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  1. Long-term academic stress enhances early processing of facial expressions.

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    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.

  2. Long Term 1 Enhanced Surface Water Treatment Rule Documents

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    The Long Term 1 Enhanced Surface Water Treatment Rule (LT1ESWTR) builds on the requirements of the Surface Water Treatment Rule and specifies treatment requirements to address Cryptosporidium m and other microbial contaminants in public water systems.

  3. `Snacking' causes long term attenuation of HPA axis stress responses and enhancement of brain FosB/delta FosB expression in rats

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    Christiansen, A.M.; DeKloet, A.D; Ulrich-Lai, Y.M.; Herman, J.P.

    2011-01-01

    A history of limited, intermittent intake of palatable food (sucrose drink) attenuates hypothalamic-pituitary-adrenal (HPA) axis stress responses and induces markers of neuronal plasticity in stress- and reward-regulatory brain regions. Synaptic plasticity could provide a mechanism for long-term changes in neuronal function, implying that sucrose stress-dampening may endure over long periods of time. The present study tests the persistence of HPA axis dampening and plasticity after cessation of palatable drinking. Adult, male Long-Evans rats (n = 10–13) with free access to water and chow were given additional twice-daily access to 4 ml sucrose (30%) or water for 14 days. Rats were subsequently tested for HPA responsiveness to an acute (20-minute) restraint stress at 1, 6 and 21 days after the cessation of sucrose. Brains were collected for immunohistochemical analysis of FosB/deltaFosB, a marker of long-term neuronal plasticity, in the basolateral amygdala and nucleus accumbens. Prior sucrose consumption significantly decreased the plasma corticosterone response to restraint at one day after the last palatable drink presentation, and also increased FosB/deltaFosB-positive cells in the basolateral amygdala and in the nucleus accumbens core. This HPA-dampening persisted through 21 days after the termination of the palatable drink, as did the increased FosB/deltaFosB immunoreactivity in both the BLA and the NuAc core. These data suggest that chronic palatable food intake causes lasting changes in stress/reward-modulatory circuitry and that the suppressed hormonal response to stress that can persist well beyond periods of palatable drink exposure. PMID:21262247

  4. Long-term insulin-like growth factor-I expression in skeletal muscles attenuates the enhanced in vitro proliferation ability of the resident satellite cells in transgenic mice

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    Chakravarthy, M. V.; Fiorotto, M. L.; Schwartz, R. J.; Booth, F. W.

    2001-01-01

    Insulin-like growth factor-I (IGF-I) overexpression for 1-month in mouse skeletal muscle increases satellite cell proliferation potential. However, it is unknown whether this beneficial enhancement by IGF-I expression would persist over a longer-term duration in aged mice. This is an important issue to address if a prolonged course of IGF-I is to be used clinically in muscle-wasting conditions where satellite cells may become limiting. Using the IGF-I transgenic (IGF-I Tg) mouse that selectively expresses the IGF-I transgene in striated muscles, we found that 18-months of continuous IGF-I overexpression led to a loss in the enhanced in vitro proliferative capacity of satellite cells from Tg skeletal muscles. Also 18-month-old IGF-I Tg satellite cells lost the enhanced BrdU incorporation, greater pRb and Akt phosphorylations, and decreased p27(Kip1) levels initially observed in cells from 1-month-old IGF-I Tg mice. The levels of those biochemical markers reverted to similar values seen in the 18-months WT littermates. These findings, therefore, suggest that there is no further beneficial effect on enhancing satellite cell proliferation ability with persistent long-term expression of IGF-I in skeletal muscles of these transgenic mice.

  5. Enhancing Long-Term Retention of New Vocabulary Using Visual Images.

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    Igelsrud, Karen

    A practicum used a new learning tool to enhance long-term retention of new vocabulary. Sixteen seventh-graders in Language Arts, who had a long-term retention mean score of approximately 40% of newly learned vocabulary, increased their long-term retention of new vocabulary by 25% (a new mean of 65% of new vocabulary). Additional objectives…

  6. Dynamics of Hippocampal Protein Expression During Long-term Spatial Memory Formation*

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    Borovok, Natalia; Nesher, Elimelech; Levin, Yishai; Reichenstein, Michal; Pinhasov, Albert

    2016-01-01

    Spatial memory depends on the hippocampus, which is particularly vulnerable to aging. This vulnerability has implications for the impairment of navigation capacities in older people, who may show a marked drop in performance of spatial tasks with advancing age. Contemporary understanding of long-term memory formation relies on molecular mechanisms underlying long-term synaptic plasticity. With memory acquisition, activity-dependent changes occurring in synapses initiate multiple signal transduction pathways enhancing protein turnover. This enhancement facilitates de novo synthesis of plasticity related proteins, crucial factors for establishing persistent long-term synaptic plasticity and forming memory engrams. Extensive studies have been performed to elucidate molecular mechanisms of memory traces formation; however, the identity of plasticity related proteins is still evasive. In this study, we investigated protein turnover in mouse hippocampus during long-term spatial memory formation using the reference memory version of radial arm maze (RAM) paradigm. We identified 1592 proteins, which exhibited a complex picture of expression changes during spatial memory formation. Variable linear decomposition reduced significantly data dimensionality and enriched three principal factors responsible for variance of memory-related protein levels at (1) the initial phase of memory acquisition (165 proteins), (2) during the steep learning improvement (148 proteins), and (3) the final phase of the learning curve (123 proteins). Gene ontology and signaling pathways analysis revealed a clear correlation between memory improvement and learning phase-curbed expression profiles of proteins belonging to specific functional categories. We found differential enrichment of (1) neurotrophic factors signaling pathways, proteins regulating synaptic transmission, and actin microfilament during the first day of the learning curve; (2) transcription and translation machinery, protein

  7. Dynamics of Hippocampal Protein Expression During Long-term Spatial Memory Formation.

    Science.gov (United States)

    Borovok, Natalia; Nesher, Elimelech; Levin, Yishai; Reichenstein, Michal; Pinhasov, Albert; Michaelevski, Izhak

    2016-02-01

    Spatial memory depends on the hippocampus, which is particularly vulnerable to aging. This vulnerability has implications for the impairment of navigation capacities in older people, who may show a marked drop in performance of spatial tasks with advancing age. Contemporary understanding of long-term memory formation relies on molecular mechanisms underlying long-term synaptic plasticity. With memory acquisition, activity-dependent changes occurring in synapses initiate multiple signal transduction pathways enhancing protein turnover. This enhancement facilitates de novo synthesis of plasticity related proteins, crucial factors for establishing persistent long-term synaptic plasticity and forming memory engrams. Extensive studies have been performed to elucidate molecular mechanisms of memory traces formation; however, the identity of plasticity related proteins is still evasive. In this study, we investigated protein turnover in mouse hippocampus during long-term spatial memory formation using the reference memory version of radial arm maze (RAM) paradigm. We identified 1592 proteins, which exhibited a complex picture of expression changes during spatial memory formation. Variable linear decomposition reduced significantly data dimensionality and enriched three principal factors responsible for variance of memory-related protein levels at (1) the initial phase of memory acquisition (165 proteins), (2) during the steep learning improvement (148 proteins), and (3) the final phase of the learning curve (123 proteins). Gene ontology and signaling pathways analysis revealed a clear correlation between memory improvement and learning phase-curbed expression profiles of proteins belonging to specific functional categories. We found differential enrichment of (1) neurotrophic factors signaling pathways, proteins regulating synaptic transmission, and actin microfilament during the first day of the learning curve; (2) transcription and translation machinery, protein

  8. Enhanced nigrostriatal neuron-specific, long-term expression by using neural-specific promoters in combination with targeted gene transfer by modified helper virus-free HSV-1 vector particles

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    Kong Lingxin

    2008-04-01

    Full Text Available Abstract Background Direct gene transfer into neurons has potential for developing gene therapy treatments for specific neurological conditions, and for elucidating neuronal physiology. Due to the complex cellular composition of specific brain areas, neuronal type-specific recombinant gene expression is required for many potential applications of neuronal gene transfer. One approach is to target gene transfer to a specific type of neuron. We developed modified Herpes Simplex Virus (HSV-1 particles that contain chimeric glycoprotein C (gC – glial cell line-derived neurotrophic factor (GDNF or brain-derived neurotrophic factor (BDNF proteins. HSV-1 vector particles containing either gC – GDNF or gC – BDNF target gene transfer to nigrostriatal neurons, which contain specific receptors for GDNF or BDNF. A second approach to achieve neuronal type-specific expression is to use a cell type-specific promoter, and we have used the tyrosine hydroxylase (TH promoter to restrict expression to catecholaminergic neurons or a modified neurofilament heavy gene promoter to restrict expression to neurons, and both of these promoters support long-term expression from HSV-1 vectors. To both improve nigrostriatal-neuron specific expression, and to establish that targeted gene transfer can be followed by long-term expression, we performed targeted gene transfer with vectors that support long-term, neuronal-specific expression. Results Helper virus-free HSV-1 vector packaging was performed using either gC – GDNF or gC – BDNF and vectors that contain either the TH promoter or the modified neurofilament heavy gene promoter. Vector stocks were injected into the midbrain proximal to the substantia nigra, and the rats were sacrificed at either 4 days or 1 month after gene transfer. Immunofluorescent costaining was performed to detect both recombinant gene products and nigrostriatal neurons. The combination of targeted gene transfer with neuronal

  9. Enhanced Polyhydroxybutyrate Production for Long-Term Spaceflight Applications

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    Putman, Ryan J.; Rahman, Asif; Miller, Charles D.; Hadi, Masood Z.

    2015-01-01

    Synthetic biology holds the promise of advancing long term space fight by the production of medicine, food, materials, and energy. One such application of synthetic biology is the production of biomaterials, specifically polyhydroxyalkanoates (PHAs), using purposed organisms such as Escherichia coli. PHAs are a group of biodegradable bioplastics that are produced by a wide variety of naturally occurring microorganisms, mainly as an energy storage intermediate. PHAs have similar melting point to polypropylene and a Youngs modulus close to polystyrene. Due to limited resources and cost of transportation, large-scale extraction of biologically produced products in situ is extremely cumbersome during space flight. To that end, we are developing a secretion systems for exporting PHA from the cell in order to reduce unit operations. PHAs granules deposited inside bacteria are typically associated with proteins bound to the granule surface. Phasin, a granule bound protein, was targeted for type I secretion by fusion with HlyA signal peptide for indirect secretion of PHAs. In order to validate our secretion strategy, a green fluorescent protein (GFP) was tagged to the PHA polymerase enzyme (phaC), this three part gene cassette consists of phaA and phaB and are required for PHA production. Producing PHAs in situ during space flight or planet colonization will enable mission success by providing a valuable source of biomaterials that can have many potential applications thereby reducing resupply requirements. Biologically produced PHAs can be used in additive manufacturing such as three dimensional (3D) printing to create products that can be made on demand during space flight. After exceeding their lifetime, the PHAs could be melted and recycled back to 3D print other products. We will discuss some of our long term goals of this approach.

  10. 77 FR 12227 - Long Term 2 Enhanced Surface Water Treatment Rule: Uncovered Finished Water Reservoirs; Public...

    Science.gov (United States)

    2012-02-29

    ... AGENCY 40 CFR Parts 141 and 142 Long Term 2 Enhanced Surface Water Treatment Rule: Uncovered Finished Water Reservoirs; Public Meeting AGENCY: Environmental Protection Agency (EPA). ACTION: Notice of public... requirement in the Long Term 2 Enhanced Surface Water Treatment Rule (LT2 rule). At this meeting, EPA will...

  11. 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.

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    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

  12. Skilled motor learning does not enhance long-term depression in the motor cortex in vivo.

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    Cohen, Jeremy D; Castro-Alamancos, Manuel A

    2005-03-01

    Learning of motor skills may occur as a consequence of changes in the efficacy of synaptic connections in the primary motor cortex. We investigated if learning in a reaching task affects the excitability, short-term plasticity, and long-term plasticity of horizontal connections in layers II-III of the motor cortex. Because training in this task requires animals to be food-deprived, we compared the trained animals with similarly food-deprived untrained animals and normal controls. The results show that the excitability, short-term plasticity, and long-term plasticity of the studied horizontal connections were unaffected by motor learning. However, stress-related effects produced by food deprivation and handling significantly enhanced the expression of long-term depression in these pathways. These results are compatible with the hypothesis that the acquisition of a complex motor skill produces bi-directional changes in synaptic strength that are distributed throughout the complex neural networks of motor cortex, which remains synaptically balanced during learning. The results are incompatible with the idea that learning causes large unidirectional changes in the population response of these neural networks, which may occur instead during certain behavioral states, such as stress.

