support of tsunami detection and warning. Measurements were made at more than 40 locations sited predominately within the Pacific Ocean, with a lesser number made at sites in the North Atlantic. Since 2003, time series data were collected at isolated locations and at those in close proximity to sites measuring other ocean and atmosphere parameters (e.g. TAO/TRITON), at depths ranging from approximately 1800 m to nearly 6000 m. A full 2300 months of temperature measurements were made by DART systems deployed at or below 4000 m. These time series offer the potential of narrowing a gap in the global ocean observing system (OceanObs09) by exposing long-term climate trends at more locations in the ocean deep then now available. The potential held by these data given specific limitations is the focus of this investigation. Limitations stem from the primary function of temperature being to correct pressure. The sole function of temperature has historically been to provide a correction to pressure so little attention has been paid to optimizing temperature measurements for long-term investigations. Temperature counts, like those of pressure, are converted to engineering units using calibration coefficients supplied by the manufacturer but temperatures are only coarsely calibrated. In addition, the response of each pressure transducer to ocean pressure varies by deployment and location. Time series of DART temperature frequency counts recorded during specific single deployments were processed and analyzed to identify consistent trends and explore methodologies that could be adopted in order to improve the utility (NOAA, 2014) of DART temperature measurements for climate studies. These data represent a vast amount of untapped

  7. Long-Term Collections

    CERN Multimedia

    Staff Association

    2016-01-01

    45 years helping in developing countries! CERN personnel have been helping the least fortunate people on the planet since 1971. How? With the Long-Term Collections! Dear Colleagues, The Staff Association’s Long-Term Collections (LTC) Committee is delighted to share this important milestone in the life of our Laboratory with you. Indeed, whilst the name of CERN is known worldwide for scientific discoveries, it also shines in the many humanitarian projects which have been supported by the LTC since 1971. Several schools and clinics, far and wide, carry its logo... Over the past 45 years, 74 projects have been supported (9 of which are still ongoing). This all came from a group of colleagues who wanted to share a little of what life offered them here at CERN, in this haven of mutual understanding, peace and security, with those who were less fortunate elsewhere. Thus, the LTC were born... Since then, we have worked as a team to maintain the dream of these visionaries, with the help of regular donat...

  8. Long-Term Collection

    CERN Multimedia

    Staff Association

    2016-01-01

    Dear Colleagues, As previously announced in Echo (No. 254), your delegates took action to draw attention to the projects of the Long-Term Collections (LTC), the humanitarian body of the CERN Staff Association. On Tuesday, 11 October, at noon, small Z-Cards were widely distributed at the entrances of CERN restaurants and we thank you all for your interest. We hope to have achieved an important part of our goal, which was to inform you, convince you and find new supporters among you. We will find out in the next few days! An exhibition of the LTC was also set up in the Main Building for the entire week. The Staff Association wants to celebrate the occasion of the Long-Term Collection’s 45th anniversary at CERN because, ever since 1971, CERN personnel have showed great support in helping the least fortunate people on the planet in a variety of ways according to their needs. On a regular basis, joint fundraising appeals are made with the Directorate to help the victims of natural disasters around th...

  9. Collectes à long terme

    CERN Multimedia

    Collectes à long terme

    2014-01-01

    En cette fin d’année 2014 qui approche à grands pas, le Comité des Collectes à Long Terme remercie chaleureusement ses fidèles donatrices et donateurs réguliers pour leurs contributions à nos actions en faveur des plus démunis de notre planète. C’est très important, pour notre Comité, de pouvoir compter sur l’appui assidu que vous nous apportez. Depuis plus de 40 ans maintenant, le modèle des CLT est basé principalement sur des actions à long terme (soit une aide pendant 4-5 ans par projet, mais plus parfois selon les circonstances), et sa planification demande une grande régularité de ses soutiens financiers. Grand MERCI à vous ! D’autres dons nous parviennent au cours de l’année, et ils sont aussi les bienvenus. En particulier, nous tenons à remercier...

  10. Improvement in Memory and Brain Long-term Potentiation Deficits Due to Permanent Hypoperfusion/Ischemia by Grape Seed Extract in Rats

    Directory of Open Access Journals (Sweden)

    Alireza Sarkaki

    2013-09-01

    Full Text Available   Objective(s: Cerebral hypoperfusion/ischemia (CHI is a neurological disease where impaired hippocampus electrical activity and cognition caused by a serial pathophysiological events. This study aimed to evaluate the effects of chronic oral administration of grape seed extract (GSE on passive avoidance memory and long-term potentiation (LTP after permanent bilateral common carotid arteries occlusion (2CCAO in male adult rats.   Materials and Methods: Thirty-two adult male Wistar rats were randomly divided into: 1 Sham+Veh, 2 Isch+Veh, 3 Sham+GSE, 4 Isch+GSE. In order to make 2CCAO as an animal model of CHI, carotid arteries were ligatured and then cut bilaterally. To evaluation of passive avoidance memory, step-down latency (STL was measured and LTP was recorded from hippocampal dentate gyrus (DG after high frequency stimulation (HFS in all rats. Results: We found that memory was significantly impaired in rats after CHI (P

  11. The effects of CCK-8S on spatial memory and long-term potentiation at CA1 during induction of stress in rats

    Directory of Open Access Journals (Sweden)

    Malihe Sadeghi

    2017-12-01

    Full Text Available Objective(s: Cholecystokinin (CCK has been proposed as a mediator in stress. However, it is still not fully documented what are its effects. We aimed to evaluate the effects of systemic administration of CCK exactly before induction of stress on spatial memory and synaptic plasticity at CA1 in rats. Materials and Methods: Male Wistar rats were divided into 4 groups: the control, the control-CCK, the stress and the stress-CCK. Restraint stress was induced 6 hr per day, for 24 days. Cholecystokinin sulfated octapeptide (CCK-8S was injected (1.6 µg/kg, IP before each session of stress induction. Spatial memory was evaluated by Morris water maze test. Long term potentiation (LTP in Schaffer collateral-CA1 synapses was assessed (by 100 Hz tetanization in order to investigate synaptic plasticity. Results: Stress impaired spatial memory significantly (P

  12. Low-fat, high-carbohydrate parenteral nutrition (PN) may potentially reverse liver disease in long-term PN-dependent infants

    DEFF Research Database (Denmark)

    Jakobsen, Marianne Skytte; Jørgensen, Marianne Hørby; Husby, Steffen

    2015-01-01

    INTRODUCTION: Parenteral nutrition-associated cholestasis (PNAC) is a complication of long-term parenteral nutrition (PN). Removal of lipids may reverse PNAC but compromises the energy to ensure infant growth. The purpose of this study was to test whether a low-fat, high-carbohydrate PN regimen......, which prevents and reverses PNAC in adults, could do the same in infants. This regimen could potentially avoid the problem of diminished energy input after removing nutritional lipids. METHODS: Infants developing PNAC over a 2-year period were started on a low-fat PN regimen with calories primarily from...... carbohydrates. The fat-free PN, containing 314 kJ/ml, was provided 5-6 times a week and fat, including essential fatty acids and fat-soluble vitamins, 1-2 times a week. Enteral feeding was continued according to individual tolerance. RESULTS: The study included 10 infants with short bowel syndrome (six...

  13. Effect of Prenatal Protein Malnutrition on Long-Term Potentiation and BDNF Protein Expression in the Rat Entorhinal Cortex after Neocortical and Hippocampal Tetanization

    Directory of Open Access Journals (Sweden)

    Alejandro Hernández

    2008-01-01

    Full Text Available Reduction of the protein content from 25 to 8% casein in the diet of pregnant rats results in impaired neocortical long-term potentiation (LTP of the offspring together with lower visuospatial memory performance. The present study was aimed to investigate whether this type of maternal malnutrition could result in modification of plastic capabilities of the entorhinal cortex (EC in the adult progeny. Unlike normal eutrophic controls, 55–60-day-old prenatally malnourished rats were unable to develop LTP in the medial EC to tetanizing stimulation delivered to either the ipsilateral occipital cortex or the CA1 hippocampal region. Tetanizing stimulation of CA1 also failed to increase the concentration of brain-derived neurotrophic factor (BDNF in the EC of malnourished rats. Impaired capacity of the EC of prenatally malnourished rats to develop LTP and to increase BDNF levels during adulthood may be an important factor contributing to deficits in learning performance having adult prenatally malnourished animals.

  14. Reversal of Impaired Hippocampal Long-term Potentiation and Contextual Fear Memory Deficits in Angelman Syndrome Model Mice by ErbB Inhibitors

    Science.gov (United States)

    Kaphzan, Hanoch; Hernandez, Pepe; Jung, Joo In; Cowansage, Kiriana K.; Deinhardt, Katrin; Chao, Moses V.; Abel, Ted; Klann, Eric

    2012-01-01

    Background Angelman syndrome (AS) is a human neuropsychiatric disorder associated with autism, mental retardation, motor abnormalities, and epilepsy. In most cases, AS is caused by the deletion of the maternal copy of UBE3A gene, which encodes the enzyme ubiquitin ligase E3A, also termed E6-AP. A mouse model of AS has been generated and these mice exhibit many of the observed neurological alterations in humans. Because of clinical and neuroanatomical similarities between AS and schizophrenia, we examined AS model mice for alterations in the neuregulin-ErbB4 pathway, which has been implicated in the pathophysiology of schizophrenia. We focused our studies on the hippocampus, one of the major brain loci impaired in AS mice. Methods We determined the expression of NRG1 and ErbB4 receptors in AS mice and wild-type littermates (ages 10-16 weeks), and studied the effects of ErbB inhibition on long-term potentiation (LTP) in hippocampal area CA1 and on hippocampus-dependent contextual fear memory. Results We observed enhanced neuregulin-ErbB4 signaling in the hippocampus of AS model mice and found that ErbB inhibitors could reverse deficits in LTP, a cellular substrate for learning and memory. In addition, we found that an ErbB inhibitor enhanced long-term contextual fear memory in AS model mice. Conclusions Our findings suggest that neuregulin-ErbB4 signaling is involved in synaptic plasticity and memory impairments in AS model mice, suggesting that ErbB inhibitors have therapeutic potential for the treatment of AS. PMID:22381732

  15. Effects of Joint Attention on Long-Term Memory in 9-Month-Old Infants: An Event-Related Potentials Study

    Science.gov (United States)

    Kopp, Franziska; Lindenberger, Ulman

    2011-01-01

    Joint attention develops during the first year of life but little is known about its effects on long-term memory. We investigated whether joint attention modulates long-term memory in 9-month-old infants. Infants were familiarized with visually presented objects in either of two conditions that differed in the degree of joint attention (high…

  16. Enhancement of Glutamate Release by l-Fucose Changes Effects of Glutamate Receptor Antagonists on Long-Term Potentiation in the Rat Hippocampus

    Science.gov (United States)

    Matthies, Henry; Schroeder, Helmut; Smalla, Karl-Heinz; Krug, Manfred

    2000-01-01

    In previous studies l-fucose has been shown to facilitate long-term memory formation and to enhance and prolong long-term potentiation (LTP). To search for possible presynaptic or postsynaptic mechanisms that are affected by l-fucose, we examined the effect of l-fucose on (1) inhibition of LTP induction via glutamate receptors by antagonists, (2) paired-pulse facilitation, and (3) presynaptic transmitter release. Coapplication of 0.2 mm l-fucose with the competitive N-methyl-d-aspartate (NMDA) receptor antagonist, d-2-amino-5-phosphonovalerate (AP5), or coapplication of 0.2 mml-fucose in the presence of an inhibitor for class I/II metabotropic glutamate receptors, (S)-α-methyl-4-carboxyphenylglycine (MCPG), reversed LTP blockade in the CA1-region of hippocampal slices. In contrast, l-fucose had no effect on the LTP blockade by the noncompetitive NMDA ion-channel blocker (5R,10S)-(+)-5-Methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5, 10-imine hydrogen maleate (MK-801). Paired-pulse facilitation, which is a primarily presynaptic phenomenon of short-term plasticity, was decreased in the presence of 0.2 mm l-fucose. Furthermore, l-fucose enhanced the K+-stimulated release of [3H]-d-aspartate from preloaded hippocampal slices in a concentration-dependent manner. These observations demonstrate an influence of l-fucose on transmitter release that in turn can increase transmitter availability at postsynaptic glutamate receptors. This effect of l-fucose may contribute to the LTP facilitation seen in vitro and in vivo as well as to improvement in memory formation. PMID:10940323

  17. The Screening of Genes Sensitive to Long-Term, Low-Level Microwave Exposure and Bioinformatic Analysis of Potential Correlations to Learning and Memory.

    Science.gov (United States)

    Zhao, Ya Li; Li, Ying Xian; Ma, Hong Bo; Li, Dong; Li, Hai Liang; Jiang, Rui; Kan, Guang Han; Yang, Zhen Zhong; Huang, Zeng Xin

    2015-08-01

    To gain a better understanding of gene expression changes in the brain following microwave exposure in mice. This study hopes to reveal mechanisms contributing to microwave-induced learning and memory dysfunction. Mice were exposed to whole body 2100 MHz microwaves with specific absorption rates (SARs) of 0.45 W/kg, 1.8 W/kg, and 3.6 W/kg for 1 hour daily for 8 weeks. Differentially expressing genes in the brains were screened using high-density oligonucleotide arrays, with genes showing more significant differences further confirmed by RT-PCR. The gene chip results demonstrated that 41 genes (0.45 W/kg group), 29 genes (1.8 W/kg group), and 219 genes (3.6 W/kg group) were differentially expressed. GO analysis revealed that these differentially expressed genes were primarily involved in metabolic processes, cellular metabolic processes, regulation of biological processes, macromolecular metabolic processes, biosynthetic processes, cellular protein metabolic processes, transport, developmental processes, cellular component organization, etc. KEGG pathway analysis showed that these genes are mainly involved in pathways related to ribosome, Alzheimer's disease, Parkinson's disease, long-term potentiation, Huntington's disease, and Neurotrophin signaling. Construction of a protein interaction network identified several important regulatory genes including synbindin (sbdn), Crystallin (CryaB), PPP1CA, Ywhaq, Psap, Psmb1, Pcbp2, etc., which play important roles in the processes of learning and memorye. Long-term, low-level microwave exposure may inhibit learning and memory by affecting protein and energy metabolic processes and signaling pathways relating to neurological functions or diseases. Copyright © 2015 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

  18. Neurogenesis and Alzheimer's Disease

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    Philippe Taupin

    2006-01-01

    Full Text Available Alzheimer’s disease (AD is a neurodegenerative disease, characterized in the brain by amyloid plaque deposits and neurofibrillary tangles. It is the most common form of dementia among older people. There is at present no cure for AD, and current treatments consist mainly in drug therapy. Potential therapies for AD involve gene and cellular therapy. The recent confirmation that neurogenesis occurs in the adult brain and neural stem cells (NSCs reside in the adult central nervous system (CNS provide new opportunities for cellular therapy in the CNS, particularly for AD, and to better understand brain physiopathology. Hence, researchers have aimed at characterizing neurogenesis in patients with AD. Studies show that neurogenesis is increased in these patients, and in animal models of AD. The effect of drugs used to treat AD on neurogenesis is currently being investigated, to identify whether neurogenesis contributes to their therapeutic activities.

  19. Nitrogen transformations in a Vertisol under long-term tillage and no tillage management in dryland agricultual systems: key genes and potential rates

    Science.gov (United States)

    Melero, Sebastiana; Perez de Mora, Alfredo; Murillo, J. Manuel; Buegger, Franz; Kleinedam, Kristina; Kublik, Susanne; Vanderlinden, Karl; Moreno, Felix; Schloter, Michael

    2010-05-01

    The impact of tillage practices on microbial N transformations in semiarid regions is poorly understood and data from long-term field experiments are scarce. In this study, we evaluated the effects of traditional tillage (TT) vs no-tillage (NT) on key processes of the N cycle such as nitrification and denitrification in a long-term field experiment under a rainfed crop rotation system (cereal-sunflower-legumes) on a vertisol (SW Spain). Besides general soil chemical and biological parameters, we quantified the size of the ammonia oxidizing and denitrifying bacterial populations via real-time PCR (amoA, nirS and nosZ genes), and measured potential nitrification and denitrification rates. Soil was sampled at two depths (0-30, till layer; and 30-50 cm), once during the growing period of the crop (wheat) and another time after harvesting. Conservation tillage slightly increased total organic carbon and microbial biomass C content, whereas no effect on nutrient availability (C and N) was observed, likely due to the fertilization regime and the textural characteristics of the soil type (Vertisol). Gene abundance and potential rates were influenced by the interaction between tillage treatment and sampling period, mainly at 0-30 cm depth. In general, ammonia oxidizers and potential nitrification were enhanced under TT, particularly after harvesting. By contrast, higher abundance of denitrifiers, as reflected by both nirS and nosZ gene copy numbers and larger potential denitrification rates were found under NT during the growing period, but not after harvesting. Results also showed that the N2O/N2 ratio was constant throughout the experiment and thus was affected more significantly by environmental parameters such as the availability carbon than by changes in denitrifier abundance. Our results stress the importance of quantifying microbial populations to address the impact of agricultural practices on N transformations in soil. Furthermore, results suggest that the spatial

  20. Pattern Separation: A Potential Marker of Impaired Hippocampal Adult Neurogenesis in Major Depressive Disorder

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    Kellen Gandy

    2017-10-01

    Full Text Available Adult neurogenesis involves the generation of new neurons, particularly in the dentate gyrus of the hippocampus. Decreased hippocampal neurogenesis has been implicated in both animal models of depression and in patients with major depressive disorder (MDD, despite some inconsistency in the literature. Here, we build upon current models to generate a new testable hypothesis, linking impaired neurogenesis to downstream psychological outcomes commonly observed in MDD. We contend that disruption in adult neurogenesis impairs pattern separation, a hippocampus-dependent function requiring the careful discrimination and storage of highly similar, but not identical, sensory inputs. This, in turn, can affect downstream processing and response selection, of relevance to emotional wellbeing. Specifically, disrupted pattern separation leads to misperceived stimuli (i.e., stimulus confusion, triggering the selection and deployment of established responses inappropriate for the actual stimuli. We speculate that this may be akin to activation of automatic thoughts, described in the Cognitive Behavior Theory of MDD. Similarly, this impaired ability to discriminate information at a fundamental sensory processing level (e.g., impaired pattern separation could underlie impaired psychological flexibility, a core component of Acceptance and Commitment Therapy of MDD. We propose that research is needed to test this model by examining the relationship between cognitive functioning (e.g., pattern separation ability, psychological processes (e.g., perseveration and psychological inflexibility, and neurogenesis, taking advantage of emerging magnetic resonance spectroscopy-based imaging that measures neurogenesis in-vivo.

  1. A Power-Efficient Bio-Potential Acquisition Device with DS-MDE Sensors for Long-Term Healthcare Monitoring Applications

    Science.gov (United States)

    Chang, Chia-Lin; Chang, Chih-Wei; Huang, Hong-Yi; Hsu, Chen-Ming; Huang, Chia-Hsuan; Chiou, Jin-Chern; Luo, Ching-Hsing

    2010-01-01

    This work describes a power-efficient bio-potential acquisition device for long-term healthcare applications that is implemented using novel microelectromechanical dry electrodes (MDE) and a low power bio-potential processing chip. Using micromachining technology, an attempt is also made to enhance the sensing reliability and stability by fabricating a diamond-shaped MDE (DS-MDE) that has a satisfactory self-stability capability and superior electric conductivity when attached onto skin without any extra skin tissue injury technology. To acquire differential bio-potentials such as ECG signals, the proposed processing chip fabricated in a standard CMOS process has a high common mode rejection ratio (C.M.R.R.) differential amplifier and a 12-bit analog-to-digital converter (ADC). Use of the proposed system and integrate simple peripheral commercial devices can obtain the ECG signal efficiently without additional skin tissue injury and ensure continuous monitoring more than 70 hours with a 400 mAh battery. PMID:22399907

  2. LONG TERM COLLECTIONS

    CERN Multimedia

    STAFF ASSOCIATION

    2010-01-01

    ACKNOWLEDGMENTS The Long-Term Collections (CLT) committee would like to warmly thank its faithful donors who, year after year, support our actions all over the world. Without you, all this would not be possible. We would like to thank, in particular, the CERN Firemen’s Association who donated 5000 CHF in the spring thanks to the sale of their traditional calendar, and the generosity of the CERN community. A huge thank you to the firemen for their devotion to our cause. And thank you to all those who have opened their door, their heart, and their purses! Similarly, we warmly thank the CERN Yoga Club once again for its wonderful donation of 2000 CHF we recently received. We would also like to tell you that all our projects are running well. Just to remind you, we are currently supporting the activities of the «Réflexe-Partage» Association in Mali; the training centre of «Education et Développement» in Abomey, Benin; and the orphanage and ...

  3. Modulation of DL-. alpha. -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/quisqualate receptors by phospholipase A sub 2 : A necessary step in long-term potentiation

    Energy Technology Data Exchange (ETDEWEB)

    Massicotte, G.; Baudry, M. (Univ. of Southern California, Los Angeles (United States)); Vanderklish, P.; Lynch, G. (Univ. of California, Irvine (United States))

    1991-03-01

    The effects of kainate (KA)-induced epileptic seizures on the binding properites of hippocampal glutamate receptors, on the modulation of DL-{alpha}-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/quisqualate receptor by phospholipase A{sub 2} (PLA{sub 2}), and on the formation of long-term potentiation (LTP) were studied in hippocampal membranes and hippocampal slices. Systemic administration of KA produced specific changes in the binding properties of the AMPA/quisqualate receptors and its regulation. Whereas the binding of various ligands to the N-methyl-D-aspartate receptors was not modified by KA treatment, there was a singificant decrease in the maximal number of binding sites for ({sup 3}H)AMPA. The loss of LTP was not due to changes in postsynaptic responses elicited by the bursts that trigger the potentiation effect, thus suggesting that KA treatment disrupts processes that follow N-methyl-D-aspartate receptor activation. Systemic administration of KA was associated with calpain activation as the amount of spectrin breakdown products was increased severalfold in hippocampus but not in cerebellum. Pretreatment of telencephalic membranes with calpain greatly reduced the PLA{sub 2}-induced increase in ({sup 3}H)AMPA binding. The results provide evidence in favor of an essential role of PLA{sub 2} in the development of LTP and suggest that the order of activation of different calcium-dependent processes is critical for producing the final changes underlying LTP.

  4. Long-term Potentiation Decay and Poor Long-lasting Memory Process in the Wild Rodents Proechimys from Brazil’s Amazon Rainforest

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    Marcia J. Guimarães Marques

    2018-01-01

    Full Text Available Proechimys are small terrestrial rodents from Amazon rainforest. Each animal species is adapted to a specific environment in which the animal evolved therefore without comparative approaches unique characteristics of distinct species cannot be fully recognized. Laboratory rodents are exceedingly inbred strains dissociated from their native habitats and their fundamental ecological aspects are abstracted. Thus, the employment of exotic non-model species can be informative and complement conventional animal models. With the aim of promoting comparative studies between the exotic wildlife populations in the laboratory and traditional rodent model, we surveyed a type of synaptic plasticity intimately related to memory encoding in animals. Using theta-burst paradigm, in vitro long-term potentiation (LTP in the CA1 subfield of hippocampal slices was assessed in the Amazon rodents Proechimys and Wistar rats. Memory, learning and anxiety were investigated through the plus-maze discriminative avoidance task (PM-DAT and object recognition test. In PM-DAT, both animal species were submitted to two test sessions (3-h and 24-h after the conditioning training. Proechimys exhibited higher anxiety-like behavior in the training session but during test sessions both species exhibited similar patterns of anxiety-related behavior. After 3-h of the training, Proechimys and Wistar spent significantly less time in the aversive enclosed arm than in the non-aversive arm. But, at 24-h after training, Wistar rats remained less time in the aversive closed arm in comparison with the non-aversive one, while Proechimys rodents spent the same amount of time in both enclosed arms. In the object recognition test, both species were evaluated at 24-h after the acquisition session and similar findings than those of the PM-DAT (24-h were obtained, suggesting that long-term memory duration did not persist for 24-h in the Amazon rodent. Field excitatory post-synaptic potentials

  5. Novel potential predictive markers of sunitinib outcomes in long-term responders versus primary refractory patients with metastatic clear-cell renal cell carcinoma.

    Science.gov (United States)

    Puente, Javier; Laínez, Nuria; Dueñas, Marta; Méndez-Vidal, María José; Esteban, Emilio; Castellano, Daniel; Martinez-Fernández, Mónica; Basterretxea, Laura; Juan-Fita, María José; Antón, Luis; León, Luis; Lambea, Julio; Pérez-Valderrama, Begoña; Vázquez, Sergio; Suarez, Cristina; Del Muro, Xavier Garcia; Gallardo, Enrique; Maroto, José Pablo; Samaniego, M Luz; Suárez-Paniagua, Beatriz; Sanz, Julián; Paramio, Jesús M

    2017-05-02

    Several potential predictive markers of efficacy of targeted agents in patients with metastatic renal cell carcinoma (mRCC) have been identified. Interindividual heterogeneity warrants further investigation. Multicenter, observational, retrospective study in patients with clear-cell mRCC treated with sunitinib. Patients were classified in two groups: long-term responders (LR) (progression-free survival (PFS)≥22 months and at least stable disease), and primary refractory (PR) (progressive disease within 3-months of sunitinib onset). Objectives were to compare baseline clinical factors in both populations and to correlate tumor expression of selected signaling pathways components with sunitinib PFS. 123 patients were analyzed (97 LR, 26 PR). In the LR cohort, overall response rate was 79% and median duration of best response was 30 months. Median PFS and overall survival were 43.2 (95% confidence intervals[CI]:37.2-49.3) and 63.5 months (95%CI:55.1-71.9), respectively. At baseline PR patients had a significantly lower proportion of nephrectomies, higher lactate dehydrogenase and platelets levels, lower hemoglobin, shorter time to and higher presence of metastases, and increased Fuhrman grade. Higher levels of HEYL, HEY and HES1 were observed in LR, although only HEYL discriminated populations significantly (AUC[ROC]=0.704; cut-off=34.85). Increased levels of hsa-miR-27b, hsa-miR-23b and hsa-miR-628-5p were also associated with prolonged survival. No statistical significant associations between hsa-miR-23b or hsa-miR-27b and the expression of c-Met were found. Certain mRCC patients treated with sunitinib achieve extremely long-term responses. Favorable baseline hematology values and longer time to metastasis may predict longer PFS. HEYL, hsa-miR-27b, hsa-miR-23b and hsa-miR-628-5p could be potentially used as biomarkers of sunitinib response.

  6. Sustained increase of spontaneous input and spike transfer in the CA3-CA1 pathway following long term potentiation in vivo

    Directory of Open Access Journals (Sweden)

    Oscar eHerreras

    2012-10-01

    Full Text Available Long term potentiation (LTP is commonly used to study synaptic plasticity but the associated changes in the spontaneous activity of individual neurons or the computational properties of neural networks in vivo remain largely unclear. The multisynaptic origin of spontaneous spikes makes difficult estimating the impact of a particular potentiated input. Accordingly, we adopted an approach that isolates pathway-specific postsynaptic activity from raw local field potentials (LFPs in the rat hippocampus in order to study the effects of LTP on ongoing spike transfer between cell pairs in the CA3-CA1 pathway. CA1 Schaffer-specific LFPs elicited by spontaneous clustered firing of CA3 pyramidal cells involved a regular succession of elementary micro-field-EPSPs (gamma-frequency that fired spikes in CA1 units. LTP increased the amplitude but not the frequency of these ongoing excitatory quanta. Also, the proportion of Schaffer-driven spikes in both CA1 pyramidal cells and interneurons increased in a cell-specific manner only in previously connected CA3-CA1 cell pairs, i.e., when the CA3 pyramidal cell had shown pre-LTP significant correlation with firing of a CA1 unit and potentiated spike-triggered average of Schaffer LFPs following LTP. Moreover, LTP produced subtle reorganization of presynaptic CA3 cell assemblies. These findings show effective enhancement of pathway specific ongoing activity which leads to increased spike transfer in potentiated segments of a network. These indicate that plastic phenomena induced by external protocols may intensify spontaneous information flow across specific channels as proposed in transsynaptic propagation of plasticity and synfire chain hypotheses that may be the substrate for different types of memory involving multiple brain structures.

  7. Different contributions of platelet-activating factor and nitric oxide in long-term potentiation of the rat medial vestibular nuclei.

    Science.gov (United States)

    Pettorossi, V E; Grassi, S

    2001-01-01

    In rat brainstem slices, we investigated the differential role of nitric oxide (NO) and platelet-activating factor (PAF) in long-term potentiation (LTP) induced in the ventral portion of the medial vestibular nuclei (MVN) by high-frequency stimulation (HFS) of the primary vestibular afferents. The NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (carboxy-PTIO) and the PAF receptor antagonist ginkgolide B (BN-52021) were administered before and after induction of potentiation. The effect of carboxy-PTIO was to completely prevent LTP. By contrast, BN-52021 only reduced the amplitude of HFS potentiation, which could develop fully at the drug washout or decline to zero, becoming a short-term phenomenon, in the case of long-lasting PAF receptor block. Both drugs, when given after HFS, had no effect on the already established potentiation, but whilst BN-52021 showed an influence within 5 min of the LTP induction, carboxy-PTIO did not affect the response once HFS was delivered. Moreover, we showed that the NO donor, sodium nitroprusside, and methylcarbamyl PAF (mc-PAF) induced LTP which was associated with an increase in glutamate release as shown by reduction in the paired-pulse facilitation ratio. The mc-PAF LTP was prevented by the NO scavenger, while NO LTP was only reduced by BN-52021. We suggest that NO and PAF are implicated as retrograde messengers in two different phases of vestibular LTP: NO in the induction phase; and PAF in the full expression phase.

  8. Purposeful Activity in Psychiatric Rehabilitation: Is Neurogenesis a Key Player?

    Directory of Open Access Journals (Sweden)

    Joyce Siu-Chong Cheung

    2016-06-01

    Full Text Available Adult neurogenesis, defined as the generation of new neurons in adulthood, has been a fascinating discovery in neuroscience, as the continuously replenishing neuronal population provides a new perspective to understand neuroplasticity. Besides maintaining normal physiological function, neurogenesis also plays a key role in pathophysiology and symptomatology for psychiatric conditions. In the past decades, extensive effort has been spent on the understanding of the functional significance of neurogenesis in psychiatric conditions, mechanisms of pharmacological treatment, and discovery of novel drug candidates for different conditions. In a clinical situation, however, long-term rehabilitation treatment, in which occupational therapy is the key discipline, is a valuable, economical, and commonly used treatment alternative to psychotropic medications. Surprisingly, comparatively few studies have investigated the biological and neurogenic effects of different psychiatric rehabilitative treatments. To address the possible linkage between psychiatric rehabilitation and neurogenesis, this review discusses the role of neurogenesis in schizophrenia, major depression, and anxiety disorders. The review also discusses the potential neurogenic effect of currently used psychiatric rehabilitation treatments. With a better understanding of the biological effect of psychiatric rehabilitation methods and future translational studies, it is hoped that the therapeutic effect of psychiatric rehabilitation methods could be explained with a novel perspective. Furthermore, this knowledge will benefit future formulation of treatment methods, especially purposeful activities in occupational therapy, for the treatment of psychiatric disorders.

  9. Right hemicolectomy for mesenteric phlebosclerosis potentially caused by long-term use of herbal medicine: A case report and literature review.

    Science.gov (United States)

    Hoshino, Nobuaki; Hasegawa, Suguru; Hida, Koya; Kawada, Kenji; Sakai, Yoshiharu

    2016-01-01

    Mesenteric phlebosclerosis is a rare ischemic disease affecting the colon. Systemic disease and herbal medicine have been pointed out as possible causes, and the disease is characterized by calcifications involved the mesocolic veins. Patients who do not respond to conservative therapy require surgical treatment. In surgical intervention, an adequate extent of colonic resection is important. We present a case of an 87-year-old woman with mesenteric phlebosclerosis who had consumed herbal medicine for 40 years. She suffered from ileus caused by mesenteric phlebosclerosis, and the symptoms did not improve with conservative therapy. Right hemicolectomy was performed since the disease was localized in the right colon. Long-term use of herbal medicine was considered the potential cause of mesenteric phlebosclerosis. The postoperative course was mostly uneventful. The patient stopped using herbal medicine and had no signs of recurrence 2 years after surgery. The greatest concern in surgery for mesenteric phleboscrerosis is to detect the affected area, which should be removed. Characteristic findings in computed tomography and intraoperative findings can help to determine the optimal extent of colonic resection. Mesenteric phlebosclerosis caused by herbal medicines occurs as localized disease in the right colon compared with mesenteric phlebosclerosis caused by other pathogenesis. Limited colonic resection is usually indicated for mesenteric phlebosclerosis caused by herbal medicine. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  10. Myosin II ATPase activity mediates the long-term potentiation-induced exodus of stable F-actin bound by drebrin A from dendritic spines.

    Directory of Open Access Journals (Sweden)

    Toshiyuki Mizui

    Full Text Available The neuronal actin-binding protein drebrin A forms a stable structure with F-actin in dendritic spines. NMDA receptor activation causes an exodus of F-actin bound by drebrin A (DA-actin from dendritic spines, suggesting a pivotal role for DA-actin exodus in synaptic plasticity. We quantitatively assessed the extent of DA-actin localization to spines using the spine-dendrite ratio of drebrin A in cultured hippocampal neurons, and found that (1 chemical long-term potentiation (LTP stimulation induces rapid DA-actin exodus and subsequent DA-actin re-entry in dendritic spines, (2 Ca(2+ influx through NMDA receptors regulates the exodus and the basal accumulation of DA-actin, and (3 the DA-actin exodus is blocked by myosin II ATPase inhibitor, but is not blocked by myosin light chain kinase (MLCK or Rho-associated kinase (ROCK inhibitors. These results indicate that myosin II mediates the interaction between NMDA receptor activation and DA-actin exodus in LTP induction. Furthermore, myosin II seems to be activated by a rapid actin-linked mechanism rather than slow MLC phosphorylation. Thus the myosin-II mediated DA-actin exodus might be an initial event in LTP induction, triggering actin polymerization and spine enlargement.

  11. Methodological Aspects of the Potential Use of Dendrochronological Techniques When Analyzing the Long-Term Impact of Tourism on Protected Areas.

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    Szymon Ciapała

    Full Text Available Intensification of pedestrian tourism causes damage to trees near tourist tracks, and likewise changes the soil structure. As a result, one may expect that annual amount of trees growing near tracks is significantly lower than deeper in the forest. However, during the study of the long-term impact of tourism on the environment (determined from tree increment dynamics, some methodological problems may occur. It is particularly important in protected areas where law and administrative regulations related to nature conservation force research to be conducted using small samples. In this paper we have analyzed the data collected in the Polish part of the Tatra National Park in the two study plots divided into two zones each: the area directly under the influence of the tourist's trampling and the control group. The aim of such analyses was to present the potential effects of the factors which may affect the results of dendrochronological analysis: (i small size of samples that affects their representativeness, (ii spatial differences in the rates of the process, as a result of spatial variability of environmental factors and (iii temporal differences in the rates of the process. This study confirms that the factors mentioned above could significantly influence the results and should be taken into consideration during the analysis.

  12. Differential Induction of Long-Term Potentiation in the Horizontal versus Columnar Superficial Connections to Layer II Cells of the Entorhinal Cortex

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    Clayton T. Dickson

    2008-06-01

    Full Text Available The entorhinal cortex (EC is a nodal and independent mnemonic element of the medial temporal lobe memory circuit as it forms a bidirectional interface between the neocortex and hippocampus. Within the EC, intra- and inter-lamellar associational connections occur via horizontal and columnar projections, respectively. We undertook a comparative study of these two inputs as they converge upon EC layer II cells using whole-cell patch techniques in an adult rat EC horizontal slice preparation in which the deepest layers (V-VI had been dissected out. Electrical stimulation of layers I and III during GABA blockade allowed us to study excitatory synaptic properties and plasticity in the horizontal and columnar fibre systems, respectively. Both pathways exhibited AMPA- and NMDA-receptor mediated transmission and both exhibited long-term potentiation (LTP after high-frequency (tetanic stimulation. LTP in the horizontal, but not in the columnar pathway, was blocked by NMDA receptor antagonism. Intriguingly, LTP in both appeared to be mediated by post synaptic increases in Ca2+ that may be coupled to differing second messenger pathways. Thus, the superficial excitatory horizontal and columnar associative pathways to layer II have divergent mechanisms for LTP which may endow the EC with even more complex and dynamic processing characteristics than previously thought.

  13. Transgenic Overexpression of the Type I Isoform of Neuregulin 1 Affects Working Memory and Hippocampal Oscillations but not Long-term Potentiation

    Science.gov (United States)

    Deakin, Inga H.; Nissen, Wiebke; Law, Amanda J.; Lane, Tracy; Kanso, Riam; Schwab, Markus H.; Nave, Klaus-Armin; Lamsa, Karri P.; Paulsen, Ole; Bannerman, David M.

    2012-01-01

    Neuregulin 1 (NRG1) is a growth factor involved in neurodevelopment and plasticity. It is a schizophrenia candidate gene, and hippocampal expression of the NRG1 type I isoform is increased in the disorder. We have studied transgenic mice overexpressing NRG1 type I (NRG1tg-type I) and their wild-type littermates and measured hippocampal electrophysiological and behavioral phenotypes. Young NRG1tg-type I mice showed normal memory performance, but in older NRG1tg-type I mice, hippocampus-dependent spatial working memory was selectively impaired. Hippocampal slice preparations from NRG1tg-type I mice exhibited a reduced frequency of carbachol-induced gamma oscillations and an increased tendency to epileptiform activity. Long-term potentiation in NRG1tg-type I mice was normal. The results provide evidence that NRG1 type I impacts on hippocampal function and circuitry. The effects are likely mediated via inhibitory interneurons and may be relevant to the involvement of NRG1 in schizophrenia. However, the findings, in concert with those from other genetic and pharmacological manipulations of NRG1, emphasize the complex and pleiotropic nature of the gene, even with regard to a single isoform. PMID:21878485

  14. The effects of CCK-8S on spatial memory and long-term potentiation at CA1 during induction of stress in rats.

    Science.gov (United States)

    Sadeghi, Malihe; Reisi, Parham; Radahmadi, Maryam

    2017-12-01

    Cholecystokinin (CCK) has been proposed as a mediator in stress. However, it is still not fully documented what are its effects. We aimed to evaluate the effects of systemic administration of CCK exactly before induction of stress on spatial memory and synaptic plasticity at CA1 in rats. Male Wistar rats were divided into 4 groups: the control, the control-CCK, the stress and the stress-CCK. Restraint stress was induced 6 hr per day, for 24 days. Cholecystokinin sulfated octapeptide (CCK-8S) was injected (1.6 µg/kg, IP) before each session of stress induction. Spatial memory was evaluated by Morris water maze test. Long-term potentiation (LTP) in Schaffer collateral-CA1 synapses was assessed (by 100 Hz tetanization) in order to investigate synaptic plasticity. Stress impaired spatial memory significantly (Pstress group. With respect to the control group, both fEPSP amplitude and slope were significantly (Pstress group. However, there were no differences between responses of the control-CCK and Stress-CCK groups compared to the control group. The present results suggest that high levels of CCK-8S during induction of stress can modulate the destructive effects of stress on hippocampal synaptic plasticity and memory. Therefore, the mediatory effects of CCK in stress are likely as compensatory responses.