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

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    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

  14. Long-term expression of glomerular genes in diabetic nephropathy.

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    Chittka, Dominik; Banas, Bernhard; Lennartz, Laura; Putz, Franz Josef; Eidenschink, Kathrin; Beck, Sebastian; Stempfl, Thomas; Moehle, Christoph; Reichelt-Wurm, Simone; Banas, Miriam C

    2018-01-11

    Although diabetic nephropathy (DN) is the most common cause for end-stage renal disease in western societies, its pathogenesis still remains largely unclear. A different gene pattern of diabetic and healthy kidney cells is one of the probable explanations. Numerous signalling pathways have emerged as important pathophysiological mechanisms for diabetes-induced renal injury. Glomerular cells, as podocytes or mesangial cells, are predominantly involved in the development of diabetic renal lesions. While many gene assays concerning DN are performed with whole kidney or renal cortex tissue, we isolated glomeruli from black and tan, brachyuric (BTBR) obese/obese (ob/ob) and wildtype mice at four different timepoints (4, 8, 16 and 24 weeks) and performed an mRNA microarray to identify differentially expressed genes (DEGs). In contrast to many other diabetic mouse models, these homozygous ob/ob leptin-deficient mice develop not only a severe type 2 diabetes, but also diabetic kidney injury with all the clinical and especially histologic features defining human DN. By functional enrichment analysis we were able to investigate biological processes and pathways enriched by the DEGs at different disease stages. Altered expression of nine randomly selected genes was confirmed by quantitative polymerase chain reaction from glomerular RNA. Ob/ob type 2 diabetic mice showed up- and downregulation of genes primarily involved in metabolic processes and pathways, including glucose, lipid, fatty acid, retinol and amino acid metabolism. Members of the CYP4A and ApoB family were found among the top abundant genes. But more interestingly, altered gene loci showed enrichment for processes and pathways linked to angioneogenesis, complement cascades, semaphorin pathways, oxidation and reduction processes and renin secretion. The gene profile of BTBR ob/ob type 2 diabetic mice we conducted in this study can help to identify new key players in molecular pathogenesis of diabetic kidney

  15. Mechanisms of Hippocampal Long-Term Depression Are Required for Memory Enhancement by Novelty Exploration

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    Dong, Zhifang; Gong, Bo; Li, Hongjie; Bai, Yanrui; Wu, Xiaoyan; Huang, Yan; He, Wenting; Li, Tingyu; Wang, Yu Tian

    2013-01-01

    It is well known that novel environments can enhance learning and memory. However, the underlying mechanisms remain poorly understood. Here, we report that, in freely moving rats, novelty exploration facilitates the production of hippocampal CA1 long-term depression (LTD), a well characterized form of synaptic plasticity believed to be a cellular substrate of spatial learning, and thereby converts short-term memory (STM) into long-term memory (LTM) in an inhibitory avoidance learning procedure. Blocking the induction or the expression of CA1 LTD with two mechanistically and structurally distinct inhibitors prevents not only novelty acquisition but also the novelty exploration-promoted conversion of STM into LTM. Moreover, production of LTD with a strong electrical stimulation induction protocol or facilitation of hippocampal LTD by pharmacological inhibition of glutamate transporter activity mimics the behavioral effects of novelty exploration, sufficiently promoting the conversion of STM into LTM. Together, our findings suggest that induction of LTD may play an essential role not only in novelty acquisition but also in novelty-mediated memory enhancement. PMID:22933783

  16. Retention of gene expression in porcine islets after agarose encapsulation and long-term culture

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    Dumpala, Pradeep R., E-mail: pdumpala@rixd.org [The Rogosin Institute – Xenia Division, 740 Birch Road, Xenia, OH 45385 (United States); Holdcraft, Robert W.; Martis, Prithy C.; Laramore, Melissa A. [The Rogosin Institute – Xenia Division, 740 Birch Road, Xenia, OH 45385 (United States); Parker, Thomas S.; Levine, Daniel M. [The Rogosin Institute, 505 East 70th Street, New York, NY 10021 (United States); Smith, Barry H. [The Rogosin Institute, 505 East 70th Street, New York, NY 10021 (United States); NewYork-Presbyterian Hospital, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10021 (United States); Gazda, Lawrence S. [The Rogosin Institute – Xenia Division, 740 Birch Road, Xenia, OH 45385 (United States)

    2016-08-05

    Agarose encapsulation of porcine islets allows extended in vitro culture, providing ample time to determine the functional capacity of the islets and conduct comprehensive microbiological safety testing prior to implantation as a treatment for type 1 diabetes mellitus. However, the effect that agarose encapsulation and long-term culture may have on porcine islet gene expression is unknown. The aim of the present study was to compare the transcriptome of encapsulated porcine islets following long-term in vitro culture against free islets cultured overnight. Global gene expression analysis revealed no significant change in the expression of 98.47% of genes. This indicates that the gene expression profile of free islets is highly conserved following encapsulation and long-term culture. Importantly, the expression levels of genes that code for critical hormones secreted by islets (insulin, glucagon, and somatostatin) as well as transcripts encoding proteins involved in their packaging and secretion are unchanged. While a small number of genes known to play roles in the insulin secretion and insulin signaling pathways are differentially expressed, our results show that overall gene expression is retained following islet isolation, agarose encapsulation, and long-term culture. - Highlights: • Effect of agarose encapsulation and 8 week culture on porcine islets was analyzed. • Transcriptome analysis revealed no significant change in a majority (98%) of genes. • Agarose encapsulation allows for long-term culture of porcine islets. • Islet culture allows for functional and microbial testing prior to clinical use.

  17. Long-term cognitive enrichment affects opioid receptor expression in the amygdala of domestic pigs.

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    Kalbe, C; Puppe, B

    2010-02-01

    Enriching the housing environment by stimuli that challenge both reward and cognitive mechanisms may enhance behavioural experiences and can improve animal welfare, particularly in farm animals. A newly developed experimental feeding system for domestic pigs using food-rewarded learning of discriminatory and instrumental tasks enabled the animals to successfully master a cognitive challenge and to be rewarded ca. 30 times per day with small food portions. Reward-related behaviour is expected to be modulated by endogenous opioid systems. Furthermore, recent evidence supports a role for the amygdala in processing positive affects by stimulus-reward learning. Hence, the present study investigates mRNA expression of cerebral receptors, which are involved in these processes. In an initial step, reverse transcription-polymerase chain reaction (RT-PCR) provided the first evidence that transcripts of three different opioid receptors (MOR, DOR, KOR), as well as the neuropeptide Y 5 receptor (NPY5R), leptin receptor (LEPR) and proopiomelanocortin (POMC), are expressed in both the porcine amygdala and hypothalamus. Using real-time PCR we could show that the expression of two receptors of the opioid system (amygdala: KOR, DOR), in addition to the expression of NPY5R (hypothalamus) in eight enriched housed pigs was markedly downregulated compared to that of conventionally housed and fed pigs. Focusing on opioid receptors in the amygdala, the present study shows that long-term cognitive enrichment acts as a biologically relevant stimulus that causes modifications of gene expression of reward-sensitive cerebral receptors in domestic pigs.

  18. Post-training intrahippocampal inhibition of class I histone deacetylases enhances long-term object-location memory

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    Hawk, Joshua D.; Florian, Cédrick; Abel, Ted

    2011-01-01

    Long-term memory formation involves covalent modification of the histone proteins that package DNA. Reducing histone acetylation by mutating histone acetyltransferases impairs long-term memory, and enhancing histone acetylation by inhibiting histone deacetylases (HDACs) improves long-term memory. Previous studies using HDAC inhibitors to enhance long-term memory have focused on the fear-conditioning task using broad-spectrum HDAC inhibitors. We have found that post-training intrahippocampal a...

  19. Transgenic Mice Expressing an Inhibitory Truncated Form of p300 Exhibit Long-Term Memory Deficits

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    Oliveira, Ana M. M.; Wood, Marcelo A.; McDonough, Conor B.; Abel, Ted

    2007-01-01

    The formation of many forms of long-term memory requires several molecular mechanisms including regulation of gene expression. The mechanisms directing transcription require not only activation of individual transcription factors but also recruitment of transcriptional coactivators. CBP and p300 are transcriptional coactivators that interact with…

  20. Synaptic Transmission Optimization Predicts Expression Loci of Long-Term Plasticity.

    Science.gov (United States)

    Costa, Rui Ponte; Padamsey, Zahid; D'Amour, James A; Emptage, Nigel J; Froemke, Robert C; Vogels, Tim P

    2017-09-27

    Long-term modifications of neuronal connections are critical for reliable memory storage in the brain. However, their locus of expression-pre- or postsynaptic-is highly variable. Here we introduce a theoretical framework in which long-term plasticity performs an optimization of the postsynaptic response statistics toward a given mean with minimal variance. Consequently, the state of the synapse at the time of plasticity induction determines the ratio of pre- and postsynaptic modifications. Our theory explains the experimentally observed expression loci of the hippocampal and neocortical synaptic potentiation studies we examined. Moreover, the theory predicts presynaptic expression of long-term depression, consistent with experimental observations. At inhibitory synapses, the theory suggests a statistically efficient excitatory-inhibitory balance in which changes in inhibitory postsynaptic response statistics specifically target the mean excitation. Our results provide a unifying theory for understanding the expression mechanisms and functions of long-term synaptic transmission plasticity. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  1. Post-Training Intrahippocampal Inhibition of Class I Histone Deacetylases Enhances Long-Term Object-Location Memory

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    Hawk, Joshua D.; Florian, Cedrick; Abel, Ted

    2011-01-01

    Long-term memory formation involves covalent modification of the histone proteins that package DNA. Reducing histone acetylation by mutating histone acetyltransferases impairs long-term memory, and enhancing histone acetylation by inhibiting histone deacetylases (HDACs) improves long-term memory. Previous studies using HDAC inhibitors to enhance…

  2. Enhancement of both long-term depression induction and optokinetic response adaptation in mice lacking delphilin.

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    Tomonori Takeuchi

    Full Text Available In the cerebellum, Delphilin is expressed selectively in Purkinje cells (PCs and is localized exclusively at parallel fiber (PF synapses, where it interacts with glutamate receptor (GluR delta2 that is essential for long-term depression (LTD, motor learning and cerebellar wiring. Delphilin ablation exerted little effect on the synaptic localization of GluRdelta2. There were no detectable abnormalities in cerebellar histology, PC cytology and PC synapse formation in contrast to GluRdelta2 mutant mice. However, LTD induction was facilitated at PF-PC synapses in Delphilin mutant mice. Intracellular Ca(2+ required for the induction of LTD appeared to be reduced in the mutant mice, while Ca(2+ influx through voltage-gated Ca(2+ channels and metabotropic GluR1-mediated slow synaptic response were similar between wild-type and mutant mice. We further showed that the gain-increase adaptation of the optokinetic response (OKR was enhanced in the mutant mice. These findings are compatible with the idea that LTD induction at PF-PC synapses is a crucial rate-limiting step in OKR gain-increase adaptation, a simple form of motor learning. As exemplified in this study, enhancing synaptic plasticity at a specific synaptic site of a neural network is a useful approach to understanding the roles of multiple plasticity mechanisms at various cerebellar synapses in motor control and learning.

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

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    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. Nicotine Uses Neuron-Glia Communication to Enhance Hippocampal Synaptic Transmission and Long-term Memory

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    López-Hidalgo, Mónica; Salgado-Puga, Karla; Alvarado-Martínez, Reynaldo; Medina, Andrea Cristina; Prado-Alcalá, Roberto A.; García-Colunga, Jesús

    2012-01-01

    Nicotine enhances synaptic transmission and facilitates long-term memory. Now it is known that bi-directional glia-neuron interactions play important roles in the physiology of the brain. However, the involvement of glial cells in the effects of nicotine has not been considered until now. In particular, the gliotransmitter D-serine, an endogenous co-agonist of NMDA receptors, enables different types of synaptic plasticity and memory in the hippocampus. Here, we report that hippocampal long-term synaptic plasticity induced by nicotine was annulled by an enzyme that degrades endogenous D-serine, or by an NMDA receptor antagonist that acts at the D-serine binding site. Accordingly, both effects of nicotine: the enhancement of synaptic transmission and facilitation of long-term memory were eliminated by impairing glial cells with fluoroacetate, and were restored with exogenous D-serine. Together, these results show that glial D-serine is essential for the long-term effects of nicotine on synaptic plasticity and memory, and they highlight the roles of glial cells as key participants in brain functions. PMID:23185511

  5. Long term expression of bicistronic vector driven by the FGF-1 IRES in mouse muscle

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    Van den Berghe Loïc

    2007-10-01

    Full Text Available Abstract Background Electrotransfer of plasmid DNA into skeletal muscle is a promising strategy for the delivery of therapeutic molecules targeting various muscular diseases, cancer and lower-limb ischemia. Internal Ribosome Entry Sites (IRESs allow co-expression of proteins of interest from a single transcriptional unit. IRESs are RNA elements that have been found in viral RNAs as well as a variety of cellular mRNAs with long 5' untranslated regions. While the encephalomyocarditis virus (EMCV IRES is often used in expression vectors, we have shown that the FGF-1 IRES is equally active to drive short term transgene expression in mouse muscle. To compare the ability of the FGF-1 IRES to drive long term expression against the EMCV and FGF-2 IRESs, we performed analyses of expression kinetics using bicistronic vectors that express the bioluminescent renilla and firefly luciferase reporter genes. Long term expression of bicistronic vectors was also compared to that of monocistronic vectors. Bioluminescence was quantified ex vivo using a luminometer and in vivo using a CCD camera that monitors luminescence within live animals. Results Our data demonstrate that the efficiency of the FGF-1 IRES is comparable to that of the EMCV IRES for long term expression of bicistronic transgenes in mouse muscle, whereas the FGF-2 IRES has a very poor activity. Interestingly, we show that despite the global decrease of vector expression over time, the ratio of firefly to renilla luciferase remains stable with bicistronic vectors containing the FGF-1 or FGF-2 IRES and is slightly affected with the EMCV IRES, whereas it is clearly unstable for mixed monocistronic vectors. In addition, long term expression more drastically decreases with monocistronic vectors, and is different for single or mixed vector injection. Conclusion These data validate the use of bicistronic vectors rather than mixed monocistronic vectors for long term expression, and support the use of the

  6. Long term expression of bicistronic vector driven by the FGF-1 IRES in mouse muscle.

    Science.gov (United States)

    Allera-Moreau, Camille; Delluc-Clavières, Aurélie; Castano, Caroline; Van den Berghe, Loïc; Golzio, Muriel; Moreau, Marc; Teissié, Justin; Arnal, Jean-François; Prats, Anne-Catherine

    2007-10-28

    Electrotransfer of plasmid DNA into skeletal muscle is a promising strategy for the delivery of therapeutic molecules targeting various muscular diseases, cancer and lower-limb ischemia. Internal Ribosome Entry Sites (IRESs) allow co-expression of proteins of interest from a single transcriptional unit. IRESs are RNA elements that have been found in viral RNAs as well as a variety of cellular mRNAs with long 5' untranslated regions. While the encephalomyocarditis virus (EMCV) IRES is often used in expression vectors, we have shown that the FGF-1 IRES is equally active to drive short term transgene expression in mouse muscle. To compare the ability of the FGF-1 IRES to drive long term expression against the EMCV and FGF-2 IRESs, we performed analyses of expression kinetics using bicistronic vectors that express the bioluminescent renilla and firefly luciferase reporter genes. Long term expression of bicistronic vectors was also compared to that of monocistronic vectors. Bioluminescence was quantified ex vivo using a luminometer and in vivo using a CCD camera that monitors luminescence within live animals. Our data demonstrate that the efficiency of the FGF-1 IRES is comparable to that of the EMCV IRES for long term expression of bicistronic transgenes in mouse muscle, whereas the FGF-2 IRES has a very poor activity. Interestingly, we show that despite the global decrease of vector expression over time, the ratio of firefly to renilla luciferase remains stable with bicistronic vectors containing the FGF-1 or FGF-2 IRES and is slightly affected with the EMCV IRES, whereas it is clearly unstable for mixed monocistronic vectors. In addition, long term expression more drastically decreases with monocistronic vectors, and is different for single or mixed vector injection. These data validate the use of bicistronic vectors rather than mixed monocistronic vectors for long term expression, and support the use of the FGF-1 IRES. The use of a cellular IRES over one of viral

  7. Differential Gene Expression Profiling of Enriched Human Spermatogonia after Short- and Long-Term Culture

    Directory of Open Access Journals (Sweden)

    Sabine Conrad

    2014-01-01

    Full Text Available This study aimed to provide a molecular signature for enriched adult human stem/progenitor spermatogonia during short-term (<2 weeks and long-term culture (up to more than 14 months in comparison to human testicular fibroblasts and human embryonic stem cells. Human spermatogonia were isolated by CD49f magnetic activated cell sorting and collagen−/laminin+ matrix binding from primary testis cultures obtained from ten adult men. For transcriptomic analysis, single spermatogonia-like cells were collected based on their morphology and dimensions using a micromanipulation system from the enriched germ cell cultures. Immunocytochemical, RT-PCR and microarray analyses revealed that the analyzed populations of cells were distinct at the molecular level. The germ- and pluripotency-associated genes and genes of differentiation/spermatogenesis pathway were highly expressed in enriched short-term cultured spermatogonia. After long-term culture, a proportion of cells retained and aggravated the “spermatogonial” gene expression profile with the expression of germ and pluripotency-associated genes, while in the majority of long-term cultured cells this molecular profile, typical for the differentiation pathway, was reduced and more genes related to the extracellular matrix production and attachment were expressed. The approach we provide here to study the molecular status of in vitro cultured spermatogonia may be important to optimize the culture conditions and to evaluate the germ cell plasticity in the future.

  8. Enhancing nursing leadership in long-term care. A review of the literature.

    Science.gov (United States)

    Harvath, Theresa A; Swafford, Kristen; Smith, Kathryn; Miller, Lois L; Volpin, Miriam; Sexson, Kathryn; White, Diana; Young, Heather A

    2008-07-01

    The quality of care provided to nursing home residents has been the subject of broad criticism for years. Mounting evidence suggests that the quality of nursing home care can be improved by strengthening the roles of nurses in these facilities. This article reviews the literature on programs designed to enhance nursing leadership in long-term care, examines outcomes associated with leadership in long-term care, and outlines recommendations for programs to enhance nursing leadership in nursing home settings. The findings suggest that nursing leadership training programs for nurses working in nursing homes are urgently needed to improve quality in the nation's nursing homes and stabilize the workforce. To maximize their effectiveness, these leadership training programs should be part of a continuum of leadership development that begins in nursing education programs and persists throughout a nurse's career trajectory. Copyright 2009, SLACK Incorporated.

  9. Long-term lowering of tumour interstitial fluid pressure reduces Ki-67 expression.

    Science.gov (United States)

    Hofmann, Matthias; Schultz, Maike; Bernd, August; Bereiter-Hahn, Jürgen; Kaufmann, Roland; Kippenberger, Stefan

    2007-01-01

    High tumour interstitial fluid pressure (TIFP) is a characteristic of most solid tumours. Recent data give first evidence that mechanical stretch induced by TIFP triggers proliferation in solid tumours. In the present study we compared two protocols of TIFP reduction on the expression of the tumour proliferation marker Ki-67: (a) short-term lowering of TIFP by a singular puncture and (b) long-term lowering of TIFP by catheterization. Utilizing two experimental tumours (A431, A549) it was found that the TIFP broke down rapidly after a singular puncture but recovered within 6h. In case of permanent catheterization no TIFP recovery was observed. After 24h tumours were excised and stained against the proliferation marker Ki-67. While a singular puncture had no effect catheterized tumours showed a significant decrease in Ki-67 expression. Our data suggest that long-term lowering of TIFP is required to reduce tumour proliferation.

  10. 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.

  11. 77 FR 57545 - Long Term 2 Enhanced Surface Water Treatment Rule: Public Meeting on Monitoring Data Analysis...

    Science.gov (United States)

    2012-09-18

    ... AGENCY 40 CFR Parts 141 and 142 Long Term 2 Enhanced Surface Water Treatment Rule: Public Meeting on... toolbox information as part of the regulatory review of the Long Term 2 Enhanced Surface Water Treatment... monitoring that are used to determine which one of the four categories (i.e., bins) a public drinking water...

  12. LONG-TERM DEMONSTRATION OF SORBENT ENHANCEMENT ADDITIVE TECHNOLOGY FOR MERCURY CONTROL

    Energy Technology Data Exchange (ETDEWEB)

    Jason D. Laumb; Dennis L. Laudal; Grant E. Dunham; John P. Kay; Christopher L. Martin; Jeffrey S. Thompson; Nicholas B. Lentz; Alexander Azenkeng; Kevin C. Galbreath; Lucinda L. Hamre

    2011-05-27

    Long-term demonstration tests of advanced sorbent enhancement additive (SEA) technologies have been completed at five coal-fired power plants. The targeted removal rate was 90% from baseline conditions at all five stations. The plants included Hawthorn Unit 5, Mill Creek Unit 4, San Miguel Unit 1, Centralia Unit 2, and Hoot Lake Unit 2. The materials tested included powdered activated carbon, treated carbon, scrubber additives, and SEAs. In only one case (San Miguel) was >90% removal not attainable. The reemission of mercury from the scrubber at this facility prevented >90% capture.

  13. c-Fos expression predicts long-term social memory retrieval in mice.

    Science.gov (United States)

    Lüscher Dias, Thomaz; Fernandes Golino, Hudson; Moura de Oliveira, Vinícius Elias; Dutra Moraes, Márcio Flávio; Schenatto Pereira, Grace

    2016-10-15

    The way the rodent brain generally processes socially relevant information is rather well understood. How social information is stored into long-term social memory, however, is still under debate. Here, brain c-Fos expression was measured after adult mice were exposed to familiar or novel juveniles and expression was compared in several memory and socially relevant brain areas. Machine Learning algorithm Random Forest was then used to predict the social interaction category of adult mice based on c-Fos expression in these areas. Interaction with a familiar co-specific altered brain activation in the olfactory bulb, amygdala, hippocampus, lateral septum and medial prefrontal cortex. Remarkably, Random Forest was able to predict interaction with a familiar juvenile with 100% accuracy. Activity in the olfactory bulb, amygdala, hippocampus and the medial prefrontal cortex were crucial to this prediction. From our results, we suggest long-term social memory depends on initial social olfactory processing in the medial amygdala and its output connections synergistically with non-social contextual integration by the hippocampus and medial prefrontal cortex top-down modulation of primary olfactory structures. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Omega-3 polyunsaturated fatty acids enhance cerebral angiogenesis and provide long-term protection after stroke

    Science.gov (United States)

    Wang, Jiayin; Shi, Yejie; Zhang, Lili; Zhang, Feng; Hu, Xiaoming; Zhang, Wengting; Leak, Rehana K.; Gao, Yanqin; Chen, Ling; Chen, Jun

    2014-01-01

    Stroke is a devastating neurological disorder and one of the leading causes of death and serious disability. After cerebral ischemia, revascularization in the ischemic boundary zone provides nutritive blood flow as well as various growth factors to promote the survival and activity of neurons and neural progenitor cells. Enhancement of angiogenesis and the resulting improvement of cerebral microcirculation are key restorative mechanisms and represent an important therapeutic strategy for ischemic stroke. In the present study, we tested the hypothesis that post-stroke angiogenesis would be enhanced by omega-3 polyunsaturated fatty acids (n-3 PUFAs), a major component of dietary fish oil. To this end, we found that transgenic fat-1 mice that overproduce n-3 PUFAs exhibited long-term behavioral and histological protection against transient focal cerebral ischemia (tFCI). Importantly, fat-1 transgenic mice also exhibited robust improvements in revascularization and angiogenesis compared to wild type littermates, suggesting a potential role for n-3 fatty acids in post-stroke cerebrovascular remodeling. Mechanistically, n-3 PUFAs induced upregulation of angiopoietin 2 (Ang 2) in astrocytes after tFCI and stimulated extracellular Ang 2 release from cultured astrocytes after oxygen and glucose deprivation. Ang 2 facilitated endothelial proliferation and barrier formation in vitro by potentiating the effects of VEGF on phospholipase Cγ1 and Src signaling. Consistent with these findings, blockade of Src activity in post-stroke fat-1 mice impaired n-3 PUFA-induced angiogenesis and exacerbated long-term neurological outcomes. Taken together, our findings strongly suggest that n-3 PUFA supplementation is a potential angiogenic treatment capable of augmenting brain repair and improving long-term functional recovery after cerebral ischemia. PMID:24794156

  15. MHC II expression in the CNS after long-term demyelination

    Energy Technology Data Exchange (ETDEWEB)

    Cannella, B.; Aquino, D.A.; Raine, C.S.