  15. Differential contribution of extracellular and intracellular calcium sources to basal transmission and long-term potentiation in the sympathetic ganglion of the rat.

    Science.gov (United States)

    Vargas, R; Cifuentes, F; Morales, M A

    2007-04-01

    Calcium involved in basal ganglionic transmission and long-term potentiation (LTP) can arise either by influx from the extracellular medium or release from intracellular stores. No attempts have yet been made to concurrently explore the contributions of extracellular and intracellular Ca2+ to basal ganglionic transmission or LTP. Here, we investigate this subject using the superior cervical ganglion of the rat. To explore the extracellular Ca2+ contribution, we evaluated basal transmission and LTP at different extracellular Ca2+ concentrations. To assess intracellular Ca2+ release, we explored the contribution of the calcium-induced calcium release process by overactivation or blockade of ryanodine-sensitive Ca2+ receptor channel with caffeine, and also by blocking either IP3R with Xestospongin C or the sarco(endo)plasmic reticulum Ca2+-ATPase pump with thapsigargin. Extracellular Ca2+ affected ganglionic basal transmission and LTP to different extents. While 25% of the physiological Ca2+ concentration supported 80% of basal transmission, 50% of normal Ca2+ was required to achieve 80% of LTP. Notably, disruption of intracellular Ca2+ release by all the drugs tested apparently did not affect basal ganglionic transmission but impaired LTP. We conclude that basal transmission requires only a small level of Ca2+ entry, while LTP expression not only requires more Ca2+ entry but is also dependent on Ca2+ release from intracellular stores. Copyright (c) 2007 Wiley Periodicals, Inc.

  16. Pyruvate prevents the inhibition of the long-term potentiation induced by amyloid-β through protein phosphatase 2A inactivation.

    Science.gov (United States)

    Wang, Xiaonan; Takata, Toshihiro; Bai, Xiaojuan; Ou, Fengrong; Yokono, Koichi; Sakurai, Takashi

    2012-01-01

    Amyloid-β (Aβ) oligomers are derived from proteolytic cleavage of amyloid-β protein precursor and can impair memory and hippocampal long-term potentiation (LTP) in vivo and in vitro. They are recognized as the primary neurotoxic agents in Alzheimer's disease. Pyruvate has a protective effect against Aβ-induced neuronal cell death in hippocampal slice cultures. However, whether pyruvate also has a protective effect against the inhibition of neuronal plasticity induced by Aβ remains to be elucidated. This study examined the effect of pyruvate on the Aβ-induced inhibition of LTP in the rat hippocampus. We found that pyruvate prevented the Aβ-induced inhibition of LTP as strong as fostriecin, a specific protein phosphatase 2A (PP2A) inhibitor. Pyruvate prevented the Aβ block of Ca(2+)/calmodulin dependent protein kinase 2 (CaMK2) autophosphorylation and the Aβ-induced PP2A activation. Pyruvate, but not lactate, decreased reactive oxygen species levels in CA1 slices exposed to Aβ. We propose that pyruvate could prevent the Aβ-induced inhibition of LTP by the re-autophosphorylation of CaMK2 through PP2A inactivation. The reduction of reactive oxygen species production is considered to be the upstream mechanism of this observed pyruvate protection.

  17. Evalution of Renal Involvement in Patients with Behçet Disease: Need to be Aware About Potential Hypertension in Long Term Follow Up?

    Science.gov (United States)

    Ozel, Deniz; Ozel, Betul Duran; Ozkan, Fuat; Kutlu, Ramazan

    2016-01-01

    The aim of this study was to evaluate frequency and severity of kidney involvement with some clinical, ultrasonography and color Doppler measurements in patients with Behçet disease. This study was including 32 patients with Behçet disease and 32 healthy sex and age-matched control subjects. Patients were divided into two groups as period of disease 0-6 years and 7 years and above to evaluate effect of duration of disease. We evaluated some biochemical tests in both blood and urine related to renal functions, blood pressure values. Gray scale and color Doppler findings were noted. Renal artery volume flow in patients with a duration of 7 years or above was significantly decreased compared to control group (p<0.05). However, gray scale ultrasound and color Doppler measurements reveal there was not statistically significant change compared to control group. There was no biochemical abnormalities in any patient. Four patients had elevated blood pressure but mean blood pressure values were not statistically different compared to volunteers. Renal involvement ratios varies in different studies but not common. End stage renal failure can be seen very rare. Furthermore, vasculitic changes can lead renal artery narrowness and can result to decrease in renal blood flow. It has a potential to activate renin angiotensin aldosterone cascade to elevate blood pressure. We must be aware about blood pressure of patients with Behçet disease, especially with long term follow up.

  18. Predicting long-term contamination potential of perched groundwater in a mine-waste heap using a random-walk method

    Science.gov (United States)

    Gandy, Catherine J.; Younger, Paul L.

    2008-05-01

    Mine-waste heaps are potential long-term sources of contamination for surface-water courses and groundwater systems. Application of a novel physically based particle-tracking model to a mine-waste heap in northern England, UK, has enabled predictions to be made of the lifetime of contaminants leaching, revealing a pattern of source-mineral depletion. A mine-waste heap is conceptualised by a series of one-dimensional unsaturated “columns” in which active weathering of source minerals takes place. These columns drain into a saturated zone, through which the contaminants are transported to the heap discharge. Solute transport is simulated within the model by the random-walk method while reaction kinetics are incorporated to account for the timescales of source mineral depletion. Results reveal that the mine-waste heap is likely to remain polluting for several centuries, with the governing factor in the magnitude of pollution being the transport of the reactant, oxygen, to the source-mineral surfaces.

  19. Dietary 2'-Fucosyllactose Enhances Operant Conditioning and Long-Term Potentiation via Gut-Brain Communication through the Vagus Nerve in Rodents.

    Directory of Open Access Journals (Sweden)

    Enrique Vazquez

    Full Text Available 2´-fucosyllactose (2´-FL is an abundant human milk oligosaccharide (HMO in human milk with diverse biological effects. We recently reported ingested 2´-FL stimulates central nervous system (CNS function, such as hippocampal long term potentiation (LTP and learning and memory in rats. Conceivably the effect of 2´-FL on CNS function may be via the gut-brain axis (GBA, specifically the vagus nerve, and L-fucose (Fuc may play a role. This study had two aims: (1 determine if the effect of ingested 2´-FL on the modulation of CNS function is dependent on the integrity of the molecule; and (2 confirm if oral 2´-FL modified hippocampal LTP and associative learning related skills in rats submitted to bilateral subdiaphragmatic vagotomy. Results showed that 2´-FL but not Fuc enhanced LTP, and vagotomy inhibited the effects of oral 2´-FL on LTP and associative learning related paradigms. Taken together, the data show that dietary 2´-FL but not its Fuc moiety affects cognitive domains and improves learning and memory in rats. This effect is dependent on vagus nerve integrity, suggesting GBA plays a role in 2´-FL-mediated cognitive benefits.

  20. Methodological Aspects of the Potential Use of Dendrochronological Techniques When Analyzing the Long-Term Impact of Tourism on Protected Areas.

    Science.gov (United States)

    Ciapała, Szymon; Adamski, Paweł

    2015-01-01

    Intensification of pedestrian tourism causes damage to trees near tourist tracks, and likewise changes the soil structure. As a result, one may expect that annual amount of trees growing near tracks is significantly lower than deeper in the forest. However, during the study of the long-term impact of tourism on the environment (determined from tree increment dynamics), some methodological problems may occur. It is particularly important in protected areas where law and administrative regulations related to nature conservation force research to be conducted using small samples. In this paper we have analyzed the data collected in the Polish part of the Tatra National Park in the two study plots divided into two zones each: the area directly under the influence of the tourist's trampling and the control group. The aim of such analyses was to present the potential effects of the factors which may affect the results of dendrochronological analysis: (i) small size of samples that affects their representativeness, (ii) spatial differences in the rates of the process, as a result of spatial variability of environmental factors and (iii) temporal differences in the rates of the process. This study confirms that the factors mentioned above could significantly influence the results and should be taken into consideration during the analysis.

  1. Reduction of long-term potentiation at Schaffer collateral-CA1 synapses in the rat hippocampus at the acute stage of vestibular compensation

    Science.gov (United States)

    Lee, Gyoung Wan; Kim, Jae Hyo

    2017-01-01

    Vestibular compensation is a recovery process from vestibular symptoms over time after unilateral loss of peripheral vestibular end organs. The aim of the present study was to observe time-dependent changes in long-term potentiation (LTP) at Schaffer collateral-CA1 synapses in the CA1 area of the hippocampus during vestibular compensation. The input-output (I/O) relationships of fEPSP amplitudes and LTP induced by theta burst stimulation to Schaffer's collateral commissural fibers were evaluated from the CA1 area of hippocampal slices at 1 day, 1 week, and 1 month after unilateral labyrinthectomy (UL). The I/O relationships of fEPSPs in the CA1 area was significantly reduced within 1 week post-op and then showed a non-significant reduction at 1 month after UL. Compared with sham-operated animals, there was a significant reduction of LTP induction in the hippocampus at 1 day and 1 week after UL. However, LTP induction levels in the CA1 area of the hippocampus also returned to those of sham-operated animals 1 month following UL. These data suggest that unilateral injury of the peripheral vestibular end organs results in a transient deficit in synaptic plasticity in the CA1 hippocampal area at acute stages of vestibular compensation. PMID:28706456

  2. Cystathionine-β-synthase-derived hydrogen sulfide is required for amygdalar long-term potentiation and cued fear memory in rats.

    Science.gov (United States)

    Chen, Hai-Bo; Wu, Wen-Ning; Wang, Wei; Gu, Xun-Hu; Yu, Bin; Wei, Bo; Yang, Yuan-Jian

    2017-04-01

    Hydrogen sulfide (H2S) is an endogenous gaseous molecule that functions as a neuromodulator in the brain. We previously reported that H2S regulated amygdalar synaptic plasticity and cued fear memory in rats. However, whether endogenous H2S is required for amygdalar long-term potentiation (LTP) induction and cued fear memory formation remains unclear. Here, we show that cystathionine-β-synthase (CBS), the predominant H2S-producing enzyme in the brain, was highly expressed in the amygdala of rats. Suppressing CBS activity by inhibitor prevented activity-triggered generation of H2S in the lateral amygdala (LA) region. Incubating brain slices with CBS inhibitor significantly prevented the induction of NMDA receptors (NMDARs)-dependent LTP in the thalamo-LA pathway, and intra-LA infusion of CBS inhibitor impaired cued fear memory in rats. Notably, treatment with H2S donor, but not CBS activator, significantly reversed the impairments of LTP and fear memory caused by CBS inhibition. Mechanismly, inhibition of CBS activity led to a reduction in NMDAR-mediated synaptic response in the thalamo-LA pathway, and treatment with H2S donor restored the function of NMDARs. Collectively, these results indicate that CBS-derived H2S is required for amygdalar synaptic plasticity and cued fear memory in rats, and the effects of endogenous H2S might involve the regulation of NMDAR function. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Dopamine D1-like receptor in lateral habenula nucleus affects contextual fear memory and long-term potentiation in hippocampal CA1 in rats.

    Science.gov (United States)

    Chan, Jiangping; Guan, Xin; Ni, Yiling; Luo, Lilu; Yang, Liqiang; Zhang, Pengyue; Zhang, Jichuan; Chen, Yanmei

    2017-03-15

    The Lateral Habenula (LHb) plays an important role in emotion and cognition. Recent experiments suggest that LHb has functional interaction with the hippocampus and plays an important role in spatial learning. LHb is reciprocally connected with midbrain monoaminergic brain areas such as the ventral tegmental area (VTA). However, the role of dopamine type 1 receptor (D1R) in LHb in learning and memory is not clear yet. In the present study, D1R agonist or antagonist were administered bilaterally into the LHb in rats. We found that both D1R agonist and antagonist impaired the acquisition of contextual fear memory in rats. D1R agonist or antagonist also impaired long term potentiation (LTP) in hippocampal CA3-CA1 synapses in freely moving rats and attenuated learning induced phosphorylation of α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor (AMPAR) subunit 1 (GluA1) at Ser831 and Ser845 in hippocampus. Taken together, our results suggested that dysfunction of D1R in LHb affected the function of hippocampus. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. A Substrate Trapping Mutant Form of the Tyrosine Phosphatase STEP Prevents Amphetamine-induced Stereotypies and Long-term Potentiation in the Striatum

    Science.gov (United States)

    Tashev, Roman; Moura, Paula J.; Venkitaramani, Deepa V.; Prosperetti, Chiara; Centonze, Diego; Paul, Surojit; Lombroso, Paul J.

    2009-01-01

    Background Chronic, intermittent exposure to psychostimulants results in striatal neuroadaptations leading to an increase in an array of behavioral responses on subsequent challenge days. STEP, a brain-specific STriatal Enriched tyrosine Phosphatase, regulates synaptic strengthening by dephosphorylating and inactivating several key synaptic proteins. This study tests the hypothesis that a substrate-trapping form of STEP will prevent the development of amphetamine-induced stereotypies. Methods A substrate-trapping STEP protein, TAT-STEP (C-S), was infused into the ventrolateral striatum on each of five consecutive exposure days and 1 hour prior to amphetamine injection. Animals were challenged to see whether sensitization to the stereotypy-producing effects of amphetamine developed. The same TAT-STEP (C-S) protein was used on acute striatal slices to determine the impact on long-term potentiation and depression. Results Infusion of TAT-STEP (C-S) blocks the increase of amphetamine-induced stereotypies when given during the 5-day period of sensitization. TAT-STEP (C-S) has no effect if only infused on the challenge day. Treatment of acute striatal slices with TAT-STEP (C-S) blocks the induction of LTP and potentates LTD. Conclusions A substrate trapping form of STEP blocks the induction of amphetamine-induced neuroplasticity within the ventrolateral striatum, and supports the hypothesis that STEP functions as a tonic break on synaptic strengthening. PMID:19026408

  5. Expression of p53 Target Genes in the Early Phase of Long-Term Potentiation in the Rat Hippocampal CA1 Area

    Directory of Open Access Journals (Sweden)

    Vladimir O. Pustylnyak

    2015-01-01

    Full Text Available Gene expression plays an important role in the mechanisms of long-term potentiation (LTP, which is a widely accepted experimental model of synaptic plasticity. We have studied the expression of at least 50 genes that are transcriptionally regulated by p53, as well as other genes that are related to p53-dependent processes, in the early phase of LTP. Within 30 min after Schaffer collaterals (SC tetanization, increases in the mRNA and protein levels of Bax, which are upregulated by p53, and a decrease in the mRNA and protein levels of Bcl2, which are downregulated by p53, were observed. The inhibition of Mdm2 by nutlin-3 increased the basal p53 protein level and rescued its tetanization-induced depletion, which suggested the involvement of Mdm2 in the control over p53 during LTP. Furthermore, nutlin-3 caused an increase in the basal expression of Bax and a decrease in the basal expression of Bcl2, whereas tetanization-induced changes in their expression were occluded. These results support the hypothesis that p53 may be involved in transcriptional regulation during the early phase of LTP. We hope that the presented data may aid in the understanding of the contribution of p53 and related genes in the processes that are associated with synaptic plasticity.

  6. Neurocognitive and psychotiform behavioral alterations and enhanced hippocampal long-term potentiation in transgenic mice displaying neuropathological features of human alpha-mannosidosis.

    Science.gov (United States)

    D'Hooge, Rudi; Lüllmann-Rauch, Renate; Beckers, Tom; Balschun, Detlef; Schwake, Michael; Reiss, Karina; von Figura, Kurt; Saftig, Paul

    2005-07-13

    Mice with alpha-mannosidase gene inactivation provide an experimental model for alpha-mannosidosis, a lysosomal storage disease with severe neuropsychological and psychopathological complications. Neurohistological alterations in these mice were similar to those in patients and included vacuolations and axonal spheroids in the CNS and peripheral nervous system. Vacuolation was most prominent and evenly distributed in neuronal perikarya of the hippocampal CA2 and CA3 regions, whereas CA1 and dentate gyrus were weakly or not affected. Field potential recordings from CA1 region in hippocampal slices showed enhanced theta burst-induced long-term potentiation (LTP) in alpha-mannosidase-deficient mice. Longitudinal assessment in age-matched alpha-mannosidase-deficient and wild-type littermates, using an extended test battery, demonstrated a neurocognitive and psychotiform profile that may relate to the psychopathological alterations in clinical alpha-mannosidosis. Brainstem auditory-evoked potentials and basic neuromotor abilities were not impaired and did not deteriorate with age. Exploratory and conflict tests revealed consistent decreases in exploratory activity and emotional blunting in the knock-out group. alpha-Mannosidosis mice were also impaired in aversively motivated learning and acquisition of signal-shock associations. Acquisition and reversal learning in the water maze task, passive avoidance learning in the step-through procedure, as well as emotional response conditioning in an operant procedure were all impaired. Acquisition or shaping of an appetitive instrumental conditioning task was unchanged. Appetitive odor discrimination learning was only marginally impaired during shaping, whereas both the discrimination and reversal subtasks were normal. We propose that prominent storage and enhanced LTP in hippocampus have contributed to these specific behavioral alterations in alpha-mannosidase-deficient mice.

  7. Neurotoxicity of developmental hypothyroxinemia and hypothyroidism in rats: Impairments of long-term potentiation are mediated by phosphatidylinositol 3-kinase signaling pathway

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    Wang, Yi; Wei, Wei; Wang, Yuan; Dong, Jing; Song, Binbin; Min, Hui [Department of Occupational and Environmental Health, School of Public Health, China Medical University, Shenyang (China); Teng, Weiping, E-mail: twpendocrine@yahoo.com.cn [Liaoning Provincial Key Laboratory of Endocrine Diseases, the First Hospital of China Medical University, Shenyang (China); Chen, Jie, E-mail: chenjie@mail.cmu.edu.cn [Department of Occupational and Environmental Health, School of Public Health, China Medical University, Shenyang (China)

    2013-09-01

    Neurotoxicity of iodine deficiency-induced hypothyroidism during developmental period results in serious impairments of brain function, such as learning and memory. These impairments are largely irreversible, and the underlying mechanisms remain unclear. In addition to hypothyroidism, iodine deficiency may cause hypothyroxinemia, a relatively subtle form of thyroid hormone deficiency. Neurotoxicity of developmental hypothyroxinemia also potentially impairs learning and memory. However, more direct evidence of the associations between developmental hypothyroxinemia and impairments of learning and memory should be provided, and the underlying mechanisms remain to be elucidated. Thus, in the present study, we investigated the effects of developmental hypothyroxinemia and hypothyroidism on long-term potentiation (LTP), a widely accepted cellular model of learning and memory, in the hippocampal CA1 region. The activation of the phosphatidylinositol 3-kinase (PI3K) signaling pathway – a pathway closely associated with synaptic plasticity and learning and memory – was also investigated. Wistar rats were treated with iodine deficient diet or methimazole (MMZ) to induce developmental hypothyroxinemia or hypothyroidism. The results showed that developmental hypothyroxinemia caused by mild iodine deficiency and developmental hypothyroidism caused by severe iodine deficiency or MMZ significantly reduced the field-excitatory postsynaptic potential (f-EPSP) slope and the population spike (PS) amplitude. Decreased activation of the PI3K signaling pathway was also observed in rats subjected to developmental hypothyroxinemia or hypothyroidism. Our results may support the hypothesis that neurotoxicity of both developmental hypothyroxinemia and hypothyroidism causes damages to learning and memory. Our results also suggest that decreased activation of the PI3K signaling pathway may contribute to impairments of LTP caused by neurotoxicity of both developmental hypothyroxinemia and

  8. Neurotoxicity of developmental hypothyroxinemia and hypothyroidism in rats: Impairments of long-term potentiation are mediated by phosphatidylinositol 3-kinase signaling pathway.

    Science.gov (United States)

    Wang, Yi; Wei, Wei; Wang, Yuan; Dong, Jing; Song, Binbin; Min, Hui; Teng, Weiping; Chen, Jie

    2013-09-01

    Neurotoxicity of iodine deficiency-induced hypothyroidism during developmental period results in serious impairments of brain function, such as learning and memory. These impairments are largely irreversible, and the underlying mechanisms remain unclear. In addition to hypothyroidism, iodine deficiency may cause hypothyroxinemia, a relatively subtle form of thyroid hormone deficiency. Neurotoxicity of developmental hypothyroxinemia also potentially impairs learning and memory. However, more direct evidence of the associations between developmental hypothyroxinemia and impairments of learning and memory should be provided, and the underlying mechanisms remain to be elucidated. Thus, in the present study, we investigated the effects of developmental hypothyroxinemia and hypothyroidism on long-term potentiation (LTP), a widely accepted cellular model of learning and memory, in the hippocampal CA1 region. The activation of the phosphatidylinositol 3-kinase (PI3K) signaling pathway - a pathway closely associated with synaptic plasticity and learning and memory - was also investigated. Wistar rats were treated with iodine deficient diet or methimazole (MMZ) to induce developmental hypothyroxinemia or hypothyroidism. The results showed that developmental hypothyroxinemia caused by mild iodine deficiency and developmental hypothyroidism caused by severe iodine deficiency or MMZ significantly reduced the field-excitatory postsynaptic potential (f-EPSP) slope and the population spike (PS) amplitude. Decreased activation of the PI3K signaling pathway was also observed in rats subjected to developmental hypothyroxinemia or hypothyroidism. Our results may support the hypothesis that neurotoxicity of both developmental hypothyroxinemia and hypothyroidism causes damages to learning and memory. Our results also suggest that decreased activation of the PI3K signaling pathway may contribute to impairments of LTP caused by neurotoxicity of both developmental hypothyroxinemia and

  9. α1-Adrenoceptors in the hippocampal dentate gyrus involved in learning-dependent long-term potentiation during active-avoidance learning in rats.

    Science.gov (United States)

    Lv, Jing; Zhan, Su-Yang; Li, Guang-Xie; Wang, Dan; Li, Ying-Shun; Jin, Qing-Hua

    2016-11-09

    The hippocampus is the key structure for learning and memory in mammals and long-term potentiation (LTP) is an important cellular mechanism responsible for learning and memory. The influences of norepinephrine (NE) on the modulation of learning and memory, as well as LTP, through β-adrenoceptors are well documented, whereas the role of α1-adrenoceptors in learning-dependent LTP is not yet clear. In the present study, we measured extracellular concentrations of NE in the hippocampal dentate gyrus (DG) region using an in-vivo brain microdialysis and high-performance liquid chromatography techniques during the acquisition and extinction of active-avoidance behavior in freely moving conscious rats. Next, the effects of prazosin (an antagonist of α1-adrenoceptor) and phenylephrine (an agonist of the α1-adrenoceptor) on amplitudes of field excitatory postsynaptic potential were measured in the DG region during the active-avoidance behavior. Our results showed that the extracellular concentration of NE in the DG was significantly increased during the acquisition of active-avoidance behavior and gradually returned to the baseline level following extinction training. A local microinjection of prazosin into the DG significantly accelerated the acquisition of the active-avoidance behavior, whereas a local microinjection of phenylephrine retarded the acquisition of the active-avoidance behavior. Furthermore, in all groups, the changes in field excitatory postsynaptic potential amplitude were accompanied by corresponding changes in active-avoidance behavior. Our results suggest that NE activation of α1-adrenoceptors in the hippocampal DG inhibits active-avoidance learning by modulation of synaptic efficiency in rats.

  10. The role of BRAF V600E mutation as a potential marker for prognostic stratification of papillary thyroid carcinoma: a long-term follow-up study.

    Science.gov (United States)

    Daliri, Mahdi; Abbaszadegan, Mohammad Reza; Bahar, Mostafa Mehrabi; Arabi, Azadeh; Yadollahi, Mona; Ghafari, Azar; Taghehchian, Negin; Zakavi, Seyed Rasoul

    2014-01-01

    Abstract Papillary carcinoma is the most prevalent malignancy of thyroid gland, and its incidence has been recently increased. The BRAF(V600E) mutation is the most frequent genetic alteration in papillary thyroid carcinoma (PTC). The role of BRAF(V600E) mutation as a potential prognostic factor has been controversially reported in different studies, with short-term follow-up. In this study, we evaluated the role of BRAF(V600E) mutation as a potential marker for prognostic stratification of patients with PTC in long-term follow-up. We studied 69 PTC patients with a mean follow-up period of 63.9 months (median: 60 m). The BRAF(V600E) mutation was analyzed by PCR-single-strand conformational polymorphism and sequencing. The correlation between the presence or absence of the BRAF(V600E) mutation, clinicopathological features and prognosis of PTC patients were studied. The BRAF(V600E) mutation was found in 28 of 69 (40.6%) PTC patients, and it was significantly more frequent in older patients (p history of radiation exposure (p = 0.037). Incomplete response to treatment in PTC patients was significantly correlated with certain clinicopathological characteristics (follow-up time, distant metastases, advanced stage, first thyroglobulin (fTg) level, history of reoperation and external radiotherapy and delay in iodine therapy) but it was not related to the presence of BRAF(V600E) mutation. Prevalence of BRAF(V600E) mutation was 40.6% in patients with papillary thyroid cancer in northeast of Iran. The BRAF(V600E) mutation was associated with older age and advanced tumor stage but was not correlated with incomplete response during follow-up.

  11. Chronic deep cerebellar stimulation promotes long-term potentiation, microstructural plasticity, and reorganization of perilesional cortical representation in a rodent model.

    Science.gov (United States)

    Cooperrider, Jessica; Furmaga, Havan; Plow, Ela; Park, Hyun-Joo; Chen, Zhihong; Kidd, Grahame; Baker, Kenneth B; Gale, John T; Machado, Andre G

    2014-07-02

    Control over postinjury CNS plasticity is a major frontier of science that, if conquered, would open new avenues for treatment of neurological disorders. Here we investigate the functional, physiological, and structural changes in the cerebral cortex associated with chronic deep brain stimulation of the cerebellar output, a treatment approach that has been shown to improve postischemia motor recovery in a rodent model of cortical infarcts. Long-Evans rats were pretrained on the pasta-matrix retrieval task, followed by induction of focal cortical ischemia and implantation of a macroelectrode in the contralesional lateral cerebellar nucleus. Animals were assigned to one of three treatment groups pseudorandomly to balance severity of poststroke motor deficits: REGULAR stimulation, BURST stimulation, or SHAM. Treatment initiated 2 weeks post surgery and continued for 5 weeks. At the end, animals were randomly selected for perilesional intracortical microstimulation mapping and tissue sampling for Western blot analysis or contributed tissue for 3D electron microscopy. Evidence of enhanced cortical plasticity with therapeutically effective stimulation is shown, marked by greater perilesional reorganization in stimulation- treated animals versus SHAM. BURST stimulation was significantly effective for promoting distal forepaw cortical representation. Stimulation-treated animals showed a twofold increase in synaptic density compared with SHAM. In addition, treated animals demonstrated increased expression of synaptic markers of long-term potentiation and plasticity, including synaptophysin, NMDAR1, CaMKII, and PSD95. These findings provide a critical foundation of how deep cerebellar stimulation may guide plastic reparative reorganization after nonprogressive brain injury and indicate strong translational potential. Copyright © 2014 the authors 0270-6474/14/349040-11$15.00/0.

  12. Temporal Variation in Honey Production by the Stingless Bee Melipona subnitida (Hymenoptera: Apidae): Long-Term Management Reveals its Potential as a Commercial Species in Northeastern Brazil.

    Science.gov (United States)

    Koffler, Sheina; Menezes, Cristiano; Menezes, Paulo Roberto; Kleinert, Astrid de Matos Peixoto; Imperatriz-Fonseca, Vera Lucia; Pope, Nathaniel; Jaffé, Rodolfo

    2015-06-01

    Even though stingless beekeeping has a great potential as a sustainable development tool, the activity remains essentially informal, technical knowledge is scarce, and management practices lack the sophistication and standardization found in apiculture. Here, we contributed to the further development of stingless beekeeping by investigating the long-term impact of management and climate on honey production and colony survival in the stingless bee Melipona subnitida Ducke (1910). We analyzed a 10-yr record of 155 M. subnitida colonies kept by a commercial honey producer of northeastern Brazil. This constitutes the longest and most accurate record available for a stingless bee. We modeled honey production in relation to time (years), age, management practices (colony division and food supplementation), and climatic factors (temperature and precipitation), and used a model selection approach to identify which factors best explained honey production. We also modeled colony mortality in relation to climatic factors. Although the amount of honey produced by each colony decreased over time, we found that the probability of producing honey increased over the years. Colony divisions decreased honey production, but did not affect honey presence, while supplementary feeding positively affected honey production. In warmer years, the probability of producing honey decreased and the amount of honey produced was lower. In years with lower precipitation, fewer colonies produced honey. In contrast, colony mortality was not affected by climatic factors, and some colonies lived up to nine years, enduring extreme climatic conditions. Our findings provide useful guidelines to improve management and honey production in stingless bees. © The Authors 2015. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  13. Leptin facilitates learning and memory performance and enhances hippocampal CA1 long-term potentiation and CaMK II phosphorylation in rats.

    Science.gov (United States)

    Oomura, Y; Hori, N; Shiraishi, T; Fukunaga, K; Takeda, H; Tsuji, M; Matsumiya, T; Ishibashi, M; Aou, S; Li, X L; Kohno, D; Uramura, K; Sougawa, H; Yada, T; Wayner, M J; Sasaki, K

    2006-11-01

    Leptin, an adipocytokine encoded by an obesity gene and expressed in adipose tissue, affects feeding behavior, thermogenesis, and neuroendocrine status via leptin receptors distributed in the brain, especially in the hypothalamus. Leptin may also modulate the synaptic plasticity and behavioral performance related to learning and memory since: leptin receptors are found in the hippocampus, and both leptin and its receptor share structural and functional similarities with the interleukin-6 family of cytokines that modulate long-term potentiation (LTP) in the hippocampus. We therefore examined the effect of leptin on (1) behavioral performance in emotional and spatial learning tasks, (2) LTP at Schaffer collateral-CA1 synapses, (3) presynaptic and postsynaptic activities in hippocampal CA1 neurons, (4) the intracellular Ca(2+) concentration ([Ca(2+)](i)) in CA1 neurons, and (5) the activity of Ca(2+)/calmodulin protein kinase II (CaMK II) in the hippocampal CA1 tissue that exhibits LTP. Intravenous injection of 5 and/or 50mug/kg, but not of 500mug/kg leptin, facilitated behavioral performance in passive avoidance and Morris water-maze tasks. Bath application of 10(-12)M leptin in slice experiments enhanced LTP and increased the presynaptic transmitter release, whereas 10(-10)M leptin suppressed LTP and reduced the postsynaptic receptor sensitivity to N-methyl-d-aspartic acid. The increase in the [Ca(2+)](i) induced by 10(-10)M leptin was two times greater than that induced by 10(-12)M leptin. In addition, the facilitation (10(-12)M) and suppression (10(-10)M) of LTP by leptin was closely associated with an increase and decrease in Ca(2+)-independent activity of CaMK II. Our results show that leptin not only affects hypothalamic functions (such as feeding, thermogenesis, and neuroendocrine status), but also modulates higher nervous functions, such as the behavioral performance related to learning and memory and hippocampal synaptic plasticity.

  14. Investigating the potential for long-term permeable reactive barrier (PRB) monitoring from the electrical signatures associated with the reduction in reactive iron performance

    Energy Technology Data Exchange (ETDEWEB)

    Slater, Lee D.; Korte, N.; Baker, J.

    2005-12-14

    The objective of this work was to conduct laboratory and field experiments to determine the sensitivity of low frequency electrical measurements (resistivity and induced polarization) to the processes of corrosion and precipitation that are believed to limit permeable reactive barrier (PRB) performance. The research was divided into four sets of experiments that were each written up and submitted to a peer-reviewed journal: [1] A laboratory experiment to define the controls of aqueous chemistry (electrolyte activity; pH; valence) and total zero valent iron (Fe0) available surface area on the electrical properties of Fe0 columns. [2] A laboratory experiment to determine the impact of corrosion and precipitation on the electrical response of synthetic Fe0 columns as a result of geochemical reactions with NaSO4 and NaCO3 electrolytes. [3] Laboratory experiments on a sequence of cores retrieved from the Kansas City PRB to determine the magnitude of electrical and geochemical changes within a field active PRB after eight years of operation [4] Field-scale cross borehole resistivity and induced polarization monitoring of the Kansas City PRB to evaluate the potential of electrical imaging as a technology for non-invasive, long-term monitoring of indicators of reduced PRB performance This report first summarizes the findings of the four major experiments conducted under this research. The reader is referred to the four papers in Appendices 1-4 for a full description of each experiment, including motivation and significance, technical details, findings and implications. The deliverables of the project, including the publications, conference papers and new collaborative arrangements that have resulted are then described. Appendices 5-6 contain two technical reports written by co-PI Korte describing (1) supporting geochemical measurements, and (2) the coring procedure, conducted at the Kansas City PRB as part of this project.

  15. Control of cerebellar long-term potentiation by P-Rex-family guanine-nucleotide exchange factors and phosphoinositide 3-kinase.

    Directory of Open Access Journals (Sweden)

    Claire Jackson

    2010-08-01

    Full Text Available Long-term potentiation (LTP at the parallel fibre-Purkinje cell synapse in the cerebellum is a recently described and poorly characterized form of synaptic plasticity. The induction mechanism for LTP at this synapse is considered reciprocal to "classical" LTP at hippocampal CA1 pyramidal neurons: kinases promote increased trafficking of AMPA receptors into the postsynaptic density in the hippocampus, whereas phosphatases decrease internalization of AMPA receptors in the cerebellum. In the hippocampus, LTP occurs in overlapping phases, with the transition from early to late phases requiring the consolidation of initial induction processes by structural re-arrangements at the synapse. Many signalling pathways have been implicated in this process, including PI3 kinases and Rho GTPases.We hypothesized that analogous phases are present in cerebellar LTP, and took as the starting point for investigation our recent discovery that P-Rex--a Rac guanine nucleotide exchange factor which is activated by PtdIns(3,4,5P(3--is highly expressed in mouse cerebellar Purkinje neurons and plays a role in motor coordination. We found that LTP evoked at parallel fibre synapses by 1 Hz stimulation or by NO donors was not sustained beyond 30 min when P-Rex was eliminated or Rac inhibited, suggesting that cerebellar LTP exhibits a late phase analogous to hippocampal LTP. In contrast, inhibition of PI3 kinase activity eliminated LTP at the induction stage.Our data suggest that a PI3K/P-Rex/Rac pathway is required for late phase LTP in the mouse cerebellum, and that other PI3K targets, which remain to be discovered, control LTP induction.

  16. The AMPA receptor positive allosteric modulator S 47445 rescues in vivo CA3-CA1 long-term potentiation and structural synaptic changes in old mice.

    Science.gov (United States)

    Giralt, Albert; Gómez-Climent, María Ángeles; Alcalá, Rafael; Bretin, Sylvie; Bertrand, Daniel; María Delgado-García, José; Pérez-Navarro, Esther; Alberch, Jordi; Gruart, Agnès

    2017-09-01

    Positive allosteric modulators of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) are small molecules that decrease deactivation of AMPARs via an allosteric site. These molecules keep the receptor in an active state. Interestingly, this type of modulator has been proposed for treating cognitive decline in ageing, dementias, and Alzheimer's disease (AD). S 47445 (8-cyclopropyl-3-[2-(3-fluorophenyl)ethyl]-7,8-dihydro-3H-[1,3]oxazino[6,5-g][1,2,3]benzotriazine-4,9-dione) is a novel AMPAR positive allosteric modulator (AMPA-PAM). Here, the mechanisms by which S 47445 could improve synaptic strength and connectivity were studied and compared between young and old mice. A single oral administration of S 47445 at 10 mg/kg significantly increased long-term potentiation (LTP) in CA3-CA1 hippocampal synapses in alert young mice in comparison to control mice. Moreover, chronic treatment with S 47445 at 10 mg/kg in old alert animals significantly counteracted the deficit of LTP due to age. Accordingly, chronic treatment with S 47445 at 10 mg/kg seems to preserve synaptic cytoarchitecture in old mice as compared with young control mice. It was shown that the significant decreases in number and size of pre-synaptic buttons stained for VGlut1, and post-synaptic dendritic spines stained for spinophilin, observed in old mice were significantly prevented after chronic treatment with 10 mg/kg of S 47445. Altogether, by its different effects on LTP, VGlut1-positive particles, and spinophilin, S 47445 is able to modulate both the structure and function of hippocampal excitatory synapses known to be involved in learning and memory processes. These results open a new window for the treatment of specific age-dependent cognitive decline and dementias such as AD. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  17. Long-term exposure to particulate matter, NO2 and the oxidative potential of particulates and diabetes prevalence in a large national health survey

    NARCIS (Netherlands)

    Strak, Maciej; Veldhorst-Janssen, Nicole; Beelen, Rob; Schmitz, Oliver; Vaartjes, Ilonca; Karssenberg, Derek; van den Brink, Carolien; Bots, Michiel L.; Dijst, Martin; Brunekreef, Bert; Hoek, Gerard

    2017-01-01

    Background The evidence from observational epidemiological studies of a link between long-term air pollution exposure and diabetes prevalence and incidence is currently mixed. Some studies found the strongest associations of diabetes with fine particles, other studies with nitrogen dioxide and some

  18. Understanding the potential impact of climate change on long term soil carbon dynamics in tropical cropping systems - evidence from West Africa

    Science.gov (United States)

    Cretenet, Michel; Tittonell, Pablo; Guibert, Herve

    2010-05-01

    Long term experiments offer a unique opportunity to assess sustainability and temporal dynamics of biogeochemical cycles in agriculture, as well as the gradual impact on these of relatively slow processes such as climate change. Two long term experiments on annual cropping systems representing locally common crop rotations and cultural practices were established on two contrasting agroecological zones in Ivory Coast (in 1971) and in Mali (in 1965). These experiments were designed to assess the long-term productivity of these systems under different organic matter and nutrient management regimes, applying organic and mineral soil amendments alone or in combination. Organic soil amendments - such as animal manure, compost or plant material collected from the surroundings - were included in the experiments with the double purpose of adding nutrients for immediate crop production and adding organic matter inputs to the soil to restore (or maintain) its organic C content. Here, we provide an overview of the major trends in crop productivity and soil organic C observed in these experiments that illustrates the potential impact of climate change on the effectiveness of different measures to sustain agricultural productivity. Materials and methods Both experiments compared crop productivity on control plots without any soil amendment versus plots receiving organic matter, mineral fertilisers or both combined. The experiment at Gagnoa (southern Ivory Coast) was conducted during 23 years in a zone characterised by a bimodal rainfall regime (c. 1300 mm year-1) that allows two cropping seasons per year (Alfisols 15% clay). Every year maize was planted during the first rainy season. Organic matter was added as compost at a rate of 10 t ha-1 year-1, with or without application of 160 kg N ha-1 year-1 in mineral fertiliser (Chabalier, 1986). The experiment at N'Tarla (southern Mali) was conducted during 24 years in a zone of mono-modal rainfall (c. 900 mm year-1); Alfisols 5

  19. Use of Bayesian networks classifiers for long-term mean wind turbine energy output estimation at a potential wind energy conversion site

    Energy Technology Data Exchange (ETDEWEB)

    Carta, Jose A. [Department of Mechanical Engineering, University of Las Palmas de Gran Canaria, Campus de Tafira s/n, 35017 Las Palmas de Gran Canaria, Canary Islands (Spain); Velazquez, Sergio [Department of Electronics and Automatics Engineering, University of Las Palmas de Gran Canaria, Campus de Tafira s/n, 35017 Las Palmas de Gran Canaria, Canary Islands (Spain); Matias, J.M. [Department of Statistics, University of Vigo, Lagoas Marcosende, 36200 Vigo (Spain)

    2011-02-15

    Due to the interannual variability of wind speed a feasibility analysis for the installation of a Wind Energy Conversion System at a particular site requires estimation of the long-term mean wind turbine energy output. A method is proposed in this paper which, based on probabilistic Bayesian networks (BNs), enables estimation of the long-term mean wind speed histogram for a site where few measurements of the wind resource are available. For this purpose, the proposed method allows the use of multiple reference stations with a long history of wind speed and wind direction measurements. That is to say, the model that is proposed in this paper is able to involve and make use of regional information about the wind resource. With the estimated long-term wind speed histogram and the power curve of a wind turbine it is possible to use the method of bins to determine the long-term mean energy output for that wind turbine. The intelligent system employed, the knowledgebase of which is a joint probability function of all the model variables, uses efficient calculation techniques for conditional probabilities to perform the reasoning. This enables automatic model learning and inference to be performed efficiently based on the available evidence. The proposed model is applied in this paper to wind speeds and wind directions recorded at four weather stations located in the Canary Islands (Spain). Ten years of mean hourly wind speed and direction data are available for these stations. One of the conclusions reached is that the BN with three reference stations gave fewer errors between the real and estimated long-term mean wind turbine energy output than when using two measure-correlate-predict algorithms which were evaluated and which use a linear regression between the candidate station and one reference station. (author)

  20. Ca(2+ permeable AMPA receptor induced long-term potentiation requires PI3/MAP kinases but not Ca/CaM-dependent kinase II.