    1995-07-01

    The ability of chronically demyelinated central nervous system (CNS) tissue to express major histocompatibility complex (MHC) class II molecules has been measured in mouse spinal cord cultures exposed for 1 and 3 weeks to demyelinating anti-white matter (WM) serum. From previous studies, It was known that after 3 weeks of demyelination in vitro, such cultures are incapable of remyelination. In the present report, MHC II levels were evaluated by immunocytochemistry and by Western and Northern blots. The results have shown that after both 1 and 3 weeks of exposure to myelinotoxic anti-WM serum, the cultures retained the ability to express MHC II and this could be further upregulated by incubation with interferon {gamma} (IFN{gamma}). Control groups showed increased expression of MHC II with age. By immunocytochemistry, all groups of cultures expressed high levels of MHC II and all groups showed upregulation after IFN{gamma} treatment. Anti-WM-treated cultures demonstrated slightly higher levels of MHC II than controls. Morphologically, the MHC II expression was associated with the surface of astrocytes. Semiquantitative analysis by Western blotting confirmed the increase in class II MHC expression in the long-term treated cultures after IFN{gamma} exposure, revealing no differences between anti-WM-treated and complement-treated cultures. This was also supported by Northern blotting which showed similar mRNA levels in both groups. These findings suggest that long-term demyelinated CNS tissue still possesses the ability to interact with CD4{sup +} T cells, observations of significance to the expansion of the chronic multiple sclerosis lesion. 50 refs., 6 figs., 2 tabs.

  16. Music training causes long-term enhancement of preschool children's spatial-temporal reasoning.

    Science.gov (United States)

    Rauscher, F H; Shaw, G L; Levine, L J; Wright, E L; Dennis, W R; Newcomb, R L

    1997-02-01

    Predictions from a structured cortical model led us to test the hypothesis that music training enhances young children's spatial-temporal reasoning. Seventy-eight preschool children participated in this study. Thirty-four children received private piano keyboard lessons, 20 children received private computer lessons, and 24 children provided other controls. Four standard, age-calibrated, spatial reasoning tests were given before and after training; one test assessed spatial-temporal reasoning and three tests assessed spatial recognition. Significant improvement on the spatial-temporal test was found for the keyboard group only. No group improved significantly on the spatial recognition tests. The magnitude of the spatial-temporal improvement from keyboard training was greater than one standard deviation of the standardized test and lasted at least one day, a duration traditionally classified as long term. This represents an increase in time by a factor of over 100 compared to a previous study in which listening to a Mozart piano sonata primed spatial-temporal reasoning in college students. This suggests that music training produces long-term modifications in underlying neural circuitry in regions not primarily concerned with music and might be investigated using EEG. We propose that an improvement of the magnitude reported may enhance the learning of standard curricula, such as mathematics and science, that draw heavily upon spatial-temporal reasoning.

  17. Long-term T-DNA insert stability and transgene expression consistency in field propagated sugarcane.

    Science.gov (United States)

    Caffall, Kerry Hosmer; He, Chengkun; Smith-Jones, Michele; Mayo, Kristin; Mai, Pearl; Dong, Shujie; Ke, John; Dunder, Erik; Yarnall, Michele; Whinna, Rachel; DeMaio, Joe; Gu, Weining; Sheldon, Judith; Allen, Martin; Costello, Tricia; Setliff, Kristin; Jain, Rakesh; Snyder, Ada; Lovelady, Clark; Rawls, Eric; Palmer, Eric; Zhang, Yan; Bate, Nicholas; Shi, Liang; Jepson, Ian

    2017-03-01

    This study addresses T-DNA insert stability and transgene expression consistency in multiple cycles of field propagated sugarcane. T-DNA inserts are stable; no transgene rearrangements were observed. AmCYAN1 and PMI protein accumulation levels were maintained. There was no evidence that production of either protein declined across generations and no transgene silencing was observed in three commercial sugarcane varieties through commercially relevant ratooning, propagation-by-setts, and micro-propagation generation processes over 4 years of field testing. Long term transgene expression consistency and T-DNA insert stability can be achieved in sugarcane, suggesting that it is highly probable that transgenic sugarcane can be successfully commercialized. This study addresses T-DNA insert stability and transgene expression consistency in multiple cycles of field propagated sugarcane. These data are critical supporting information needed for successful commercialization of GM sugarcane. Here seventeen transgenic events, containing the AmCYAN1 gene driven by a CMP promoter and the E. coli PMI gene driven by either a CMP or Ubi promoter, were used to monitor T-DNA insert stability and consistency of transgene encoded protein accumulation through commercially relevant ratooning, propagation-by-setts, and micro-propagation generation processes. The experiments were conducted in three commercial sugarcane varieties over 4 years of field testing. DNA gel blot analysis showed that the T-DNA inserts are stable; no transgene rearrangements were observed. Quantitative ELISA showed no evidence of decreasing AmCYAN1 and PMI protein levels across generations and no transgene silencing was observed. These results indicate that long term transgene expression consistency and T-DNA insert stability can be achieved in sugarcane, suggesting that it is highly probable that transgenic sugarcane can be successfully commercialized.

  18. 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.

  19. Intercellular adhesion molecule-1 expression in human endometrium: implications for long term progestin only contraception

    Directory of Open Access Journals (Sweden)

    Kuczynski Edward

    2006-01-01

    Full Text Available Abstract Background Neutrophils infiltrate the endometrium pre-menstrually and after long-term progestin only-contraceptive (LTPOC treatment. Trafficking of neutrophils involves endothelial cell-expressed intercellular adhesion molecule (ICAM-1. Previous studies observed that ICAM-1 was immunolocalized to the endothelium of endometrial specimens across the menstrual cycle, but disagreed as to whether extra-endothelial cell types express ICAM-1 and whether ICAM-1 expression varies across the menstrual cycle. Methods Endometrial biopsies were obtained from women across the menstrual cycle and from those on LTPOC treatment (either Mirena or Norplant. The biopsies were formalin-fixed and paraffin-embedded with subsequent immunohistochemical staining for ICAM-1. Results The current study found prominent ICAM-1 staining in the endometrial endothelium that was of equivalent intensity in different blood vessel types irrespective of the steroidal or inflammatory endometrial milieu across the menstrual cycle and during LTPOC therapy. Unlike the endothelial cells, the glands were negative and the stromal cells were weakly positive for ICAM immunostaining. Conclusion The results of the current study suggest that altered expression of ICAM-1 by endothelial cells does not account for the influx of neutrophils into the premenstrual and LTPOC-derived endometrium. Such neutrophil infiltration may depend on altered expression of neutrophil chemoattractants.

  20. 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

  1. Long-term optical stimulation of channelrhodopsin-expressing neurons to study network plasticity

    Science.gov (United States)

    Lignani, Gabriele; Ferrea, Enrico; Difato, Francesco; Amarù, Jessica; Ferroni, Eleonora; Lugarà, Eleonora; Espinoza, Stefano; Gainetdinov, Raul R.; Baldelli, Pietro; Benfenati, Fabio

    2013-01-01

    Neuronal plasticity produces changes in excitability, synaptic transmission, and network architecture in response to external stimuli. Network adaptation to environmental conditions takes place in time scales ranging from few seconds to days, and modulates the entire network dynamics. To study the network response to defined long-term experimental protocols, we setup a system that combines optical and electrophysiological tools embedded in a cell incubator. Primary hippocampal neurons transduced with lentiviruses expressing channelrhodopsin-2/H134R were subjected to various photostimulation protocols in a time window in the order of days. To monitor the effects of light-induced gating of network activity, stimulated transduced neurons were simultaneously recorded using multi-electrode arrays (MEAs). The developed experimental model allows discerning short-term, long-lasting, and adaptive plasticity responses of the same neuronal network to distinct stimulation frequencies applied over different temporal windows. PMID:23970852

  2. A novel whole-cell mechanism for long-term memory enhancement.

    Directory of Open Access Journals (Sweden)

    Iris Reuveni

    Full Text Available Olfactory-discrimination learning was shown to induce a profound long-lasting enhancement in the strength of excitatory and inhibitory synapses of pyramidal neurons in the piriform cortex. Notably, such enhancement was mostly pronounced in a sub-group of neurons, entailing about a quarter of the cell population. Here we first show that the prominent enhancement in the subset of cells is due to a process in which all excitatory synapses doubled their strength and that this increase was mediated by a single process in which the AMPA channel conductance was doubled. Moreover, using a neuronal-network model, we show how such a multiplicative whole-cell synaptic strengthening in a sub-group of cells that form a memory pattern, sub-serves a profound selective enhancement of this memory. Network modeling further predicts that synaptic inhibition should be modified by complex learning in a manner that much resembles synaptic excitation. Indeed, in a subset of neurons all GABAA-receptors mediated inhibitory synapses also doubled their strength after learning. Like synaptic excitation, Synaptic inhibition is also enhanced by two-fold increase of the single channel conductance. These findings suggest that crucial learning induces a multiplicative increase in strength of all excitatory and inhibitory synapses in a subset of cells, and that such an increase can serve as a long-term whole-cell mechanism to profoundly enhance an existing Hebbian-type memory. This mechanism does not act as synaptic plasticity mechanism that underlies memory formation but rather enhances the response of already existing memory. This mechanism is cell-specific rather than synapse-specific; it modifies the channel conductance rather than the number of channels and thus has the potential to be readily induced and un-induced by whole-cell transduction mechanisms.

  3. Exchange Protein Activated by cAMP Enhances Long-Term Memory Formation Independent of Protein Kinase A

    Science.gov (United States)

    Ma, Nan; Abel, Ted; Hernandez, Pepe J.

    2009-01-01

    It is well established that cAMP signaling within neurons plays a major role in the formation of long-term memories--signaling thought to proceed through protein kinase A (PKA). However, here we show that exchange protein activated by cAMP (Epac) is able to enhance the formation of long-term memory in the hippocampus and appears to do so…

  4. Reversibility of β-Cell-Specific Transcript Factors Expression by Long-Term Caloric Restriction in db/db Mouse

    Directory of Open Access Journals (Sweden)

    Chunjun Sheng

    2016-01-01

    Full Text Available Type 2 diabetes (T2D is characterized by β-cell dedifferentiation, but underlying mechanisms remain unclear. The purpose of the current study was to explore the mechanisms of β-cell dedifferentiation with and without long-term control of calorie intake. We used a diabetes mouse model (db/db to analyze the changes in the expression levels of β-cell-specific transcription factors (TFs and functional factors with long-term caloric restriction (CR. Our results showed that chronic euglycemia was maintained in the db/db mice with long-term CR intervention, and β-cell dedifferentiation was significantly reduced. The expression of Glut2, Pdx1, and Nkx6.1 was reversed, while MafA expression was significantly increased with long-term CR. GLP-1 pathway was reactivated with long-term CR. Our work showed that the course of β-cell dedifferentiation can intervene by long-term control of calorie intake. Key β-cell-specific TFs and functional factors play important roles in maintaining β-cell differentiation. Targeting these factors could optimize T2D therapies.

  5. Fatty-acid binding proteins modulate sleep and enhance long-term memory consolidation in Drosophila.

    Directory of Open Access Journals (Sweden)

    Jason R Gerstner

    2011-01-01

    Full Text Available Sleep is thought to be important for memory consolidation, since sleep deprivation has been shown to interfere with memory processing. However, the effects of augmenting sleep on memory formation are not well known, and testing the role of sleep in memory enhancement has been limited to pharmacological and behavioral approaches. Here we test the effect of overexpressing the brain-type fatty acid binding protein (Fabp7 on sleep and long-term memory (LTM formation in Drosophila melanogaster. Transgenic flies carrying the murine Fabp7 or the Drosophila homologue dFabp had reduced baseline sleep but normal LTM, while Fabp induction produced increases in both net sleep and LTM. We also define a post-training consolidation "window" that is sufficient for the observed Fabp-mediated memory enhancement. Since Fabp overexpression increases consolidated daytime sleep bouts, these data support a role for longer naps in improving memory and provide a novel role for lipid-binding proteins in regulating memory consolidation concurrently with changes in behavioral state.

  6. Negative emotion enhances mnemonic precision and subjective feelings of remembering in visual long-term memory.

    Science.gov (United States)

    Xie, Weizhen; Zhang, Weiwei

    2017-09-01

    Negative emotion sometimes enhances memory (higher accuracy and/or vividness, e.g., flashbulb memories). The present study investigates whether it is the qualitative (precision) or quantitative (the probability of successful retrieval) aspect of memory that drives these effects. In a visual long-term memory task, observers memorized colors (Experiment 1a) or orientations (Experiment 1b) of sequentially presented everyday objects under negative, neutral, or positive emotions induced with International Affective Picture System images. In a subsequent test phase, observers reconstructed objects' colors or orientations using the method of adjustment. We found that mnemonic precision was enhanced under the negative condition relative to the neutral and positive conditions. In contrast, the probability of successful retrieval was comparable across the emotion conditions. Furthermore, the boost in memory precision was associated with elevated subjective feelings of remembering (vividness and confidence) and metacognitive sensitivity in Experiment 2. Altogether, these findings suggest a novel precision-based account for emotional memories. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Surfactant-enhanced release of carbaryl and ethion from two long-term contaminated soils.

    Science.gov (United States)

    Ahmad, Riaz; Kookana, Rai S; Alston, Angus M

    2004-05-01

    The potential of five nonionic surfactants, Triton X-100, Brij35, Ethylan GE08, Ethylan CD127, and Ethylan CPG660 for enhancing release of carbaryl and ethion from two long-term contaminated soils was evaluated using the batch method. Incorporation of the surfactants into soils enhanced the release of both pesticides to various extents, which could be related to the type of pesticides and type and the amount of surfactants added. Release of ethion was dramatically enhanced by aqueous concentrations of surfactants above their critical micelle concentration values. This was attributed to solubility enhancement through incorporation of the highly hydrophobic compound within surfactant micelles. A concentration of 10 g L(-1) of various surfactants released >70% of the total ethion from the soil irrespective of the surfactant. For carbaryl, the surfactants were effective at low concentrations and dependence on concentration was lower than in the case of ethion. The ethylan surfactants (GE08, CD127, and CPG660) had a higher potential than Triton X-100 and Brij35 for releasing the pesticides. However, there was still a significant portion of carbaryl (11% of the total) and ethion (17% of the total) left in the soil. Our study also showed that there must be an optimal concentration of each surfactant to maximize the mass transfer of pesticides. At some threshold concentration level, additional surfactant started to inhibit the mass transfer of solute from the soil into the water. The results suggested that surfactants could help remediation of soils polluted by pesticides. The choice of surfactant should be made based on the properties of pesticides.

  8. 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

  9. Long term vitamin A restriction improves meat quality parameters and modifies gene expression in Iberian pigs.

    Science.gov (United States)

    Ayuso, M; Fernández, A; Isabel, B; Rey, A; Benítez, R; Daza, A; López-Bote, C J; Óvilo, C

    2015-06-01

    Vitamin A is a key regulator of gene expression, influencing adipogenesis and lipid metabolism in animal tissues. This experiment was conducted to assess the effect of dietary vitamin A level and administration time on productive traits, intramuscular fat (IMF) content in ham muscles, tissue fatty acid composition, and expression of a panel of adipogenic and lipogenic candidate genes in Iberian pigs. Sixty piglets of 16.3 kg (SD = 2.5 kg) live weight (LW) were either fed a vitamin A-enriched diet (10,000 IU vitamin A/kg; CONTROL, n = 20) or a diet without supplemented vitamin A, applied from 16.3 kg (SD = 2.5 kg; early restriction group, ER, n = 20) or from an average weight of 35.8 kg (SD = 3.1 kg; late restriction group, LR, n = 20). Two slaughters were performed when pigs reached the averaged weights of 101.4 (SD = 4.1 kg) and 157.9 kg LW (SD = 7 kg) and samples from liver, heart, and backfat were obtained in both sacrifice times. In addition, ham subcutaneous fat and Semimembranosus (SM) and Biceps Femoris (BF) muscles were sampled at the last sacrifice. Dietary vitamin A level produced no effect on carcass traits in any of the harvests, while a small effect was observed on fatty acid composition in backfat at 101.4 kg LW. However, at 157.9 kg LW, the ER and LR groups showed higher MUFA content and lower SFA content in backfat, ham fat, and IMF (P IMF, a decrease in n-6/n-3 PUFA ratio was observed in the restricted groups (P experiment show that long-term restriction of dietary vitamin A has a positive effect on nutritional and sensorial parameters of ham meat. Moreover, gene expression results were consistent with the vitamin A transcriptional regulation of adipogenesis and lipogenesis and with the changes observed in meat and fat composition.

  10. Enhancing patient-provider communication for long-term post-stroke spasticity management.

    Science.gov (United States)

    Sunnerhagen, K S; Francisco, G E

    2013-11-01

    Stroke is a major public health concern, with estimated 16 million people worldwide experiencing first-time strokes each year, a number that is expected to rise. Two-thirds of those experiencing a stroke are younger than 70 years of age. Stroke is a leading cause of disability in adults as a result of major sequelae that include spasticity, cognitive impairment, paresis, and depression. Disabling spasticity, defined as spasticity severe enough to require intervention, occurs in 4% of stroke survivors within 1 year of first-time stroke. The aim of this report is to focus instead on a discussion of patient-provider communication, and its role in post-stroke spasticity (PSS) rehabilitation within the context of patient-centered health care. A discussion based on a review of the literature, mainly since 2000. Problems within communication are identified and suggestion to enhance communication are proposed thus improving patient-centered goal setting/goal achievement for the effective management of spasticity rehabilitation. These are as follows: (i) involving family members, (ii) educating patients and family members on stroke and rehabilitation, and (iii) establishing a common definition for long-term goals. Increased communication among physicians, patients, and payers may bridge some of the gaps and increase the effectiveness of PSS rehabilitation and management. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. PPARγ-induced upregulation of CD36 enhances hematoma resolution and attenuates long-term neurological deficits after germinal matrix hemorrhage in neonatal rats.

    Science.gov (United States)

    Flores, Jerry J; Klebe, Damon; Rolland, William B; Lekic, Tim; Krafft, Paul R; Zhang, John H

    2016-03-01

    Germinal matrix hemorrhage remains the leading cause of morbidity and mortality in preterm infants in the United States with little progress made in its clinical management. Survivors are often afflicted with long-term neurological sequelae, including cerebral palsy, mental retardation, hydrocephalus, and psychiatric disorders. Blood clots disrupting normal cerebrospinal fluid circulation and absorption after germinal matrix hemorrhage are thought to be important contributors towards post-hemorrhagic hydrocephalus development. We evaluated if upregulating CD36 scavenger receptor expression in microglia and macrophages through PPARγ stimulation, which was effective in experimental adult cerebral hemorrhage models and is being evaluated clinically, will enhance hematoma resolution and ameliorate long-term brain sequelae using a neonatal rat germinal matrix hemorrhage model. PPARγ stimulation (15d-PGJ2) increased short-term PPARγ and CD36 expression levels as well as enhanced hematoma resolution, which was reversed by a PPARγ antagonist (GW9662) and CD36 siRNA. PPARγ stimulation (15d-PGJ2) also reduced long-term white matter loss and post-hemorrhagic ventricular dilation as well as improved neurofunctional outcomes, which were reversed by a PPARγ antagonist (GW9662). PPARγ-induced upregulation of CD36 in macrophages and microglia is, therefore, critical for enhancing hematoma resolution and ameliorating long-term brain sequelae. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Long-Term Continuous Corticosterone Treatment Decreases VEGF Receptor-2 Expression in Frontal Cortex

    OpenAIRE

    Howell, Kristy R.; Kutiyanawalla, Ammar; Pillai, Anilkumar

    2011-01-01

    Objective Stress and increased glucocorticoid levels are associated with many neuropsychiatric disorders including schizophrenia and depression. Recently, the role of vascular endothelial factor receptor-2 (VEGFR2/Flk1) signaling has been implicated in stress-mediated neuroplasticity. However, the mechanism of regulation of VEGF/Flk1 signaling under long-term continuous glucocorticoid exposure has not been elucidated. Material and Methods We examined the possible effects of long-term continuo...

  13. 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.

  14. Long-term enhancement of maze learning in mice via a generalized Mozart effect.

    Science.gov (United States)

    Aoun, Peter; Jones, Timothy; Shaw, Gordon L; Bodner, Mark

    2005-12-01

    An animal model of the 'generalized Mozart effect' (GME) - enhanced/normalized higher brain function in response to music exposure - has been established. We extend those results in two studies using another species (mice). Study 1: (1) maze testing after music exposure was extended to a minimum of 6 hours; (2) no exposure to music in utero. Study 2: (1) music exposure time further reduced; (2) maze testing extended to 24 hours. Study 1: two mouse groups were exposed to music continuously for 10 hours per day for 10 weeks (Group I: Mozart's Sonata K.448, Group II: Beethoven's Fur Elise). After 10 weeks, the ability to negotiate a T-maze was assessed (recording working time in maze, number of errors). Maze ability was tested 6 hours following the last music exposure. Study 2: two mouse groups were exposed periodically to music (58% silence) 10 hours per day for 10 weeks. Experiments after 10 weeks examined the groups' abilities to run the maze (recording working time/errors). Experiments were conducted 24 hours following the last music exposure. The Mozart group exhibited significant enhancements compared with the control mice in both studies, i.e. significantly lower working time (p<0.05) and committed fewer errors. Observation of GME in another species supports its generality for the mammalian cortex. The absence of a GME in fMRI studies for the control music also indicates a neurophysiological basis. With extended exposure, GME is a long-term effect, indicating potential clinical importance. It has been demonstrated that GME reduces neuropathological spiking significantly in epileptics. We discuss the relevance of this study for epilepsy treatment.