    Directory of Open Access Journals (Sweden)

    Suhail Asrar

    Full Text Available Ca(2+ influx via GluR2-lacking Ca(2+-permeable AMPA glutamate receptors (CP-AMPARs can trigger changes in synaptic efficacy in both interneurons and principle neurons, but the underlying mechanisms remain unknown. We took advantage of genetically altered mice with no or reduced GluR2, thus allowing the expression of synaptic CP-AMPARs, to investigate the molecular signaling process during CP-AMPAR-induced synaptic plasticity at CA1 synapses in the hippocampus. Utilizing electrophysiological techniques, we demonstrated that these receptors were capable of inducing numerous forms of long-term potentiation (referred to as CP-AMPAR dependent LTP through a number of different induction protocols, including high-frequency stimulation (HFS and theta-burst stimulation (TBS. This included a previously undemonstrated form of protein-synthesis dependent late-LTP (L-LTP at CA1 synapses that is NMDA-receptor independent. This form of plasticity was completely blocked by the selective CP-AMPAR inhibitor IEM-1460, and found to be dependent on postsynaptic Ca(2+ ions through calcium chelator (BAPTA studies. Surprisingly, Ca/CaM-dependent kinase II (CaMKII, the key protein kinase that is indispensable for NMDA-receptor dependent LTP at CA1 synapses appeared to be not required for the induction of CP-AMPAR dependent LTP due to the lack of effect of two separate pharmacological inhibitors (KN-62 and staurosporine on this form of potentiation. Both KN-62 and staurosporine strongly inhibited NMDA-receptor dependent LTP in control studies. In contrast, inhibitors for PI3-kinase (LY294002 and wortmannin or the MAPK cascade (PD98059 and U0126 significantly attenuated this CP-AMPAR-dependent LTP. Similarly, postsynaptic infusion of tetanus toxin (TeTx light chain, an inhibitor of exocytosis, also had a significant inhibitory effect on this form of LTP. These results suggest that distinct synaptic signaling underlies GluR2-lacking CP-AMPAR-dependent LTP, and reinforces

  1. Long-term Relationships

    DEFF Research Database (Denmark)

    Hémous, David; Olsen, Morten

    2017-01-01

    suppliers and start cooperation immediately with new suppliers. We first consider broad innovations: every period, one supplier has the opportunity to create a higher quality input that can be used by all producers. Since relationships are harder to break in the cooperative equilibrium the market size...... create dynamic inefficiencies and reduce broad innovations. In particular, we consider the repeated interaction between final good producers and intermediate input suppliers, where the provision of the intermediate input is noncontractible. We build a cooperative equilibrium where producers can switch...... for potential innovators is smaller and the rate of innovation might be lower than in the noncooperative equilibrium. We contrast this with a setting with relationship-specific innovations that we show are encouraged by the establishment of relational contracts. We illustrate the predictions of the model using...

  2. Brazilian network for the surveillance of maternal potentially life threatening morbidity and maternal near-miss and a multidimensional evaluation of their long term consequences

    Directory of Open Access Journals (Sweden)

    Surita Fernanda G

    2009-09-01

    Full Text Available Abstract Background It has been suggested that the study of women who survive life-threatening complications related to pregnancy (maternal near-miss cases may represent a practical alternative to surveillance of maternal morbidity/mortality since the number of cases is higher and the woman herself is able to provide information on the difficulties she faced and the long-term repercussions of the event. These repercussions, which may include sexual dysfunction, postpartum depression and posttraumatic stress disorder, may persist for prolonged periods of time, affecting women's quality of life and resulting in adverse effects to them and their babies. Objective The aims of the present study are to create a nationwide network of scientific cooperation to carry out surveillance and estimate the frequency of maternal near-miss cases, to perform a multicenter investigation into the quality of care for women with severe complications of pregnancy, and to carry out a multidimensional evaluation of these women up to six months. Methods/Design This project has two components: a multicenter, cross-sectional study to be implemented in 27 referral obstetric units in different geographical regions of Brazil, and a concurrent cohort study of multidimensional analysis. Over 12 months, investigators will perform prospective surveillance to identify all maternal complications. The population of the cross-sectional component will consist of all women surviving potentially life-threatening conditions (severe maternal complications or life-threatening conditions (the maternal near miss criteria and maternal deaths according to the new WHO definition and criteria. Data analysis will be performed in case subgroups according to the moment of occurrence and determining cause. Frequencies of near-miss and other severe maternal morbidity and the association between organ dysfunction and maternal death will be estimated. A proportion of cases identified in the cross

  3. Effect of chloramine-T on long-term potentiation at synapses between perforant path and dentate gyrus in hippocampus of rats in vivo.

    Science.gov (United States)

    Yang, Jun; Hu, Zhuang-Li; Jiang, Bo; Ni, Lan; Jin, You; Chen, Jian-Guo; Wang, Fang

    2011-03-01

    Reactive oxygen species (ROS), including superoxide, are generally considered as neurotoxic molecules whose effects can be alleviated by antioxidant enzymes. However, ROS also are known to be necessary components of the signal transduction cascades underlying normal synaptic plasticity. The oxidant chloramine-T (Ch-T), a specific oxidant to sulphur-containing residues, can oxidize methionine (Met) residues in proteins to alter protein function. To investigate the effect of Ch-T on the induction of hippocampal long-term potentiation (LTP) in dentate gyrus (DG), in vivo electrophysiological recording was employed. It was found that intracerebroventricular (ICV) injection of 0.1 μM Ch-T in 5 μL enhanced hippocampal LTP of rats slightly, whereas, 20 mM Ch-T in 5 μL greatly attenuated LTP. These effects can be reversed by pretreatment with 0.1 mM dithiothretol (DTT), a special thiol reductant. In addition, 0.1 μM Ch-T elevated LTP-induced increase in phosphorylation of Ca²+/calmodulin (CaM)-dependent protein kinase (CaMKII) and neurogranin (Ng), whereas 2 μM and 20 mM Ch-T reduced LTP-induced increase in phosphorylation status of the two key proteins, especially for 20 mM Ch-T. Pretreatment with DTT significantly prevented these effects. Taken together, these findings demonstrated that Ch-T has concentration-dependent effects on the induction of hippocampal LTP in vivo. In brief, low concentration of Ch-T facilitated hippocampal LTP by enhancing LTP-induced increase in p-CaMKII and p-Ng compared to controls, whereas high concentration of Ch-T obviously attenuated LTP accompanied by a decrease in the phosphorylated proteins, and both of these effects can be prevented by DTT. These results indicate that Ch-T modulates hippocampal LTP through regulating phosphorylation status of CaMKII and Ng. Published by Elsevier B.V.

  4. The E3 Ligase APC/C-Cdh1 Is Required for Associative Fear Memory and Long-Term Potentiation in the Amygdala of Adult Mice

    Science.gov (United States)

    Pick, Joseph E.; Malumbres, Marcos; Klann, Eric

    2013-01-01

    The anaphase promoting complex/cyclosome (APC/C) is an E3 ligase regulated by Cdh1. Beyond its role in controlling cell cycle progression, APC/C-Cdh1 has been detected in neurons and plays a role in long-lasting synaptic plasticity and long-term memory. Herein, we further examined the role of Cdh1 in synaptic plasticity and memory by generating…

  5. Evaluating potential man-induced changes in fish communities at estuarine and surf-zone areas: a long-term case study in Southern Brasil

    Directory of Open Access Journals (Sweden)

    Joao Vieira

    2015-12-01

    Full Text Available Anthropogenic impacts as environmental degradation and fisheries have been historically associated with changes in structure and dynamics of fish assemblages. A fundamental requisite to evaluate such man-induced changes on fish assemblages is the analysis of long-term time series that allow factoring out inter-annual and decadal natural variations in physical and biotic factors. Based on a standardized monthly long-term database (1997-2012 of experimental fish collections at shallow waters of estuarine and adjacent surf-zone areas of sub-tropical coastal lagoon in southern Brazil (32ºS-52ºW, we evaluated long-term trends in fish abundance and diversity and their correlates with fisheries and environmental factors. Overall species composition and species richness (S at both estuarine (95 and surf-zone (54 were quite similar across years (similarity=52.1 ± 5.8 SD, but there was high inter-annual variability correlated with local (temperature, salinity, regional (precipitation and global (ENSO factors. In the estuary, species richness decreased substantially between 2002 (S=45 and 2012 (S=22, and there were marked variability in abundance across years (CPUE mean =92.3; Min=34.5; Max=163.4. A contrasting pattern was observed at the surf-zone, with lower inter-annual variation in species richness, a marked decrease in fish abundance (CPUE mean=101.9; Min=31.3; Max=221.5. Bayesian generalized additive models (GAMs corroborate with those results and revealed a decrease in both species richness and abundance of both estuarine and adjacent surf-zone areas. Environmental conditions explained only partially the observed inter-annual and decadal variability in both estuarine and marine fish assemblages. Man-made changes associated with habitat loss and increasing fishing pressure could be responsible by some of long-term variations observed in these fish assemblages.

  6. Donor age and long-term culture do not negatively influence the stem potential of limbal fibroblast-like stem cells.

    Science.gov (United States)

    Tomasello, Laura; Musso, Rosa; Cillino, Giovanni; Pitrone, Maria; Pizzolanti, Giuseppe; Coppola, Antonina; Arancio, Walter; Di Cara, Gianluca; Pucci-Minafra, Ida; Cillino, Salvatore; Giordano, Carla

    2016-06-13

    In regenerative medicine the maintenance of stem cell properties is of crucial importance. Ageing is considered a cause of reduced stemness capability. The limbus is a stem niche of easy access and harbors two stem cell populations: epithelial stem cells and fibroblast-like stem cells. Our aim was to investigate whether donor age and/or long-term culture have any influence on stem cell marker expression and the profiles in the fibroblast-like stem cell population. Fibroblast-like stem cells were isolated and digested from 25 limbus samples of normal human corneo-scleral rings and long-term cultures were obtained. SSEA4 expression and sphere-forming capability were evaluated; cytofluorimetric assay was performed to detect the immunophenotypes HLA-DR, CD45, and CD34 and the principle stem cell markers ABCG2, OCT3/4, and NANOG. Molecular expression of the principal mesenchymal stem cell genes was investigated by real-time PCR. Two-dimensional gel electrophoresis and mass spectrometric sequencing were performed and a stable proteomic profile was identified. The proteins detected were explored by gene ontology and STRING analysis. The data were reported as means ± SD, compared by Student's unpaired t test and considering p cells did not display any hematopoietic surface marker (CD34 and CD45) and HLA-DR and they maintained these features in long-term culture. The expression of the stemness genes and the multilineage differentiation under in-vitro culture conditions proved to be well maintained. Proteomic analysis revealed a fibroblast-like stem cell profile of 164 proteins with higher expression levels. Eighty of these showed stable expression levels and were involved in maintenance of "the stem gene profile"; 84 were differentially expressed and were involved in structural activity. The fibroblast-like limbal stem cells confirmed that they are a robust source of adult stem cells and that they have good plasticity, good proliferative capability, and long-term

  7. Long term complications of diabetes

    Science.gov (United States)

    ... medlineplus.gov/ency/patientinstructions/000327.htm Long-term complications of diabetes To use the sharing features on this page, ... other tests. All these may help you keep complications of diabetes away. You will need to check your blood ...

  8. Biodegradation potential of MTBE in a fractured chalk aquifer under aerobic conditions in long-term uncontaminated and contaminated aquifer microcosms

    Science.gov (United States)

    Shah, Nadeem W.; Thornton, Steven F.; Bottrell, Simon H.; Spence, Michael J.

    2009-01-01

    occurred. The availability of dissolved O 2 did not affect MTBE biodegradation significantly, with similar MTBE biodegradation behaviour and rates down to ca. 0.7 mg/L dissolved O 2 concentration. The results indicate that aerobic MTBE biodegradation could be significant in the plume fringe, during mixing of the contaminant plume and uncontaminated groundwater and that, relative to the plume migration, aerobic biodegradation is important for MTBE attenuation. Moreover, should the groundwater dissolved O 2 concentration fall to zero such that MTBE biodegradation was inhibited, an engineered approach to enhance in situ bioremediation could supply O 2 at relatively low levels (e.g. 2-3 mg/L) to effectively stimulate MTBE biodegradation, which has significant practical advantages. The study shows that aerobic MTBE biodegradation can occur at environmentally significant rates in this aquifer, and that long-term microcosm experiments (100s days) may be necessary to correctly interpret contaminant biodegradation potential in aquifers to support site management decisions.

  9. Potential for Local Fertilization: A Benthocosm Test of Long-Term and Short-Term Effects of Mussel Excretion on the Plankton.

    Science.gov (United States)

    Cherif, Mehdi; Granados, Monica; Duffy, Sean; Robert, Pauline; Péquin, Bérangère; Mohit, Vani; McKindsey, Christopher W; Archambault, Philippe; Myrand, Bruno; Lovejoy, Connie; Tremblay, Réjean; Plourde, Stéphane; Fussmann, Gregor F

    2016-01-01

    Mussel aquaculture has expanded worldwide and it is important to assess its impact on the water column and the planktonic food web to determine the sustainability of farming practices. Mussel farming may affect the planktonic food web indirectly by excreting bioavailable nutrients in the water column (a short-term effect) or by increasing nutrient effluxes from biodeposit-enriched sediments (a long-term effect). We tested both of these indirect effects in a lagoon by using plankton-enclosing benthocosms that were placed on the bottom of a shallow lagoon either inside of a mussel farm or at reference sites with no history of aquaculture. At each site, half of the benthocosms were enriched with seawater that had held mussels (excretion treatment), the other half received non-enriched seawater as a control treatment. We monitored nutrients ([PO43-] and [NH4+]), dissolved oxygen and plankton components (bacteria, the phytoplankton and the zooplankton) over 5 days. We found a significant relationship between long-term accumulation of mussel biodeposits in sediments, water-column nutrient concentrations and plankton growth. Effects of mussel excretion were not detected, too weak to be significant given the spatial and temporal variability observed in the lagoon. Effects of mussels on the water column are thus likely to be coupled to benthic processes in such semi-enclosed water bodies.

  10. Realizing the cognitive potential of children 5-7 with a mathematics focus: post-test and long-term effects of a 2-year intervention.

    Science.gov (United States)

    Shayer, Michael; Adhami, Mundher

    2010-09-01

    In the context of the British Government's policy directed on improving standards in schools, this paper presents research on the effects of a programme intended to promote the cognitive development of children in the first 2 years of primary school (Y1 & 2, aged 5-7 years). The programme is based on earlier work dealing with classroom-based interventions with older children at both primary and secondary levels of schooling. The hypothesis tested is that it is possible to increase the cognitive ability of children by assisting teachers towards that aim in the context of mathematics. A corollary hypothesis is that such an increase would result in an increase in long-term school achievement. The participants were 8 teachers in one local education authority (LEA) and 10 teachers in another. Data were analysed on 275 children present at Year 1 pre-test in 2002 and at long-term Key Stage 2 post-test in 2008. Two intervention methods were employed: a Y1 set of interactive activities designed around Piagetian concrete operational schemata, and mathematics lessons in both Y1 and Y2 designed from a theory-base derived from both Piaget and Vygotsky. At post-test in 2004, the mean effect sizes for cognitive development of the children - assessed by the Piagetian test Spatial Relations - were 0.71 SD in one LEA and 0.60 SD in the other. Five classes achieved a median increase of 1.3 SD. The mean gains over pre-test in 2002 for all children in Key Stage 1 English in 2004 were 0.51 SD, and at Key Stage 2 English in 2008 - the long-term effect - were 0.36 SD, an improvement of 14 percentile points. The main hypothesis was supported by the data on cognitive development. The corollary hypothesis is supported by the gains in English. The implications of this study are that relative intelligence can be increased and is not fixed, and that children can be led into collaborating with each other to the benefit of their own thinking, and that there does exist a theory-based methodology

  11. Potential long-term effects of a mind-body intervention for women with major depressive disorder: sustained mental health improvements with a pilot yoga intervention.

    Science.gov (United States)

    Kinser, Patricia Anne; Elswick, R K; Kornstein, Susan

    2014-12-01

    Despite pharmacologic and psychotherapeutic advances over the past decades, many individuals with major depressive disorder (MDD) experience recurrent depressive episodes and persistent depressive symptoms despite treatment with the usual care. Yoga is a mind-body therapeutic modality that has received attention in both the lay and research literature as a possible adjunctive therapy for depression. Although promising, recent findings about the positive mental health effects of yoga are limited because few studies have used standardized outcome measures and none of them have involved long-term follow-up beyond a few months after the intervention period. The goal of our research study was to evaluate the feasibility, acceptability, and effects of a yoga intervention for women with MDD using standardized outcome measures and a long follow-up period (1year after the intervention). The key finding is that previous yoga practice has long-term positive effects, as revealed in both qualitative reports of participants' experiences and in the quantitative data about depression and rumination scores over time. Although generalizability of the study findings is limited because of a very small sample size at the 1-year follow-up assessment, the trends in the data suggest that exposure to yoga may convey a sustained positive effect on depression, ruminations, stress, anxiety, and health-related quality of life. Whether an individual continues with yoga practice, simple exposure to a yoga intervention appears to provide sustained benefits to the individual. This is important because it is rare that any intervention, pharmacologic or non-pharmacologic, for depression conveys such sustained effects for individuals with MDD, particularly after the treatment is discontinued. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. A long-term investigation of the anti-hepatocarcinogenic potential of an indigenous medicine comprised of Nigella sativa, Hemidesmus indicus and Smilax glabra

    Directory of Open Access Journals (Sweden)

    Iddamaldeniya SS

    2006-05-01

    Full Text Available Abstract Background A decoction comprised of Nigella sativa seeds, Hemidesmus indicus root bark and Smilax glabra rhizome is being recommended for cancer patients by a family of traditional medical practitioners of Sri Lanka. Previous investigations have demonstrated that a short term (10 weeks treatment with the decoction can significantly inhibit diethylnitrosamine (DEN mediated expression of Glutathione S-transferase P form (GST-P in rat liver. The objective of the present investigation was to determine whether long term (16 months treatment with the decoction would be successful in inhibiting in rat livers, not only DEN- mediated expression of GST-P, but also the carcinogen mediated development of overt tumours (OT or histopathological changes leading to tumour development (HT. Methods Thirty-six male Wistar rats were divided into 3 groups of 12 each. Groups 1 and 2 were injected intraperitoneally (i.p with DEN (200 mg/kg while group 3 was injected normal saline (NS. Twenty-four hours later, decoction (DC; 6 g/kg body weight/day was orally administered to group 1 rats, while groups 2 and 3 (DEN-control and normal control were given distilled water (DW. Treatment with DC or DW continued for 16 months. At the end of the 9th month and 16th months (study 1 and study 2 respectively, six rats from each group were sacrificed, and livers observed for OT or HT, both visually and by subjecting liver sections to staining with Haemotoxylin and Eosin (H & E, Sweet's Silver stain (for reticulin fibers, Periodic Acid Schiff (PAS staining (for glycogen, and immunohistochemical staining (for GST-P. Results At the end of 9 months (study 1 a hepatocellular adenoma (HA developed in one of the rats in the DEN + DW treated group (group 2. At the end of 16 months (study 2, livers of all rats of group 2 developed OT and HT. Large areas of GST-P positive foci were also observed. No OT, HT or GST-P positive foci were detected in any of the other groups. Conclusion

  13. Long-term effects of directed forgetting.

    Science.gov (United States)

    Hupbach, Almut

    2018-03-01

    The intention to forget reduces the accessibility of information in memory, which is commonly explained with temporary retrieval difficulties. Long-term effects have rarely been studied, and results are inconsistent. The present study re-assessed the long-term effects of directed forgetting (DF). Participants encoded a first list of items (L1), and were then instructed to forget or to remember this list. Immediately afterwards, all participants were presented with a second list to remember. In Experiment 1, memory for L1 and L2 was assessed after a 24-h delay. The forget cue reduced the number of items that were recalled from L1. Experiment 2 implemented a 12-h delay between encoding and test that was either filled with day-time wakefulness or night-time sleep. Replicating the findings of Exp. 1, recall of L1 was reduced in the forget in comparison to the remember condition. Sleep in comparison to wakefulness significantly strengthened L1 memory in the remember group only. Taken together, the present study shows that the intention to forget can have long-lasting consequences. This suggests that different mechanisms underlie the short- and long-term effects of DF, with long-term effects potentially reflecting the preferential consolidation of information that has been identified as important during encoding.

  14. Growth and metal removal potential of a Phormidium bigranulatum-dominated mat following long-term exposure to elevated levels of copper.

    Science.gov (United States)

    Kumar, Dhananjay; Gaur, J P

    2014-09-01

    The present study explores the tolerance and metal removal response of a well-developed 2-week-old Phormidium mat after long-term exposure to Cu(2+)-enriched medium. Cu(2+) enrichment inhibited increase in mat biomass in a concentration-dependent manner. Mat area and the number of entrapped air bubbles decreased as Cu(2+) concentration increased in the medium. Decrease in number of air bubbles obviously reflects the adverse effect of Cu(2+) on photosynthetic performance of the mat. Metal enrichment did not substantially alter the amount of pigments, such as chlorophyll a, chlorophyll b, carotenoids, and phycocyanin, in the mat. Enhancement of Cu(2+) concentration in the medium led to changes in species composition of the test mat; however, Phormidium bigranulatum always remained the dominant organism. Relative share of green algae and some cyanobacterial taxa, namely, Lyngbya sp. and Oscillatoria tenuis, in the mat were increased by Cu(2+) enrichment. The mat successfully removed 80 to 94 % Cu(2+) from the growth medium containing 10 to 100 μM Cu(2+). Extracellular polysaccharides, whose share increased in the mat community after metal addition, seem to have contributed substantially to metal binding by the mat biomass.

  15. Unilateral lesion of dorsal hippocampus in adult rats impairs contralateral long-term potentiation in vivo and spatial memory in the early postoperative phase.

    Science.gov (United States)

    Li, Hongjie; Wu, Xiaoyan; Bai, Yanrui; Huang, Yan; He, Wenting; Dong, Zhifang

    2012-05-01

    It is well documented that bilateral hippocampal lesions or unilateral hippocampal lesion at birth causes impairment of contralateral LTP and long-term memory. However, effects of unilateral hippocampal lesion in adults on contralateral in vivo LTP and memory are not clear. We here examined the influence of unilateral electrolytic dorsal hippocampal lesion in adult rats on contralateral LTP in vivo and spatial memory during different postoperative phases. We found that acute unilateral hippocampal lesion had no effect on contralateral LTP. However, contralateral LTP was impaired at 1 week after lesion, and was restored to the control level at postoperative week 4. Similarly, spatial memory was also impaired at postoperative week 1, and was restored at postoperative week 4. In addition, the rats at postoperative week 1 showed stronger spatial exploratory behavior in a novel open-field environment. The sham operation had no effects on contralateral LTP, spatial memory and exploration at either postoperative week 1 or week 4. These results suggest that unilateral dorsal hippocampal lesion in adult rats causes transient contralateral LTP impairment and spatial memory deficit. Copyright © 2012 Elsevier B.V. All rights reserved.

  16. Long-term data archiving

    Energy Technology Data Exchange (ETDEWEB)

    Moore, David Steven [Los Alamos National Laboratory

    2009-01-01

    Long term data archiving has much value for chemists, not only to retain access to research and product development records, but also to enable new developments and new discoveries. There are some recent regulatory requirements (e.g., FDA 21 CFR Part 11), but good science and good business both benefit regardless. A particular example of the benefits of and need for long term data archiving is the management of data from spectroscopic laboratory instruments. The sheer amount of spectroscopic data is increasing at a scary rate, and the pressures to archive come from the expense to create the data (or recreate it if it is lost) as well as its high information content. The goal of long-term data archiving is to save and organize instrument data files as well as any needed meta data (such as sample ID, LIMS information, operator, date, time, instrument conditions, sample type, excitation details, environmental parameters, etc.). This editorial explores the issues involved in long-term data archiving using the example of Raman spectral databases. There are at present several such databases, including common data format libraries and proprietary libraries. However, such databases and libraries should ultimately satisfy stringent criteria for long term data archiving, including readability for long times into the future, robustness to changes in computer hardware and operating systems, and use of public domain data formats. The latter criterion implies the data format should be platform independent and the tools to create the data format should be easily and publicly obtainable or developable. Several examples of attempts at spectral libraries exist, such as the ASTM ANDI format, and the JCAMP-DX format. On the other hand, proprietary library spectra can be exchanged and manipulated using proprietary tools. As the above examples have deficiencies according to the three long term data archiving criteria, Extensible Markup Language (XML; a product of the World Wide Web

  17. Leukodepleted blood components do not remove the potential for long-term transfusion-associated microchimerism in Australian major trauma patients.

    Science.gov (United States)

    Hirani, Rena; Balogh, Zsolt J; Lott, Natalie J; Hsu, Jeremy M; Irving, David O

    2014-01-01

    Despite the introduction of leukodepleted blood components, it has been shown that donor leukocyte engraftment (microchimerism) remains a long-term consequence of red blood cell (RBC) transfusion. The incidence of microchimerism may be affected by international disparities in blood processing methods or variations in transfusion practices. This study was conducted to determine the prevalence of microchimerism in Australian trauma patients. A secondary aim was to examine whether any patient complications correlated to the incidence of microchimerism. Australian trauma patients (n = 86) who had been transfused with red blood cell (RBC) units between 2000 and 2012 with an injury severity score (ISS) of greater than 15 were recruited. The prevalence of microchimerism was determined using genetic screening with a panel of insertion/deletion biallelic polymorphisms. The mean storage age of the transfused RBC units was 20 ± 8 days and the mean length of stay (LOS) in hospital was 40 ± 39 days. There were no significant associations in this study sample to bias for patient age, gender, number of transfused RBC units or ISS. Nine of the 55 (16.3%) patients transfused with non-leukodepleted blood components displayed an incidence of microchimerism. Of the 31 patients transfused with leukodepleted RBC units, 3 (9.6%) displayed an incidence of microchimerism. Therefore, despite the universal introduction of leukodepleted blood components in Australia, the prevalence of transfusion-associated microchimerism was found to be unchanged. Furthermore, half of the patients exhibiting microchimerism were recorded to have had splenic injury or required splenectomy at the time of transfusion.

  18. Long-term follow-up of the potential benefits of early nutritional intervention in adults with upper gastrointestinal cancer: a pilot randomised trial.

    Science.gov (United States)

    Furness, Kate; Silvers, Mary Anne; Savva, June; Huggins, Catherine E; Truby, Helen; Haines, Terry

    2017-11-01

    This study aimed to evaluate the long-term survival of all patients who participated in a pilot randomised trial of an early nutritional intervention for adults with upper gastrointestinal cancer. It also sought to identify factors that predicted patient mortality. All participants (n = 21) who were randomised into the original study were followed for a maximum of 5 years and 2 months (final follow-up April 2016). The primary outcome measure was time from date of recruitment until date of death, ascertained by the Victorian Cancer Registry and/or Monash Health Scanned Medical Records. Secondary analyses were conducted to identify factors that adversely affected survival. At the end of the follow-up period, three patients were alive in the nutrition intervention group whilst only two patients were living from the standard care group. Visual evaluation of the Kaplan-Meier survival curves demonstrated a possible survival benefit from being exposed to the intervention between 6 months and 1.4 years post-recruitment, though this benefit dissipated soon after. The intervention was not associated with increased survival in univariate analyses, but was after adjustment for other factors found to adversely impact on survival (adjusted hazard ratio 0.12 (95% CI 0.02-0.72) p = 0.02). These factors were being a smoker (14.2 (1.43 to 140.67), p = 0.02); low baseline physical functioning (1.11 (1.01 to 1.21), p = 0.03); high baseline fatigue (1.09 (1.02-1.16), p = 0.007); and high baseline dyspnoea (1.08 (1.02-1.13), p = 0.003). Early and intensive nutrition intervention may increase the survival of people with upper gastrointestinal cancer.

  19. Leukodepleted blood components do not remove the potential for long-term transfusion-associated microchimerism in Australian major trauma patients

    Science.gov (United States)

    Hirani, Rena; Balogh, Zsolt J; Lott, Natalie J; Hsu, Jeremy M; Irving, David O

    2014-01-01

    Despite the introduction of leukodepleted blood components, it has been shown that donor leukocyte engraftment (microchimerism) remains a long-term consequence of red blood cell (RBC) transfusion. The incidence of microchimerism may be affected by international disparities in blood processing methods or variations in transfusion practices. This study was conducted to determine the prevalence of microchimerism in Australian trauma patients. A secondary aim was to examine whether any patient complications correlated to the incidence of microchimerism. Australian trauma patients (n = 86) who had been transfused with red blood cell (RBC) units between 2000 and 2012 with an injury severity score (ISS) of greater than 15 were recruited. The prevalence of microchimerism was determined using genetic screening with a panel of insertion/deletion biallelic polymorphisms. The mean storage age of the transfused RBC units was 20 ± 8 days and the mean length of stay (LOS) in hospital was 40 ± 39 days. There were no significant associations in this study sample to bias for patient age, gender, number of transfused RBC units or ISS. Nine of the 55 (16.3%) patients transfused with non-leukodepleted blood components displayed an incidence of microchimerism. Of the 31 patients transfused with leukodepleted RBC units, 3 (9.6%) displayed an incidence of microchimerism. Therefore, despite the universal introduction of leukodepleted blood components in Australia, the prevalence of transfusion-associated microchimerism was found to be unchanged. Furthermore, half of the patients exhibiting microchimerism were recorded to have had splenic injury or required splenectomy at the time of transfusion. PMID:26252809

  20. The Potential Role of Metalloproteinases in Neurogenesis in the Gerbil Hippocampus Following Global Forebrain Ischemia

    Science.gov (United States)

    Wójcik-Stanaszek, Luiza; Sypecka, Joanna; Szymczak, Patrycja; Ziemka-Nalecz, Malgorzata; Khrestchatisky, Michel; Rivera, Santiago; Zalewska, Teresa

    2011-01-01

    Background Matrix metalloproteinases (MMPs) have recently been considered to be involved in the neurogenic response of adult neural stem/progenitor cells. However, there is a lack of information showing direct association between the activation of MMPs and the development of neuronal progenitor cells involving proliferation and/or further differentiation in vulnerable (Cornus Ammoni-CA1) and resistant (dentate gyrus-DG) to ischemic injury areas of the brain hippocampus. Principal Findings We showed that dynamics of MMPs activation in the dentate gyrus correlated closely with the rate of proliferation and differentiation of progenitor cells into mature neurons. In contrast, in the damaged CA1 pyramidal cells layer, despite the fact that some proliferating cells exhibited antigen specific characteristic of newborn neuronal cells, these did not attain maturity. This coincides with the low, near control-level, activity of MMPs. The above results are supported by our in vitro study showing that MMP inhibitors interfered with both the proliferation and differentiation of the human neural stem cell line derived from umbilical cord blood (HUCB-NSCs) toward the neuronal lineage. Conclusion Taken together, the spatial and temporal profiles of MMPs activity suggest that these proteinases could be an important component in neurogenesis-associated processes in post-ischemic brain hippocampus. PMID:21799862

  1. Role of Brine Chemistry and Sorption in Potential Long-Term Storage of Radioactive Waste in Geologic Salt Formations: Experimental Evaluation of Sorption Parameters

    Science.gov (United States)

    Dittrich, T. M.; Emerson, H. P.; Michael, D. P.; Reed, D. T.

    2016-12-01

    Bedded geologic salt formations have been shown to have many favorable properties for the disposal of radioactive waste (i.e., reducing conditions, fracture healing). Performance assessment (PA) modeling for a 10,000 year period for the Waste Isolation Pilot Plant (WIPP) near Carlsbad, NM have predicted an extremely low risk of radioactive material reaching the surrounding environment after the 100 year period required for creep to seal the waste panels and access shafts. Human intrusion caused by drilling operations for oil and gas exploration is the main pathway of concern for environmental release of radioactive material due to pressurized brine pockets located within the salt formation below the repository. Our work focuses on the long-term capability of salt repositories and the associated geologic media to safely isolate stored radioactive waste from the surrounding environment, even in the event of a human intrusion scenario such as a direct brine release (DBR) due to a drilling operation intersecting a brine pocket. In particular, we are revisiting the degree of conservatism in the estimated sorption partition coefficients (Kds) used in the PA model based on complementary batch and column experimental methods (Dittrich and Reimus, 2016). The main focus of this work is to investigate the role of ionic strength, solution chemistry, and oxidation state (III-VI) in actinide sorption to dolomite rock. Based on redox conditions and solution chemistry expected in the WIPP, possible actinide species include Pu(III), Pu(IV), U(IV), U(VI), Np(IV), Np(V), Am(III), and Th(IV). We will present (1) a conceptual overview of Kd use in the PA model, (2) background and evolution of the Kd ranges used, and (3) results from batch and column experiments and model predictions for Kds with WIPP-relevant geologic media. We will also briefly discuss the challenges of upscaling from lab experiments to field scale predictions, the presence of ligands (e.g., acetate, citrate, EDTA

  2. The noradrenergic component in tapentadol action counteracts μ-opioid receptor-mediated adverse effects on adult neurogenesis.

    Science.gov (United States)

    Meneghini, Vasco; Cuccurazzu, Bruna; Bortolotto, Valeria; Ramazzotti, Vera; Ubezio, Federica; Tzschentke, Thomas M; Canonico, Pier Luigi; Grilli, Mariagrazia

    2014-05-01

    Opiates were the first drugs shown to negatively impact neurogenesis in the adult mammalian hippocampus. Literature data also suggest that norepinephrine is a positive modulator of hippocampal neurogenesis in vitro and in vivo. On the basis of these observations, we investigated whether tapentadol, a novel central analgesic combining μ-opioid receptor (MOR) agonism with norepinephrine reuptake inhibition (NRI), may produce less inhibition of hippocampal neurogenesis compared with morphine. When tested in vitro, morphine inhibited neuronal differentiation, neurite outgrowth, and survival of adult mouse hippocampal neural progenitors and their progeny, via MOR interaction. By contrast, tapentadol was devoid of these adverse effects on cell survival and reduced neurite outgrowth and the number of newly generated neurons only at nanomolar concentrations where the MOR component is predominant. On the contrary, at higher (micromolar) concentrations, tapentadol elicited proneurogenic and antiapoptotic effects via activation of β2 and α2 adrenergic receptors, respectively. Altogether, these data suggest that the noradrenergic component in tapentadol has the potential to counteract the adverse MOR-mediated effects on hippocampal neurogenesis. As a proof of concept, we showed that reboxetine, an NRI antidepressant, counteracted both antineurogenic and apoptotic effects of morphine in vitro. In line with these observations, chronic tapentadol treatment did not negatively affect hippocampal neurogenesis in vivo. In light of the increasing long-term use of opiates in chronic pain, in principle, the tapentadol combined mechanism of action may result in less or no reduction in adult neurogenesis compared with classic opiates.

  3. Long term stability of power systems

    Energy Technology Data Exchange (ETDEWEB)

    Kundur, P.; Gao, B. [Powertech Labs. Inc., Surrey, BC (Canada)

    1994-12-31

    Power system long term stability is still a developing subject. In this paper we provide our perspectives and experiences related to long term stability. The paper begins with the description of the nature of the long term stability problem, followed by the discussion of issues related to the modeling and solution techniques of tools for long term stability analysis. Cases studies are presented to illustrate the voltage stability aspect and plant dynamics aspect of long term stability. (author) 20 refs., 11 figs.