  15. Enhancement of cancer stem-like and epithelial−mesenchymal transdifferentiation property in oral epithelial cells with long-term nicotine exposure: Reversal by targeting SNAIL

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Cheng-Chia [Institute of Oral Science, Chung Shan Medical University, Taichung, Taiwan (China); School of Dentistry, Chung Shan Medical University, Taichung, Taiwan (China); Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan (China); Chang, Yu-Chao, E-mail: cyc@csmu.edu.tw [School of Dentistry, Chung Shan Medical University, Taichung, Taiwan (China); Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan (China)

    2013-02-01

    Cigarette smoking is one of the major risk factors in the development and further progression of tumorigenesis, including oral squamous cell carcinoma (OSCC). Recent studies suggest that interplay cancer stem-like cells (CSCs) and epithelial−mesenchymal transdifferentiation (EMT) properties are responsible for the tumor maintenance and metastasis in OSCC. The aim of the present study was to investigate the effects of long-term exposure with nicotine, a major component in cigarette, on CSCs and EMT characteristics. The possible reversal regulators were further explored in nicotine-induced CSCs and EMT properties in human oral epithelial (OE) cells. Long-term exposure with nicotine was demonstrated to up-regulate ALDH1 population in normal gingival and primary OSCC OE cells dose-dependently. Moreover, long-term nicotine treatment was found to enhance the self-renewal sphere-forming ability and stemness gene signatures expression and EMT regulators in OE cells. The migration/cell invasiveness/anchorage independent growth and in vivo tumor growth by nude mice xenotransplantation assay was enhanced in long-term nicotine-stimulated OE cells. Knockdown of Snail in long-term nicotine-treated OE cells was found to reduce their CSCs properties. Therapeutic delivery of Si-Snail significantly blocked the xenograft tumorigenesis of long-term nicotine-treated OSCC cells and largely significantly improved the recipient survival. The present study demonstrated that the enrichment of CSCs coupled EMT property in oral epithelial cells induced by nicotine is critical for the development of OSCC tumorigenesis. Targeting Snail might offer a new strategy for the treatment of OSCC patients with smoking habit. -- Highlights: ► Sustained nicotine treatment induced CSCs properties of oral epithelial cells. ► Long-term nicotine treatment enhance EMT properties of oral epithelial cells. ► Long-term nicotine exposure increased tumorigenicity of oral epithelial cells. ► Si

  16. Long-term health-enhancing physical activity in rheumatoid arthritis - the PARA 2010 study

    Directory of Open Access Journals (Sweden)

    Nordgren Birgitta

    2012-07-01

    Full Text Available Abstract Background People with rheumatoid arthritis (RA suffer increased risk of disability andpremature mortality. Health-enhancing physical activity (HEPA could be one importantfactor to reduce this risk. Rising health care costs call for the development and evaluation ofnew modes of rehabilitation, including physical activity in settings outside the health caresystem. Methods/Design This cohort study targets 450 patients with RA that do not currently meet HEPA recommendations, recruited from six hospitals reporting to the Swedish Rheumatology Quality Registers (SRQ. We have developed a two-year real-life intervention program including a minimum of twice-weekly circuit training, moderately intense physical activity the remaining days of the week and group meetings to support behavior change every other week. Our hypothesis is that increased physical activity and exercise will improve perceived health, reduce pain and fatigue, increase muscle function and aerobic capacity, impact psychosocial factors and prevent future cardiovascular events. Research questions regard outcomes, retention rates, dose–response matters and the exploration of responder characteristics. This protocol outlines recruitment procedure, design, assessment methods and the intervention program of the study. Discussion The PARA 2010 project is designed to expand the knowledge on HEPA in RA by a progressive approach regarding population, setting, intervention, time frames and outcome measures. To our knowledge this is the first long-term HEPA program based on Social Cognitive Theory, and performed in a real life environment to demonstrate if this new setting can promote increased and maintained physical activity in people with RA. Trial registration number ISRCTN25539102

  17. Studying frequency processing of the brain to enhance long-term memory and develop a human brain protocol.

    Science.gov (United States)

    Friedrich, Wernher; Du, Shengzhi; Balt, Karlien

    2015-01-01

    The temporal lobe in conjunction with the hippocampus is responsible for memory processing. The gamma wave is involved with this process. To develop a human brain protocol, a better understanding of the relationship between gamma and long-term memory is vital. A more comprehensive understanding of the human brain and specific analogue waves it uses will support the development of a human brain protocol. Fifty-eight participants aged between 6 and 60 years participated in long-term memory experiments. It is envisaged that the brain could be stimulated through binaural beats (sound frequency) at 40 Hz (gamma) to enhance long-term memory capacity. EEG recordings have been transformed to sound and then to an information standard, namely ASCII. Statistical analysis showed a proportional relationship between long-term memory and gamma activity. Results from EEG recordings indicate a pattern. The pattern was obtained through the de-codification of an EEG recording to sound and then to ASCII. Stimulation of gamma should enhance long term memory capacity. More research is required to unlock the human brains' protocol key. This key will enable the processing of information directly to and from human memory via gamma, the hippocampus and the temporal lobe.

  18. Long-term adaptive evolution of Leuconostoc mesenteroides for enhancement of lactic acid tolerance and production.

    Science.gov (United States)

    Ju, Si Yeon; Kim, Jin Ho; Lee, Pyung Cheon

    2016-01-01

    Lactic acid has been approved by the United States Food and Drug Administration as Generally Regarded As Safe (GRAS) and is commonly used in the cosmetics, pharmaceutical, and food industries. Applications of lactic acid have also emerged in the plastics industry. Lactic acid bacteria (LAB), such as Leuconostoc and Lactobacillus, are widely used as lactic acid producers for food-related and biotechnological applications. Nonetheless, industrial mass production of lactic acid in LAB is a challenge mainly because of growth inhibition caused by the end product, lactic acid. Thus, it is important to improve acid tolerance of LAB to achieve balanced cell growth and a high titer of lactic acid. Recently, adaptive evolution has been employed as one of the strategies to improve the fitness and to induce adaptive changes in bacteria under specific growth conditions, such as acid stress. Wild-type Leuconostoc mesenteroides was challenged long term with exogenously supplied lactic acid, whose concentration was increased stepwise (for enhancement of lactic acid tolerance) during 1 year. In the course of the adaptive evolution at 70 g/L lactic acid, three mutants (LMS50, LMS60, and LMS70) showing high specific growth rates and lactic acid production were isolated and characterized. Mutant LMS70, isolated at 70 g/L lactic acid, increased d-lactic acid production up to 76.8 g/L, which was twice that in the wild type (37.8 g/L). Proteomic, genomic, and physiological analyses revealed that several possible factors affected acid tolerance, among which a mutation of ATPase ε subunit (involved in the regulation of intracellular pH) and upregulation of intracellular ammonia, as a buffering system, were confirmed to contribute to the observed enhancement of tolerance and production of d-lactic acid. During adaptive evolution under lethal stress conditions, the fitness of L. mesenteroides gradually increased to accumulate beneficial mutations according to the stress level. The

  19. Long-term effects of ionizing radiation on gene expression in a zebrafish model.

    Directory of Open Access Journals (Sweden)

    Lahcen Jaafar

    Full Text Available Understanding how initial radiation injury translates into long-term effects is an important problem in radiation biology. Here, we define a set of changes in the transcription profile that are associated with the long-term response to radiation exposure. The study was performed in vivo using zebrafish, an established radiobiological model organism. To study the long-term response, 24 hour post-fertilization embryos were exposed to 0.1 Gy (low dose or 1.0 Gy (moderate dose of whole-body gamma radiation and allowed to develop for 16 weeks. Liver mRNA profiles were then analyzed using the Affymetrix microarray platform, with validation by quantitative PCR. As a basis for comparison, 16-week old adults were exposed at the same doses and analyzed after 4 hours. Statistical analysis was performed in a way to minimize the effects of multiple comparisons. The responses to these two treatment regimes differed greatly: 360 probe sets were associated primarily with the long-term response, whereas a different 2062 probe sets were associated primarily with the response when adults of the same age were irradiated 4 hours before exposure. Surprisingly, a ten-fold difference in radiation dose (0.1 versus 1.0 Gy had little effect. Analysis at the gene and pathway level indicated that the long-term response includes the induction of cytokine and inflammatory regulators and transcription and growth factors. The acute response includes the induction of p53 target genes and modulation of the hypoxia-induced transcription factor-C/EBP axis. Results help define genes and pathways affected in the long-term, low and moderate dose radiation response and differentiate them from those affected in an acute response in the same tissue.

  20. 76 FR 71560 - Notice of a Public Meeting on Long Term 2 Enhanced Surface Water Treatment Rule: Initiate...

    Science.gov (United States)

    2011-11-18

    ... AGENCY Notice of a Public Meeting on Long Term 2 Enhanced Surface Water Treatment Rule: Initiate Regulatory Review--Cryptosporidium Analytical Method Improvements and Update on Source Water Monitoring... Water Treatment Rule (LT2 rule). This is the first of at least two meetings on the LT2 rule that EPA...

  1. Androgen receptor expression in human ovarian and uterine tissue of long term androgen-treated transsexual women

    NARCIS (Netherlands)

    D. Chadha; T.D. Pache; F.J. Huikeshoven (Frans); A.O. Brinkmann (Albert); Th.H. van der Kwast (Theo)

    1994-01-01

    textabstractAndrogen receptor (AR) modulation in human uteri and ovaries of long term androgen-treated transsexual female patients was investigated. Androgen receptor expression was evaluated immunohistochemically in the ovaries of 11 and the endometria and myometria of six androgen-treated

  2. Effects of long-term football training on the expression profile of genes involved in muscle oxidative metabolism

    DEFF Research Database (Denmark)

    Alfieri, A; Martone, D; Randers, Morten Bredsgaard

    2015-01-01

    We investigated whether long-term recreational football training affects the expression of health-related biochemical and molecular markers in healthy untrained subjects. Five untrained healthy men trained for 1 h 2.4 times/week for 12 weeks and 1.3 times/week for another 52 weeks. Blood samples ...

  3. Reinstatement of long-term memory following erasure of its behavioral and synaptic expression in Aplysia

    Science.gov (United States)

    Chen, Shanping; Cai, Diancai; Pearce, Kaycey; Sun, Philip Y-W; Roberts, Adam C; Glanzman, David L

    2014-01-01

    Long-term memory (LTM) is believed to be stored in the brain as changes in synaptic connections. Here, we show that LTM storage and synaptic change can be dissociated. Cocultures of Aplysia sensory and motor neurons were trained with spaced pulses of serotonin, which induces long-term facilitation. Serotonin (5HT) triggered growth of new presynaptic varicosities, a synaptic mechanism of long-term sensitization. Following 5HT training, two antimnemonic treatments—reconsolidation blockade and inhibition of PKM—caused the number of presynaptic varicosities to revert to the original, pretraining value. Surprisingly, the final synaptic structure was not achieved by targeted retraction of the 5HT-induced varicosities but, rather, by an apparently arbitrary retraction of both 5HT-induced and original synapses. In addition, we find evidence that the LTM for sensitization persists covertly after its apparent elimination by the same antimnemonic treatments that erase learning-related synaptic growth. These results challenge the idea that stable synapses store long-term memories. DOI: http://dx.doi.org/10.7554/eLife.03896.001 PMID:25402831

  4. Behavioral Specifications of Reward-Associated Long-Term Memory Enhancement in Humans

    Science.gov (United States)

    Wittmann, Bianca C.; Dolan, Raymond J.; Duzel, Emrah

    2011-01-01

    Recent functional imaging studies link reward-related activation of the midbrain substantia nigra-ventral tegmental area (SN/VTA), the site of origin of ascending dopaminergic projections, with improved long-term episodic memory. Here, we investigated in two behavioral experiments how (1) the contingency between item properties and reward, (2) the…

  5. Enhanced photovoltaic properties and long-term stability in plasmonic dye-sensitized solar cells via noncorrosive redox mediator.

    Science.gov (United States)

    Jung, Heesuk; Koo, Bonkee; Kim, Jae-Yup; Kim, Taehee; Son, Hae Jung; Kim, BongSoo; Kim, Jin Young; Lee, Doh-Kwon; Kim, Honggon; Cho, Jinhan; Ko, Min Jae

    2014-11-12

    We demonstrate the localized surface plasmon resonance (LSPR) effect, which can enhance the photovoltaic properties of dye-sensitized solar cells (DSSCs), and the long-term stability of size-controlled plasmonic structures using a noncorrosive redox mediator. Gold nanoparticles (Au NPs) were synthesized with a phase transfer method based on ligand exchange. This synthetic method is advantageous because the uniformly sized Au NPs, can be mass produced and easily applied to DSSC photoanodes. The plasmonic DSSCs showed an 11% improvement of power conversion efficiency due to the incorporation of 0.07 wt % Au NPs, compared to the reference DSSCs without Au NPs. The improved efficiency was primarily due to the enhanced photocurrent generation by LSPR effect. With the cobalt redox mediator, the long-term stability of the plasmonic structures also significantly increased. The plasmonic DSSCs with cobalt(II/III) tris(2,2'-bipyridine) ([Co(bpy)3](2+/3+)) redox mediator maintained the LSPR effect with stable photovoltaic performance for 1000 h. This is, to our knowledge, the first demonstration of the long-term stability of plasmonic nanostructures in plasmonic DSSCs based on liquid electrolytes. As a result, the enhanced long-term stability of plasmonic NPs via a noncorrosive redox mediator will increase the feasibility of plasmonic DSSCs.