  4. Potential long-term chemical effects of diesel fuel emissions on a mining environment: A preliminary assessment based on data from a deep subsurface tunnel at Rainer Mesa, Nevada test site

    Energy Technology Data Exchange (ETDEWEB)

    Meike, A.; Bourcier, W.L.; Alai, M. [and others

    1995-09-01

    The general purpose of the Yucca Mountain Site Characterization Project (YMSCP) Introduced Materials Task is to understand and predict potential long-term modifications of natural water chemistry related to the construction and operation of a radioactive waste repository that may significantly affect performance of the waste packages. The present study focuses on diesel exhaust. Although chemical information on diesel exhaust exists in the literature, it is either not explicit or incomplete, and none of it establishes mechanisms that might be used to predict long-term behavior. In addition, the data regarding microbially mediated chemical reactions are not well correlated with the abiotic chemical data. To obtain some of the required long-term information, we chose a historical analog: the U12n tunnel at Rainier Mesa, Nevada Test Site. This choice was based on the tunnel`s extended (30-year) history of diesel usage, its geological similarity to Yucca Mountain, and its availability. The sample site within the tunnel was chosen based on visual inspection and on information gathered from miners who were present during tunnel operations. The thick layer of dark deposit at that site was assumed to consist primarily of rock powder and diesel exhaust. Surface samples and core samples were collected with an intent to analyze the deposit and to measure potential migration of chemical components into the rock. X-ray diffraction (XRD), x-ray fluorescence (XRF), scanning electron microscopy (SEM) with energy dispersive spectra (EDS) analysis, secondary-ion mass spectrometry (SIMS), and Fourier transform infrared (FTIR) analysis were used to measure both spatial distribution and concentration for the wide variety of chemical components that were expected based on our literature survey.

  5. IMPAIRMENT IN SHORT-TERM BUT ENHANCED LONG-TERM SYNAPTIC POTENTIATION AND ERK ACTIVATION IN ADULT HIPPOCAMPAL AREA CA1 FOLLOWING DEVELOPMENTAL HYPOTHYROIDISM.

    Science.gov (United States)

    The EPA must evaluate the risk of exposure of the developing brain to chemicals with the potential to disrupt thyroid hormone homeostasis. The existing literature identifies morphological and neurochemical indices of severe neonatal hypothyroidism in the early postnatal period i...

  6. Potential groundwater sampling sites for installation of a well network for long-term monitoring of agricultural chemicals in the High Plains Aquifer, Colorado

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — These data are in support of report DS 456 (Arnold and others, 2009). This dataset includes 90 potential groundwater sampling sites randomly generated using...

  7. Navigating Long-Term Care

    Directory of Open Access Journals (Sweden)

    James D. Holt MD

    2017-03-01

    Full Text Available Americans over age 65 constitute a larger percentage of the population each year: from 14% in 2010 (40 million elderly to possibly 20% in 2030 (70 million elderly. In 2015, an estimated 66 million people provided care to the ill, disabled, and elderly in the United States. In 2000, according to the Centers for Disease Control and Prevention (CDC, 15 million Americans used some form of long-term care: adult day care, home health, nursing home, or hospice. In all, 13% of people over 85 years old, compared with 1% of those ages 65 to 74, live in nursing homes in the United States. Transitions of care, among these various levels of care, are common: Nursing home to hospital transfer, one of the best-studied transitions, occurs in more than 25% of nursing home residents per year. This article follows one patient through several levels of care.

  8. Effects of neonatal exposure to the flame retardant tetrabromobisphenol-A, aluminum diethylphosphinate or zinc stannate on long-term potentiation and synaptic protein levels in mice

    NARCIS (Netherlands)

    Hendriks, Hester S; Koolen, Lucas A E; Dingemans, Milou M L; Viberg, Henrik; Lee, Iwa; Leonards, Pim E G; Ramakers, Geert M J; Westerink, Remco H S

    2015-01-01

    Brominated flame retardants such as tetrabromobisphenol-A (TBBPA) may exert (developmental) neurotoxic effects. However, data on (neuro)toxicity of halogen-free flame retardants (HFFRs) are scarce. Recent in vitro studies indicated a high neurotoxic potential for some HFFRs, e.g., zinc stannate

  9. Effects of neonatal exposure to the flame retardant tetrabromobisphenol-A, aluminum diethylphosphinate or zinc stannate on long-term potentiation and synaptic protein levels in mice

    NARCIS (Netherlands)

    Hendriks, Hester; Koolen, Lucas; Dingemans, Milou; Viberg, Henrik; Lee, Iwa; Leonards, P.E.G.; Ramakers, G.M.J.; Westerink, Remco

    2014-01-01

    Brominated flame retardants such as tetrabromobisphenol-A (TBBPA) may exert (developmental) neurotoxic effects. However, data on (neuro)toxicity of halogen-free flame retardants (HFFRs) are scarce. Recent in vitro studies indicated a high neurotoxic potential for some HFFRs, e.g., zinc stannate

  10. High incidence of potentially virus-induced malignancies in systemic lupus erythematosus: a long-term followup study in a Danish cohort

    DEFF Research Database (Denmark)

    Dreyer, Lene; Faurschou, Mikkel; Mogensen, Mette

    2011-01-01

    Patients with systemic lupus erythematosus (SLE) seem to experience an increased prevalence of oncogenic virus infections. The aim of the present study was to investigate whether SLE patients have an increased risk of virus-associated malignancies, defined as malignancies potentially caused...

  11. An investigation of trends in precious metal and copper content of RAM modules in WEEE: Implications for long term recycling potential.

    Science.gov (United States)

    Charles, Rhys Gareth; Douglas, Peter; Hallin, Ingrid Liv; Matthews, Ian; Liversage, Gareth

    2017-02-01

    Precious metal (PM) and copper content of dynamic-RAM modules placed on the market during 1991-2008 has been analysed by AAS following comminution and acid digestion. Linear regression analysis of compositional data ordered according to sample chronology was used to identify historic temporal trends in module composition resulting from changes in manufacturing practices, and to project future trends for use in more accurate assessment of future recycling potential. DRAM was found to be 'high grade' waste with: stable levels of gold and silver over time; 80% reduction in palladium content during 1991-2008; and 0.23g/module/year increase in copper content with a 75% projected increase from 2008 by 2020. The accuracy of future recycling potential projections for WEEE using current methods based on static compositional data from current devices is questionable due to likely changes in future device composition. The impact on recycling potential projections of waste laptops, smart phones, cell phones and tablets arising in Europe in 2020 resulting from a 75% increase in copper content is considered against existing projections using static compositional data. The results highlight that failing to consider temporal variations in PM content may result in significant discrepancies between projections and future recycling potential. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  12. Cataractogenic potential of quetiapine versus risperidone in the long-term treatment of patients with schizophrenia or schizoaffective disorder: a randomized, open-label, ophthalmologist-masked, flexible-dose, non-inferiority trial.

    Science.gov (United States)

    Laties, Alan M; Flach, Allan J; Baldycheva, Irina; Rak, Ihor; Earley, Willie; Pathak, Sanjeev

    2015-01-01

    Clinical observations indicate no cataractogenic potential for quetiapine, in contrast to studies in laboratory animals. This randomized, non-inferiority study compared changes in lens opacity during long-term treatment with quetiapine versus risperidone. Patients with schizophrenia or schizoaffective disorder participated in the 2-year, randomized, multicentre, open-label, ophthalmologist-masked, flexible-dose, parallel-group study. Two ophthalmologists examined each patient 6-monthly for presence of nuclear opalescence (N) and cortical (C) or posterior subcapsular opacification (P), according to the lens opacities classification system II. 1098 patients were randomized to treatment. Mean doses were 386.3 mg/day quetiapine and 3.2 mg/day risperidone. Estimated absolute risk differences in cataractogenic events for quetiapine versus risperidone over 2 years were -0.035 (C), -0.012 (N) and -0.017 (P), with upper margins of confidence intervals within the non-inferiority margin of 10%. In post hoc analysis, risk of any lens opacification event was significantly lower for quetiapine than risperidone (6 and 16 events, respectively; risk difference: -0.058; P = 0.035). Efficacy and other safety assessments were in agreement with known profiles of these medications. Quetiapine was non-inferior to risperidone for changes in lens opacity grade in patients with schizophrenia or schizoaffective disorder, indicating that quetiapine does not have clinically significant cataractogenic potential during long-term treatment. © The Author(s) 2014.

  13. Polyaromatic hydrocarbon (PAH) degradation potential of a new acid tolerant, diazotrophic P-solubilizing and heavy metal resistant bacterium Cupriavidus sp. MTS-7 isolated from long-term mixed contaminated soil.

    Science.gov (United States)

    Kuppusamy, Saranya; Thavamani, Palanisami; Megharaj, Mallavarapu; Lee, Yong Bok; Naidu, Ravi

    2016-11-01

    An isolate of Cupriavidus (strain MTS-7) was identified from a long-term PAHs and heavy metals mixed contaminated soil with the potential to biodegrade both LMW and HMW PAHs with added unique traits of acid and alkali tolerance, heavy metal tolerance, self-nutrient assimilation by N fixation and P solubilization. This strain completely degraded the model 3 (150 mg L(-1) Phe), 4 (150 mg L(-1) Pyr) and 5 (50 mg L(-1) BaP) ring PAHs in 4, 20 and 30 days, respectively. It could mineralize 90-100% of PAHs (200 mg L(-1) of Phe and Pyr) within 15 days across pH ranging from 5 to 8 and even in the presence of toxic metal contaminations. During biodegradation, the minimum inhibitory concentrations were 5 (Cu(2+)) and 3 (Cd(2+), Pb(2+), Zn(2+)) mg L(-1) of the potentially bioavailable metal ions and over 17 mg L(-1) metal levels was lethal for the microbe. Further, it could fix 217-274 μg mL(-1) of N and solubilize 79-135 μg mL(-1) of P while PAHs degradation. MTS-7 as a superior candidate could be thus used in the enhanced bioaugmentation and/or phytoremediation of long-term mixed contaminated sites. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. A Multi-Parametric Device with Innovative Solid Electrodes for Long-Term Monitoring of pH, Redox-Potential and Conductivity in a Nuclear Waste Repository.

    Science.gov (United States)

    Daoudi, Jordan; Betelu, Stephanie; Tzedakis, Theodore; Bertrand, Johan; Ignatiadis, Ioannis

    2017-06-13

    We present an innovative electrochemical probe for the monitoring of pH, redox potential and conductivity in near-field rocks of deep geological radioactive waste repositories. The probe is composed of a monocrystalline antimony electrode for pH sensing, four AgCl/Ag-based reference or Cl - selective electrodes, one Ag₂S/Ag-based reference or S 2- selective electrode, as well as four platinum electrodes, a gold electrode and a glassy-carbon electrode for redox potential measurements. Galvanostatic electrochemistry impedance spectroscopy using AgCl/Ag-based and platinum electrodes measure conductivity. The use of such a multi-parameter probe provides redundant information, based as it is on the simultaneous behaviour under identical conditions of different electrodes of the same material, as well as on that of electrodes made of different materials. This identifies the changes in physical and chemical parameters in a solution, as well as the redox reactions controlling the measured potential, both in the solution and/or at the electrode/solution interface. Understanding the electrochemical behaviour of selected materials thus is a key point of our research, as provides the basis for constructing the abacuses needed for developing robust and reliable field sensors.

  15. Long-Term Corrosion Potential Behavior of Alloy 22 in Hot 5 m CaCl2 + 5 m Ca(NO3)2 Brines

    Energy Technology Data Exchange (ETDEWEB)

    Rodriguez, M A; Carranza, R M; Stuart, M L; Rebak, R B

    2007-02-20

    Alloy 22 is a nickel base alloy highly resistant to all forms of corrosion. In very aggressive conditions (e.g. hot concentrated chloride containing brines) Alloy 22 could suffer localized attack, namely pitting and crevice corrosion. The occurrence of localized corrosion in a given environment is governed by the values of the critical potential (E{sub crit}) for crevice corrosion and the corrosion potential (E{sub corr}) that the alloy may establish in the studied environment. If E{sub corr} is equal or higher than E{sub crit}, localized corrosion may be expected. This paper discusses the evolution of E{sub corr} of Alloy 22 specimens in 5 m CaCl{sub 2} + 5 m Ca(NO{sub 3}){sub 2} brines at 100 C and 120 C. Two types of specimens were used, polished as-welded (ASW) creviced and noncreviced specimens and as-welded plus solution heat-treated (ASW+SHT) creviced specimens. The latter contained the black annealing oxide film on the surface. Results show that, for all types of Alloy 22 specimens the E{sub corr} was higher at 120 C than at 100 C, probably because a more protective film formed at the higher temperature. Specimens with the black oxide film on the surface showed more oscillations in the potential. None of the tested specimens suffered crevice corrosion probably because of the relatively high concentration of nitrate in the electrolyte, R = [NO3]/[Cl] = 1.

  16. Early Stress Evokes Age-Dependent Biphasic Changes in Hippocampal Neurogenesis, Bdnf Expression, and Cognition

    Science.gov (United States)

    Suri, Deepika; Veenit, Vandana; Sarkar, Ambalika; Thiagarajan, Devi; Kumar, Arvind; Nestler, Eric J.; Galande, Sanjeev; Vaidya, Vidita A.

    2014-01-01

    Background Adult-onset stressors exert opposing effects on hippocampal neurogenesis and cognition, with enhancement observed following mild stress and dysfunction following severe chronic stress. While early life stress evokes persistent changes in anxiety, it is unknown whether early stress differentially regulates hippocampal neurogenesis, trophic factor expression, and cognition across the life span. Methods Hippocampal-dependent cognitive behavior, neurogenesis, and epigenetic regulation of brain-derived neurotrophic factor (Bdnf) expression was examined at distinct time points across the life span in rats subjected to the early stress of maternal separation (ES) and control groups. We also examined the influence of chronic antidepressant treatment on the neurogenic, neurotrophic, and cognitive changes in middle-aged ES animals. Results Animals subjected to early stress of maternal separation examined during postnatal life and young adulthood exhibited enhanced hippocampal neurogenesis, decreased repressive histone methylation at the Bdnf IV promoter along with enhanced Bdnf levels, and improved performance on the stress-associated Morris water maze. Strikingly, opposing changes in hippocampal neurogenesis and epigenetic regulation of Bdnf IV expression, concomitant with impairments on hippocampal-dependent cognitive tasks, were observed in middle-aged ES animals. Chronic antidepressant treatment with amitriptyline attenuated the maladaptive neurogenic, epigenetic, transcriptional, and cognitive effects in middle-aged ES animals. Conclusions Our study provides novel insights into the short- and long-term consequences of ES, demonstrating both biphasic and unique, age-dependent changes at the molecular, epigenetic, neurogenic, and behavioral levels. These results indicate that early stress may transiently endow animals with a potential adaptive advantage in stressful environments but across a life span is associated with long-term deleterious effects. PMID

  17. A neuroligin-1-derived peptide stimulates phosphorylation of the NMDA receptor NR1 subunit and rescues MK-801-induced decrease in long-term potentiation and memory impairment

    DEFF Research Database (Denmark)

    Korshunova, Irina; Gjørlund, Michelle D; Jacobsen, Sylwia Owczarek

    2015-01-01

    , neurolide-2, reduces sociability and increase animal aggression. We hypothesized that interfering with NL1 function at the excitatory synapses might regulate synaptic plasticity and learning, and counteract memory deficits induced by N-methyl-d-aspartate (NMDA) receptor inhibition. First, neuronal NMDA...... important for synaptic trafficking, potentially favoring synaptic receptor retention. Our findings emphasize the role of NL1-NMDA receptor interaction in cognition, and identify neurolide-1, as a valuable pharmacological tool to examine the in vivo role of postsynaptic NL1 in cognitive behavior...

  18. Long-Term Memory Performance in Adult ADHD.

    Science.gov (United States)

    Skodzik, Timo; Holling, Heinz; Pedersen, Anya

    2017-02-01

    Memory problems are a frequently reported symptom in adult ADHD, and it is well-documented that adults with ADHD perform poorly on long-term memory tests. However, the cause of this effect is still controversial. The present meta-analysis examined underlying mechanisms that may lead to long-term memory impairments in adult ADHD. We performed separate meta-analyses of measures of memory acquisition and long-term memory using both verbal and visual memory tests. In addition, the influence of potential moderator variables was examined. Adults with ADHD performed significantly worse than controls on verbal but not on visual long-term memory and memory acquisition subtests. The long-term memory deficit was strongly statistically related to the memory acquisition deficit. In contrast, no retrieval problems were observable. Our results suggest that memory deficits in adult ADHD reflect a learning deficit induced at the stage of encoding. Implications for clinical and research settings are presented.

  19. [Long-term clinical effects of antidepressive agents].

    Science.gov (United States)

    Sechter, D

    1995-03-01

    According to long term studies with antidepressants versus placebo, the therapeutic efficacy is prolonged: a long term treatment in full dosage seems to reduce from almost half the risk of relapse and recurrence till five years, during recurrent major affective disorders. We should therefore be cautious and we should not have a systematic prescription for all types of depressions; antidepressants are efficacious but have side effects and we do not know well their abilities in long term use. During bipolar disorders the prescription of long term antidepressants, even in association with normothymics, does not give benefits and can induce rapid cycles. In dysthymias and depressions with personality disorders, a psychotherapy is indicated, and it is difficult to evaluate the efficacy of a long term antidepressant treatment. Tricyclics antidepressants, MAOI's and SSRI's have classical side effects, and they can also induce: modifications of the symptomatology, of cognitive functions, of sleep, eating and sexual behaviours; modifications of the course of depressive illness, induction of manic switches, and may be sometimes an exacerbation of suicidal ideation ... pharmacogenetic modifications with their action on hepatic metabolism, neuroendocrine alterations and long term effects on monoamines. We have also to take into account the long term treatment consequences on quality of life, on self esteem with the importance of psychodynamic and relationships modifications. The use of a long term antidepressant treatment should be adapted to each individual, being cautious of its potential benefits and risks.

  20. Extractability and crop transfer of potentially toxic elements from mediterranean agricultural soils following long-term sewage sludge applications as a fertilizer replacement to barley and maize crops.

    Science.gov (United States)

    Iglesias, Mònica; Marguí, Eva; Camps, Francesc; Hidalgo, Manuela

    2018-01-22

    Sewage sludge is used as a fertilizer replacement in agricultural soils for its chemical properties, such as organic matter content, and for its capability to improve physical soil characteristics like porosity. This is also an appealing disposal option for residue whose production is increasing worldwide. However, there is some concern about the presence of potentially toxic elements (PTEs) that can accumulate in soils and become available for crops. In this work, a study was conducted to evaluate the extractability and crops transfer of thirteen PTEs from soils that had been amended with biosolids each year for 15 years as a regular agricultural practice. The study was conducted with barley (winter cereal) and maize (spring cereal) crops. After this long period, an increase in the amount of Pb, Hg, Zn and Ag in soils amended by biosolids was confirmed. However, it is important to emphasize that the PTE total content in croplands was still far below the thresholds established by US and European regulations. Statistically significant differences were also found between the soils fertilized with biosolids and other treatments compared with the potential phytoavailable amount of Cu, Se, Sb and especially for As and Zn, by a DTPA leaching test. Despite these results, the concentration of PTEs in the barley and maize grains grown in fields repeatedly amended with biosolids was not statistically different from those grown with chemical fertilization, except for As in barley grains. In this case, a significant correlation was found between the DTPA-extractable As content in soils and the total content in grains (r = 0.83). Copyright © 2018 Elsevier Ltd. All rights reserved.

  1. Effects of long-term ultraviolet radiation: the white form of Metridium senile (Anthozoa: Actiniaria) as a potential biological indicator for ultraviolet

    Science.gov (United States)

    Westholt, R.; Kestler, P.; Sicken, O.; Westheide, W.

    2001-03-01

    Genetically identical individuals of the white form of Metridium senile were kept in the laboratory for 40 months, during almost 2 years of which they were irradiated with ultraviolet (UV) radiation simulating the shape of the solar UV spectrum. The living and experimental conditions were largely matched to the conditions in the sea anemones' natural habitat on the North Sea coast. Controls were shielded from direct radiation or irradiated with only the visible range of the spectrum; for the UV tests, the UV component corresponded either to the conditions in the natural habitat or to twice or 4 times this dose. All experiments were preceded by a several-month settling-in period, and UV irradiation was always begun at a low intensity. Under these conditions UV was not lethal but produced many parameter changes, of which only those that were irreversible for the entire duration of the experiment, from September 1992 to August 1994, are described here. The body mass fell significantly in all three UV-radiation modes. All irradiated animals positioned themselves so as to be less exposed to the radiation, and all changed colour from white to brown. These responses are discussed with reference to the potential of M. senile as an indicator or monitor for UV in the northern European coastal region. Field analyses are currently being conducted to demonstrate the extent to which the present results apply to field conditions.

  2. Long-term experiences in cryopreservation of mobilized peripheral blood stem cells using a closed-bag system: a technology with potential for broader application.

    Science.gov (United States)

    Spoerl, Silvia; Peter, Robert; Wäscher, Dagmar; Verbeek, Mareike; Menzel, Helge; Peschel, Christian; Krackhardt, Angela M

    2015-11-01

    In several European countries, preparation of cellular products with open manufacturing systems as used for cryopreservation of peripheral blood stem cells (PBSCs) needs to be performed in a clean-room facility. However, this form of manufacturing is highly expensive and laborious. Thus, safe techniques providing improved efficacy regarding time and material, which are in accordance with legal requirements are highly desirable. We have developed, validated, and applied a simple method for cryopreservation of PBSCs within a functionally closed-bag system using the closed cryo freeze prep set. This process fulfills good manufacturing practice requirements and allows for the cryopreservation of PBSCs without a clean-room facility. In addition to cryopreservation of PBSCs, we have recently successfully modified our system for processing, portioning, and cryopreservation of allogeneic donor lymphocytes. Since 2010, cryopreservation of PBSCs using a closed-bag system has been performed in our facility on a routine basis and 210 patients and healthy donors have been included in this analysis. No significant reduction in viability of CD34+ cells and no process-related contamination were observed. Outcome of hematopoietic stem cell transplantation regarding time of engraftment and infectious complications is comparable to products manufactured in conventional clean-room facilities. Our data confirm that cryopreservation of PBSCs within a functionally closed-bag system is safe, effective, and economical. Furthermore, the system has the potential to be extended to other manufacturing processes of cellular products. © 2015 AABB.

  3. Examining the potential use and long-term stability of guaiac faecal occult blood test cards for microbial DNA 16S rRNA sequencing.

    Science.gov (United States)

    Taylor, Morag; Wood, Henry M; Halloran, Stephen P; Quirke, Philip

    2017-07-01

    With a growing interest in the influence the gut microbiome has on the development of colorectal cancer (CRC), we investigated the feasibility and stability of isolating and typing microbial DNA from guaiac faecal occult blood test (gFOBt) cards. This has the future potential to screen the microbial populations present in confirmed colorectal neoplasia cases with aims to predict the presence and development of CRC. Fresh stool samples from three healthy volunteers were applied to gFOBt cards. DNA was extracted from both the cards and fresh stool samples. A series of additional cards were prepared from one volunteer, and extracted at time points between 2 weeks and 3 years. The V4 region of the 16S rRNA gene was amplified and sequenced on an Illumina MiSeq at 2×250 bp read lengths. Data were analysed using QIIME software. Samples were grouped both by volunteer and by type (fresh or gFOBt), and compared a variety of ways: visual inspection of taxa, α and β diversity, intraclass correlation. In all comparisons, samples grouped by volunteer, and not by sample type. The different time points showed no appreciable differences with increased storage time. This study has demonstrated that there is good concordance between microbial DNA isolated from fresh stool sample, and from the matched gFOBt card. Samples stored for up to 3 years showed no detrimental effect on measureable microbial DNA. This study has important future implications for investigating microbial influence on CRC development and other pathologies. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  4. Japan's Long-term Energy Demand and Supply Scenario to 2050 - Estimation for the Potential of Massive CO2 Mitigation

    Energy Technology Data Exchange (ETDEWEB)

    Komiyama, Ryoichi; Marnay, Chris; Stadler, Michael; Lai, Judy; Borgeson, Sam; Coffey, Brian; Azevedo, Ines Lima

    2009-09-01

    In this analysis, the authors projected Japan's energy demand/supply and energy-related CO{sub 2} emissions to 2050. Their analysis of various scenarios indicated that Japan's CO{sub 2} emissions in 2050 could be potentially reduced by 26-58% from the current level (FY 2005). These results suggest that Japan could set a CO{sub 2} emission reduction target for 2050 at between 30% and 60%. In order to reduce CO{sub 2} emissions by 60% in 2050 from the present level, Japan will have to strongly promote energy conservation at the same pace as an annual rate of 1.9% after the oil crises (to cut primary energy demand per GDP (TPES/GDP) in 2050 by 60% from 2005) and expand the share of non-fossil energy sources in total primary energy supply in 2050 to 50% (to reduce CO{sub 2} emissions per primary energy demand (CO{sub 2}/TPES) in 2050 by 40% from 2005). Concerning power generation mix in 2050, nuclear power will account for 60%, solar and other renewable energy sources for 20%, hydro power for 10% and fossil-fired generation for 10%, indicating substantial shift away from fossil fuel in electric power supply. Among the mitigation measures in the case of reducing CO{sub 2} emissions by 60% in 2050, energy conservation will make the greatest contribution to the emission reduction, being followed by solar power, nuclear power and other renewable energy sources. In order to realize this massive CO{sub 2} abatement, however, Japan will have to overcome technological and economic challenges including the large-scale deployment of nuclear power and renewable technologies.

  5. Long term study of mechanical

    Directory of Open Access Journals (Sweden)

    Ahmed M. Diab

    2016-06-01

    Full Text Available In this study, properties of limestone cement concrete containing different replacement levels of limestone powder were examined. It includes 0%, 5%, 10%, 15%, 20% and 25% of limestone powder as a partial replacement of cement. Silica fume was added incorporated with limestone powder in some mixes to enhance the concrete properties. Compressive strength, splitting tensile strength and modulus of elasticity were determined. Also, durability of limestone cement concrete with different C3A contents was examined. The weight loss, length change and cube compressive strength loss were measured for concrete attacked by 5% sodium sulfate using an accelerated test up to 525 days age. The corrosion resistance was measured through accelerated corrosion test using first crack time, cracking width and steel reinforcement weight loss. Consequently, for short and long term, the use of limestone up to 10% had not a significant reduction in concrete properties. It is not recommended to use blended limestone cement in case of sulfate attack. The use of limestone cement containing up to 25% limestone has insignificant effect on corrosion resistance before cracking.

  6. Studies of breakeven prices and electricity supply potentials of nuclear fusion by a long-term world energy and environment model

    Science.gov (United States)

    Tokimatsu, K.; Asaoka, Y.; Konishi, S.; Fujino, J.; Ogawa, Y.; Okano, K.; Nishio, S.; Yoshida, T.; Hiwatari, R.; Yamaji, K.

    2002-11-01

    In response to social demand, this paper investigates the breakeven price (BP) and potential electricity supply of nuclear fusion energy in the 21st century by means of a world energy and environment model. We set the following objectives in this paper: (i) to reveal the economics of the introduction conditions of nuclear fusion; (ii) to know when tokamak-type nuclear fusion reactors are expected to be introduced cost-effectively into future energy systems; (iii) to estimate the share in 2100 of electricity produced by the presently designed reactors that could be economically selected in the year. The model can give in detail the energy and environment technologies and price-induced energy saving, and can illustrate optimal energy supply structures by minimizing the costs of total discounted energy systems at a discount rate of 5%. The following parameters of nuclear fusion were considered: cost of electricity (COE) in the nuclear fusion introduction year, annual COE reduction rates, regional introduction year, and regional nuclear fusion capacity projection. The investigations are carried out for three nuclear fusion projections one of which includes tritium breeding constraints, four future CO2 concentration constraints, and technological assumptions on fossil fuels, nuclear fission, CO2 sequestration, and anonymous innovative technologies. It is concluded that: (1) the BPs are from 65 to 125 mill kW-1 h-1 depending on the introduction year of nuclear fusion under the 550 ppmv CO2 concentration constraints; those of a business-as-usual (BAU) case are from 51 to 68 mill kW-1h-1. Uncertainties resulting from the CO2 concentration constraints and the technological options influenced the BPs by plus/minus some 10 30 mill kW-1h-1, (2) tokamak-type nuclear fusion reactors (as presently designed, with a COE range around 70 130 mill kW-1h-1) would be favourably introduced into energy systems after 2060 based on the economic criteria under the 450 and 550 ppmv CO2

  7. Long-term aerosol and trace gas measurements in Eastern Lapland, Finland: the impact of Kola air pollution to new particle formation and potential CCN

    Science.gov (United States)

    Kyrö, Ella-Maria; Väänänen, Riikka; Kerminen, Veli-Matti; Virkkula, Aki; Asmi, Ari; Nieminen, Tuomo; Dal Maso, Miikka; Petäjä, Tuukka; Keronen, Petri; Aalto, Pasi; Riipinen, Ilona; Lehtipalo, Katrianne; Hari, Pertti; Kulmala, Markku

    2014-05-01

    Sulphur and primary emissions have been decreasing largely all over Europe, resulting in improved air quality and decreased direct radiation forcing by aerosols. The smelter industry in Kola Peninsula is one of largest sources of anthropogenic SO2 within the Arctic domain and since late 1990s the sulphur emissions have been decreasing rapidly (Paatero et al., 2008; Prank et al., 2010). New particle formation (NPF) is tightly linked with the oxidizing product of SO2, namely sulphuric acid (H2SO4), since it is known to be the key component in atmospheric nucleation (Sipilä et al., 2010). Thus, decreasing sulphur pollution may lead to less NPF. However, low values of condensation sink (CS), which is determined by the amount of pre-existing particles, favours NPF. We used 14 years (1998-2011) of aerosol number size distribution and trace gas data from SMEAR I station in Eastern Lapland, Finland, to investigate these relationships between SO2, NPF and CS. The station is a clean background station with occasional sulphur pollution episodes when the air masses arrive over Kola Peninsula. We found that while SO2 decreased by 11.3 % / year, the number of clear NPF event days was also decreasing by 9.9 % / year. At the same time, CS was decreasing also (-8.0 % / year) leading to formation of more particles per single NPF event (J3 increased by 29.7 % / year in 2006-2011) but the low vapour concentrations of H2SO4 (proxy decreased by 6.2 % / year) did not allow them to grow into climatically relevant sizes. Over the time, concentrations of potential CCN (cloud condensing nuclei) were also decreasing with more moderate pace, -4.0 % / year. The events started on average earlier after sunrise when the SO2 concentration during the start of the event was higher and NPF occurred more frequently in air masses which were travelling over Kola. Despite the total decrease in sulphur pollution originating from Kola there is currently no evidence of cleaning of the emissions, rather the

  8. General practitioners' views on (long-term) prescription and use of problematic and potentially inappropriate medication for oldest-old patients-A qualitative interview study with GPs (CIM-TRIAD study).

    Science.gov (United States)

    Pohontsch, Nadine Janis; Heser, Kathrin; Löffler, Antje; Haenisch, Britta; Parker, Debora; Luck, Tobias; Riedel-Heller, Steffi G; Maier, Wolfgang; Jessen, Frank; Scherer, Martin

    2017-02-17

    Potentially inappropriate medication (PIM) is defined as medication with uncertain therapeutic effects and/or potential adverse drug reactions outweighing the clinical benefits. The prescription rate of PIM for oldest-old patients is high despite the existence of lists of PIM (e.g. the PRISCUS list) and efforts to raise awareness. This study aims at identifying general practitioners' views on PIM and aspects affecting the (long-term) use of PIM. As part of the CIM-TRIAD study, we conducted semi-structured, qualitative interviews with 47 general practitioners, discussing 25 patients with and 22 without PIM (according to the PRISCUS list). The interview guideline included generic and patient-specific questions. Interviews were digitally recorded and transcribed verbatim. We content analyzed the interviews using deductive and inductive category development. The majority of the general practitioners were not aware of the PRISCUS list. Agents deemed potentially inappropriate from the general practitioners' point of view and the PRISCUS list are not completely superimposable. General practitioners named their criteria to identify appropriate medication for elderly patients (e.g. renal function, cognitive state) and emphasized the importance of monitoring. We identified prescription- (e.g. benzodiazepines on alternative private prescription), medication- (e.g. subjective perception that PIM has no alternative), general practitioner- (e.g. general practitioner relies on specialists), patient- (e.g. "demanding high-user", positive subjective benefit-risk-ratio) and system-related aspects (e.g. specialists lacking holistic view, interface problems) related to the (long term) use of PIM. While the PRISCUS list does not seem to play a decisive role in general practice, general practitioners are well aware of risks associated with PIM. Our study identifies some starting points for a safer handling of PIM, e.g. stronger dissemination of the PRISCUS list, better compensation of

  9. Long term testing of PSI-membranes

    Energy Technology Data Exchange (ETDEWEB)

    Huslage, J.; Brack, H.P.; Geiger, F.; Buechi, F.N.; Tsukada, A.; Scherer, G.G. [Paul Scherrer Inst. (PSI), Villigen (Switzerland)

    1999-08-01

    Long term tests of PSI membranes based on radiation-grafted FEP and ETFE films were carried out and FEP-based membranes were evaluated by monitoring the in-situ membrane area resistance measured by a current pulse method. By modifying our irradiation procedure and using the double crosslinking concept we obtain reproducible membrane cell lifetimes (in term of in-situ membrane resistance) of greater than 5000 hours at 60-65{sup o}C. Preliminary tests at 80-85{sup o}C with lifetimes of greater than 2500 demonstrate the potential long term stability of PSI proton exchange membranes based on FEP over the whole operating temperature range of low-temperature polymer electrolyte fuel cells. Radiation grafted PSI membranes based on ETFE have better mechanical properties than those of the FEP membranes. Mechanical properties are particularly important in large area cells and fuel cell stacks. ETFE membranes have been tested successfully for approximately 1000 h in a 2-cell stack (100 cm{sup 2} active area each cell). (author) 4 figs., 4 refs.

  10. Antidepressant and anxiolytic potential of the multimodal antidepressant vortioxetine (Lu AA21004) assessed by behavioural and neurogenesis outcomes in mice.

    Science.gov (United States)

    Guilloux, Jean-Philippe; Mendez-David, Indira; Pehrson, Alan; Guiard, Bruno P; Repérant, Christelle; Orvoën, Sophie; Gardier, Alain M; Hen, René; Ebert, Bjarke; Miller, Silke; Sanchez, Connie; David, Denis J

    2013-10-01

    Vortioxetine (Lu AA21004) is an investigational novel antidepressant with multimodal activity that functions as a 5-HT3, 5-HT7 and 5-HT(1D) receptor antagonist, 5-HT(1B) receptor partial agonist, 5-HT(1A) receptor agonist and inhibitor of the 5-HT transporter in vitro. Here we explore its anxiolytic and antidepressant potential in adult mice. Vortioxetine was assessed in BalB/cJ@RJ mice using the open-field and forced-swim tests (acute: p.o. 1 h, repeated: daily p.o. 21 days), and in 129S6/SvEvTac mice using the novelty suppressed feeding paradigm (acute: p.o. 1 h, sustained: daily p.o. 14 or 21 days). Fluoxetine and diazepam were controls. Acute and repeated dosing of vortioxetine produced more pronounced anxiolytic- and antidepressant-like activities than fluoxetine. Vortioxetine significantly increased cell proliferation and cell survival and stimulated maturation of immature granule cells in the subgranular zone of the dentate gyrus of the hippocampus after 21 days of treatment. After 14 days, a high dose of vortioxetine increased dendritic length and the number of dendrite intersections, suggesting that vortioxetine accelerates the maturation of immature neurons. Vortioxetine displays an antidepressant and anxiolytic profile following repeated administration associated with increased neurogenesis at several stages. Vortioxetine effects were observed at low levels of 5-HT transporter occupancy, suggesting an alternative mechanism of action to 5-HT reuptake inhibition. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

  11. Prediction of Long-Term Treatment Response to Selective Serotonin Reuptake Inhibitors (SSRIs Using Scalp and Source Loudness Dependence of Auditory Evoked Potentials (LDAEP Analysis in Patients with Major Depressive Disorder

    Directory of Open Access Journals (Sweden)

    Bun-Hee Lee

    2015-03-01

    Full Text Available Background: Animal and clinical studies have demonstrated that the loudness dependence of auditory evoked potentials (LDAEP is inversely related to central serotonergic activity, with a high LDAEP reflecting weak serotonergic neurotransmission and vice versa, though the findings in humans have been less consistent. In addition, a high pretreatment LDAEP appears to predict a favorable response to antidepressant treatments that augment the actions of serotonin. The aim of this study was to test whether the baseline LDAEP is correlated with response to long-term maintenance treatment in patients with major depressive disorder (MDD. Methods: Scalp N1, P2 and N1/P2 LDAEP and standardized low resolution brain electromagnetic tomography-localized N1, P2, and N1/P2 LDAEP were evaluated in 41 MDD patients before and after they received antidepressant treatment (escitalopram (n = 32, 10.0 ± 4.0 mg/day, sertraline (n = 7, 78.6 ± 26.7 mg/day, and paroxetine controlled-release formulation (n = 2, 18.8 ± 8.8 mg/day for more than 12 weeks. A treatment response was defined as a reduction in the Beck Depression Inventory (BDI score of >50% between baseline and follow-up. Results: The responders had higher baseline scalp P2 and N1/P2 LDAEP than nonresponders (p = 0.017; p = 0.036. In addition, changes in total BDI score between baseline and follow-up were larger in subjects with a high baseline N1/P2 LDAEP than those with a low baseline N1/P2 LDAEP (p = 0.009. There were significantly more responders in the high-LDAEP group than in the low-LDAEP group (p = 0.041. Conclusions: The findings of this study reveal that a high baseline LDAEP is associated with a clinical response to long-term antidepressant treatment.

  12. HOME LONG-TERM CARE IN POLAND

    Directory of Open Access Journals (Sweden)

    Ewa Kułagowska

    2011-06-01

    Full Text Available The considerable proportion of the elderly, the chronically ill and the disabled in community is an economic and organizational challenge for the state social policy. It requires a large, steadily increasing financing from the public funds and creating an optional care model to fulfill the needs of citizens and guarantee high quality services. Development of the long-term care is one of the problems to be solved. This paper presents: – a long-term care forms, organization and tasks; – a role of long-term care but particularly home longterm care to protect health in Poland; – problems related with home long-term care functioning.

  13. Effects of neuroleptics administration on adult neurogenesis in the rat hypothalamus.

    Science.gov (United States)

    Rojczyk, Ewa; Pałasz, Artur; Wiaderkiewicz, Ryszard

    2015-12-01

    Among many factors influencing adult neurogenesis, pharmacological modulation has been broadly studied. It is proven that neuroleptics positively affect new neuron formation in canonical neurogenic sites - subgranular zone of the hippocampal dentate gyrus and subventricular zone of the lateral ventricles. Latest findings suggest that adult neurogenesis also occurs in several additional regions like the hypothalamus, amygdala, neocortex and striatum. As the hypothalamus is considered an important target of neuroleptics, a hypothesis can be made that these substances are able to modulate local neural proliferation. Experiments were performed on adult male rats injected for 28 days or 1 day by three neuroleptics: olanzapine, chlorpromazine and haloperidol. Immunohistochemistry was used to determine expression of proliferation marker (Ki-67) and the marker of neuroblasts - doublecortin (DCX) - which may inform about drug influence on adult neurogenesis at the level of the hypothalamus. It was shown that a single injection of antipsychotics causes significant decrease in hypothalamic DCX expression, but after chronic treatment with chlorpromazine, but not olanzapine, there is an increase in the number of newly formed neuroblasts. Haloperidol has the opposite effect - its long-term administration decreases the number of DCX-positive cells. Cell proliferation levels (Ki-67 expression) increase after long-term drug administration, whereas their single doses do not have any modulatory effect on proliferation potential. Our results throw a new light on the neuroleptics mechanism of action. They also support the potential role of antipsychotics as a factor that can modulate hypothalamic neurogenesis with putative clinical applications. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  14. Neurogenesis and The Effect of Antidepressants

    Directory of Open Access Journals (Sweden)

    Philippe Taupin

    2006-01-01

    Full Text Available The recent evidence that neurogenesis occurs throughout adulthood and neural stem cells (NSCs reside in the adult central nervous system (CNS suggests that the CNS has the potential for self-repair. Beside this potential, the function of newly generated neuronal cells in the adult brain remains the focus of intense research. The hippocampus of patients with depression show signs of atrophy and neuronal loss. This suggests that adult neurogenesis may contribute to the biology of depression. The observations that antidepressants, like fluoxetine, increase neurogenesis in the dentate gyrus (DG and neurogenesis is required for the behavioral effect of antidepressants, lead to a new theory for depression and the design of new strategies and drugs for the treatment of depression. However, the role of adult neurogenesis in the etiology of depression remains the source of controversies and debates.

  15. Scientific Understanding from Long Term Observations: Insights from the Long Term Ecological Research (LTER) Program

    Science.gov (United States)

    Gosz, J.

    2001-12-01

    estuaries below by removing all incoming freshwater. At Toolik Lake, long-term experiments of removing top predators from the good web of lakes showed dramatic alterations of lake populations of small fish and zooplankton. In New Mexico, LTER research on small mammal populations is successfully predicting rodent increases and the potential for increased zoonotic diseases such as Hantavirus and bubonic plague. This ability to forecast based on El Nino prediction is being used to increase scientific awareness and public health awareness through media based communication with the public. In Oregon, the Andrews Forest LTER program has had long, strong links with natural resource policy and management. Basic understanding of forest-stream interactions, characteristics of old-growth forests, roles of woody debris in temperate forest ecosystems, invertebrate biodiversity and ecosystem function have been incorporated in management guidelines, plans and regulations for public and private lands throughout the Pacific Northwest. Other examples of the values of long-term research and monitoring will be presented.

  16. The fatty acid amide hydrolase inhibitor URB597 exerts anti-inflammatory effects in hippocampus of aged rats and restores an age-related deficit in long-term potentiation

    Directory of Open Access Journals (Sweden)

    Murphy Niamh

    2012-04-01

    Full Text Available Abstract Background Several factors contribute to the deterioration in synaptic plasticity which accompanies age and one of these is neuroinflammation. This is characterized by increased microglial activation associated with increased production of proinflammatory cytokines like interleukin-1β (IL-1β. In aged rats these neuroinflammatory changes are associated with a decreased ability of animals to sustain long-term potentiation (LTP in the dentate gyrus. Importantly, treatment of aged rats with agents which possess anti-inflammatory properties to decrease microglial activation, improves LTP. It is known that endocannabinoids, such as anandamide (AEA, have anti-inflammatory properties and therefore have the potential to decrease the age-related microglial activation. However, endocannabinoids are extremely labile and are hydrolyzed quickly after production. Here we investigated the possibility that inhibiting the degradation of endocannabinoids with the fatty acid amide hydrolase (FAAH inhibitor, URB597, could ameliorate age-related increases in microglial activation and the associated decrease in LTP. Methods Young and aged rats received subcutaneous injections of the FAAH inhibitor URB597 every second day and controls which received subcutaneous injections of 30% DMSO-saline every second day for 28 days. Long-term potentiation was recorded on day 28 and the animals were sacrificed. Brain tissue was analyzed for markers of microglial activation by PCR and for levels of endocannabinoids by liquid chromatography coupled to tandem mass spectrometry. Results The data indicate that expression of markers of microglial activation, MHCII, and CD68 mRNA, were increased in the hippocampus of aged, compared with young, rats and that these changes were associated with increased expression of the proinflammatory cytokines interleukin (IL-1β and tumor necrosis factor-α (TNFα which were attenuated by treatment with URB597. Coupled with these changes, we

  17. Peripheral administration of the soluble TNF inhibitor XPro1595 modifies brain immune cell profiles, decreases beta-amyloid plaque load, and rescues impaired long-term potentiation in 5xFAD mice.

    Science.gov (United States)

    MacPherson, Kathryn P; Sompol, Pradoldej; Kannarkat, George T; Chang, Jianjun; Sniffen, Lindsey; Wildner, Mary E; Norris, Christopher M; Tansey, Malú G

    2017-06-01

    Clinical and animal model studies have implicated inflammation and peripheral immune cell responses in the pathophysiology of Alzheimer's disease (AD). Peripheral immune cells including T cells circulate in the cerebrospinal fluid (CSF) of healthy adults and are found in the brains of AD patients and AD rodent models. Blocking entry of peripheral macrophages into the CNS was reported to increase amyloid burden in an AD mouse model. To assess inflammation in the 5xFAD (Tg) mouse model, we first quantified central and immune cell profiles in the deep cervical lymph nodes and spleen. In the brains of Tg mice, activated (MHCII + , CD45 high , and Ly6C high ) myeloid-derived CD11b + immune cells are decreased while CD3 + T cells are increased as a function of age relative to non-Tg mice. These immunological changes along with evidence of increased mRNA levels for several cytokines suggest that immune regulation and trafficking patterns are altered in Tg mice. Levels of soluble Tumor Necrosis Factor (sTNF) modulate blood-brain barrier (BBB) permeability and are increased in CSF and brain parenchyma post-mortem in AD subjects and Tg mice. We report here that in vivo peripheral administration of XPro1595, a novel biologic that sequesters sTNF into inactive heterotrimers, reduced the age-dependent increase in activated immune cells in Tg mice, while decreasing the overall number of CD4 + T cells. In addition, XPro1595 treatment in vivo rescued impaired long-term potentiation (LTP) measured in brain slices in association with decreased Aβ plaques in the subiculum. Selective targeting of sTNF may modulate brain immune cell infiltration, and prevent or delay neuronal dysfunction in AD. Immune cells and cytokines perform specialized functions inside and outside the brain to maintain optimal brain health; but the extent to which their activities change in response to neuronal dysfunction and degeneration is not well understood. Our findings indicate that neutralization of s

  18. Long-term survival after perforated diverticulitis

    NARCIS (Netherlands)

    J. Vermeulen (Jan); M.P. Gosselink (Martijn Pieter); W.C.J. Hop (Wim); E. van der Harst (Erwin); B.E. Hansen (Bettina); G.H.H. Mannaerts (Guido); P-P. Coene (Peter Paul); W.F. Weidema (Wibo); J.F. Lange (Johan)

    2011-01-01

    textabstractAim: Short-term survival after emergency surgery for perforated diverticulitis is poor. Less is known about long-term survival. The aims of this study were to evaluate long-term survival after discharge from hospital and to identify factors associated with prognosis. Method: All patients

  19. The Long-Term Swap Rate and a General Analysis of Long-Term Interest Rates

    OpenAIRE

    Francesca Biagini; Alessandro Gnoatto; Maximilian H\\"artel

    2015-01-01

    We introduce here for the first time the long-term swap rate, characterised as the fair rate of an overnight indexed swap with infinitely many exchanges. Furthermore we analyse the relationship between the long-term swap rate, the long-term yield, see [4], [5], and [25], and the long-term simple rate, considered in [8] as long-term discounting rate. We finally investigate the existence of these long-term rates in two term structure methodologies, the Flesaker-Hughston model and the linear-rat...

  20. Long-term installations of the DC-potential drop method in four nuclear power plants and the accuracies thereby obtained for monitoring of crack initiation and crack growth

    Energy Technology Data Exchange (ETDEWEB)

    Oppermann, W.; Hofstoetter, P.; Keller, H.P. [TUEV Rheinland Anlagentechnik GmbH, Koeln (Germany)

    1997-10-01

    After a total monitored operational timescale of almost five years on long-term installations, both in the laboratory and in four nuclear power plants, evidence can be put forward that the DC-potential drop method is now, at its current stage of development, suitable for inspecting and monitoring material regions such as, e.g. weld seams in pipework, for crack initiation and crack growth at power plant temperatures. This function can be performed with reliability and high sensitivity. The inspection and monitoring of cracks on the internal surface of the pipework can also be carried out from the external surface. The studies have shown that the method is basically able to monitor the growth of cracks found at discontinuous intervals using permanently installed potential probes, i.e. from plant inspection to plant inspection, while a transition to continuous monitoring is possible at any time. Thus a measure of redundancy can be provided for conventional ultrasonic and radiographic inspection, in particular for difficult to check austenitic weld seams. The method can also be seen as an alternative to the conventional techniques. When necessary, the cracks found can be measured more accurately than was previously possible with conventional ultrasonic and radiographic inspections. The total exposure to radiation can be reduced in comparison to other methods of inspection. (orig.) 5 refs.

  1. NR2B subunit-dependent long-term potentiation enhancement in the rat cortical auditory system in vivo following masking of patterned auditory input by white noise exposure during early postnatal life.

    Science.gov (United States)

    Hogsden, Jennifer L; Dringenberg, Hans C

    2009-08-01

    The composition of N-methyl-D-aspartate (NMDA) receptor subunits influences the degree of synaptic plasticity expressed during development and into adulthood. Here, we show that theta-burst stimulation of the medial geniculate nucleus reliably induced NMDA receptor-dependent long-term potentiation (LTP) of field postsynaptic potentials recorded in the primary auditory cortex (A1) of urethane-anesthetized rats. Furthermore, substantially greater levels of LTP were elicited in juvenile animals (30-37 days old; approximately 55% maximal potentiation) than in adult animals (approximately 30% potentiation). Masking patterned sound via continuous white noise exposure during early postnatal life (from postnatal day 5 to postnatal day 50-60) resulted in enhanced, juvenile-like levels of LTP (approximately 70% maximal potentiation) relative to age-matched controls reared in unaltered acoustic environments (approximately 30%). Rats reared in white noise and then placed in unaltered acoustic environments for 40-50 days showed levels of LTP comparable to those of adult controls, indicating that white noise rearing results in a form of developmental arrest that can be overcome by subsequent patterned sound exposure. We explored the mechanisms mediating white noise-induced plasticity enhancements by local NR2B subunit antagonist application in A1. NR2B subunit antagonists (Ro 25-6981 or ifenprodil) completely reversed white noise-induced LTP enhancement at concentrations that did not affect LTP in adult or age-matched controls. We conclude that white noise exposure during early postnatal life results in the maintenance of juvenile-like, higher levels of plasticity in A1, an effect that appears to be critically dependent on NR2B subunit activation.

  2. In Vivo Post-Cardiac Arrest Myocardial Dysfunction Is Supported by Ca2+/Calmodulin-Dependent Protein Kinase II-Mediated Calcium Long-Term Potentiation and Mitigated by Alda-1, an Agonist of Aldehyde Dehydrogenase Type 2.

    Science.gov (United States)

    Woods, Christopher; Shang, Ching; Taghavi, Fouad; Downey, Peter; Zalewski, Adrian; Rubio, Gabriel R; Liu, Jing; Homburger, Julian R; Grunwald, Zachary; Qi, Wei; Bollensdorff, Christian; Thanaporn, Porama; Ali, Ayyaz; Riemer, Kirk; Kohl, Peter; Mochly-Rosen, Daria; Gerstenfeld, Edward; Large, Stephen; Ali, Ziad; Ashley, Euan

    2016-09-27

    Survival after sudden cardiac arrest is limited by postarrest myocardial dysfunction, but understanding of this phenomenon is constrained by a lack of data from a physiological model of disease. In this study, we established an in vivo model of cardiac arrest and resuscitation, characterized the biology of the associated myocardial dysfunction, and tested novel therapeutic strategies. We developed rodent models of in vivo postarrest myocardial dysfunction using extracorporeal membrane oxygenation resuscitation followed by invasive hemodynamics measurement. In postarrest isolated cardiomyocytes, we assessed mechanical load and Ca(2) (+)-induced Ca(2+) release (CICR) simultaneously using the microcarbon fiber technique and observed reduced function and myofilament calcium sensitivity. We used a novel fiberoptic catheter imaging system and a genetically encoded calcium sensor, GCaMP6f, to image CICR in vivo. We found potentiation of CICR in isolated cells from this extracorporeal membrane oxygenation model and in cells isolated from an ischemia/reperfusion Langendorff model perfused with oxygenated blood from an arrested animal but not when reperfused in saline. We established that CICR potentiation begins in vivo. The augmented CICR observed after arrest was mediated by the activation of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII). Increased phosphorylation of CaMKII, phospholamban, and ryanodine receptor 2 was detected in the postarrest period. Exogenous adrenergic activation in vivo recapitulated Ca(2+) potentiation but was associated with lesser CaMKII activation. Because oxidative stress and aldehydic adduct formation were high after arrest, we tested a small-molecule activator of aldehyde dehydrogenase type 2, Alda-1, which reduced oxidative stress, restored calcium and CaMKII homeostasis, and improved cardiac function and postarrest outcome in vivo. Cardiac arrest and reperfusion lead to CaMKII activation and calcium long-term potentiation, which

  3. Long-term live cell imaging and automated 4D analysis of drosophila neuroblast lineages.

    Science.gov (United States)

    Homem, Catarina C F; Reichardt, Ilka; Berger, Christian; Lendl, Thomas; Knoblich, Juergen A

    2013-01-01

    The developing Drosophila brain is a well-studied model system for neurogenesis and stem cell biology. In the Drosophila central brain, around 200 neural stem cells called neuroblasts undergo repeated rounds of asymmetric cell division. These divisions typically generate a larger self-renewing neuroblast and a smaller ganglion mother cell that undergoes one terminal division to create two differentiating neurons. Although single mitotic divisions of neuroblasts can easily be imaged in real time, the lack of long term imaging procedures has limited the use of neuroblast live imaging for lineage analysis. Here we describe a method that allows live imaging of cultured Drosophila neuroblasts over multiple cell cycles for up to 24 hours. We describe a 4D image analysis protocol that can be used to extract cell cycle times and growth rates from the resulting movies in an automated manner. We use it to perform lineage analysis in type II neuroblasts where clonal analysis has indicated the presence of a transit-amplifying population that potentiates the number of neurons. Indeed, our experiments verify type II lineages and provide quantitative parameters for all cell types in those lineages. As defects in type II neuroblast lineages can result in brain tumor formation, our lineage analysis method will allow more detailed and quantitative analysis of tumorigenesis and asymmetric cell division in the Drosophila brain.

  4. Long-term live cell imaging and automated 4D analysis of drosophila neuroblast lineages.

    Directory of Open Access Journals (Sweden)

    Catarina C F Homem

    Full Text Available The developing Drosophila brain is a well-studied model system for neurogenesis and stem cell biology. In the Drosophila central brain, around 200 neural stem cells called neuroblasts undergo repeated rounds of asymmetric cell division. These divisions typically generate a larger self-renewing neuroblast and a smaller ganglion mother cell that undergoes one terminal division to create two differentiating neurons. Although single mitotic divisions of neuroblasts can easily be imaged in real time, the lack of long term imaging procedures has limited the use of neuroblast live imaging for lineage analysis. Here we describe a method that allows live imaging of cultured Drosophila neuroblasts over multiple cell cycles for up to 24 hours. We describe a 4D image analysis protocol that can be used to extract cell cycle times and growth rates from the resulting movies in an automated manner. We use it to perform lineage analysis in type II neuroblasts where clonal analysis has indicated the presence of a transit-amplifying population that potentiates the number of neurons. Indeed, our experiments verify type II lineages and provide quantitative parameters for all cell types in those lineages. As defects in type II neuroblast lineages can result in brain tumor formation, our lineage analysis method will allow more detailed and quantitative analysis of tumorigenesis and asymmetric cell division in the Drosophila brain.

  5. Neuronal Differentiation in Schwann Cell Lineage Underlies Postnatal Neurogenesis in the Enteric Nervous System.

    Science.gov (United States)

    Uesaka, Toshihiro; Nagashimada, Mayumi; Enomoto, Hideki

    2015-07-08

    Elucidation of the cellular identity of neuronal precursors provides mechanistic insights into the development and pathophysiology of the nervous system. In the enteric nervous system (ENS), neurogenesis persists from midgestation to the postnatal period. Cellular mechanism underlying the long-term neurogenesis in the ENS has remained unclear. Using genetic fate mapping in mice, we show here that a subset of Schwann cell precursors (SCPs), which invades the gut alongside the extrinsic nerves, adopts a neuronal fate in the postnatal period and contributes to the ENS. We found SCP-derived neurogenesis in the submucosal region of the small intestine in the absence of vagal neural crest-derived ENS precursors. Under physiological conditions, SCPs comprised up to 20% of enteric neurons in the large intestine and gave rise mainly to restricted neuronal subtypes, calretinin-expressing neurons. Genetic ablation of Ret, the signaling receptor for glial cell line-derived neurotrophic factor, in SCPs caused colonic oligoganglionosis, indicating that SCP-derived neurogenesis is essential to ENS integrity. Identification of Schwann cells as a physiological neurogenic source provides novel insight into the development and disorders of neural crest-derived tissues. Elucidating the cellular identity of neuronal precursors provides novel insights into development and function of the nervous system. The enteric nervous system (ENS) is innervated richly by extrinsic nerve fibers, but little is known about the significance of extrinsic innervation to the structural integrity of the ENS. This report reveals that a subset of Schwann cell precursors (SCPs), which invades the gut alongside the extrinsic nerves, adopts a neuronal fate and differentiates into specific neuronal subtypes. SCP-specific ablation of the Ret gene leads to colonic oligoganglionosis, demonstrating a crucial role of SCP-derived neurogenesis in ENS development. Cross-lineage differentiation capacity in SCPs suggests

  6. Long-Term Ownership by Industrial Foundations

    DEFF Research Database (Denmark)

    Børsting, Christa Winther; Kuhn, Johan Moritz; Poulsen, Thomas

    2016-01-01

    in several respects. Foundations hold on to their shares for longer. Foundation-owned companies replace managers less frequently. They have more conservative capital structures with less leverage. Their companies survive longer. Their business decisions appear to be more long term. This paper supports...... in Denmark. Industrial foundations are independent legal entities without owners or members typically with the dual objective of preserving the company and using excess profits for charity. We use a unique Danish data set to examine the governance of foundation-owned companies. We show that they are long-term......Short-termism has become a serious concern for businesses and policy makers and this has inspired a search for governance arrangement to promote long term decision making. In this paper we study a particularly long-term ownership structure, which is fairly common in Northern Europe, particularly...

  7. Reforming long-term care in Europe

    National Research Council Canada - National Science Library

    Costa-i-Font, Joan

    2011-01-01

    .... Offers the very latest analysis of long-term care reform agendas in Europe. Compares countries comparatively less studied with the experiences of reform in Germany, the UK, Netherlands and Sweden...

  8. Long Term Care Minimum Data Set (MDS)

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Long-Term Care Minimum Data Set (MDS) is a standardized, primary screening and assessment tool of health status that forms the foundation of the comprehensive...

  9. Pituitary diseases : long-term clinical consequences

    NARCIS (Netherlands)

    Klaauw, Agatha Apolonia van der

    2008-01-01

    This thesis describes various studies during the long-term follow-up of patients after treatment for pituitary diseases. The focus of this thesis is acromegaly, growth hormone deficiency, sleep and quality of life. Various aspects are described.

  10. Long-term weight loss maintenance

    National Research Council Canada - National Science Library

    Wing, Rena R; Phelan, Suzanne

    2005-01-01

    ...% of initial body weight and maintaining the loss for at least 1 y. The National Weight Control Registry provides information about the strategies used by successful weight loss maintainers to achieve and maintain long-term weight loss...

  11. Manganese in long term paediatric parenteral nutrition.

    OpenAIRE

    Reynolds, A P; Kiely, E; Meadows, N

    1994-01-01

    The current practice of providing manganese supplementation to neonates on long term parenteral nutrition is leading to a high incidence of hypermanganesaemia. Magnetic resonance imaging (MRI) studies in adults on long term manganese parenteral nutrition have shown changes in TI weighted MRI images and similar findings in a neonate receiving trace element supplementation are reported here. Whole blood manganese concentration in the infant was 1740 nmol/l (or 8.3 times upper reference limit). ...

  12. Long-term outcomes after severe shock.

    Science.gov (United States)

    Pratt, Cristina M; Hirshberg, Eliotte L; Jones, Jason P; Kuttler, Kathryn G; Lanspa, Michael J; Wilson, Emily L; Hopkins, Ramona O; Brown, Samuel M

    2015-02-01

    Severe shock is a life-threatening condition with very high short-term mortality. Whether the long-term outcomes among survivors of severe shock are similar to long-term outcomes of other critical illness survivors is unknown. We therefore sought to assess long-term survival and functional outcomes among 90-day survivors of severe shock and determine whether clinical predictors were associated with outcomes. Seventy-six patients who were alive 90 days after severe shock (received ≥1 μg/kg per minute of norepinephrine equivalent) were eligible for the study. We measured 3-year survival and long-term functional outcomes using the Medical Outcomes Study 36-Item Short-Form Health Survey, the EuroQOL 5-D-3L, the Hospital Anxiety and Depression Scale, the Impact of Event Scale-Revised, and an employment instrument. We also assessed the relationship between in-hospital predictors and long-term outcomes. The mean long-term survival was 5.1 years; 82% (62 of 76) of patients survived, of whom 49 were eligible for follow-up. Patients who died were older than patients who survived. Thirty-six patients completed a telephone interview a mean of 5 years after hospital admission. The patients' Physical Functioning scores were below U.S. population norms (P shock had a high 3-year survival rate. Patients' long-term physical and psychological outcomes were similar to those reported for cohorts of less severely ill intensive care unit survivors. Anxiety and depression were relatively common, but only a few patients had symptoms of posttraumatic stress disorder. This study supports the observation that acute illness severity does not determine long-term outcomes. Even extremely critically ill patients have similar outcomes to general intensive care unit survivor populations.

  13. In vivo Post-Cardiac Arrest Myocardial Dysfunction is Supported by CaMKII-Mediated Calcium Long-Term Potentiation and Mitigated by Alda-1, an Agonist of Aldehyde Dehydrogenase Type 2

    Science.gov (United States)

    Downey, Peter; Zalewski, Adrian; Rubio, Gabriel R.; Liu, Jing; Homburger, Julian R.; Grunwald, Zachary; Qi, Wei; Bollensdorff, Christian; Thanaporn, Porama; Ali, Ayyaz; Riemer, Kirk; Kohl, Peter; Mochly-Rosen, Daria; Gerstenfeld, Edward; Large, Stephen; Ali, Ziad; Ashley, Euan

    2016-01-01

    Background Survival after sudden cardiac arrest is limited by post-arrest myocardial dysfunction but understanding of this phenomenon is constrained by lack of data from a physiological model of disease. In this study, we established an in vivo model of cardiac arrest and resuscitation, characterized the biology of the associated myocardial dysfunction, and tested novel therapeutic strategies. Methods We developed rodent models of in vivo post-arrest myocardial dysfunction using extra-corporeal membrane oxygenation (ECMO) resuscitation followed by invasive hemodynamics measurement. In post-arrest isolated cardiomyocytes, we assessed mechanical load and Ca2+ induced Ca2+ release (CICR) simultaneously using the micro-carbon-fiber technique and observed reduced function and myofilament calcium sensitivity. We used a novel-designed fiber optic catheter imaging system, and a genetically encoded calcium sensor GCaMP6f, to image CICR in vivo. Results We found potentiation of CICR in isolated cells from this ECMO model and also in cells isolated from an ischemia-reperfusion Langendorff model perfused with oxygenated blood from an arrested animal, but not when reperfused in saline. We established that CICR potentiation begins in vivo. The augmented CICR observed post-arrest was mediated by the activation of Ca2+/calmodulin kinase II (CaMKII). Increased phosphorylation of CaMKII, phospholamban and ryanodine receptor 2 (RyR2) was detected in the post-arrest period. Exogenous adrenergic activation in vivo recapitulated Ca2+ potentiation but was associated with lesser CaMKII activation. Since oxidative stress and aldehydic adduct formation were high post arrest, we tested a small molecule activator of aldehyde dehydrogenase type 2, Alda-1, which reduced oxidative stress, restored calcium and CaMKII homeostasis, and improved cardiac function and post-arrest outcome in vivo. Conclusions Cardiac arrest and reperfusion lead to CaMKII activation and calcium long-term potentiation

  14. Long-term human-robot interaction with young users

    NARCIS (Netherlands)

    Baxter, P.; Belpaeme, T.; Canamero, L.; Cosi, P.; Demiris, Y.; Enescu, V.; Et al.

    2011-01-01

    Artificial companion agents have the potential to combine novel means for effective health communication with young patients support and entertainment. However, the theory and practice of long-term child-robot interaction is currently an underdeveloped area of research. This paper introduces an

  15. Going Solar Yields Long-Term Economical, Educational Benefits

    Science.gov (United States)

    von Moos, Brian

    2009-01-01

    Going solar is not an easy decision, but a long-term investment with a potentially substantial up-front cost. While some schools have enough capital in reserve, can raise bond money, or can solicit sufficient donations, many schools rely on creative financial programs to make a solar energy system economically feasible. Thinking about going solar…

  16. Acute mastoiditis in children: presentation and long term consequences.

    LENUS (Irish Health Repository)

    Glynn, F

    2008-03-01

    Acute mastoiditis, a destructive bacterial infection of the mastoid bone and air cell system, is relatively uncommon today but remains a potentially serious condition. There is a lack of information in the literature regarding the long term otological problems that children may face following an episode of this condition.

  17. Dying with Dementia in Long-Term Care

    Science.gov (United States)

    Sloane, Philip D.; Zimmerman, Sheryl; Williams, Christianna S.; Hanson, Laura C.

    2008-01-01

    Purpose: To better understand the experiences and potential unmet need of persons who die in long-term care. Design and Methods: We conducted after-death interviews with staff who had cared for 422 decedents with dementia and 159 who were cognitively intact and received terminal care in U.S. nursing homes (NHs) or residential care-assisted living…

  18. The long-term consequences of anaesthetic management

    African Journals Online (AJOL)

    management might influence long-term outcomes. The distinction being made here is between the classical definition of anaesthetic complications, which is restricted to the immediate perioperative period, perhaps extending to a few days after surgery, and the potential effects of anaesthetic management on events weeks, ...

  19. Long-term prisoner in prison isolation

    Directory of Open Access Journals (Sweden)

    Karolina Grudzińska

    2013-06-01

    Full Text Available Long-term prisoner belongs to a particular category of people who are imprisoned in prisons. On the one hand in this group are often heavily demoralized people who committed the most serious crimes, on the other hand it is a group of prisoners, who should be well thought out and programmed the impact of rehabilitation. The situation of man trapped for years poses in a complicated situation not only the prisoners, but also the entire prison staff. They have to take care of the fact that the prison isolation did not cause the state in which convicts form itself in learned helplessness and lack of skills for self-planning and decision-making. In addition, planning the rehabilitation impact of long-term prisoners should not be forgotten that these prisoners in the short or the long term will return to the libertarian environment therefore, should prevent any negative effects of long-term imprisonment. This article presents the main issues related to the execution of imprisonment against long-term prisoners. It is an attempt to systematize the knowledge of this category of people living in prison isolation.

  20. Long-term follow-up study and long-term care of childhood cancer survivors

    Directory of Open Access Journals (Sweden)

    Hyeon Jin Park

    2010-04-01

    Full Text Available The number of long-term survivors is increasing in the western countries due to remarkable improvements in the treatment of childhood cancer. The long-term complications of childhood cancer survivors in these countries were brought to light by the childhood cancer survivor studies. In Korea, the 5-year survival rate of childhood cancer patients is approaching 70%; therefore, it is extremely important to undertake similar long-term follow-up studies and comprehensive long-term care for our population. On the basis of the experiences of childhood cancer survivorship care of the western countries and the current Korean status of childhood cancer survivors, long-term follow-up study and long-term care systems need to be established in Korea in the near future. This system might contribute to the improvement of the quality of life of childhood cancer survivors through effective intervention strategies.

  1. Acute rosmarinic acid treatment enhances long-term potentiation, BDNF and GluR-2 protein expression, and cell survival rate against scopolamine challenge in rat organotypic hippocampal slice cultures.

    Science.gov (United States)

    Hwang, Eun-Sang; Kim, Hyun-Bum; Choi, Ga-Young; Lee, Seok; Lee, Sung-Ok; Kim, SangSeong; Park, Ji-Ho

    2016-06-17

    Rosmarinic acid (RA) is a polyphenolic ester of caffeic acid and is commonly found in the Nepetoideae subfamily of flowering mint plants. Because RA has previously exhibited antioxidant, neuroprotective, and antidepressant-like effects, we evaluated its influences on cellular functions in neuronal cultures. To elucidate possible mechanisms of RA, we investigated the influences of acute RA administration on long-term potentiation (LTP), plasticity-related protein expression, and scopolamine-induced cell death in organotypic hippocampal slice cultures. LTP analysis in organotypic hippocampal slice cultures (OHSCs) was carried out with various ion channel blockers, such as AP5 (10 μM), CNQX (10 μM), niflumic acid (100 μM), and scopolamine (300 μM) in response to RA (1, 10 or 100 μg/mL) treatment. Protein expression and cell death assays in the presence of scopolamine were examined to observe the effects of RA. For LTP analysis, baseline field excitatory postsynaptic potentials (fEPSPs) were recorded in CA1 by a 60-channel multielectrode array (MEA) every min for 40 min before 15 min of high-frequency stimulation (HFS) to the Schaffer collaterals and commissural pathways, followed by a successive 50 min of recording. For protein expression measurements, anti-BDNF and anti-GluR2 antibodies were used for Western blotting assays in whole-hippocampal tissue homogenate. Finally, for cell death assays, OHSCs were exposed to a culture medium containing propidium iodide (PI) for 24 or 48 h, followed by the assessment of cell death by fluorescent image analysis of PI uptake. and discussion: Our results indicate that RA treatment enhances fEPSPs following HFS in CA1 synapses at 1 and 10 μg/ml RA, an effect that was inhibited by CNQX and NFA but not by AP5. RA treatment also increases the expression of BDNF and GluR-2 proteins and prevents cell death of scopolamine-exposed OHSCs. Our results suggest the possibility that rosmarinic acid can enhance neural

  2. MK-801 (Dizocilpine) Regulates Multiple Steps of Adult Hippocampal Neurogenesis and Alters Psychological Symptoms via Wnt/β-Catenin Signaling in Parkinsonian Rats.

    Science.gov (United States)

    Singh, Sonu; Mishra, Akanksha; Srivastava, Neha; Shukla, Shubha

    2017-03-15

    Adult hippocampal neurogenesis is directly involved in regulation of stress, anxiety, and depression that are commonly observed nonmotor symptoms in Parkinson's disease (PD). These symptoms do not respond to pharmacological dopamine replacement therapy. Excitotoxic damage to neuronal cells by N-methyl-d-aspartate (NMDA) receptor activation is also a major contributing factor in PD development, but whether it regulates hippocampal neurogenesis and nonmotor symptoms in PD is yet unexplored. Herein, for the first time, we studied the effect of MK-801, an NMDA receptor antagonist, on adult hippocampal neurogenesis and behavioral functions in 6-OHDA (6-hydroxydopamine) induced rat model of PD. MK-801 treatment (0.2 mg/kg, ip) increased neural stem cell (NSC) proliferation, self-renewal capacity, long-term survival, and neuronal differentiation in the hippocampus of rat model of PD. MK-801 potentially enhanced long-term survival, improved dendritic arborization of immature neurons, and reduced 6-OHDA induced neurodegeneration via maintaining the NSC pool in hippocampus, leading to decreased anxiety and depression-like phenotypes in the PD model. MK-801 inhibited glycogen synthase kinase-3β (GSK-3β) through up-regulation of Wnt-3a, which resulted in the activation of Wnt/β-catenin signaling leading to enhanced hippocampal neurogenesis in PD model. Additionally, MK-801 treatment protected the dopaminergic (DAergic) neurons in the nigrostriatal pathway and improved motor functions by increasing the expression of Nurr-1 and Pitx-3 in the PD model. Therefore, MK-801 treatment serves as a valuable tool to enhance hippocampal neurogenesis in PD, but further studies are needed to revisit the role of MK-801 in the neurodegenerative disorder before proposing a potential therapeutic candidate.

  3. Aspects of long - term intensive care

    OpenAIRE

    Picková, Jana

    2015-01-01

    My thesis deals with aspects of long-term intensive care. The goal of my thesis is to determine the basic needs of patients and family preparedness aspects of intensive home care. Other stated goals is find out the possibility of returning patients to home care and also find out what is the use of basal stimulation in long-term intensive care department. In the theoretical part of my thesis are included the chapters about definition of intensive care and home intensive care, for the full comp...

  4. Long-term home care scheduling

    DEFF Research Database (Denmark)

    Gamst, Mette; Jensen, Thomas Sejr

    In several countries, home care is provided for certain citizens living at home. The long-term home care scheduling problem is to generate work plans spanning several days such that a high quality of service is maintained and the overall cost is kept as low as possible. A solution to the problem...... provides detailed information on visits and visit times for each employee on each of the covered days. We propose a branch-and-price algorithm for the long-term home care scheduling problem. The pricing problem generates one-day plans for an employee, and the master problem merges the plans with respect...

  5. A Long-term Plan for Kalk

    DEFF Research Database (Denmark)

    2017-01-01

    In this case, the author demonstrates together with the owner-manager of KALK A/S, Mr Rasmus Jorgensen, how to use the Family Business Map to frame a constructive discussion about long-term planning. The Family Business Map is a tool for long-term planning in family firms developed by Professor...... Morten Bennedsen, INSEAD and Professor Joseph Fan, Chinese University of Hong Kong. It consists of 40 questions regarding assets in the family and roadblocks facing the family firm. The Family Business Map determines that the level of family assets in KALK is high, while the level of roadblocks is severe...

  6. F3/Contactin promotes hippocampal neurogenesis, synaptic plasticity, and memory in adult mice.

    Science.gov (United States)

    Puzzo, Daniela; Bizzoca, Antonella; Privitera, Lucia; Furnari, Dario; Giunta, Salvatore; Girolamo, Francesco; Pinto, Marco; Gennarini, Gianfranco; Palmeri, Agostino

    2013-12-01

    F3/contactin, a cell-adhesion molecule belonging to the immunoglobulin supergene family, is involved in several aspects of neural development including synapse building, maintenance and functioning. Here, we examine F3/contactin function in adult hippocampal neurogenesis, synaptic plasticity, and memory, using as a model TAG/F3 transgenic mice, where F3/contactin overexpression was induced under control of regulatory sequences from the human TAG-1 (TAX-1) gene. Transgenic mice aged 5 (M5) and 12 (M12) months exhibited an increase in hippocampal size, which correlated with positive effects on precursor proliferation and NeuN expression, these data suggesting a possible role for F3/contactin in promoting adult hippocampal neurogenesis. On the functional level, TAG/F3 mice exhibited increased CA1 long-term potentiation and improved spatial and object recognition memory, notably at 12 months of age. Interestingly, these mice showed an increased expression of the phosphorylated transcription factor CREB, which may represent the main molecular correlate of the observed morphological and functional effects. Altogether, these findings indicate for the first time that F3/contactin plays a role in promoting adult hippocampal neurogenesis and that this effect correlates with improved synaptic function and memory. Copyright © 2013 Wiley Periodicals, Inc.

  7. Paradoxical (REM) Sleep Deprivation Causes a Large and Rapidly Reversible Decrease in Long-Term Potentiation, Synaptic Transmission, Glutamate Receptor Protein Levels, and ERK/MAPK Activation in the Dorsal Hippocampus

    Science.gov (United States)

    Ravassard, Pascal; Pachoud, Bastien; Comte, Jean-Christophe; Mejia-Perez, Camila; Scoté-Blachon, Céline; Gay, Nadine; Claustrat, Bruno; Touret, Monique; Luppi, Pierre-Hervé; Salin, Paul Antoine

    2009-01-01

    Study Objectives: It has been shown that wake (W) and slow wave sleep (SWS) modulate synaptic transmission in neocortical projections. However the impact of paradoxical sleep (PS) quantities on synaptic transmission remains unknown. We examined whether PS modulated the excitatory transmission and expression of glutamate receptor subtypes and phosphorylated extracellular signal-regulated kinases (p-ERK1/2). Design: PS deprivation (PSD) was carried out with the multiple platforms method on adult male Sprague-Dawley rats. LTP, late-LTP, and synaptic transmission were studied in the dorsal and ventral hippocampus of controls, 75-h PSD and 150-min PS rebound (PSR). GluR1 and NR1 protein and mRNA expression were evaluated by western blot and real-time PCR. P-ERK1/2 level was quantified by western blot and immunohistochemistry. Measurement and Results: PSD decreased synaptic transmission and LTP selectively in dorsal CA1 and PSR rescued these deficits. PSD-induced synaptic modifications in CA1 were associated with a decrease in GluR1, NR1, and p-ERK1/2 levels in dorsal CA1 without change in GluR1 and NR1 mRNA expression. Regression analysis shows that LTP is positively correlated with both PS quantities and SWS episodes duration, whereas synaptic transmission and late-LTP are positively correlated with PS quantities and negatively correlated with SWS quantities. Conclusions: These findings unveil previously unrecognized roles of PSD on synaptic transmission and LTP in the dorsal, but not in the ventral, hippocampus. The fact that the decrease in protein expression of GluR1 and NR1 was not associated with a change in mRNA expression of these receptors suggests that a sleep-induced modulation of translational mechanisms occurs in dorsal CA1. Citation: Ravassard P; Pachoud B; Comte JC; Mejia-Perez C; Scoté-Blachon C; Gay N; Claustrat B; Touret M; Luppi PH; Salin PA. Paradoxical (REM) sleep deprivation causes a large and rapidly reversible decrease in long-term potentiation

  8. Role of the Phosphoinositide 3-Kinase-Akt-Mammalian Target of the Rapamycin Signaling Pathway in Long-Term Potentiation and Trace Fear Conditioning Memory in Rat Medial Prefrontal Cortex

    Science.gov (United States)

    Sui, Li; Wang, Jing; Li, Bao-Ming

    2008-01-01

    Phosphatidylinositol 3-kinase (PI3K) and its downstream targets, including Akt (also known as protein kinase B, PKB), mammalian target of rapamycin (mTOR), the 70-kDa ribosomal S6 kinase (p70S6k), and the eukaryotic initiation factor 4E (eIF4E)-binding protein 1 (4E-BP1), may play important roles in long-term synaptic plasticity and memory in many…

  9. Professionalism in Long-Term Care Settings

    Science.gov (United States)

    Lubinski, Rosemary

    2006-01-01

    Speech-language pathologists who serve elders in a variety of long-term care settings have a variety of professional skills and responsibilities. Fundamental to quality service is knowledge of aging and communication changes and disorders associated with this process, institutional alternatives, and the changing nature of today's elders in…

  10. Long-term maintenance needs planning.

    Science.gov (United States)

    2005-09-01

    This research contributes to Kentucky's knowledge base of long-term maintenance needs in two parts. Part I presents an estimate of the average revenue needed to maintain four categories of highway in the first fifteen years after each is built or res...