  6. AAV-mediated expression of CNTF promotes long-term survival and regeneration of adult rat retinal ganglion cells.

    Science.gov (United States)

    Leaver, S G; Cui, Q; Plant, G W; Arulpragasam, A; Hisheh, S; Verhaagen, J; Harvey, A R

    2006-09-01

    We compared the effects of intravitreal injection of bi-cistronic adeno-associated viral (AAV-2) vectors encoding enhanced green fluorescent protein (GFP) and either ciliary neurotrophic factor (CNTF), brain-derived neurotrophic factor (BDNF) or growth-associated protein-43 (GAP43) on adult retinal ganglion cell (RGC) survival and regeneration following (i) optic nerve (ON) crush or (ii) after ON cut and attachment of a peripheral nerve (PN). At 7 weeks after ON crush, quantification of betaIII-tubulin immunostaining revealed that, compared to AAV-GFP controls, RGC survival was not enhanced by AAV-GAP43-GFP but was increased in AAV-CNTF-GFP (mean RGCs/retina: 17 450+/-358 s.e.m.) and AAV-BDNF-GFP injected eyes (10 200+/-4064 RGCs/retina). Consistent with increased RGC viability in AAV-CNTF-GFP and AAV-BDNF-GFP injected eyes, these animals possessed many betaIII-tubulin- and GFP-positive fibres proximal to the ON crush. However, only in the AAV-CNTF-GFP group were regenerating RGC axons seen in distal ON (1135+/-367 axons/nerve, 0.5 mm post-crush), some reaching the optic chiasm. RGCs were immunoreactive for CNTF and quantitative RT-PCR revealed a substantial increase in CNTF mRNA expression in retinas transduced with AAV-CNTF-GFP. The combination of AAV-CNTF-GFP transduction of RGCs with autologous PN-ON transplantation resulted in even greater RGC survival and regeneration. At 7 weeks after PN transplantation there were 27 954 (+/-2833) surviving RGCs/retina, about 25% of the adult RGC population. Of these, 13 352 (+/-1868) RGCs/retina were retrogradely labelled after fluorogold injections into PN grafts. In summary, AAV-mediated expression of CNTF promotes long-term survival and regeneration of injured adult RGCs, effects that are substantially enhanced by combining gene and cell-based therapies/interventions.

  7. Long-term consequences of chronic fluoxetine exposure on the expression of myelination-related genes in the rat hippocampus

    Science.gov (United States)

    Kroeze, Y; Peeters, D; Boulle, F; van den Hove, D L A; van Bokhoven, H; Zhou, H; Homberg, J R

    2015-01-01

    The selective serotonin reuptake inhibitor (SSRI) fluoxetine is widely prescribed for the treatment of symptoms related to a variety of psychiatric disorders. After chronic SSRI treatment, some symptoms remediate on the long term, but the underlying mechanisms are not yet well understood. Here we studied the long-term consequences (40 days after treatment) of chronic fluoxetine exposure on genome-wide gene expression. During the treatment period, we measured body weight; and 1 week after treatment, cessation behavior in an SSRI-sensitive anxiety test was assessed. Gene expression was assessed in hippocampal tissue of adult rats using transcriptome analysis and several differentially expressed genes were validated in independent samples. Gene ontology analysis showed that upregulated genes induced by chronic fluoxetine exposure were significantly enriched for genes involved in myelination. We also investigated the expression of myelination-related genes in adult rats exposed to fluoxetine at early life and found two myelination-related genes (Transferrin (Tf) and Ciliary neurotrophic factor (Cntf)) that were downregulated by chronic fluoxetine exposure. Cntf, a neurotrophic factor involved in myelination, showed regulation in opposite direction in the adult versus neonatally fluoxetine-exposed groups. Expression of myelination-related genes correlated negatively with anxiety-like behavior in both adult and neonatally fluoxetine-exposed rats. In conclusion, our data reveal that chronic fluoxetine exposure causes on the long-term changes in expression of genes involved in myelination, a process that shapes brain connectivity and contributes to symptoms of psychiatric disorders. PMID:26393488

  8. Testing during Training: Why Does It Enhance Long-Term Motor Task Retention?

    Science.gov (United States)

    1981-07-01

    improvements associated with t-trial repetition been reported. Research- ers have shown that with verbal tasks t-trials not only contribute to acquisition...test trials on long-term recognition and recall. Journal of Verbal Learning and Verbal Behavior, 1971, 10, 562-567. Jones, B. Role of central...ideas. Journal of Experimental Psychology, 1970, 83, 304-308. ,,d-.. ," 13 -l - - -" W~ll .Wi.~ Roy, E. A. Toward a typology of apraxia . Mouvement

  9. General circulation of Venus from a long-term synoptic study of tropospheric CO by Venus Express/VIRTIS

    Science.gov (United States)

    Tsang, Constantine C. C.; McGouldrick, Kevin

    2017-06-01

    The understanding of spatial and temporal variations in tropospheric abundances of the trace gas carbon monoxide (CO) is key to understanding the deep atmospheric circulation on Venus. CO is entrained in the global circulation, as well as being key ingredients in the multi-reaction chemical cycle that creates and destroys the sulfuric acid that is a primary constituent of the clouds. Long-term temporal variations of CO across Venus' disc would provide critical insights and constraints into the large-scale circulation and cloud forming processes in the troposphere. Here, we present an in-depth look at the CO as a function of latitude, longitude and local time as seen by the VIRTIS-M-IR instrument onboard the Venus Express spacecraft during its three years of operation. We find that CO is slightly enhanced on the dusk hemisphere near the poles (by ∼2 ppmv) and the equatorial concentrations from 22:00 - 03:00 are also elevated. Longitudinal variations of CO are largely absent, except for a potential correlation of anomalous CO around Themis Regio. These observations provide the most stringent constraints yet on global dynamics and CO chemistry of the deep troposphere on Venus.

  10. Presynaptic D2 dopamine receptors control long-term depression expression and memory processes in the temporal hippocampus.

    Science.gov (United States)

    Rocchetti, Jill; Isingrini, Elsa; Dal Bo, Gregory; Sagheby, Sara; Menegaux, Aurore; Tronche, François; Levesque, Daniel; Moquin, Luc; Gratton, Alain; Wong, Tak Pan; Rubinstein, Marcelo; Giros, Bruno

    2015-03-15

    Dysfunctional mesocorticolimbic dopamine signaling has been linked to alterations in motor and reward-based functions associated with psychiatric disorders. Converging evidence from patients with psychiatric disorders and use of antipsychotics suggests that imbalance of dopamine signaling deeply alters hippocampal functions. However, given the lack of full characterization of a functional mesohippocampal pathway, the precise role of dopamine transmission in memory deficits associated with these disorders and their dedicated therapies is unknown. In particular, the positive outcome of antipsychotic treatments, commonly antagonizing D2 dopamine receptors (D2Rs), on cognitive deficits and memory impairments remains questionable. Following pharmacologic and genetic manipulation of dopamine transmission, we performed anatomic, neurochemical, electrophysiologic, and behavioral investigations to uncover the role of D2Rs in hippocampal-dependent plasticity and learning. Naïve mice (n = 4-21) were used in the different procedures. Dopamine modulated both long-term potentiation and long-term depression in the temporal hippocampus as well as spatial and recognition learning and memory in mice through D2Rs. Although genetic deletion or pharmacologic blockade of D2Rs led to the loss of long-term potentiation expression, the specific genetic removal of presynaptic D2Rs impaired long-term depression and performances on spatial memory tasks. Presynaptic D2Rs in dopamine fibers of the temporal hippocampus tightly modulate long-term depression expression and play a major role in the regulation of hippocampal learning and memory. This direct role of mesohippocampal dopamine input as uncovered here adds a new dimension to dopamine involvement in the physiology underlying deficits associated with neuropsychiatric disorders. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  11. Noradrenergic control of gene expression and long-term neuronal adaptation evoked by learned vocalizations in songbirds.

    Directory of Open Access Journals (Sweden)

    Tarciso A F Velho

    Full Text Available Norepinephrine (NE is thought to play important roles in the consolidation and retrieval of long-term memories, but its role in the processing and memorization of complex acoustic signals used for vocal communication has yet to be determined. We have used a combination of gene expression analysis, electrophysiological recordings and pharmacological manipulations in zebra finches to examine the role of noradrenergic transmission in the brain's response to birdsong, a learned vocal behavior that shares important features with human speech. We show that noradrenergic transmission is required for both the expression of activity-dependent genes and the long-term maintenance of stimulus-specific electrophysiological adaptation that are induced in central auditory neurons by stimulation with birdsong. Specifically, we show that the caudomedial nidopallium (NCM, an area directly involved in the auditory processing and memorization of birdsong, receives strong noradrenergic innervation. Song-responsive neurons in this area express α-adrenergic receptors and are in close proximity to noradrenergic terminals. We further show that local α-adrenergic antagonism interferes with song-induced gene expression, without affecting spontaneous or evoked electrophysiological activity, thus dissociating the molecular and electrophysiological responses to song. Moreover, α-adrenergic antagonism disrupts the maintenance but not the acquisition of the adapted physiological state. We suggest that the noradrenergic system regulates long-term changes in song-responsive neurons by modulating the gene expression response that is associated with the electrophysiological activation triggered by song. We also suggest that this mechanism may be an important contributor to long-term auditory memories of learned vocalizations.

  12. rhEPO Enhances Cellular Anti-oxidant Capacity to Protect Long-Term Cultured Aging Primary Nerve Cells.

    Science.gov (United States)

    Wang, Huqing; Fan, Jiaxin; Chen, Mengyi; Yao, Qingling; Gao, Zhen; Zhang, Guilian; Wu, Haiqin; Yu, Xiaorui

    2017-08-01

    Erythropoietin (EPO) may protect the nervous system of animals against aging damage, making it a potential anti-aging drug for the nervous system. However, experimental evidence from natural aging nerve cell models is lacking, and the efficacy of EPO and underlying mechanism of this effect warrant further study. Thus, the present study used long-term cultured primary nerve cells to successfully mimic the natural aging process of nerve cells. Starting on the 11th day of culture, cells were treated with different concentrations of recombinant human erythropoietin (rhEPO). Using double immunofluorescence labeling, we found that rhEPO significantly improved the morphology of long-term cultured primary nerve cells and increased the total number of long-term cultured primary cells. However, rhEPO did not improve the ratio of nerve cells. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to measure nerve cell activity and showed that rhEPO significantly improved the activity of long-term cultured primary nerve cells. Moreover, Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) double immunofluorescence labeling flow cytometry revealed that rhEPO reduced the apoptotic rate of long-term cultured primary nerve cells. Senescence-associated β-galactosidase (SA-β-gal) immunohistochemistry staining showed that rhEPO significantly reduced the aging rate of long-term cultured primary nerve cells. Immunochemistry revealed that rhEPO enhanced intracellular superoxide dismutase (SOD) activity and glutathione (GSH) abundance and reduced the intracellular malondialdehyde (MDA) level. In addition, this effect depended on the dose, was maximized at a dose of 100 U/ml and was more pronounced than that of vitamin E. In summary, this study finds that rhEPO protects long-term cultured primary nerve cells from aging in a dose-dependent manner. The mechanism of this effect may be associated with the enhancement of the intracellular anti

  13. Teaching in small portions dispersed over time enhances long-term knowledge retention.

    Science.gov (United States)

    Raman, Maitreyi; McLaughlin, Kevin; Violato, Claudio; Rostom, Alaa; Allard, J P; Coderre, Sylvain

    2010-01-01

    A primary goal of education is to promote long-term knowledge storage and retrieval. A prospective interventional study design was used to investigate our research question: Does a dispersed curriculum promote better short- and long-term retention over a massed course? Participants included 20 gastroenterology residents from the University of Calgary (N = 10) and University of Toronto (N = 10). Participants completed a baseline test of nutrition knowledge. The nutrition course was imparted to University of Calgary residents for 4 h occurring 1 h weekly over 4 consecutive weeks: dispersed delivery (DD). At the University of Toronto the course was taught in one 4h academic half-day: massed delivery (MD). Post-curriculum tests were administered at 1 week and 3 months to assess knowledge retention. The baseline scores were 46.39 +/- 6.14% and 53.75 +/- 10.69% in the DD and MD groups, respectively. The 1 week post-test scores for the DD and MD groups were 81.67 +/- 8.57%, p < 0.001 and 78.75 +/- 4.43, p < 0.001 which was significantly higher than baseline. The 3-month score was significantly higher in the DD group, but not in the MD group (65.28 +/- 9.88%, p = 0.02 vs. 58.93 +/- 12.06%, p = 0.18). The absolute pre-test to 1-week post-test difference was significantly higher at 35.28 +/- 7.65% among participants in the DD group compared to 25.0 +/- 11.80% in the MD group, p = 0.048. Similarly, the absolute pre-test to 3-month post-test difference was significantly higher at 18.9 +/- 6.7% among the participants in the DD group, compared to 6.8 +/- 11.8% in the MD group, p = 0.021. Long-term nutrition knowledge is improved with DD compared with MD.