  11. Timber joints under long-term loading

    DEFF Research Database (Denmark)

    Feldborg, T.; Johansen, M.

    This report describes tests and results from stiffness and strength testing of splice joints under long-term loading. During two years of loading the spicimens were exposed to cyclically changing relative humidity. After the loading period the specimens were short-term tested. The connectors were...

  12. Long-Term Memory and Learning

    Science.gov (United States)

    Crossland, John

    2011-01-01

    The English National Curriculum Programmes of Study emphasise the importance of knowledge, understanding and skills, and teachers are well versed in structuring learning in those terms. Research outcomes into how long-term memory is stored and retrieved provide support for structuring learning in this way. Four further messages are added to the…

  13. Long term consequences of early childhood malnutrition

    NARCIS (Netherlands)

    Kinsey, B.H.; Hoddinott, J; Alderman, H.

    2006-01-01

    This paper examines the impact of pre-school malnutrition on subsequent human capital formation in rural Zimbabwe using a maternal fixed effects - instrumental variables (MFE-IV) estimator with a long term panel data set. Representations of civil war and drought shocks are used to identify

  14. Long-Term Care Services for Veterans

    Science.gov (United States)

    2017-02-14

    palliative care ,  adult day health care ,  homemaker/home health aide care ,  respite care , Long-Term Care Services for...8111A; §1785. 2 The VHA also provides dementia care ; transitional care ; health care workforce development; Geriatric Research Education, and...text (bold) = both VA and purchased community care . In addition, the VHA provides dementia care ; transitional care ; health care

  15. Long-term disability in anxiety disorders.

    Science.gov (United States)

    Hendriks, Sanne M; Spijker, Jan; Licht, Carmilla M M; Hardeveld, Florian; de Graaf, Ron; Batelaan, Neeltje M; Penninx, Brenda W J H; Beekman, Aartjan T F

    2016-07-19

    This longitudinal study aims to investigate differences in long-term disability between social anxiety disorder (SAD), panic disorder with agoraphobia (PDA), panic disorder without agoraphobia (PD), generalized anxiety disorder (GAD) and multiple anxiety disorders (multiple AD), focusing on the effects of different course trajectories (remission, recurrence and chronic course) and specific symptom dimensions (anxiety arousal and avoidance behaviour). Data were used from participants with no psychiatric diagnosis (healthy controls, n = 647) or with a current anxiety disorder (SAD, n = 191; PDA, n = 90; PD, n = 84; GAD, n = 110; multiple AD, n = 480). Severity of anxiety arousal and avoidance behaviour symptoms was measured using the Beck Anxiety Inventory and the Fear Questionnaire. The World Health Organization Disability Assessment Schedule II was used to measure disability. Long-term disability was most prevalent in participants with SAD and multiple AD, and lowest in PDA and PD. GAD had an intermediate position. Anxiety arousal and avoidance behaviour were associated with more long-term disability in anxiety disorders than course trajectories. Various anxiety disorders have different disability levels over 4 years of time, therefore diagnostic distinction is important for treatment focus. Anxiety arousal and avoidance behaviour are major predictors for long-term disability in anxiety disorders.

  16. Workshop on long-term contraceptives.

    Science.gov (United States)

    1996-01-01

    The National Population Council Secretariat (NPCS) of Ghana held a three-day workshop on long-term contraceptives in 1996 in collaboration with the Ministry of Health, the Association of Voluntary Surgical Contraception, and the Johns Hopkins Population Communication Services. The session was funded by USAID. The executive director of NPCS, Dr. Richard Turkson, said that the slow rate of contraceptive acceptance was an obstacle to population control despite political concern that rapid population growth exerted an adverse impact on the economy. Only 10% of married women were using long-term or permanent methods of contraception. The hope was voiced that the participants would devise practical and cost-effective education, information, and communication (IEC) strategies to boost the demand for long-term contraceptive methods among sexually active people in Ghana. It was essential that these strategies and activities were based on a realist assessment of the demographic and social situation of the country. The examination of case studies in cultures similar to Ghana would also offer valuable lessons. The factors that hinder the acceptance of long-term methods include misconceptions, myths, and false rumors rooted in a general lack of knowledge among the people. Participants were urged to come up with strategies to counter these problems, and service providers were encouraged to improve their knowledge about contraceptive methods and counseling skills. Male involvement in contraception was also advocated. Statistics show that most Ghanians practicing contraception were using short-term methods such as foaming tablets, pills, and condoms. However, it is necessary to shift to long-term methods such as injectables, implants, and sterilization in order to achieve significant reductions in fertility.

  17. Detrimental role of prolonged sleep deprivation on adult neurogenesis

    Directory of Open Access Journals (Sweden)

    Carina eFernandes

    2015-04-01

    Full Text Available Adult mammalian brains continuously generate new neurons, a phenomenon called neurogenesis. Both environmental stimuli and endogenous factors are important regulators of neurogenesis. Sleep has an important role in normal brain physiology and its disturbance causes very stressful conditions, which disrupt normal brain physiology. Recently, an influence of sleep in adult neurogenesis has been established, mainly based on sleep deprivation studies. This review provides an overview on how rhythms and sleep cycles regulate hippocampal and subventricular zone neurogenesis, discussing some potential underlying mechanisms. In addition, our review highlights some interacting points between sleep and neurogenesis in brain function, such as learning, memory and mood states, and provides some insights on the effects of antidepressants and hypnotic drugs on neurogenesis.

  18. Adult hippocampal neurogenesis and its role in Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Mu Yangling

    2011-12-01

    Full Text Available Abstract The hippocampus, a brain area critical for learning and memory, is especially vulnerable to damage at early stages of Alzheimer's disease (AD. Emerging evidence has indicated that altered neurogenesis in the adult hippocampus represents an early critical event in the course of AD. Although causal links have not been established, a variety of key molecules involved in AD pathogenesis have been shown to impact new neuron generation, either positively or negatively. From a functional point of view, hippocampal neurogenesis plays an important role in structural plasticity and network maintenance. Therefore, dysfunctional neurogenesis resulting from early subtle disease manifestations may in turn exacerbate neuronal vulnerability to AD and contribute to memory impairment, whereas enhanced neurogenesis may be a compensatory response and represent an endogenous brain repair mechanism. Here we review recent findings on alterations of neurogenesis associated with pathogenesis of AD, and we discuss the potential of neurogenesis-based diagnostics and therapeutic strategies for AD.

  19. Detrimental role of prolonged sleep deprivation on adult neurogenesis

    Science.gov (United States)

    Fernandes, Carina; Rocha, Nuno Barbosa F.; Rocha, Susana; Herrera-Solís, Andrea; Salas-Pacheco, José; García-García, Fabio; Murillo-Rodríguez, Eric; Yuan, Ti-Fei; Machado, Sergio; Arias-Carrión, Oscar

    2015-01-01

    Adult mammalian brains continuously generate new neurons, a phenomenon called adult neurogenesis. Both environmental stimuli and endogenous factors are important regulators of adult neurogenesis. Sleep has an important role in normal brain physiology and its disturbance causes very stressful conditions, which disrupt normal brain physiology. Recently, an influence of sleep in adult neurogenesis has been established, mainly based on sleep deprivation studies. This review provides an overview on how rhythms and sleep cycles regulate hippocampal and subventricular zone neurogenesis, discussing some potential underlying mechanisms. In addition, our review highlights some interacting points between sleep and adult neurogenesis in brain function, such as learning, memory, and mood states, and provides some insights on the effects of antidepressants and hypnotic drugs on adult neurogenesis. PMID:25926773

  20. Detrimental role of prolonged sleep deprivation on adult neurogenesis.

    Science.gov (United States)

    Fernandes, Carina; Rocha, Nuno Barbosa F; Rocha, Susana; Herrera-Solís, Andrea; Salas-Pacheco, José; García-García, Fabio; Murillo-Rodríguez, Eric; Yuan, Ti-Fei; Machado, Sergio; Arias-Carrión, Oscar

    2015-01-01

    Adult mammalian brains continuously generate new neurons, a phenomenon called adult neurogenesis. Both environmental stimuli and endogenous factors are important regulators of adult neurogenesis. Sleep has an important role in normal brain physiology and its disturbance causes very stressful conditions, which disrupt normal brain physiology. Recently, an influence of sleep in adult neurogenesis has been established, mainly based on sleep deprivation studies. This review provides an overview on how rhythms and sleep cycles regulate hippocampal and subventricular zone neurogenesis, discussing some potential underlying mechanisms. In addition, our review highlights some interacting points between sleep and adult neurogenesis in brain function, such as learning, memory, and mood states, and provides some insights on the effects of antidepressants and hypnotic drugs on adult neurogenesis.

  1. Neurogenesis in the adult peripheral nervous system☆

    Science.gov (United States)

    Czaja, Krzysztof; Fornaro, Michele; Geuna, Stefano

    2012-01-01

    Most researchers believe that neurogenesis in mature mammals is restricted only to the subgranular zone of the dentate gyrus and the subventricular zone of the lateral ventricle in the central nervous system. In the peripheral nervous system, neurogenesis is thought to be active only during prenatal development, with the exception of the olfactory neuroepithelium. However, sensory ganglia in the adult peripheral nervous system have been reported to contain precursor cells that can proliferate in vitro and be induced to differentiate into neurons. The occurrence of insult-induced neurogenesis, which has been reported by several investigators in the brain, is limited to a few recent reports for the peripheral nervous system. These reports suggest that damage to the adult nervous system induces mechanisms similar to those that control the generation of new neurons during prenatal development. Understanding conditions under which neurogenesis can be induced in physiologically non-neurogenic regions in adults is one of the major challenges for developing therapeutic strategies to repair neurological damage. However, the induced neurogenesis in the peripheral nervous system is still largely unexplored. This review presents the history of research on adult neurogenesis in the peripheral nervous system, which dates back more than 100 years and reveals the evidence on the under estimated potential for generation of new neurons in the adult peripheral nervous system. PMID:25722694

  2. Long-term Outcomes Following Syme's Amputation.

    Science.gov (United States)

    Finkler, Elissa S; Marchwiany, Daniel A; Schiff, Adam P; Pinzur, Michael S

    2017-07-01

    The metabolic cost of walking after Syme's ankle disarticulation amputation is minimally more than that for nonamputation. The ability to end weightbearing makes prosthetic fitting relatively simple, and very few patients require extensive rehabilitation or placement in a skilled nursing or rehabilitation facility. In spite of these potential benefits, there is a paucity of objective information on the actual long-term outcomes. Fifty-one patients were identified who underwent single-stage Syme's ankle disarticulation amputation with excision of the lateral and medial malleoli by a single surgeon during a 23-year period. None of these patients had sufficient tissue to allow amputation at the transmetatarsal or tarsometatarsal levels. Thirty-three underwent amputation due to a diabetic forefoot infection, 11 secondary to a crush injury, 3 for a nondiabetic infection, 3 for a noncorrectable acquired deformity, and 1 for neoplasm. The average age at surgery for the diabetic patients was 62.1 years (range, 36-81 years), with an average follow-up of 6.8 years (range, 4.0-11.6 years). The nondiabetic patients had an average age of 37.8 years (range, 21-65 years), with an average follow-up of 9.3 years (range, 2.2-25.0 years). Patients who were alive and could be contacted were invited to complete the Short Musculoskeletal Function Assessment (SMFA) questionnaire that was scored for functional, mobility, and bothersome indices. Seventeen of the 33 diabetic patients died. Four (12.1%) were converted to transtibial amputation. One of the nondiabetic patients died, and 1 (5.5%) was converted to transtibial amputation. Eleven of the 33 patients who were contacted completed the SMFA. All of these patients demonstrated favorable outcome scores in the mobility, functional, and bothersome indices (average mobility index of 17.2, functional index of 14.7, and bothersome index of 16.7 for nondiabetic patients compared to 34.7, 29.9, and 30.6 for diabetic patients, respectively

  3. Simulation of a Potential CO2 Storage in the West Paris Basin: Site Characterization and Assessment of the Long-Term Hydrodynamical and Geochemical Impacts Induced by the CO2 Injection

    Directory of Open Access Journals (Sweden)

    Estublier Audrey

    2017-07-01

    Full Text Available This article presents the preliminary results of a study carried out as part of a demonstration project of CO2 storage in the Paris Basin. This project funded by ADEME (French Environment and Energy Management Agency and several industrial partners (TOTAL, ENGIE, EDF, Lafarge, Air Liquide, Vallourec aimed to study the possibility to set up an experimental infrastructure of CO2 transport and storage. Regarding the storage, the objectives were: (1 to characterize the selected site by optimizing the number of wells in a CO2 injection case of 200 Mt over 50 years in the Trias, (2 to simulate over time the CO2 migration and the induced pressure field, and (3 to analyze the geochemical behavior of the rock over the long term (1,000 years. The preliminary site characterization study revealed that only the southern area of Keuper succeeds to satisfy this injection criterion using only four injectors. However, a complementary study based on a refined fluid flow model with additional secondary faults concluded that this zone presents the highest potential of CO2 injection but without reaching the objective of 200 Mt with a reasonable number of wells. The simulation of the base scenario, carried out before the model refinement, showed that the overpressure above 0.1 MPa covers an area of 51,869 km2 in the Chaunoy formation, 1,000 years after the end of the injection, which corresponds to the whole West Paris Basin, whereas the CO2 plume extension remains small (524 km2. This overpressure causes brine flows at the domain boundaries and a local overpressure in the studied oil fields. Regarding the preliminary risk analysis of this project, the geochemical effects induced by the CO2 injection were studied by simulating the fluid-rock interactions with a coupled geochemical and fluid flow model in a domain limited to the storage complex. A one-way coupling of two models based on two domains fitting into each other was developed using dynamic boundary

  4. Globalization, women's migration, and the long-term-care workforce.

    Science.gov (United States)

    Browne, Colette V; Braun, Kathryn L

    2008-02-01

    With the aging of the world's population comes the rising need for qualified direct long-term-care (DLTC) workers (i.e., those who provide personal care to frail and disabled older adults). Developed nations are increasingly turning to immigrant women to fill these needs. In this article, we examine the impact of three global trends-population aging, globalization, and women's migration-on the supply and demand for DLTC workers in the United States. Following an overview of these trends, we identify three areas with embedded social justice issues that are shaping the DLTC workforce in the United States, with a specific focus on immigrant workers in these settings. These include world poverty and economic inequalities, the feminization and colorization of labor (especially in long-term care), and empowerment and women's rights. We conclude with a discussion of the contradictory effects that both population aging and globalization have on immigrant women, source countries, and the long-term-care workforce in the United States. We raise a number of policy, practice, and research implications and questions. For policy makers and long-term-care administrators in receiver nations such as the United States, the meeting of DLTC worker needs with immigrants may result in greater access to needed employees but also in the continued devaluation of eldercare as a profession. Source (supply) nations must balance the real and potential economic benefits of remittances from women who migrate for labor with the negative consequences of disrupting family care traditions and draining the long-term-care workforce of those countries.

  5. Long-term prevention of diabetic nephropathy

    DEFF Research Database (Denmark)

    Schjoedt, K J; Hansen, H P; Tarnow, L

    2008-01-01

    . Glycaemic control and blood pressure remained nearly unchanged. CONCLUSIONS/INTERPRETATION: In our outpatient clinic, the implementation of RAAS-blocking treatment in type 1 diabetic patients with microalbuminuria successfully reduced long-term progression to overt DN to a rate similar to those previously......AIMS/HYPOTHESIS: In type 1 diabetic patients with microalbuminuria not receiving antihypertensive treatment, an increase in urinary AER (UAER) of 6-14%/year and a risk of developing diabetic nephropathy (DN) of 3-30%/year have been reported. We audited the long-term effect of blocking the renin......-angiotensin-aldosterone system (RAAS) with an ACE inhibitor (ACEI) or angiotensin II receptor blocker (ARB) in microalbuminuric type 1 diabetic patients on progression of microalbuminuria and development of DN. METHODS: All patients with type 1 diabetes and persistent microalbuminuria (30-300 mg/24 h) were identified (n=227...

  6. Long-term opioid therapy in Denmark

    DEFF Research Database (Denmark)

    Birke, H; Ekholm, Ola; Sjøgren, P

    2017-01-01

    BACKGROUND: Longitudinal population-based studies of long-term opioid therapy (L-TOT) in chronic non-cancer pain (CNCP) patients are sparse. Our study investigated incidence and predictors for initiating L-TOT and changes in self-rated health, pain interference and physical activities in long......-term opioid users. METHODS: Data were obtained from the national representative Danish Health and Morbidity Surveys and The Danish National Prescription Registry. Respondents with no dispensed opioids the year before the survey were followed from 2000 and from 2005 until the end of 2012 (n = 12...... defined as those who were dispensed at least one opioid prescription in six separate months within a year. RESULTS: The incidence of L-TOT was substantially higher in CNCP patients at baseline than in others (9/1000 vs. 2/1000 person-years). Smoking behaviour and dispensed benzodiazepines were...

  7. Learning A Physical Long-term Predictor

    OpenAIRE

    Ehrhardt, Sebastien; Monszpart, Aron; Mitra, Niloy J.; Vedaldi, Andrea

    2017-01-01

    Evolution has resulted in highly developed abilities in many natural intelligences to quickly and accurately predict mechanical phenomena. Humans have successfully developed laws of physics to abstract and model such mechanical phenomena. In the context of artificial intelligence, a recent line of work has focused on estimating physical parameters based on sensory data and use them in physical simulators to make long-term predictions. In contrast, we investigate the effectiveness of a single ...

  8. Long-term course of opioid addiction.

    Science.gov (United States)

    Hser, Yih-Ing; Evans, Elizabeth; Grella, Christine; Ling, Walter; Anglin, Douglas

    2015-01-01

    Opioid addiction is associated with excess mortality, morbidities, and other adverse conditions. Guided by a life-course framework, we review the literature on the long-term course of opioid addiction in terms of use trajectories, transitions, and turning points, as well as other factors that facilitate recovery from addiction. Most long-term follow-up studies are based on heroin addicts recruited from treatment settings (mostly methadone maintenance treatment), many of whom are referred by the criminal justice system. Cumulative evidence indicates that opioid addiction is a chronic disorder with frequent relapses. Longer treatment retention is associated with a greater likelihood of abstinence, whereas incarceration is negatively related to subsequent abstinence. Over the long term, the mortality rate of opioid addicts (overdose being the most common cause) is about 6 to 20 times greater than that of the general population; among those who remain alive, the prevalence of stable abstinence from opioid use is low (less than 30% after 10-30 years of observation), and many continue to use alcohol and other drugs after ceasing to use opioids. Histories of sexual or physical abuse and comorbid mental disorders are associated with the persistence of opioid use, whereas family and social support, as well as employment, facilitates recovery. Maintaining opioid abstinence for at least five years substantially increases the likelihood of future stable abstinence. Recent advances in pharmacological treatment options (buprenorphine and naltrexone) include depot formulations offering longer duration of medication; their impact on the long-term course of opioid addiction remains to be assessed.

  9. Long term evolution 4G and beyond

    CERN Document Server

    Yacoub, Michel; Figueiredo, Fabrício; Tronco, Tania

    2016-01-01

    This book focus on Long Term Evolution (LTE) and beyond. The chapters describe different aspects of research and development in LTE, LTE-Advanced (4G systems) and LTE-450 MHz such as telecommunications regulatory framework, voice over LTE, link adaptation, power control, interference mitigation mechanisms, performance evaluation for different types of antennas, cognitive mesh network, integration of LTE network and satellite, test environment, power amplifiers and so on. It is useful for researchers in the field of mobile communications.

  10. Long-Term Hearing Results After Ossiculoplasty.

    Science.gov (United States)

    Cox, Matthew D; Trinidade, Aaron; Russell, James Shep; Dornhoffer, John L

    2017-04-01

    To determine if the OOPS index is predictive of long-term hearing results after ossiculoplasty. Case series with retrospective chart review. Tertiary care otology practice. Adult and pediatric patients (3-88 years of age). Ossiculoplasty with cartilage tympanoplasty, with or without mastoidectomy. Primary outcome measures included short-term hearing results (pure-tone average air-bone gap [PTA-ABG] measured between 60 days and 1 year after surgery), long-term hearing results (PTA-ABG measured ≥5 years after surgery), and the rate of successful ABG closure to ≤20 dB. Secondary measures included the need for revision surgery, delayed tympanic membrane graft failure, worsening conductive hearing loss (after an initially satisfactory hearing result), and recurrence of cholesteatoma. There was no significant difference between adults and children for short-term hearing results (average post-op PTA-ABG was 18.9 dB vs. 19.8 dB, respectively; p = 0.544), long-term hearing results (average final PTA-ABG was 19.3 dB vs. 19.4 dB, respectively; p = 0.922), or rate of ABG closure to less than 20 dB (63.1% vs. 58.0%, p = 0.282). Spearman's rank-order correlation (ρ) identified a strong positive correlation between OOPS index score and average post-operative PTA-ABG (ρ = 0.983; p hearing outcomes in adult and pediatric patients undergoing ossiculoplasty in both the short term and the long term.

  11. Timber joints under long-term loading

    DEFF Research Database (Denmark)

    Feldborg, T.; Johansen, M.

    This report describes tests and results from stiffness and strength testing of splice joints under long-term loading. During two years of loading the spicimens were exposed to cyclically changing relative humidity. After the loading period the specimens were short-term tested. The connectors were...... integral nail-plates and nailed steel and plywood gussets. The report is intended for designers and researchers in timber engineering....

  12. Long-Term Trends in World Politics

    Directory of Open Access Journals (Sweden)

    George Modelski

    2015-08-01

    Full Text Available A revisit, and an extension, of the paper “From Leadership to Organization: The Evolution of Global Politics,” originally presented at the University of Zurich in 1993. Three long-term processes: the evolution of global politics (or political globalization; the rise and decline of world powers (the long cycle of global politics; and the emergence of the world system, have been reviewed and updated.

  13. National Security Implications of Long-Term Deficit Spending

    Science.gov (United States)

    2010-02-01

    debate , it is evident that many Americans do not appreciate the long-term ramifications of the national debt problem, either in terms of impacts on... debate on the roles of the state in the economic and social life of the nation.”19 Financing the Debt Otherwise, we live beyond our means and are...increasingly precarious fiscal situation can be characterized as a failure of leadership . Without doubt, it is far better to “avert a potential

  14. The Reintegration of Military Families Following Long Term Separation

    Science.gov (United States)

    2005-05-01

    again during reunion most dramatically lead to successful reintegration and what leads to negative outcomes such as domestic violence or divorce...best as possible to adapt to separation and reunion. Potentially, programs can be developed that foster traits associated with successful reintegration ...reunifies, it must be discovered what successful reintegration is for AF families after they experienced a long-term separation. Since single parenting

  15. 47 CFR 54.303 - Long term support.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 3 2010-10-01 2010-10-01 false Long term support. 54.303 Section 54.303... SERVICE Universal Service Support for High Cost Areas § 54.303 Long term support. (a) Beginning January 1... shall receive Long Term Support. Beginning July 1, 2004, no carrier shall receive Long Term Support. (b...

  16. Health in the long-term unemployed.

    Science.gov (United States)

    Herbig, Britta; Dragano, Nico; Angerer, Peter

    2013-06-01

    Although the unemployment rate in Germany is currently low, more than a million persons in the country have been out of work for more than a year. In this review article, we address these persons' state of health, the effect of unemployment on health, and the influence of macroeconomic factors and social policy. This article is based on a selective review of pertinent literature in the PubMed database. Large-scale meta-analyses and systematic reviews have shown that the long-term unemployed have an at least twofold risk of mental illness, particularly depression and anxiety disorders, compared to employed persons. Their mortality is 1.6-fold higher. Unemployment seems to be not only an effect of illness, but also a cause of it (i.e., there is evidence for both selection and causality). Learned helplessness is an important psychological explanatory model. Limited evidence indicates that the long-term unemployed have a moderately elevated prevalence of alcoholism; unemployment can be both an effect and a cause of alcoholism. Unemployment also seems to be associated with higher risks of heart attack and stroke. Cancer can lead to loss of employment. The link between unemployment and poorer health is strengthened by macroeconomic crises and weakened by governmental social interventions. The long-term unemployed carry a markedly higher burden of disease, particularly mental illness, than employed persons and those who are unemployed only for a short time. The burden of disease increases with the duration of unemployment. The vicious circle of unemployment and disease can be broken only by the combined effects of generally available health care, special health-promoting measures among the unemployed, and social interventions.

  17. Long-term EARLINET dust observations

    Science.gov (United States)

    Mona, Lucia; Amiridis, Vassilis; Amodeo, Aldo; Binietoglou, Ioannis; D'Amico, Giuseppe; Schwarz, Anja; Papagiannopoulos, Nikolaos; Papayannis, Alexandros; Sicard, Michael; Comeron, Adolfo; Pappalardo, Gelsomina

    2015-04-01

    Systematic observations of Saharan dust events over Europe are performed from May 2000 by EARLINET, the European Aerosol Research LIdar NETwork. EARLINET is a coordinated network of stations that make use of advanced lidar methods for the vertical profiling of aerosols. The backbone of EARLINET network is a common schedule for performing the measurements and the quality assurance of instruments/data. Particular attention is paid to monitoring the Saharan dust intrusions over the European continent. The geographical distribution of the EARLINET stations is particularly appealing for the dust observation, with stations located all around the Mediterranean and in the center of the Mediterranean (Italian stations) where dust intrusions are frequent, and with several stations in the central Europe where dust penetrates occasionally. All aerosol backscatter and extinction profiles related to observations collected during these alerts are grouped in the devoted "Saharan dust" category of the EARLINET database. This category consists of about 4700 files (as of December 2013). Case studies involving several stations around Europe selected from this long-term database have been provided the opportunity to investigate dust modification processes during transport over the continent. More important, the long term EARLINET dust monitoring allows the investigation of the horizontal and vertical extent of dust outbreaks over Europe and the climatological analysis of dust optical intensive and extensive properties at continental scale. This long-term database is also a unique tool for a systematic comparison with dust model outputs and satellite-derived dust products. Because of the relevance for both dust modeling and satellite retrievals improvement, results about desert dust layers extensive properties as a function of season and source regions are investigated and will be presented at the conference. First comparisons with models outputs and CALIPSO dust products will be

  18. Long-Term Recency in Anterograde Amnesia

    Science.gov (United States)

    Talmi, Deborah; Caplan, Jeremy B.; Richards, Brian; Moscovitch, Morris

    2015-01-01

    Amnesia is usually described as an impairment of a long-term memory (LTM) despite an intact short-term memory (STM). The intact recency effect in amnesia had supported this view. Although dual-store models of memory have been challenged by single-store models based on interference theory, this had relatively little influence on our understanding and treatment of amnesia, perhaps because the debate has centred on experiments in the neurologically intact population. Here we tested a key prediction of single-store models for free recall in amnesia: that people with amnesia will exhibit a memory advantage for the most recent items even when all items are stored in and retrieved from LTM, an effect called long-term recency. People with amnesia and matched controls studied, and then free-recalled, word lists with a distractor task following each word, including the last (continual distractor task, CDFR). This condition was compared to an Immediate Free Recall (IFR, no distractors) and a Delayed Free Recall (DFR, end-of-list distractor only) condition. People with amnesia demonstrated the full long-term recency pattern: the recency effect was attenuated in DFR and returned in CDFR. The advantage of recency over midlist items in CDFR was comparable to that of controls, confirming a key prediction of single-store models. Memory deficits appeared only after the first word recalled in each list, suggesting the impairment in amnesia may emerge only as the participant’s recall sequence develops, perhaps due to increased susceptibility to output interference. Our findings suggest that interference mechanisms are preserved in amnesia despite the overall impairment to LTM, and challenge strict dual-store models of memory and their dominance in explaining amnesia. We discuss the implication of our findings for rehabilitation. PMID:26046770

  19. Long-Term Scenario of International Developments

    Directory of Open Access Journals (Sweden)

    Alexey I. Podberezkin

    2015-01-01

    Full Text Available This paper proposes an approach to long-term scenario building in international relations, based on the analysis of changes in the dialectics of war and peace. Long-term trends in the development of forms and manifestations of violence in international relations, as well as the methods and approaches to its control and management determines the development of international relations. In solving the methodological problem of long-term forecasting, it must be as-sumed that the mere mechanical extrapolation even in the medium term has no meaning. The key current trend in terms of political violence is a blurring of the distinction between war and peace. This trend can be described as networking of war. Network war theory is a model of military strategy in the context of postmodernism. As a model of the new economy based on information and high technologies demonstrates its superiority over traditional capitalist and socialist models of the industrial age, and network war claims qualitative superiority over previous strategic concept of the industrial era. In modern political networks violent and non-violent instruments of influence co-exist in undifferentiated form. Network politics becomes total. Victory in the network war is the fact that the opponent should become part of the network. Since the network is formed around shared values, the network war can be reduced to a war of values. The clash between the networks will most likely wear un-compromising nature, so that in the end there will be only one network. Uncompromising network war is like the uncompromising religious wars and clashes of civilizations.

  20. Long-term EEG in children.

    Science.gov (United States)

    Montavont, A; Kaminska, A; Soufflet, C; Taussig, D

    2015-03-01

    Long-term video-EEG corresponds to a recording ranging from 1 to 24 h or even longer. It is indicated in the following situations: diagnosis of epileptic syndromes or unclassified epilepsy, pre-surgical evaluation for drug-resistant epilepsy, follow-up of epilepsy or in cases of paroxysmal symptoms whose etiology remains uncertain. There are some specificities related to paediatric care: a dedicated pediatric unit; continuous monitoring covering at least a full 24-hour period, especially in the context of pre-surgical evaluation; the requirement of presence by the parents, technician or nurse; and stronger attachment of electrodes (cup electrodes), the number of which is adapted to the age of the child. The chosen duration of the monitoring also depends on the frequency of seizures or paroxysmal events. The polygraphy must be adapted to the type and topography of movements. It is essential to have at least an electrocardiography (ECG) channel, respiratory sensor and electromyography (EMG) on both deltoids. There is no age limit for performing long-term video-EEG even in newborns and infants; nevertheless because of scalp fragility, strict surveillance of the baby's skin condition is required. In the specific context of pre-surgical evaluation, long-term video-EEG must record all types of seizures observed in the child. This monitoring is essential in order to develop hypotheses regarding the seizure onset zone, based on electroclinical correlations, which should be adapted to the child's age and the psychomotor development. Copyright © 2015. Published by Elsevier SAS.

  1. Cranial Radiation Therapy and Damage to Hippocampal Neurogenesis

    Science.gov (United States)

    Monje, Michelle

    2008-01-01

    Cranial radiation therapy is associated with a progressive decline in cognitive function, prominently memory function. Impairment of hippocampal neurogenesis is thought to be an important mechanism underlying this cognitive decline. Recent work has elucidated the mechanisms of radiation-induced failure of neurogenesis. Potential therapeutic…

  2. The long term stability of lidar calibrations

    DEFF Research Database (Denmark)

    Courtney, Michael; Gayle Nygaard, Nicolai

    Wind lidars are now used extensively for wind resource measurements. One of the requirements for the data to be accepted in support of project financing (so-called ‘banka-bility’) is to demonstrate the long-term stability of lidar cali-brations. Calibration results for six Leosphere WindCube li-dars......-ters pertaining in the different calibration periods. This is supported by sliding-window analyses of one lidar at one location where the same order of variation is observed as between pre-service and post-service calibrations....

  3. Transverse dimension and long-term stability.

    Science.gov (United States)

    Vanarsdall, R L

    1999-09-01

    This article emphasizes the critical importance of the skeletal differential between the width of the maxilla and the width of the mandible. Undiagnosed transverse discrepancy leads to adverse periodontal response, unstable dental camouflage, and less than optimal dentofacial esthetics. Hundreds of adult retreatment patients corrected for significant maxillary transverse deficiency using surgically assisted maxillary expansion (similar to osseous distraction) has produced excellent stability. Eliciting tooth movement for children (orthopedics, lip bumper, Cetlin plate) in all three planes of space by muscles, eruption, and growth, develops the broader arch form (without the mechanical forces of fixed or removable appliances) and has also demonstrated impressive long term stability.

  4. Long-term population studies of seabirds.

    Science.gov (United States)

    Wooller, R D; Bradley, J S; Croxall, J P

    1992-04-01

    Long-term studies of seabirds, some now 30-40 years old, have begun to reveal significant age-related changes in the survival and reproduction o f these long-lived animals. Evidence for density-dependent regulation of seabird numbers, however, remains sparse whereas unpredictable, disastrous breeding years may be an important influence. Critical evaluation will require better data on (1) the extent of movements of seabirds between colonies, (2) the characteristics of those individuals that contribute disproportionately to the next generation, and (3) the importance of year and/or cohort effects on population processes. Copyright © 1992. Published by Elsevier Ltd.

  5. Long Term Planning at IQ Metal

    DEFF Research Database (Denmark)

    2017-01-01

    This is a Danish version. This case about long term planning at the owner-managed manufacturing firm IQ Metal shows how the future management and ownership may be organized to utilize owner assets and minimize roadblocks. Initially, the owner-manager Bo Fischer Larsen explains how he acquired...... in The Owner Strategy Map into the questionnaire available on www.ejerstrategi-kortet.dk. Lastly, the Owner Strategy Map's recommendation of how to organize the future management and ownership of IQ Metal is explained....

  6. Terminating a long-term clinical trial.

    Science.gov (United States)

    Klimt, C R

    1981-05-01

    Long-term clinical trials often include more than one active treatment group. These may be discontinued independently if found to be ineffective or possibly harmful. Certain subgroups of patients may be discovered, in the course of a clinical trial, who do not respond satisfactorily and are, therefore, excluded during the course of a trial. Yet another kind of termination comes when we have a therapeutic breakthrough or when hope has to be abandoned for demonstrating beneficial effects for one, several, or all treatments included in a trial. Examples from the authors' experience are presented, as are successful and unsuccessful techniques in managing terminations of various types.

  7. Long-Term Monitoring Research Needs: A DOE Perspective

    Science.gov (United States)

    Moore, B.; Davis, C. B.

    2002-05-01

    critically on the validity and uncertainty in models used to predict contaminant fate and transport. This is an area of active research at the present time. We survey joint research initiatives in this area involving DOE along with USGS, U.S. EPA, U.S. NRC, and U.S. DOA and non-Federal collaborators, and explore their potential for furthering DOE long-term monitoring needs and objectives.

  8. Long-term ecological research in a human-dominated world

    Science.gov (United States)

    G. Philip Robertson; Scott L. Collins; David R. Foster; Nicholas Brokaw; Hugh W. Ducklow; Ted L. Gragson; Corinna Gries; Stephen K. Hamilton; A. David McGuire; John C. Moore; Emily H. Stanley; Robert B. Waide; Mark W. Williams

    2012-01-01

    The US Long Term Ecological Research (LTER) Network enters its fourth decade with a distinguished record of achievement in ecological science. The value of long-term observations and experiments has never been more important for testing ecological theory and for addressing today’s most difficult environmental challenges. The network’s potential for tackling emergent...

  9. Institutionalization and Organizational Long-term Success

    Directory of Open Access Journals (Sweden)

    Denise L. Fleck

    2007-05-01

    Full Text Available Institutionalization processes have an ambivalent effect on organizational long-term success. Even though they foster organizational stability and permanence, they also bring about rigidity and resistance to change. As a result, successful organizations are likely to lose their competitive advantage over time. The paper addresses this issue through the investigation of the institutionalization processes of two long-lived companies: General Electric, a firm that has been a long-term success and its rival, Westinghouse, which was broken up after eleven decades of existence. The longitudinal, multilevel analysis of firms and industry has identified two different modes of organizational institutionalization. The reactive mode gives rise to rigidity and change resistance, much like institutional theory predicts; the proactive mode, on the other hand, neutralizes those negative effects of institutionalization processes. In the reactive mode, structure predominates. In the proactive mode, agency plays a major role in organizational institutionalization, and in managing the organization’s relations with the environment, clearly contributing to environmental institutionalization.

  10. Sleep facilitates long-term face adaptation.

    Science.gov (United States)

    Ditye, Thomas; Javadi, Amir Homayoun; Carbon, Claus-Christian; Walsh, Vincent

    2013-10-22

    Adaptation is an automatic neural mechanism supporting the optimization of visual processing on the basis of previous experiences. While the short-term effects of adaptation on behaviour and physiology have been studied extensively, perceptual long-term changes associated with adaptation are still poorly understood. Here, we show that the integration of adaptation-dependent long-term shifts in neural function is facilitated by sleep. Perceptual shifts induced by adaptation to a distorted image of a famous person were larger in a group of participants who had slept (experiment 1) or merely napped for 90 min (experiment 2) during the interval between adaptation and test compared with controls who stayed awake. Participants' individual rapid eye movement sleep duration predicted the size of post-sleep behavioural adaptation effects. Our data suggest that sleep prevented decay of adaptation in a way that is qualitatively different from the effects of reduced visual interference known as 'storage'. In the light of the well-established link between sleep and memory consolidation, our findings link the perceptual mechanisms of sensory adaptation--which are usually not considered to play a relevant role in mnemonic processes--with learning and memory, and at the same time reveal a new function of sleep in cognition.

  11. Long-term environmental behaviour of radionuclides

    Energy Technology Data Exchange (ETDEWEB)

    Brechignac, F.; Moberg, L.; Suomela, M

    2000-04-01

    The radioactive pollution of the environment results from the atmospheric nuclear weapons testing (during the mid-years of twentieth century), from the development of the civilian nuclear industry and from accidents such as Chernobyl. Assessing the resulting radiation that humans might receive requires a good understanding of the long-term behaviour of radionuclides in the environment. This document reports on a joint European effort to advance this understanding, 3 multinational projects have been coordinated: PEACE, EPORA and LANDSCAPE. This report proposes an overview of the results obtained and they are presented in 6 different themes: (i) redistribution in the soil-plant system, (ii) modelling, (iii) countermeasures, (iv) runoff (v) spatial variations, and (vi) dose assessment. The long term behaviour of the radionuclides {sup 137}Cs, {sup 90}Sr and {sup 239-240}Pu is studied through various approaches, these approaches range from in-situ experiments designed to exploit past contamination events to laboratory simulations. A broad scope of different ecosystems ranging from arctic and boreal regions down to mediterranean ones has been considered. (A.C.)

  12. Linking adult olfactory neurogenesis to social behavior

    Directory of Open Access Journals (Sweden)

    Claudia E Feierstein

    2012-11-01

    Full Text Available In the adult brain, new neurons are added to two brain areas: the olfactory bulb and the hippocampus. Newly-generated neurons integrate into the preexisting circuits, bringing a set of unique properties, such as increased plasticity and responsiveness to stimuli. However, the functional implications of the constant addition of these neurons remain unclear, although they are believed to be important for learning and memory. The levels of neurogenesis are regulated by a variety of environmental factors, as well as during learning, suggesting that new neurons could be important for coping with changing environmental demands. Notably, neurogenesis has been shown to be physiologically regulated in relation to reproductive behavior: neurogenesis increases in female mice upon exposure to cues of the mating partners, during pregnancy and lactation, and in male mice upon exposure to their offspring. In this scenario, and because of the key contribution of olfaction to maternal behavior, we sought to investigate the contribution of adult-generated neurons in the olfactory system to maternal behavior and offspring recognition. To do so, we selectively disrupted neurogenesis in the olfactory pathway of female mice using focal irradiation. Disruption of adult neurogenesis in the olfactory bulb did not affect maternal behavior, or the ability of female mice to discriminate familiar from unfamiliar pups. However, reduction of olfactory neurogenesis resulted in abnormal social interaction of female mice, specifically with male conspecifics. Because the olfactory system is crucial for sex recognition, we suggest that the abnormal interaction with males could result from the inability to detect or discriminate male-specific odors and could therefore have implications for the recognition of potential mating partners. Here, I review the results of this and other studies, and discuss their implications for our understanding of the function of adult neurogenesis.

  13. Long-term outcomes of thalidomide in refractory Crohn's disease.

    Science.gov (United States)

    Gerich, M E; Yoon, J L; Targan, S R; Ippoliti, A F; Vasiliauskas, E A

    2015-03-01

    Several open-label and retrospective studies have indicated that thalidomide may be beneficial in patients with refractory Crohn's disease (CD). To report our long-term experience with the use of thalidomide for adults with refractory Crohn's disease. We conducted a retrospective study of long-term clinical and safety outcomes among adults treated with thalidomide for refractory Crohn's disease. Response was defined as a clinician's assessment of improvement after at least 7 days treatment of one or more of the following: bowel movement frequency, fistula output, rectal bleeding, abdominal pain, extraintestinal manifestations, or well-being. Remission required all of the following: thalidomide for a median of 4.4 months and followed up for a median of 58 months. Clinical response and remission rates were 54% and 19%, respectively. About 40% of patients were able to stop steroids. Response rates were higher for those treated with more than 50 mg/day (85%) than for those treated with a maximum of 50 mg/day (40%; P = 0.01). An adverse event occurred in 68% of patients. Approximately one-third of patients (38%) experienced neuropathy. Thalidomide appears to be safe and effective in some patients with refractory Crohn's disease. Although side effects may limit long-term use, thalidomide has potential to induce significant clinical responses. © 2014 John Wiley & Sons Ltd.

  14. Results of a Survey of Long-Term Archiving Implementations

    Science.gov (United States)

    Gurman, Joseph B.; Spencer, Jennifer L.

    2015-04-01

    NASA’s Heliophysics Data Management Policy calls for discipline-specific “final archives,” which will be responsible for the long-term archiving and service of Heliophysics mission data. Long-term archival functions, such as periodic revalidation of the data and migration to newer storage media when appropriate, have never been part of the Solar Data Analysis Center core capabilities. We also recognize that the largest space solar physics data set, the SDO AIA and HMI data at the Stanford Joint Science and Operations Center (JSOC), will eventually need preservation and long-term access, as will the potentially much larger data archive of DKIST observations. We have carried out a study of data archiving best practices in other disciplines and organizations, including NASA’s Space Physics Data Facility (SPDF), the National Institute of Standards and Technology (NIST), and private industry, and report on the lessons learned and possible cost models. We seek input from the broader solar physics community on the relative value of various levels of preservation effort.

  15. Unconjugated bilirubin exposure impairs hippocampal long-term synaptic plasticity.

    Directory of Open Access Journals (Sweden)

    Fang-Yu Chang

    Full Text Available BACKGROUND: Jaundice is one of the most common problems encountered in newborn infants, due to immaturity of hepatic conjugation and transport processes for bilirubin. Although the majority of neonatal jaundice is benign, some neonates with severe hyperbilirubinemia develop bilirubin encephalopathy or kernicterus. Accumulation of unconjugated bilirubin (UCB in selected brain regions may result in temporary or permanent impairments of auditory, motor, or cognitive function; however, the molecular mechanisms by which UCB elicits such neurotoxicity are still poorly understood. The present study is undertaken to investigate whether prolonged exposure of rat organotypic hippocampal slice cultures to UCB alters the induction of long-term synaptic plasticity. METHODOLOGY/PRINCIPAL FINDINGS: Using electrophysiological recording techniques, we find that exposure of hippocampal slice cultures to clinically relevant concentrations of UCB for 24 or 48 h results in an impairment of CA1 long-term potentiation (LTP and long-term depression (LTD induction in a time- and concentration-dependent manner. Hippocampal slice cultures stimulated with UCB show no changes in the secretion profiles of the pro-inflammatory cytokines, interleukin-1beta and tumor necrosis factor-alpha, or the propidium ioide uptake. UCB treatment produced a significant decrease in the levels of NR1, NR2A and NR2B subunits of N-methyl-D-aspartate (NMDA receptors through a calpain-mediated proteolytic cleavage mechanism. Pretreatment of the hippocampal slice cultures with NMDA receptor antagonist or calpain inhibitors effectively prevented the UCB-induced impairment of LTP and LTD. CONCLUSION/SIGNIFICANCE: Our results indicate that the proteolytic cleavage of NMDA receptor subunits by calpain may play a critical role in mediating the UCB-induced impairment of long-term synaptic plasticity in the hippocampus. These observations provide new insights into the molecular mechanisms underlying UCB

  16. Long-Term Results of Primary Vertical Banded Gastroplasty.

    Science.gov (United States)

    van Wezenbeek, M R; Smulders, J F; de Zoete, J P J G M; Luyer, M D; van Montfort, G; Nienhuijs, S W

    2015-08-01

    The vertical banded gastroplasty (VBG) used to be a common restrictive bariatric procedure but has been abandoned by many due to a high failure rate, a high incidence of long-term complications, and the newer adjustable gastric band (AGB) and sleeve. However, potential favorable long-term results and the upcoming banded gastric bypass, with a similar mechanical outlet restriction and control of the pouch size, renewed our interest in the VBG. Therefore, we investigated the long-term outcome of primary VBG at the Catharina Hospital in the Netherlands. Patients that underwent a primary VBG between 1998 and 2008 were included. Patients' characteristics, operative details, evolution on weight and comorbidities, complications, and outcome of revisions were reviewed. A total of 392 patients (80 % female) were reviewed with a mean age of 40 ± 9 years and body mass index of 44 ± 5 kg/m(2). Mean follow-up after VBG was 66 ± 50 months and showed a mean excess weight loss (EWL) of 53 ± 27 % and comorbidity reduction of 54 %. One hundred fifty-two patients (39 %) out of 227 patients (58 %) with long-term complaints underwent revisional surgery. Main reasons for revision were weight regain and vomiting/food intolerance. Analysis before revision showed an outlet dilatation (17 %), pouch dilatation (16 %), and outlet stenosis (10 %). After revision, an additional EWL of 23 % and 33 % further reduction in comorbidities was seen. Primary VBG has an acceptable EWL of 53 % and 55 % of comorbidities were improved. However, the high complication rate, often necessitating revision, underlines the limits of this procedure.

  17. Regulation and Function of Adult Neurogenesis: From Genes to Cognition

    Science.gov (United States)

    Aimone, James B.; Li, Yan; Lee, Star W.; Clemenson, Gregory D.; Deng, Wei; Gage, Fred H.

    2014-01-01

    Adult neurogenesis in the hippocampus is a notable process due not only to its uniqueness and potential impact on cognition but also to its localized vertical integration of different scales of neuroscience, ranging from molecular and cellular biology to behavior. This review summarizes the recent research regarding the process of adult neurogenesis from these different perspectives, with particular emphasis on the differentiation and development of new neurons, the regulation of the process by extrinsic and intrinsic factors, and their ultimate function in the hippocampus circuit. Arising from a local neural stem cell population, new neurons progress through several stages of maturation, ultimately integrating into the adult dentate gyrus network. The increased appreciation of the full neurogenesis process, from genes and cells to behavior and cognition, makes neurogenesis both a unique case study for how scales in neuroscience can link together and suggests neurogenesis as a potential target for therapeutic intervention for a number of disorders. PMID:25287858

  18. On the Role of Neurogenesis and Neural Plasticity in the Evolution of Animal Personalities and Stress Coping Styles.

    Science.gov (United States)

    Øverli, Øyvind; Sørensen, Christina

    2016-08-24

    Individual variation in how animals react to stress and environmental change has become a central topic in a wide range of biological disciplines, from evolutionary ecology to biomedicine. Such variation manifests phenotypically as correlated trait-clusters (referred to as coping styles, behavioral syndromes, shyness-boldness, or personality traits). Thresholds for switching from active coping (fight-flight) to inhibition and passive behavior when exposed to stress depend on experience and genetic factors. Comparative research has revealed a range of neuroendocrine-behavioral associations which are conserved throughout the vertebrate subphylum, including factors affecting perception, learning, and memory of stimuli and events. Here we review conserved aspects of the contribution of neurogenesis and other aspects of neural plasticity to stress coping. In teleost fish, brain cell proliferation and neurogenesis have received recent attention. This work reveals that brain cell proliferation and neurogenesis are associated with heritable variation in stress coping style, and they are also differentially affected by short- and long-term stress in a biphasic manner. Routine-dependent and inflexible behavior in proactive individuals is associated with limited neural plasticity. These evolutionarily conserved relationships hold the potential to illuminate the biological background for stress-related neurobiological disorders. © 2016 S. Karger AG, Basel.

  19. Propofol Inhibits Neurogenesis of Rat Neural Stem Cells by Upregulating MicroRNA-141-3p.

    Science.gov (United States)

    Jiang, Qiliang; Wang, Yingwei; Shi, Xueyin

    2017-02-01

    Prolonged or high-dose exposure to anesthetics, such as propofol, can cause brain cell degeneration and subsequent long-term learning or memory deficits, particularly in the developing brain. However, the cellular and molecular mechanisms underlying the deleterious effects of propofol at certain stages of development remain unclear. In this study we found that propofol inhibited the proliferation, neuronal differentiation, and migration of neural stem cells (NSCs) while upregulating miR-141-3p. Silencing of miR-141-3p abrogated the effects of propofol on NSC neurogenesis. Propofol treatment downregulated IGF2BP2, a direct target of miR-141-3p, whereas overexpression of IGF2BP2 attenuated the effects of propofol and miR-141-3p on NSC neurogenesis. In short, propofol inhibits NSC neurogenesis through a mechanism involving the miR-141-3p/IGF2BP2 axis. Our results may provide a potential approach for preventing the neurodegenerative effects of propofol in the developing brain.

  20. Long-term opioid therapy in Denmark

    DEFF Research Database (Denmark)

    Birke, H; Ekholm, O; Sjøgren, P

    2017-01-01

    BACKGROUND: Longitudinal population-based studies of long-term opioid therapy (L-TOT) in chronic non-cancer pain (CNCP) patients are sparse. Our study investigated incidence and predictors for initiating L-TOT and changes in self-rated health, pain interference and physical activities in long...... defined as those who were dispensed at least one opioid prescription in six separate months within a year. RESULTS: The incidence of L-TOT was substantially higher in CNCP patients at baseline than in others (9/1000 vs. 2/1000 person-years). Smoking behaviour and dispensed benzodiazepines were...... individuals indicated a dose-response relationship between longer treatment duration and the risk of experiencing negative changes. CONCLUSIONS: Individuals on L-TOT seemed not to achieve the key goals of opioid therapy: pain relief, improved quality of life and functional capacity. SIGNIFICANCE: Long...

  1. [Enteral nutrition through long-term jejunostomy].

    Science.gov (United States)

    Fernández, T; Neira, P; Enríquez, C

    2008-01-01

    We present the case of a female patient suffering a peritonitis episode after subtotal gastrectomy due to gastric neoplasm in relation to lesser curvature necrosis extending to the anterior esophageal wall. This an uncommon andsevere complication that made mandatory further aggressive surgery: transection of the abdominal esophagus, transection of the gastric stump, and cervical esophagostomy with creation of a jejunostomy with a needle catheter for feeding. This digestive tube access technique is generally used during major abdominal post-surgery until oral intake is reestablished. Our patient has been 187 days with this therapy since reconstruction of the GI tract was ruled out due to tumoral infiltration of the colon and tumor recurrence at the gastrohepatic omentum. To date, there has been no complication from permanence and/or long-term use of this technique.

  2. Rising Long-term Interest Rates

    DEFF Research Database (Denmark)

    Hallett, Andrew Hughes

    Rather than chronicle recent developments in European long-term interest rates as such, this paper assesses the impact of increases in those interest rates on economic performance and inflation. That puts us in a position to evaluate the economic pressures for further rises in those rates......, the first question posed in this assignment, and the scope for overshooting (the second question), and then make some illustrative predictions of future interest rates in the euro area. We find a wide range of effects from rising interest rates, mostly small and mostly negative, focused on investment...... till the emerging European recovery is on a firmer basis and capable of overcoming increases in the cost of borrowing and shrinking fiscal space. There is also an implication that worries about rising/overshooting interest rates often reflect the fact that inflation risks are unequally distributed...

  3. Long-term stability of salivary cortisol

    DEFF Research Database (Denmark)

    Garde, A H; Hansen, Åse Marie

    2005-01-01

    The measurement of salivary cortisol provides a simple, non-invasive, and stress-free measure frequently used in studies of the hypothalamic-pituitary-adrenal axis activity. In research projects, samples are often required to be stored for longer periods of time either because of the protocol...... of the project or because of lack of funding for analysis. The aim of the present study was to explore the effects of long-term storage of samples on the amounts of measurable cortisol. Ten pools of saliva were collected on polyester Salivette tampons from five subjects. After centrifugation the samples were...... either stored in small vials or spiked to polyester Salivette tampons before analysis for cortisol using Spectria RIA kits. The effects of storage were evaluated by a linear regression model (mixed procedure) on a logarithmic scale. No effects on cortisol concentrations were found after storage of saliva...

  4. Autobiographical reasoning in long-term fandom

    Directory of Open Access Journals (Sweden)

    C. Lee Harrington

    2010-09-01

    Full Text Available We explore the social psychological processes through which fan-based experiences become situated in fans' larger life narratives. Drawing on original survey data with long-term U.S. soap opera fans, we examine how the psychological mechanism of autobiographical reasoning functions in fans' construction of self-narratives over time. The case study presented here is a subset of a larger investigation into the age-related structure of fans' activities, identities, and interpretive capacities. Situated at the intersections of gerontological (life span/life course theory and contemporary fan studies, our project mines relatively uninvestigated theoretical terrain. We conclude with a brief discussion of implications for future fan studies.

  5. Globalization: a long-term view.

    Science.gov (United States)

    Suter, Keith

    2003-01-01

    The process of globalization is now the most important development in world affairs. It is the end of the world order dominated by nation states (or countries) and the beginning of an era in which national governments have to share their power with other entities, most notably transnational corporations (TNCs), inter-governmental organizations (IGOs) and non-governmental organizations (NGOs). The process has to be viewed in its long-term historical evolution. Unfortunately, the process was seen as a technical international law issue by most people so there was a lack of attention to ensuring that the process worked for the benefit of all of humanity. The current (belated) controversy, such as the 1999 Battle of Seattle, could be a window of opportunity for NGOs to encourage a more informed public debate on how to create proposals for a better world.

  6. Dynamics of long-term genomic selection

    Directory of Open Access Journals (Sweden)

    Jannink Jean-Luc

    2010-08-01

    Full Text Available Abstract Background Simulation and empirical studies of genomic selection (GS show accuracies sufficient to generate rapid gains in early selection cycles. Beyond those cycles, allele frequency changes, recombination, and inbreeding make analytical prediction of gain impossible. The impacts of GS on long-term gain should be studied prior to its implementation. Methods A simulation case-study of this issue was done for barley, an inbred crop. On the basis of marker data on 192 breeding lines from an elite six-row spring barley program, stochastic simulation was used to explore the effects of large or small initial training populations with heritabilities of 0.2 or 0.5, applying GS before or after phenotyping, and applying additional weight on low-frequency favorable marker alleles. Genomic predictions were from ridge regression or a Bayesian analysis. Results Assuming that applying GS prior to phenotyping shortened breeding cycle time by 50%, this practice strongly increased early selection gains but also caused the loss of many favorable QTL alleles, leading to loss of genetic variance, loss of GS accuracy, and a low selection plateau. Placing additional weight on low-frequency favorable marker alleles, however, allowed GS to increase their frequency earlier on, causing an initial increase in genetic variance. This dynamic led to higher long-term gain while mitigating losses in short-term gain. Weighted GS also increased the maintenance of marker polymorphism, ensuring that QTL-marker linkage disequilibrium was higher than in unweighted GS. Conclusions Losing favorable alleles that are in weak linkage disequilibrium with markers is perhaps inevitable when using GS. Placing additional weight on low-frequency favorable alleles, however, may reduce the rate of loss of such alleles to below that of phenotypic selection. Applying such weights at the beginning of GS implementation is important.

  7. Long-term reductions in tinnitus severity

    Directory of Open Access Journals (Sweden)

    Folmer Robert L

    2002-09-01

    Full Text Available Abstract Background This study was undertaken to assess long-term changes in tinnitus severity exhibited by patients who completed a comprehensive tinnitus management program; to identify factors that contributed to changes in tinnitus severity within this population; to contribute to the development and refinement of effective assessment and management procedures for tinnitus. Methods Detailed questionnaires were mailed to 300 consecutive patients prior to their initial appointment at the Oregon Health & Science University Tinnitus Clinic. All patients were then evaluated and treated within a comprehensive tinnitus management program. Follow-up questionnaires were mailed to the same 300 patients 6 to 36 months after their initial tinnitus clinic appointment. Results One hundred ninety patients (133 males, 57 females; mean age 57 years returned follow-up questionnaires 6 to 36 months (mean = 22 months after their initial tinnitus clinic appointment. This group of patients exhibited significant long-term reductions in self-rated tinnitus loudness, Tinnitus Severity Index scores, tinnitus-related anxiety and prevalence of current depression. Patients who improved their sleep patterns or Beck Depression Inventory scores exhibited greater reductions of tinnitus severity scores than patients who continued to experience insomnia and depression at follow-up. Conclusions Individualized tinnitus management programs that were designed for each patient contributed to overall reductions in tinnitus severity exhibited on follow-up questionnaires. Identification and treatment of patients experiencing anxiety, insomnia or depression are vital components of an effective tinnitus management program. Utilization of acoustic therapy also contributed to improvements exhibited by these patients.

  8. Long-term efficacy and safety of human papillomavirus vaccination

    Directory of Open Access Journals (Sweden)

    De Vincenzo R

    2014-12-01

    Full Text Available Rosa De Vincenzo,1 Carmine Conte,1 Caterina Ricci,1 Giovanni Scambia,1 Giovanni Capelli2 1Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Catholic University of the Sacred Heart, Rome, 2Department of Human Sciences, Society and Health, University of Cassino and Southern Lazio, Cassino, Italy Abstract: In this paper, we review the published evidence about the long-term efficacy of the available human papillomavirus (HPV vaccines and their safety profile. Two prophylactic HPV vaccines – bivalent (bHPV and quadrivalent (qHPV – are now available, and vaccination programs are being widely implemented, primarily targeting adolescent girls. Efficacy has been widely demonstrated for both vaccines. Since the risk of HPV exposure potentially persists throughout a woman’s sexual life, vaccine duration of protection is critical to overall effectiveness. Interpreting the results of long-term efficacy studies for the two HPV vaccines can be puzzling, due to the heterogeneity of studies, different methods used in the assessment of immunogenicity, histopathological and virological end points, and statistical power issues. Moreover, an immunologic correlate of protection has not yet been established, and it is unknown whether higher antibody levels will really result in a longer duration of protection. Disease prevention remains the most important measure of long-term duration of vaccine efficacy. To date, the longest follow-up of an HPV vaccine has been 9.4 years for the bHPV vaccine. Long-term follow-up for qHPV vaccine goes up to 8 years. The vaccine continues to be immunogenic and well tolerated up to 9 years following vaccination. All randomized controlled clinical trials of the bHPV and the qHPV vaccines provide evidence of an excellent safety profile. The most common complaint reported is pain in the injection site, which is self-limiting and spontaneously resolved. The incidence of systemic adverse events (AEs, serious

  9. Epigenetic mechanisms in neurogenesis

    Science.gov (United States)

    Yao, Bing; Christian, Kimberly M.; He, Chuan; Jin, Peng; Ming, Guo-li; Song, Hongjun

    2017-01-01

    In the embryonic and adult brain, neural stem cells proliferate and give rise to neurons and glia through highly regulated processes. Epigenetic mechanisms — including DNA and histone modifications, as well as regulation by non-coding RNAs — have pivotal roles in different stages of neurogenesis. Aberrant epigenetic regulation also contributes to the pathogenesis of various brain disorders. Here, we review recent advances in our understanding of epigenetic regulation in neurogenesis and its dysregulation in brain disorders, including discussion of newly identified DNA cytosine modifications. We also briefly cover the emerging field of epitranscriptomics, which involves modifications of mRNAs and long non-coding RNAs. PMID:27334043

  10. 24-hour-restraint stress induces long-term depressive-like phenotypes in mice

    Science.gov (United States)

    Zhou, Ying; Hu, Zhiqiang; Lou, Jingyu; Song, Wei; Li, Jing; Liang, Xiao; Chen, Chen; Wang, Shuai; Yang, Beimeng; Chen, Lei; Zhang, Xu; Song, Jinjing; Dong, Yujie; Chen, Shiqing; He, Lin; Xie, Qingguo; Chen, Xiaoping; Li, Weidong

    2016-01-01

    There is an increasing risk of mental disorders, such as acute stress disorder (ASD), post-traumatic stress disorder (PTSD) and depression among survivors who were trapped in rubble during earthquake. Such long-term impaction of a single acute restraint stress has not been extensively explored. In this study, we subjected mice to 24-hour-restraint to simulate the trapping episode, and investigated the acute (2 days after the restraint) and long-term (35 days after the restraint) impacts. Surprisingly, we found that the mice displayed depression-like behaviors, decreased glucose uptake in brain and reduced adult hippocampal neurogenesis 35 days after the restraint. Differential expression profiling based on microarrays suggested that genes and pathways related to depression and other mental disorders were differentially expressed in both PFC and hippocampus. Furthermore, the depression-like phenotypes induced by 24-hour-restraint could be reversed by fluoxetine, a type of antidepressant drug. These findings demonstrated that a single severe stressful event could produce long-term depressive-like phenotypes. Moreover, the 24-hour-restraint stress mice could also be used for further studies on mood disorders. PMID:27609090

  11. Long-term academic stress enhances early processing of facial expressions.

    Science.gov (United States)

    Zhang, Liang; Qin, Shaozheng; Yao, Zhuxi; Zhang, Kan; Wu, Jianhui

    2016-11-01

    Exposure to long-term stress can lead to a variety of emotional and behavioral problems. Although widely investigated, the neural basis of how long-term stress impacts emotional processing in humans remains largely elusive. Using event-related brain potentials (ERPs), we investigated the effects of long-term stress on the neural dynamics of emotionally facial expression processing. Thirty-nine male college students undergoing preparation for a major examination and twenty-one matched controls performed a gender discrimination task for faces displaying angry, happy, and neutral expressions. The results of the Perceived Stress Scale showed that participants in the stress group perceived higher levels of long-term stress relative to the control group. ERP analyses revealed differential effects of long-term stress on two early stages of facial expression processing: 1) long-term stress generally augmented posterior P1 amplitudes to facial stimuli irrespective of expression valence, suggesting that stress can increase sensitization to visual inputs in general, and 2) long-term stress selectively augmented fronto-central P2 amplitudes for angry but not for neutral or positive facial expressions, suggesting that stress may lead to increased attentional prioritization to processing negative emotional stimuli. Together, our findings suggest that long-term stress has profound impacts on the early stages of facial expression processing, with an increase at the very early stage of general information inputs and a subsequent attentional bias toward processing emotionally negative stimuli. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Elevated rheumatoid factor and long term risk of rheumatoid arthritis

    DEFF Research Database (Denmark)

    Nielsen, Sune F; Bojesen, Stig E; Schnohr, Peter

    2012-01-01

    To test whether elevated concentration of rheumatoid factor is associated with long term development of rheumatoid arthritis.......To test whether elevated concentration of rheumatoid factor is associated with long term development of rheumatoid arthritis....

  13. Patent Citations and Financial Analysts’ Long-Term Growth Forecasts

    National Research Council Canada - National Science Library

    Jincheol Bae; Wonchang Hur; Jaehong Lee; Jaimin Goh

    2017-01-01

    ...’ innovation outputs, on financial analysts’ long-term growth forecasts for firms. We find that financial analysts are more likely to issue long-term forecasts for firms with higher patent citations...

  14. PBA regulates neurogenesis and cognition dysfunction after repeated electroconvulsive shock in a rat model.

    Science.gov (United States)

    Yao, Zhao-Hui; Kang, Xiang; Yang, Liu; Niu, Yi; Lu, Ye; Nie, Li

    2015-12-15

    Electroconvulsive therapy (ECT) was widely used to treat the refractory depression. But ECT led to the cognitive deficits plaguing the depression patients. The underlying mechanisms of the cognitive deficits remain elusive. Repeated electroconvulsive shock (rECS) was used to simulate ECT and explore the mechanisms of ECT during the animal studies. Previous studies showed rECS could lead to neurogenesis and cognitive impairment. But it was well known that neurogenesis could improve the cognition. So these suggested that the mechanism of the cognitive deficit after rECS was very complex. In present study, we explored the probable mechanisms of the cognitive deficit after rECS from neurogenesis aspect. We found the cognitive deficit was reversible and neurogenesis could bring a long-term beneficial effect on cognition. Astrogliosis and NR1 down-regulation probably participated in the reversible cognitive deficits after rECS. Phenylbutyric acid (PBA), generally as an agent to investigate the roles of histone acetylation, could prevent the reversible cognitive dysfunction, but PBA could diminish the long-term effect of enhanced cognition by rECS. These suggested that ECT could possibly bring the long-term beneficial cognitive effect by regulating neurogenesis. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  15. Landslide kinematics and their potential controls from hourly to decadal timescales: Insights from integrating ground-based InSAR measurements with structural maps and long-term monitoring data

    Science.gov (United States)

    Schulz, William H.; Coe, Jeffrey A.; Ricci, Pier P.; Smoczyk, Gregory M.; Shurtleff, Brett L.; Panosky, Joanna

    2017-05-01

    Knowledge of kinematics is rudimentary for understanding landslide controls and is increasingly valuable with greater spatiotemporal coverage. However, characterizing landslide-wide kinematics is rare, especially at broadly ranging timescales. We used highly detailed kinematic data obtained using photogrammetry and field mapping during the 1980s and 1990s and our 4.3-day ground-based InSAR survey during 2010 to study kinematics of the large, persistently moving Slumgullion landslide. The landslide was segregated into 11 kinematic elements using the 1980s-1990s data and the InSAR survey revealed most of these elements within a few hours. Averages of InSAR-derived displacement point measures within each element agreed well with higher quality in situ observations; averaging was deemed necessary because adverse look angles for the radar coupled with tree cover on the landslide introduced error in the InSAR results. We found that the landslide moved during 2010 at about half its 1985-1990 speed, but slowing was most pronounced at the landslide head. Gradually decreased precipitation and increased temperature between the periods likely resulted in lower groundwater levels and consequent slowing of the landslide. We used GPS survey results and limit-equilibrium modeling to analyze changing stability of the landslide head from observed thinning and found that its stability increased between the two periods, which would result in its slowing, and the consequent slowing of the entire landslide. Additionally, InSAR results suggested movement of kinematic element boundaries in the head region and our field mapping verified that they moved and changed character, likely because of the long-term increasing head stability. On an hourly basis, InSAR results were near error bounds but suggested landslide acceleration in response to seemingly negligible rainfall. Pore-pressure diffusion modeling suggested that rainfall infiltration affected frictional strength only to shallow depths

  16. Landslide kinematics and their potential controls from hourly to decadal timescales: Insights from integrating ground-based InSAR measurements with structural maps and long-term monitoring data

    Science.gov (United States)

    Schulz, William; Coe, Jeffrey A.; Ricci, P.P; Smoczyk, Gregory M.; Shurtleff, Brett L; Panosky, J

    2017-01-01

    Knowledge of kinematics is rudimentary for understanding landslide controls and is increasingly valuable with greater spatiotemporal coverage. However, characterizing landslide-wide kinematics is rare, especially at broadly ranging timescales. We used highly detailed kinematic data obtained using photogrammetry and field mapping during the 1980s and 1990s and our 4.3-day ground-based InSAR survey during 2010 to study kinematics of the large, persistently moving Slumgullion landslide. The landslide was segregated into 11 kinematic elements using the 1980s–1990s data and the InSAR survey revealed most of these elements within a few hours. Averages of InSAR-derived displacement point measures within each element agreed well with higher quality in situ observations; averaging was deemed necessary because adverse look angles for the radar coupled with tree cover on the landslide introduced error in the InSAR results. We found that the landslide moved during 2010 at about half its 1985–1990 speed, but slowing was most pronounced at the landslide head. Gradually decreased precipitation and increased temperature between the periods likely resulted in lower groundwater levels and consequent slowing of the landslide. We used GPS survey results and limit-equilibrium modeling to analyze changing stability of the landslide head from observed thinning and found that its stability increased between the two periods, which would result in its slowing, and the consequent slowing of the entire landslide. Additionally, InSAR results suggested movement of kinematic element boundaries in the head region and our field mapping verified that they moved and changed character, likely because of the long-term increasing head stability. On an hourly basis, InSAR results were near error bounds but suggested landslide acceleration in response to seemingly negligible rainfall. Pore-pressure diffusion modeling suggested that rainfall infiltration affected frictional strength only to shallow

  17. Effect of Acute and Fractionated Irradiation on Hippocampal Neurogenesis

    Directory of Open Access Journals (Sweden)

    Jin Kyu Kim

    2012-08-01

    Full Text Available Ionizing radiation has become an inevitable health concern emanating from natural sources like space travel and from artificial sources like medical therapies. In general, exposure to ionizing radiation such as γ-rays is one of the methods currently used to stress specific model systems. In this study, we elucidated the long-term effect of acute and fractionated irradiation on DCX-positive cells in hippocampal neurogenesis. Groups of two-month-old C57BL/6 female mice were exposed to whole-body irradiation at acute dose (5 Gy or fractional doses (1 Gy × 5 times and 0.5 Gy × 10 times. Six months after exposure to γ-irradiation, the hippocampus was analyzed. Doublecortin (DCX immunohistochemistry was used to measure changes of neurogenesis in the subgranular zone (SGZ of the hippocampal dentate gyrus (DG. The number of DCX-positive cells was significantly decreased in all acute and fractionally irradiation groups. The long-term changes in DCX-positive cells triggered by radiation exposure showed a very different pattern to the short-term changes which tended to return to the control level in previous studies. Furthermore, the number of DCX-positive cells was relatively lower in the acute irradiation group than the fractional irradiation groups (approximately 3.6-fold, suggesting the biological change on hippocampal neurogenesis was more susceptible to being damaged by acute than fractional irradiation. These results suggest that the exposure to γ-irradiation as a long-term effect can trigger biological responses resulting in the inhibition of hippocampal neurogenesis.

  18. [Long-term outcome after hemispheric disconnection].

    Science.gov (United States)

    Bulteau, C; Dorfmüller, G; Fohlen, M; Jalin, C; Oliver, M-V; Delalande, O

    2008-05-01

    Hemispheric disconnection has been largely proposed for patients with severe epilepsy associated with a congenital or acquired hemispheric cerebral pathology. The classical procedure of anatomical hemispherectomy was progressively abandoned by neurosurgeons in order to avoid postoperative complications since then hemispherotomy techniques have been developed. Globally, with hemispheric disconnection, the rate of patients becoming seizure-free has been between 50 and 80%. The factors affecting seizure control have not been completely elucidated, but several authors suggested that differences in etiology as well as the hemispheric disconnection technique used may partially explain this variability. The percentage of seizure-free patients is higher with hemispherotomy techniques and in the group of patients with Rasmussen encephalitis, Sturge-Weber syndrome, and vascular insults. Depending on overall long-term progression, there is an improvement compared to preoperative status even if children exhibit heterogenous abilities. The lowest scores are observed for motor skills but communication and socialization are relatively well-preserved and strongly related to the duration of epilepsy: the longer the duration, the lower the scores were. Neuropsychological outcome following hemispheric disconnection makes it possible to study the development of hemispheric specialization during infancy and to provide information on cognitive recovery. Cerebral reorganization has been proved to exist in motor and language recovery. Ipsilateral corticospinal pathways seem to be involved in the movement of hemiplegic limbs. Everyday language can be supported by both hemispheres, but there is an early hemispheric specialization of the left hemisphere according to metaphonologic abilities.

  19. Long-Term Soft Denture Lining Materials

    Science.gov (United States)

    Chladek, Grzegorz; Żmudzki, Jarosław; Kasperski, Jacek

    2014-01-01

    Long-term soft denture lining (LTSDL) materials are used to alleviate the trauma associated with wearing complete dentures. Despite their established clinical efficacy, the use of LTSDLs has been limited due to the unfavorable effects of the oral environment on some of their mechanical and performance characteristics. The unresolved issue of LTSDL colonization by Candida albicans is particularly problematic. Silicone-based LTSDL (SLTSDL) materials, which are characterized by more stable hardness, sorption and solubility than acrylic-based LTSDLs (ALTSDLs), are currently the most commonly used LTSDLs. However, SLTSDLs are more prone to debonding from the denture base. Moreover, due to their limitations, the available methods for determining bond strength do not fully reflect the actual stability of these materials under clinical conditions. SLTSDL materials exhibit favorable viscoelastic properties compared with ALTSDLs. Furthermore, all of the lining materials exhibit an aging solution-specific tendency toward discoloration, and the available cleansers are not fully effective and can alter the mechanical properties of LTSDLs. Future studies are needed to improve the microbiological resistance of LTSDLs, as well as some of their performance characteristics. PMID:28788163

  20. Alpine Soils as long-term Bioindicators

    Science.gov (United States)

    Nestroy, O.

    2009-04-01

    Alpine soils as long-term bioindicators The introductory words concern the definitions and peculiarities of alpine soils and their position in the Austrian Soil Classification 2000 in comparison with the World Reference Base for Soil Resources 2006. The important parameters for genesis and threats for these soils in steep and high positions are discussed. It must be emphasized that the main threats are the very different kinds of erosion e.g. by water, wind and snow, and also by skiing (end of season) as well as and mountain-biking (mainly summer-sport). Due the very slow regeneration and - in this connection - due to the very slow changes of the soil entities, these soils give an utmost importance as a long-time bioindicator. With regard to the climate change one can assume an increase in the content of organic matter on site, but also an increase of erosion and mass movement on the other site, e. g. in kind of "plaiken" (soil slide) as result of an increasing intensity of rainfall. It lies partly in our hands to diminish the number and the intensity of the threats, we can influence the soil development, but the result to reach a new ecological equilibrium is very long - in case of alpine soil more than two generations.

  1. Long-term predictions using natural analogues

    Energy Technology Data Exchange (ETDEWEB)

    Ewing, R.C. [Univ. of New Mexico, Albuquerque, NM (United States)

    1995-09-01

    One of the unique and scientifically most challenging aspects of nuclear waste isolation is the extrapolation of short-term laboratory data (hours to years) to the long time periods (10{sup 3}-10{sup 5} years) required by regulatory agencies for performance assessment. The direct validation of these extrapolations is not possible, but methods must be developed to demonstrate compliance with government regulations and to satisfy the lay public that there is a demonstrable and reasonable basis for accepting the long-term extrapolations. Natural systems (e.g., {open_quotes}natural analogues{close_quotes}) provide perhaps the only means of partial {open_quotes}validation,{close_quotes} as well as data that may be used directly in the models that are used in the extrapolation. Natural systems provide data on very large spatial (nm to km) and temporal (10{sup 3}-10{sup 8} years) scales and in highly complex terranes in which unknown synergisms may affect radionuclide migration. This paper reviews the application (and most importantly, the limitations) of data from natural analogue systems to the {open_quotes}validation{close_quotes} of performance assessments.

  2. CERN Services for Long Term Data Preservation

    CERN Document Server

    Shiers, Jamie; Blomer, Jakob; Ganis, Gerardo; Dallmeier-Tiessen, Sunje; Simko, Tibor; Cancio Melia, German; CERN. Geneva. IT Department

    2016-01-01

    In this paper we describe the services that are offered by CERN for Long Term preservation of High Energy Physics (HEP) data, with the Large Hadron Collider (LHC) as a key use case. Data preservation is a strategic goal for European High Energy Physics (HEP), as well as for the HEP community worldwide and we position our work in this global content. Specifically, we target the preservation of the scientific data, together with the software, documentation and computing environment needed to process, (re-)analyse or otherwise (re-)use the data. The target data volumes range from hundreds of petabytes (PB – 10^15 bytes) to hundreds of exabytes (EB – 10^18 bytes) for a target duration of several decades. The Use Cases driving data preservation are presented together with metrics that allow us to measure how close we are to meeting our goals, including the possibility for formal certification for at least part of this work. Almost all of the services that we describe are fully generic – the exception being A...

  3. Model of long-term seismogenesis

    Directory of Open Access Journals (Sweden)

    D. Rhoades

    2001-06-01

    Full Text Available A three-stage faulting model explains the observed quantitative relations between long-term precursory seismicity, mainshocks and aftershocks. Seismogenesis starts with the formation of a major crack, culminates in the corresponding major fracture and earthquake, and ends with healing. Crack formation is a self-organised critical phenomenon, and shear fracture is a delayed sequel to crack formation. It is postulated that the major crack generates a set of minor cracks, just as, later, the major fracture generates a set of minor fractures. Fracturing of the minor cracks raises the average seismicity level. By Mogi’s uniformity criterion, the major earthquake is delayed until the minor fractures have healed and the stress-field has regained relative uniformity. In accord with the scaling principle, the model applies at all magnitude levels. The size of any given initial crack determines the scale of the ensuing seismogenic process. A graphical technique of cumulative magnitude analysis gives a quantitative representation of the seismicity aspects of the model. Examples are given for large earthquakes in a region of continental collision and a subduction region. The principle of hierarchy is exemplified by the seismogenesis of a M 5.9 mainshock occurring entirely within the precursory stage of a M 7.0 mainshock. The model is capable of accommodating a variety of proposed shorter-term precursory phenomena.

  4. Long-term outcome of neuroparacoccidioidomycosis treatment

    Directory of Open Access Journals (Sweden)

    Fabio Francesconi

    2011-02-01

    Full Text Available INTRODUCTION: Neuroparacoccidioidomycosis (NPCM is a term used to describe the invasion of the central nervous system by the pathogenic fungus Paracoccidioides brasiliensis. NPCM has been described sporadically in some case reports and small case series, with little or no focus on treatment outcome and long-term follow-up. METHODS: All patients with NPCM from January 1991 to December 2006 were analyzed and were followed until December 2009. RESULTS: Fourteen (3.8% cases of NPCM were identified out of 367 patients with paracoccidioidomycosis (PCM. A combination of oral fluconazole and sulfamethoxazole/trimethoprim (SMZ/TMP was the regimen of choice, with no documented death due to Paracoccidioides brasiliensis infection. Residual neurological deficits were observed in 8 patients. Residual calcification was a common finding in neuroimaging follow-up. CONCLUSIONS: All the patients in this study responded positively to the association of oral fluconazole and sulfamethoxazole/trimethoprim, a regimen that should be considered a treatment option in cases of NPCM. Neurological sequela was a relatively common finding. For proper management of these patients, anticonvulsant treatment and physical therapy support were also needed.

  5. Long term results of mandibular distraction

    Directory of Open Access Journals (Sweden)

    Batra Puneet

    2006-03-01

    Full Text Available Mandibular distraction osteogenesis has become a popular surgical modality due to its many advantages over conventional orthognathic surgical procedures. However, in spite of the technique having been used for over 15 years, no concrete long term results are available regarding the stability of results. We discuss the various studies which have reported either in favour or against the stablility of results after distraction. We report a series of 6 cases (3 unilateral and 3 bilateral distraction where distraction was carried out before puberty and followed them up to seven years after removal of distractors. This case series shows that results achieved by distraction osteogenesis are unstable or best unpredictable with respect to producing a permanent size increase in the mandible. The role of the distraction osteogenesis in overcoming the pterygomassetric sling is questionable. We suggest a multicenter study with adequate patient numbers treated with a similar protocol and documented after growth cessation to have meaningful conclusions on the debate of distraction osteogenesis versus orthognathic surgery.

  6. Long term results of childhood dysphonia treatment.

    Science.gov (United States)

    Mackiewicz-Nartowicz, Hanna; Sinkiewicz, Anna; Bielecka, Arleta; Owczarzak, Hanna; Mackiewicz-Milewska, Magdalena; Winiarski, Piotr

    2014-05-01

    The aim of this study was to assess the long term results of treatment and rehabilitation of childhood dysphonia. This study included a group of adolescents (n=29) aged from 15 to 20 who were treated due to pediatric hyperfunctional dysphonia and soft vocal fold nodules during their pre-mutational period (i.e. between 5 and 12 years of age). The pre-mutational therapy was comprised of proper breathing pattern training, voice exercises and psychological counseling. Laryngostroboscopic examination and perceptual analysis of voice were performed in each patient before treatment and one to four years after mutation was complete. The laryngostroboscopic findings, i.e. symmetry, amplitude, mucosal wave and vocal fold closure, were graded with NAPZ scale, and the GRBAS scale was used for the perceptual voice analysis. Complete regression of the childhood dysphonia was observed in all male patients (n=14). Voice disorders regressed completely also in 8 out of 15 girls, but symptoms of dysphonia documented on perceptual scale persisted in the remaining seven patients. Complex voice therapy implemented in adolescence should be considered as either the treatment or preventive measure of persistent voice strain, especially in girls. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  7. Long term prediction of flood occurrence

    Directory of Open Access Journals (Sweden)

    C. Aguilar

    2016-05-01

    Full Text Available How long a river remembers its past is still an open question. Perturbations occurring in large catchments may impact the flow regime for several weeks and months, therefore providing a physical explanation for the occasional tendency of floods to occur in clusters. The research question explored in this paper may be stated as follows: can higher than usual river discharges in the low flow season be associated to a higher probability of floods in the subsequent high flow season? The physical explanation for such association may be related to the presence of higher soil moisture storage at the beginning of the high flow season, which may induce lower infiltration rates and therefore higher river runoff. Another possible explanation is persistence of climate, due to presence of long-term properties in atmospheric circulation. We focus on the Po River at Pontelagoscuro, whose catchment area amounts to 71 000 km2. We look at the stochastic connection between average river flows in the pre-flood season and the peak flows in the flood season by using a bivariate probability distribution. We found that the shape of the flood frequency distribution is significantly impacted by the river flow regime in the low flow season. The proposed technique, which can be classified as a data assimilation approach, may allow one to reduce the uncertainty associated to the estimation of the flood probability.

  8. Long term results of mandibular distraction.

    Science.gov (United States)

    Batra, Puneet; Ryan, F S; Witherow, H; Calvert, M L

    2006-03-01

    Mandibular distraction osteogenesis has become a popular surgical modality due to its many advantages over conventional orthognathic surgical procedures. However, in spite of the technique having been used for over 15 years, no concrete long term results are available regarding the stability of results. We discuss the various studies which have reported either in favour or against the stablility of results after distraction. We report a series of 6 cases (3 unilateral and 3 bilateral distraction) where distraction was carried out before puberty and followed them up to seven years after removal of distractors. This case series shows that results achieved by distraction osteogenesis are unstable or best unpredictable with respect to producing a permanent size increase in the mandible. The role of the distraction osteogenesis in overcoming the pterygomassetric sling is questionable. We suggest a multicenter study with adequate patient numbers treated with a similar protocol and documented after growth cessation to have meaningful conclusions on the debate of distraction osteogenesis versus orthognathic surgery.

  9. TIA and Stroke: the long-term perspective

    NARCIS (Netherlands)

    Wijk, I. van

    2006-01-01

    Background Survival after stroke has improved, but little is known about the long-term risk of new vascular events and the functioning of long-term survivors. The main objective of this thesis was to evaluate the long-term perspective of these patients. Methods Two longitudinal studies were carried

  10. The long-term consequences of anaesthetic management | Sessler ...

    African Journals Online (AJOL)

    The long-term consequences of anaesthesia were not seriously considered until relatively recently. There is increasing evidence that some intraoperative anaesthetic management decisions have long-term consequences, and that others might as well. Keywords: long-term consequences; anaesthetic management ...

  11. Comparison of long-term progestin-based estrus synchronization protocols in beef heifers

    National Research Council Canada - National Science Library

    Mallory, D A; Wilson, D J; Busch, D C; Ellersieck, M R; Smith, M F; Patterson, D J

    2010-01-01

    Two experiments evaluated long-term progestin-based estrus-synchronization programs on the basis of potential for use in facilitating fixed-time AI in estrous cycling and prepubertal beef heifers. In Exp...

  12. Energy in 2010 - 2020. Long term challenges; Energie 2010-2020. Les defis du long terme

    Energy Technology Data Exchange (ETDEWEB)

    Dessus, Benjamin [ed.] [Centre National de la Recherche Scientifique (CNRS), 75 - Paris (France)

    2000-02-02

    This report presents the results of a workshop intending to anticipate the long term challenges, to guide better the short term power options, to understand the available political, economical and technical assumptions for the prospective world situation, to give some strategic hints on the necessary transition. Indeed, the difficult issue which the workshop tried to tackle was how should we prepare to reveal the energetic challenge of the development of the eight to ten billion inhabitants of our Planet in the next century without jeopardizing its existence. The energetic problems, a hardcore of the international preoccupation of both growth and environment, as it was recently evidenced by the climatic conference in Kyoto, have ever been the object of a particular attention on the part of General Commissariat of Plan. Thus, the commission 'Energy in 2010 - 2020' has been instituted in April 1996 in order to update the works done in 1990 - 1991 by the commission 'Energy 2010'. Soon it occurred to this new commission the task of illuminating its works by a long term (2050 - 2100) world prospective analysis of the challenges and problems linked to energy, growth and environment. In conclusion, this document tried to find answers to questions like: - which are the risks the energy consumption augmentation entail? - can we control them by appropriate urbanism and transport policies or technological innovation?. Four options for immediate action are suggested: - the energy efficiency should become a priority objective of policies; -coping with the long term challenges requires acting at present; - building the transition between governmental leadership and market; - taking profit of all the possible synergies between short and long term planning.

  13. Long-term results after fibroid embolization; Langzeitergebnisse nach Myomembolisation

    Energy Technology Data Exchange (ETDEWEB)

    Mueller-Huelsbeck, S. [Medizinischer Klinikverbund Flensburg, Akademisches Lehrkrankenhaus des Universitaetsklinikums Schleswig-Holstein, Abt. Diagnostische und interventionelle Radiologie/Neuroradiologie, Ev.-Luth. Diakonissenanstalt zu Flensburg, Flensburg (Germany)

    2008-07-15

    Fibroids (leiomyoma) are the most frequent benign tumors of the uterus during female reproductive age. In the case of clinical symptoms, uterine artery embolization (UAE) is a well established treatment option for symptomatic fibroids, resulting in promising long-term results. In order to estimate long-term success after UAE, reduction of fibroids and uterus volume is less important than complete improvement and disappearance of fibroid-related symptoms. In addition to a high technical success rate and a low perioperative complication rate, UAE results in high short-term and long-term patient satisfaction (>87%) and improvement of symptoms (>81%). Candidates for UAE should be informed about potential reinterventions in terms of repeated UAE (up to 18% of cases) or surgical treatment options. (orig.) [German] Myome sind die haeufigsten gutartigen soliden Tumoren des weiblichen Genitaltrakts im reproduktiven Alter. Bei klinischen Beschwerden stellt die Uterusarterienembolisation (UAE) zur Therapie des symptomatischen Uterus myomatosus einen fest etabliertes Verfahren dar, das mit viel versprechenden Langzeitergebnissen aufwarten kann. Im Vordergrund der Abschaetzung eines lang andauernden Therapieerfolgs nach UAE stehen weniger die Volumenreduktion eines dominanten Myoms bzw. des gesamten Uterus nach der Behandlung, sondern vielmehr die Besserung oder das voellige Verschwinden der von der Patientin initial vor der UAE angegebenen (myombedingten) Beschwerden. Neben einer hohen technischen Erfolgsrate und geringen perioperativen Komplikationsrate fuehrt die fachkundig durchgefuehrte UAE sowohl im Kurz- als auch Langzeitverlauf zu einem hohen Mass an Patientenzufriedenheit (>87%), verbunden mit einer deutlichen Symptombesserung (>81%). Ueber eine Reintervention (in bis zu ca. 18% der Faelle) im Sinne einer erneuten UAE oder einer operativen Massnahme sollten die Patientinnen allerdings im Vorfeld aufgeklaert werden. (orig.)

  14. Long term stability of nanowire nanoelectronics in physiological environments.

    Science.gov (United States)

    Zhou, Wei; Dai, Xiaochuan; Fu, Tian-Ming; Xie, Chong; Liu, Jia; Lieber, Charles M

    2014-03-12

    Nanowire nanoelectronic devices have been exploited as highly sensitive subcellular resolution detectors for recording extracellular and intracellular signals from cells, as well as from natural and engineered/cyborg tissues, and in this capacity open many opportunities for fundamental biological research and biomedical applications. Here we demonstrate the capability to take full advantage of the attractive capabilities of nanowire nanoelectronic devices for long term physiological studies by passivating the nanowire elements with ultrathin metal oxide shells. Studies of Si and Si/aluminum oxide (Al2O3) core/shell nanowires in physiological solutions at 37 °C demonstrate long-term stability extending for at least 100 days in samples coated with 10 nm thick Al2O3 shells. In addition, investigations of nanowires configured as field-effect transistors (FETs) demonstrate that the Si/Al2O3 core/shell nanowire FETs exhibit good device performance for at least 4 months in physiological model solutions at 37 °C. The generality of this approach was also tested with in studies of Ge/Si and InAs nanowires, where Ge/Si/Al2O3 and InAs/Al2O3 core/shell materials exhibited stability for at least 100 days in physiological model solutions at 37 °C. In addition, investigations of hafnium oxide-Al2O3 nanolaminated shells indicate the potential to extend nanowire stability well beyond 1 year time scale in vivo. These studies demonstrate that straightforward core/shell nanowire nanoelectronic devices can exhibit the long term stability needed for a range of chronic in vivo studies in animals as well as powerful biomedical implants that could improve monitoring and treatment of disease.

  15. Adrenal insufficiency in patients on long-term opioid analgesia.

    Science.gov (United States)

    Gibb, Fraser W; Stewart, Alexandra; Walker, Brian R; Strachan, Mark W J

    2016-12-01

    Opioid analgesia has been implicated as a cause of secondary adrenal insufficiency, but little is known of the prevalence of this potentially serious adverse effect in patients with chronic pain. Cross-sectional study of chronic pain patients on long-term opioid analgesia. Patients attending tertiary chronic pain clinics at the Western General Hospital, Edinburgh, treated with long-term opioid analgesia (n = 48) with no recent exposure to exogenous glucocorticoids. Four patients (8·3%) had basal morning plasma cortisol concentrations below 100 nmol/l, of whom three failed to achieve a satisfactory cortisol response to exogenous ACTH1-24 stimulation (peak cortisol >430 nmol/l). Basal cortisol was positively associated with age (R = 0·398, P = 0·005) and negatively associated with BMI (R = -0·435, P = 0·002). Suppression of the hypothalamic-pituitary-adrenal axis is present in a clinically significant proportion of chronic pain patients treated with opioid analgesia. Studies of larger populations should be conducted to better define the prevalence and potential clinical consequences of adrenal insufficiency in this context. © 2016 John Wiley & Sons Ltd.

  16. Neurobiological problems in long-term deep space flights

    Science.gov (United States)

    Vazquez, M. E.

    Future missions in space may involve long-term travel beyond the magnetic field of the Earth, subjecting astronauts to radiation hazards posed by solar flares and galactic cosmic rays, altered gravitation fields and physiological stress. Thus, it is critical to determine if there will be any reversible or irreversible, detrimental neurological effects from this prolonged exposure to space. A question of particular importance focuses on the long-term effects of the space environment on the central nervous system (CNS) neuroplasticity, with the potential acute and/or delayed effects that such perturbations might entail. Although the short-term effects of microgravity on neural control were studied on previous low earth orbit missions, the late consequences of stress in space, microgravity and space radiation have not been addressed sufficiently at the molecular, cellular and tissue levels. The possibility that space flight factors can interact influencing the neuroplastic response in the CNS looms critical issue not only to understand the ontogeny of the CNS and its functional integrity, but also, ultimately the performance of astronauts in extended space forays. The purpose of this paper is to review the neurobiological modifications that occur in the CNS exposed to the space environment, and its potential consequences for extended deep space flight.

  17. Glioblastoma multiforme with long term survival.

    Science.gov (United States)

    Deb, Prabal; Sharma, Mehar Chand; Mahapatra, Ashok Kumar; Agarwal, Deepak; Sarkar, Chitra

    2005-09-01

    Glioblastoma multiforme (GBM) Patients generally have a dismal prognosis, with median survival of 10-12 months. GBM with long-term survival (LTS) of (3) > or = 5 years is rare, and no definite markers indicating better prognosis have been identified till date. The present study was undertaken to evaluate GBMs with LTS in order to identify additional correlates associated with favourable outcome. The cases were evaluated for relevant clinicopathological data, proliferation index and expression of tumortumour suppressor gene (p53 ), cyclin-dependant kinase-inhibitors (p27 and p16 ) and epidermal growth factor receptor (EGFR) proteins. Six cases of GBM with LTS with an average survival of 9 years (range 5-15 years) were identified. All were young patients with mean age of 27 years (range 8-45 years). Histology of three cases was consistent with conventional GBM, while two showed prominent oligodendroglial component admixed with GBM areas. One was a giant cell GBM, which progressed to gliosarcoma on recurrence. The mean MIB-1LI was 12% (range 6-20%). p53 was immunopositive in 4 out of 5 cases. EGFR and p27 were immunonegative in all, whereas p16 was immunonegative in 3 out of 5 cases. Currently, in the absence of specific molecular and genetic markers, GBM in young patients should be meticulously evaluated for foci of oligodendroglial component and/or giant cell elements, in addition to proliferative index and p53 expression, since these probably have prognostic connotations, as evident in this study. The role of p16 and p27 however needs better definition with study of more number of cases.

  18. Long term observations of Saturn's northern auroras

    Science.gov (United States)

    Nichols, Jonathan

    2011-10-01

    Auroral emissions are a vital tool in diagnosing the dynamics of planetary magnetospheres. While SaturnA?s southern UV auroras have been observed with high-sensitivity cameras onboard the Hubble Space Telescope {HST}, the northern auroras have only been observed at very oblique angles. Our understanding of SaturnA?s auroral emissions is thus only half complete. However, Saturn has now passed equinox and is moving toward summer in the northern hemisphere, such that the northern auroras are now visible from Earth, and recent results from HST have indicated that SaturnA?s northern auroras are not simply mirror images of the southern. The changing seasons are also expected to result in significant changes in magnetospheric phenomena related to the auroras. Observing these changes is a specific goal of the Cassini Solstice Mission {CSM} and, since joint HST-Cassini observations have repeatedly proved to be invaluable, CSM operations are currently being planned specifically with joint HST observations in mind. The observations proposed here will thus execute over Cycles 18-20, and will address the following science questions:What is the morphology of SaturnA?s northern auroras? Do SaturnA?s auroras change with the planetA?s season? How are the auroral emissions of different wavelengths related?The importance of long term HST observations of SaturnA?s northern auroras are highlighted by the fact that recent key discoveries would have been missed without the multiyear archive of observations of the planetA?s southern auroras. The opportunity to obtain HST images while Cassini makes specifically-tailored supporting observations is an extremely valuable opportunity, and HST is the only instrument capable of providing sustained, high time resolution observations of Saturns auroral emission.

  19. Long term cultivation of larger benthic Foraminifera

    Science.gov (United States)

    Wöger, Julia; Eder, Wolfgang; Kinoshita, Shunichi; Antonino, Briguglio; Carles, Ferrandes-Cañadell; Hohenegger, Johann

    2015-04-01

    Benthic Foraminifera are used in a variety of applications employing numerous different methods, i.e. ecological monitoring, studying the effects of ocean acidification, reconstructing palaeo-bathymetry or investigating palaeo-salinity and palaeo-temperature to name only a few. To refine our understanding of ecological influences on larger benthic foraminiferal biology and to review inferences from field observations, culture experiments have become an indispensable tool. While culture experiments on smaller benthic foraminifera have become increasingly frequent in the past century, reports of the cultivation of symbiont bearing larger Foraminifera are rare. Generally, cultivation experiments can be divided into two groups: Culturing of populations and cultivation of single specimens allowing individual investigation. The latter differ form the former by several restrictions resulting from the need to limit individual motility without abridging microenvironmental conditions in the Foraminiferans artificial habitat, necessary to enable the individual to development as unfettered as possible. In this study we present first experiences and preliminary results of the long-term cultivation of larger benthic Foraminifera conducted at the 'Tropical Biosphere Research Station Sesoko Island, University of the Ryukyus', Japan, trying to reproduce natural conditions as closely as possible. Individuals of three species of larger benthic Foraminifera (Heterostegina depressa, Palaeonummulites venosus and Operculina complanata) have been cultured since April 2014. At the time of the general assembly the cultivation experiments will have been going on for more than one year, with the aim to investigate growth rates, longevities and reproduction strategies for comparison with results statistically inferred from application of the of the 'natural laboratory' method. The most important factor influencing foraminiferal health and development was found to be light intensity and light

  20. Long term stability of atomic time scales

    Science.gov (United States)

    Petit, Gérard; Arias, Elisa Felicitas

    2012-08-01

    International Atomic Time TAI gets its stability from some 400 atomic clocks worldwide that generate the free atomic scale EA L and its accuracy from a small number of primary frequency standards (PFS) which frequency measurements are used to steer the EAL frequency. Because TAI is computed in "real - time" (every month) and has operational constraints, it is not optimal and the BIPM computes in deferred time another time scale TT(BIPM), which is based on a weighted average of the evaluations of TAI frequency by the PFS. We show that a point has been reached where the stability of atomic time scales, the accuracy of primary frequency standards, and the capabilities of frequency transfer are approximately at a similar level, in the low 10 - 16 in relative frequency. The goal is now to reach and surpass 1x10 - 16 and the three fields are in various stages of advancement towards this aim. We review the stability and accuracy recently achieved by frequency standards, focusing on primary frequency standards on one hand, and on new secondary realizations e.g. based on optical transitions on the other hand. We study how these performances can translate to the performance of atomic time scales, and the possible implications of the availability of new high - accuracy frequency standards operating on a regular basis. Finally we show how time transfer is trying to keep up with the progresses of frequency standards. Time transfer is presently the limiting factor at short averaging time (e.g. 1 - 2 weeks) but it should not be limiting the long term stability of atomic time scales, which is the main need of many applications in astronomy.

  1. Perinatal respiratory infections and long term consequences

    Directory of Open Access Journals (Sweden)

    Luciana Indinnimeo

    2015-10-01

    Full Text Available Respiratory syncytial virus (RSV is the most important pathogen in the etiology of respiratory infections in early life. 50% of children are affected by RSV within the first year of age, and almost all children become infected within two years. Numerous retrospective and prospective studies linking RSV and chronic respiratory morbidity show that RSV bronchiolitis in infancy is followed by recurrent wheezing after the acute episod. According to some authors a greater risk of wheezing in children with a history of RSV bronchiolitis would be limited to childhood, while according to others this risk would be extended into adolescence and adulthood. To explain the relationship between RSV infection and the development of bronchial asthma or the clinical pathogenetic patterns related to a state of bronchial hyperreactivity, it has been suggested that RSV may cause alterations in the response of the immune system (immunogenic hypothesis, activating directly mast cells and basophils and changing the pattern of differentiation of immune cells present in the bronchial tree as receptors and inflammatory cytokines. It was also suggested that RSV infection can cause bronchial hyperreactivity altering nervous airway modulation, acting on nerve fibers present in the airways (neurogenic hypothesis.The benefits of passive immunoprophylaxis with palivizumab, which seems to represent an effective approach in reducing the sequelae of RSV infection in the short- and long-term period, strengthen the implementation of prevention programs with this drug, as recommended by the national guidelines of the Italian Society of Neonatology. Proceedings of the 11th International Workshop on Neonatology and Satellite Meetings · Cagliari (Italy · October 26th-31st, 2015 · From the womb to the adultGuest Editors: Vassilios Fanos (Cagliari, Italy, Michele Mussap (Genoa, Italy, Antonio Del Vecchio (Bari, Italy, Bo Sun (Shanghai, China, Dorret I. Boomsma (Amsterdam, the

  2. Assessment of long-term leaching from waste incineration air-pollution-control residues

    DEFF Research Database (Denmark)

    Astrup, Thomas; Mosbæk, Hans; Christensen, Thomas Højlund

    2006-01-01

    Assessment of long-term leaching from MSWI air-pollution-control (APC) residues is discussed with respect to use in environmental impact assessment, such as life-cycle assessment (LCA). A method was proposed for estimating leaching as a function of the liquid-to-solid (L/S) ratio in a long-term p...... that uncritical use of batch leaching data for assessing the potential leaching is highly problematic, and evaluations of residue disposal should include scenario specific quantification of the long-term leaching....

  3. Increasing age reduces expression of long term depression and dynamic range of transmission plasticity in CA1 field of the rat hippocampus

    NARCIS (Netherlands)

    Gispen, W.H.; Kamal, A.; Biessels, G.J.; Urban, I.J.

    1997-01-01

    Long-term depression, depotentiation and long-term potentiation of field excitatory postsynaptic potentials in the CA1 field of the hippocampus were studied in slices from two-, 12-, 24- and 36-week-old rats. Long-term potentiation was induced by stimulating afferent fibres for 1 s at 100 Hz.

  4. Northern European long term climate archives

    Energy Technology Data Exchange (ETDEWEB)

    Hohl, Veronica [Stockholm Univ. (Sweden)

    2005-01-01

    The Swedish Nuclear Fuel and Waste Management Company is responsible for the management and disposal of Sweden's radioactive waste. It is intended to deposit the spent nuclear fuel in a deep geological repository. This repository shall keep the radiotoxic material separated from humans and the environment for extended periods, from decades to millennia and possibly to geological timescales. During this time perspective climate induced changes such as shore-level displacement and evolution of permafrost and ice sheets are expected to occur which may affect the repository. The possible occurrence, extent and duration of these long-term changes, are therefore of interest when considering the assessment of repository performance and safety. The main climate parameters determining both surface and subsurface conditions are temperature and precipitation. As a result of the last advance of the Weichselian ice sheet only few geological archives exist, which contain information on past climatic conditions in Sweden before c 16,000 years BP. The purpose of this literature review is to compile and evaluate available information from Scandinavian, Northern and Central European geological archives, which record climatic conditions during the Weichselian time period. The compilation provides paleotemperature data sets, which may be used to explore the possible evolution of periglacial permafrost in Sweden. This report is a synopsis of 22 publications detailing climatic and environmental changes during the Weichselian time period in Northwestern Europe based on quantified paleotemperature records. Some of the data is presented as temperature curves which were digitised specifically for this report. The time range covered by the different publications varies considerably. Only few authors dealt with the whole Weichselian period and the majority cover only a few thousand years. This however is not considered to influence the reliability of the archives. The reason for the

  5. Involvement of Adult Hippocampal Neurogenesis in Learning and Forgetting

    Science.gov (United States)

    Yau, Suk-yu; Li, Ang; So, Kwok-Fai

    2015-01-01

    Adult hippocampal neurogenesis is a process involving the continuous generation of newborn neurons in the hippocampus of adult animals. Mounting evidence has suggested that hippocampal neurogenesis contributes to some forms of hippocampus-dependent learning and memory; however, the detailed mechanism concerning how this small number of newborn neurons could affect learning and memory remains unclear. In this review, we discuss the relationship between adult-born neurons and learning and memory, with a highlight on recently discovered potential roles of neurogenesis in pattern separation and forgetting. PMID:26380120

  6. Nutritional Factors Affecting Adult Neurogenesis and Cognitive Function.

    Science.gov (United States)

    Poulose, Shibu M; Miller, Marshall G; Scott, Tammy; Shukitt-Hale, Barbara

    2017-11-01

    Adult neurogenesis, a complex process by which stem cells in the hippocampal brain region differentiate and proliferate into new neurons and other resident brain cells, is known to be affected by many intrinsic and extrinsic factors, including diet. Neurogenesis plays a critical role in neural plasticity, brain homeostasis, and maintenance in the central nervous system and is a crucial factor in preserving the cognitive function and repair of damaged brain cells affected by aging and brain disorders. Intrinsic factors such as aging, neuroinflammation, oxidative stress, and brain injury, as well as lifestyle factors such as high-fat and high-sugar diets and alcohol and opioid addiction, negatively affect adult neurogenesis. Conversely, many dietary components such as curcumin, resveratrol, blueberry polyphenols, sulforaphane, salvionic acid, polyunsaturated fatty acids (PUFAs), and diets enriched with polyphenols and PUFAs, as well as caloric restriction, physical exercise, and learning, have been shown to induce neurogenesis in adult brains. Although many of the underlying mechanisms by which nutrients and dietary factors affect adult neurogenesis have yet to be determined, nutritional approaches provide promising prospects to stimulate adult neurogenesis and combat neurodegenerative diseases and cognitive decline. In this review, we summarize the evidence supporting the role of nutritional factors in modifying adult neurogenesis and their potential to preserve cognitive function during aging. © 2017 American Society for Nutrition.

  7. Specific immunotherapy has long-term preventive effect of seasonal and perennial asthma

    DEFF Research Database (Denmark)

    Jacobsen, L; Niggemann, B; Dreborg, S

    2007-01-01

    BACKGROUND: 3-year subcutaneous specific immunotherapy (SIT) in children with seasonal allergic rhinoconjunctivitis reduced the risk of developing asthma during treatment and 2 years after discontinuation of SIT (5-year follow-up) indicating long-term preventive effect of SIT. OBJECTIVE: We......: Specific immunotherapy has long-term clinical effects and the potential of preventing development of asthma in children with allergic rhino conjunctivitis up to 7 years after treatment termination....

  8. Hippocampal learning, memory, and neurogenesis: Effects of sex and estrogens across the lifespan in adults.

    Science.gov (United States)

    Duarte-Guterman, Paula; Yagi, Shunya; Chow, Carmen; Galea, Liisa A M

    2015-08-01

    This article is part of a Special Issue "Estradiol and Cognition". There are sex differences in hippocampus-dependent cognition and neurogenesis suggesting that sex hormones are involved. Estrogens modulate certain forms of spatial and contextual memory and neurogenesis in the adult female rodent, and to a lesser extent male, hippocampus. This review focuses on the effects of sex and estrogens on hippocampal learning, memory, and neurogenesis in the young and aged adult rodent. We discuss how factors such as the type of estrogen, duration and dose of treatment, timing of treatment, and type of memory influence the effects of estrogens on cognition and neurogenesis. We also address how reproductive experience (pregnancy and mothering) and aging interact with estrogens to modulate hippocampal cognition and neurogenesis in females. Given the evidence that adult hippocampal neurogenesis plays a role in long-term spatial memory and pattern separation, we also discuss the functional implications of regulating neurogenesis in the hippocampus. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. The Role of Wnt/β-Catenin Signaling Pathway in Disrupted Hippocampal Neurogenesis of Temporal Lobe Epilepsy: A Potential Therapeutic Target?

    Science.gov (United States)

    Huang, Cheng; Fu, Xiang-Hui; Zhou, Dong; Li, Jin-Mei

    2015-07-01

    Temporal lobe epilepsy is one of the most common clinical neurological disorders. One of the major pathological findings in temporal lobe epilepsy is hippocampal sclerosis, characterized by massive neuronal loss and severe gliosis. The epileptogenesis process of temporal lobe epilepsy usually starts with initial precipitating insults, followed by neurodegeneration, abnormal hippocampus circuitry reorganization, and the formation of hypersynchronicity. Experimental and clinical evidence strongly suggests that dysfunctional neurogenesis is involved in the epileptogenesis. Recent data demonstrate that neurogenesis is induced by acute seizures or precipitating insults, whereas the capacity of neuronal recruitment and proliferation substantially decreases in the chronic phase of epilepsy. Participation of the Wnt/β-catenin signaling pathway in neurogenesis reveals its importance in epileptogenesis; its dysfunction contributes to the structural and functional abnormality of temporal lobe epilepsy, while rescuing this pathway exerts neuroprotective effects. Here, we summarize data supporting the involvement of Wnt/β-catenin signaling in the epileptogenesis of temporal lobe epilepsy. We also propose that the Wnt/β-catenin signaling pathway may serve as a promising therapeutic target for temporal lobe epilepsy treatment.

  10. Central Administration of the Ciliary Neurotrophic Factor Analogue, Axokine, Does Not Play a Role in Long-Term Energy Homeostasis in Adult Mice.

    Science.gov (United States)

    Borg, Melissa L; Reichenbach, Alex; Lemus, Moyra; Oldfield, Brian J; Andrews, Zane B; Watt, Matthew J

    2016-01-01

    Ciliary neurotrophic factor (CNTF) exerts powerful anorectic effects and has been suggested to regulate long-term energy balance by inducing adult neurogenesis in the arcuate nucleus of the hypothalamus. The CNTF analogue, Axokine, was infused into the lateral ventricle of high-fat-fed mice for 1 week. Food intake, energy expenditure, body mass, glucose metabolism, and neurogenesis in the arcuate nucleus (ARC) of the hypothalamus were assessed 3 weeks after cessation of Axokine treatment. Short-term administration of Axokine induced an anorexic response but did not promote sustained weight loss. Instead, a rapid rebound in food intake and body mass occurred immediately after cessation of Axokine treatment, and this tended to reduce insulin sensitivity. Immunolabeling of 5-bromo-2'-deoxyuridine revealed limited neurogenesis in the ARC 3 weeks after Axokine treatment. These findings suggest that Axokine/CNTF does not induce substantial or sustained ARC neurogenesis or contribute to the long-term regulation of energy balance in mice. © 2015 S. Karger AG, Basel.

  11. Reforming long-term care financing through insurance

    Science.gov (United States)

    Meiners, Mark R.

    1988-01-01

    Until recently, insurance for long-term care was not viewed as feasible. This perception has changed dramatically in the past few years. Several models of long-term care insurance have begun to be tested. Although the application of insurance principles to long-term care is still new, the emergence of private market interest in developing long-term care insurance has been a catalyst to renewed public-policy support for reforming the way we pay for long-term care. States, in particular, have become interested in developing public-private partnerships to support the emergence of long-term care insurance that could help relieve the mounting pressure on Medicaid budgets. PMID:10312962

  12. Long-Term Mean Wind Profiles Based on Similarity Theory

    DEFF Research Database (Denmark)

    Kelly, Mark C.; Gryning, Sven-Erik

    2010-01-01

    in turn facilitates the derivation of a long-term mean wind profile based on Monin–Obukhov similarity theory. The modelled stability distributions exhibit good agreement with measurements from sites having different local conditions. The long-term wind profile formulation is further extended to include...... the influence of the depth of the atmospheric boundary layer (h), which becomes relevant for heights above h/3, and the resultant long-term ‘tall’ profile form also matches observations....

  13. Long term behaviour of singularly perturbed parabolic degenerated equation

    OpenAIRE

    Faye, Ibrahima; Frenod, Emmanuel; Seck, Diaraf

    2011-01-01

    In this paper we consider models for short-term, mean-term and long-term morphodynamics of dunes and megariples. We give an existence and uniqueness result for long term dynamics of dunes. This result is based on a time-space periodic solution existence result for degenerated parabolic equation that we set out. Finally the mean-term and long-term models are homogenized.

  14. CHARACTERISTICS OF LONG-TERM UNEMPLOYMENT SPELLS IN ROMANIA

    Directory of Open Access Journals (Sweden)

    Daniela-Emanuela Dănăcică

    2012-12-01

    Full Text Available The aim of this paper is to analyze characteristics of long-term unemployment spells in Romania and to estimate the effect of factors influencing long-term unemployment spells. The study period is in between January 1st 2008 and December 31st 2010. 468159 long-term spells registered in the specified period at the National Agency of Employment are analyzed.

  15. A cost of long-term memory in Drosophila

    OpenAIRE

    Mery, Frederic; Kawecki, Tadeusz J.

    2005-01-01

    Two distinct forms of consolidated associative memory are known in Drosophila: long-term memory and so-called anesthesia-resistant memory. Long-term memory is more stable, but unlike anesthesia-resistant memory, its formation requires protein synthesis. We show that flies induced to form long-term memory become more susceptible to extreme stress (such as desiccation). In contrast, induction of anesthesia-resistant memory had no detectable effect on desiccation resistance. This finding may hel...

  16. Long-term bed degradation in Maryland streams (phase 2) : Blue Ridge and western Piedmont provinces [research summary].

    Science.gov (United States)

    2012-03-01

    Problem: : Estimation of potential long-term down-cutting of the stream bed is necessary for evaluation and design of bridges for scour and culverts for fish passage. Existing guidelines for assessing this potential long-term bed degradation (LTBD) i...

  17. Protein kinase M ζ and the maintenance of long-term memory.

    Science.gov (United States)

    Zhang, Yang; Zong, Wei; Zhang, Lei; Ma, Yuanye; Wang, Jianhong

    2016-10-01

    Although various molecules have been found to mediate the processes of memory acquisition and consolidation, the molecular mechanism to maintain memory still remains elusive. In recent years, a molecular pathway focusing on protein kinase Mζ (PKMζ) has become of interest to researchers because of its potential role in long-term memory maintenance. PKMζ is an isoform of protein kinase C (PKC) and has a related structure that influences its function in maintaining memory. Considerable evidence has been gathered on PKMζ activity, including loss of function studies using PKMζ inhibitors, such as PKMζ inhibitory peptide (ZIP), suggesting PKMζ plays an important role in long-term memory maintenance. This review provides an overview of the role of PKMζ in long-term memory and outlines the molecular structure of PKMζ, the molecular mechanism of PKMζ in long-term memory maintenance and future directions of PKMζ research. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Long term warranty and after sales service concept, policies and cost models

    CERN Document Server

    Rahman, Anisur

    2015-01-01

    This volume presents concepts, policies and cost models for various long-term warranty and maintenance contracts. It offers several numerical examples for estimating costs to both the manufacturer and consumer. Long-term warranties and maintenance contracts are becoming increasingly popular, as these types of aftersales services provide assurance to consumers that they can enjoy long, reliable service, and protect them from defects and the potentially high costs of repairs. Studying long-term warranty and service contracts is important to manufacturers and consumers alike, as offering long-term warranty and maintenance contracts produce additional costs for manufacturers / service providers over the product’s service life. These costs must be factored into the price, or the manufacturer / dealer will incur losses instead of making a profit. On the other hand, the buyer / consumer needs to weigh the cost of maintaining it over its service life and to decide whether or not these policies are worth purchasing....

  19. Global Horizontal Irradiance Anomalies in Long Term Series Over India

    Science.gov (United States)

    Cony, Marco; Liria, Juan; Weisenberg, Ralf; Serrano, Enrique

    2014-05-01

    India has a high potential for solar energy applications due to its geographic position within the Sun Belt and the large number of cloudless days in many regions of the country. However, certain regions of India, particularly those largely populated, can exhibit large aerosol loading in the atmosphere as a consequence of anthropogenic emissions that could have a negative feedback in the solar resource potential. This effect, named as solar dimming, has already been observed in India, and in some other regions in the world, by some authors using ground data from the last two decades. The recent interest in the promotion of solar energy applications in India highlights the need of extending and improving the knowledge of the solar radiation resources in this country, since most of the long term measurements available correspond to global horizontal radiation (GHI) and most of them are also located big cities or highly populated areas. In addition, accurate knowledge on the aerosol column quantification and on its dynamical behavior with high spatial resolution is particularly important in the case of India, due to their impact on direct normal irradiation. Long term studies of solar irradiation over India can be performed using monthly means of GHI measurements from the Indian Meteorological Department. Ground data are available from 1964 till today through the World Radiation Data Centre that publish these values in the web. This work shows a long term analysis of GHI using anomalies techniques over ten different sites over India. Besides, techniques of linear trends have been applied for to show the evolution over this period. The analysis of anomalies has also found two periods of different behavior. From 1964 till 1988 the anomalies observed were positive and the last 20 years seems to be a period of negative anomalies. The results exhibit a decreasing trend and negative anomalies confirming thus the darkening effect already reported by solar dimming studies

  20. Nitric Oxide Regulates Neurogenesis in the Hippocampus following Seizures

    Directory of Open Access Journals (Sweden)

    Bruno P. Carreira

    2015-01-01

    Full Text Available Hippocampal neurogenesis is changed by brain injury. When neuroinflammation accompanies injury, activation of resident microglial cells promotes the release of inflammatory cytokines and reactive oxygen/nitrogen species like nitric oxide (NO. In these conditions, NO promotes proliferation of neural stem cells (NSC in the hippocampus. However, little is known about the role of NO in the survival and differentiation of newborn cells in the injured dentate gyrus. Here we investigated the role of NO following seizures in the regulation of proliferation, migration, differentiation, and survival of NSC in the hippocampus using the kainic acid (KA induced seizure mouse model. We show that NO increased the proliferation of NSC and the number of neuroblasts following seizures but was detrimental to the survival of newborn neurons.