  14. Long term stability of Oligo (dT) 25 magnetic beads for the expression analysis of Euglena gracilis for long term space projects

    Science.gov (United States)

    Becker, Ina; Strauch, Sebastian M.; Hauslage, Jens; Lebert, Michael

    2017-05-01

    The unicellular freshwater flagellate Euglena gracilis has a highly developed sensory system. The cells use different stimuli such as light and gravity to orient themselves in the surrounding medium to find areas for optimal growth. Due to the ability to produce oxygen and consume carbon dioxide, Euglena is a suitable candidate for life support systems. Participation in a long-term space experiment would allow for the analysis of changes and adaptations to the new environment, and this could bring new insights into the mechanism of perception of gravity and the associated signal transduction chain. For a molecular analysis of transcription patterns, an automated system is necessary, capable of performing all steps from taking a sample, processing it and generating data. One of the developmental steps is to find long-term stable reagents and materials and test them for stability at higher-than-recommended temperature conditions during extended storage time. We investigated the usability of magnetic beads in an Euglena specific lysis buffer after addition of the RNA stabilizer Dithiothreitol over 360 days and the lysis buffer with the stabilizer alone over 455 days at the expected storage temperature of 19 °C. We can claim that the stability is not impaired at all after an incubation period of over one year. This might be an interesting result for researchers who have to work under non-standard lab conditions, as in biological or medicinal fieldwork.

  15. Fully deleted adenovirus persistently expressing GAA accomplishes long-term skeletal muscle glycogen correction in tolerant and nontolerant GSD-II mice.

    Science.gov (United States)

    Kiang, Anne; Hartman, Zachary C; Liao, Shaoxi; Xu, Fang; Serra, Delila; Palmer, Donna J; Ng, Philip; Amalfitano, Andrea

    2006-01-01

    Glycogen storage disease type II (GSD-II) patients manifest symptoms of muscular dystrophy secondary to abnormal glycogen storage in cardiac and skeletal muscles. For GSD-II, we hypothesized that a fully deleted adenovirus (FDAd) vector expressing hGAA via nonviral regulatory elements (PEPCK promoter/ApoE enhancer) would facilitate long-term efficacy and decrease propensity to generate anti-hGAA antibody responses against hepatically secreted hGAA. Intravenous delivery of FDAdhGAA into GAA-tolerant or nontolerant GAA-KO mice resulted in long-term hepatic secretion of hGAA. Specifically, nontolerant mice achieved complete reversal of cardiac glycogen storage and near-complete skeletal glycogen correction for at least 180 days and tolerant mice for minimally 300 days coupled with the preservation of muscle strength. Anti-hGAA antibody levels in both mouse strains were significantly less relative to those previously generated by CMV-driven hGAA expression in nontolerant GAA-KO mice. However, plasma GAA levels decreased in nontolerant GAA-KO mice despite long-term intrahepatic GAA expression from the persistent vector. This intriguing result is discussed in light of other examples of "tolerance" induction by gene-transfer-based approaches.

  16. Long-term effects of peripubertal binge EtOH exposure on hippocampal microRNA expression in the rat.

    Directory of Open Access Journals (Sweden)

    Sarah A Prins

    Full Text Available Adolescent binge alcohol abuse induces long-term changes in gene expression, which impacts the physiological stress response and memory formation, two functions mediated in part by the ventral (VH and dorsal (DH hippocampus. microRNAs (miRs are small RNAs that play an important role in gene regulation and are potential mediators of long-term changes in gene expression. Two genes important for regulating hippocampal functions include brain-derived neurotrophic factor (BDNF and sirtuin-1 (SIRT1, which we identified as putative gene targets of miR-10a-5p, miR-26a, miR-103, miR-495. The purpose of this study was to quantify miR-10a-5p, miR-26a, miR-103, miR-495 expression levels in the dorsal and ventral hippocampus of male Wistar rats during normal pubertal development and then assess the effects of repeated binge-EtOH exposure. In addition, we measured the effects of binge EtOH-exposure on hippocampal Drosha and Dicer mRNA levels, as well as the putative miR target genes, BDNF and SIRT1. Overall, mid/peri-pubertal binge EtOH exposure altered the normal expression patterns of all miRs tested in an age- and brain region-dependent manner and this effect persisted for up to 30 days post-EtOH exposure. Moreover, our data revealed that mid/peri-pubertal binge EtOH exposure significantly affected miR biosynthetic processing enzymes, Drosha and Dicer. Finally, EtOH-induced significant changes in the expression of a subset of miRs, which correlated with changes in the expression of their predicted target genes. Taken together, these data demonstrate that EtOH exposure during pubertal development has long-term effects on miRNA expression in the rat hippocampus.

  17. 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.

  18. Long-term no-tillage and organic input management enhanced the diversity and stability of soil microbial community.

    Science.gov (United States)

    Wang, Yi; Li, Chunyue; Tu, Cong; Hoyt, Greg D; DeForest, Jared L; Hu, Shuijin

    2017-12-31

    Intensive tillage and high inputs of chemicals are frequently used in conventional agriculture management, which critically depresses soil properties and causes soil erosion and nonpoint source pollution. Conservation practices, such as no-tillage and organic farming, have potential to enhance soil health. However, the long-term impact of no-tillage and organic practices on soil microbial diversity and community structure has not been fully understood, particularly in humid, warm climate regions such as the southeast USA. We hypothesized that organic inputs will lead to greater microbial diversity and a more stable microbial community, and that the combination of no-tillage and organic inputs will maximize soil microbial diversity. We conducted a long-term experiment in the southern Appalachian mountains of North Carolina, USA to test these hypotheses. The results showed that soil microbial diversity and community structure diverged under different management regimes after long term continuous treatments. Organic input dominated the effect of management practices on soil microbial properties, although no-tillage practice also exerted significant impacts. Both no-tillage and organic inputs significantly promoted soil microbial diversity and community stability. The combination of no-tillage and organic management increased soil microbial diversity over the conventional tillage and led to a microbial community structure more similar to the one in an adjacent grassland. These results indicate that effective management through reducing tillage and increasing organic C inputs can enhance soil microbial diversity and community stability. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Life’s Critical Role in the Long-term Carbon Cycle: the Biotic Enhancement of Weathering

    Directory of Open Access Journals (Sweden)

    David W. Schwartzman

    2017-06-01

    Full Text Available The biotic enhancement of weathering (BEW has important implications for the long-term carbon cycle, in particular as a driver of climatic cooling. The BEW factor is defined as how much faster the silicate weathering carbon sink is under biotic conditions than under abiotic conditions at the same atmospheric pCO2 level and surface temperature. The BEW factor and its evolution over geological time can potentially be inferred from consideration of empirical and theoretical weathering studies. Estimates of the global magnitude of the BEW are presented, drawing from laboratory, field, watershed data and models of the long-term carbon cycle, with values ranging from one to two orders of magnitude.

  20. Enhanced long-term organics and nitrogen removal and associated microbial community in intermittently aerated subsurface flow constructed wetlands.

    Science.gov (United States)

    Fan, Jinlin; Zhang, Jian; Guo, Wenshan; Liang, Shuang; Wu, Haiming

    2016-08-01

    The long-term enhanced removal efficiency of organics and nitrogen in subsurface flow constructed wetlands (SSF CWs) with and without intermittent aeration for decentralized domestic wastewater was evaluated, and the function of intermittent aeration on microbial community was also investigated in this study. The high and long-term 95.6% COD, 96.1% NH4(+)-N and 85.8% TN removal efficiencies were achieved in experimental intermittently aerated SSF CW compared with non-aerated SSF CW. Aerated SSF CWs also exhibited the excellent removal performance when comparatively comparing with other strategies and techniques applied in CWs. In addition, fluorescence in situ hybridization (FISH) analysis revealed that associated microbial abundance significantly increased owing to intermittent aeration. These results indicated intermittent aeration CWs might be an effective and sustainable strategy for wastewater treatment in rural areas, but require further full-scale investigation in future. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Stable immediate early gene expression patterns in medial prefrontal cortex and striatum after long-term cocaine self-administration.

    Science.gov (United States)

    Gao, Ping; Limpens, Jules H W; Spijker, Sabine; Vanderschuren, Louk J M J; Voorn, Pieter

    2017-03-01

    The transition from casual to compulsive drug use is thought to occur as a consequence of repeated drug taking leading to neuroadaptive changes in brain circuitry involved in emotion and cognition. At the basis of such neuroadaptations lie changes in the expression of immediate early genes (IEGs) implicated in transcriptional regulation, synaptic plasticity and intracellular signalling. However, little is known about how IEG expression patterns change during long-term drug self-administration. The present study, therefore, compares the effects of 10 and 60-day self-administration of cocaine and sucrose on the expression of 17 IEGs in brain regions implicated in addictive behaviour, i.e. dorsal striatum, ventral striatum and medial prefrontal cortex (mPFC). Increased expression after cocaine self-administration was found for 6 IEGs in dorsal and ventral striatum (c-fos, Mkp1, Fosb/ΔFosb, Egr2, Egr4, and Arc) and 10 IEGs in mPFC (same 6 IEGs as in striatum, plus Bdnf, Homer1, Sgk1 and Rgs2). Five of these 10 IEGs (Egr2, Fosb/ΔFosb, Bdnf, Homer1 and Jun) and Trkb in mPFC were responsive to long-term sucrose self-administration. Importantly, no major differences were found between IEG expression patterns after 10 or 60 days of cocaine self-administration, except Fosb/ΔFosb in dorsal striatum and Egr2 in mPFC, whereas the amount of cocaine obtained per session was comparable for short-term and long-term self-administration. These steady changes in IEG expression are, therefore, associated with stable self-administration behaviour rather than the total amount of cocaine consumed. Thus, sustained impulses to IEG regulation during prolonged cocaine self-administration may evoke neuroplastic changes underlying compulsive drug use. © 2015 Society for the Study of Addiction.

  2. 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...

  3. Immunohistochemical expression of platelet-derived growth factor receptors in ovarian cancer patients with long-term follow-up

    DEFF Research Database (Denmark)

    Madsen, Christine Vestergaard; Dahl Steffensen, Karina; Waldstrøm, Marianne

    2012-01-01

    relation to histopathological parameters and long-term overall survival. Methods. The immunohistochemical expression of PDGFR-α and PDGFR-β was investigated in tumor and stromal cells in 170 patients with histologically verified epithelial ovarian cancer. Results. Almost half of the tumor specimens showed......Introduction. The well-documented role of the PDGF system in tumor growth and angiogenesis has prompted the development of new biological agents targeting the PDGF system. The aim of the present study was to analyze the expression of the PDGF-receptors in ovarian cancer and to investigate its...

  4. Long-term expression of melanopsin and channelrhodopsin causes no gross alterations in the dystrophic dog retina.

    Science.gov (United States)

    Ameline, B; Tshilenge, K-T; Weber, M; Biget, M; Libeau, L; Caplette, R; Mendes-Madeira, A; Provost, N; Guihal, C; Picaud, S; Moullier, P; Pichard, V; Cronin, T; Isiegas, C

    2017-11-01

    Several preclinical studies have investigated the potential of algal channelrhodopsin and human melanopsin as optogenetic tools for vision restoration. In the present study, we assessed the potentially deleterious effects of long-term expression of these optogenes on the diseased retina in a large animal model of retinal degeneration, the RPE65-deficient Briard dog model of Leber congenital amaurosis. Intravitreal injection of adeno-associated virus vectors expressing channelrhodopsin and melanopsin had no effect on retinal thickness over a 16-month period post injection. Our data support the safety of the optogenetic approach for the treatment of blindness.

  5. Satb2 determines miRNA expression and long-term memory in the adult central nervous system.

    Science.gov (United States)

    Jaitner, Clemens; Reddy, Chethan; Abentung, Andreas; Whittle, Nigel; Rieder, Dietmar; Delekate, Andrea; Korte, Martin; Jain, Gaurav; Fischer, Andre; Sananbenesi, Farahnaz; Cera, Isabella; Singewald, Nicolas; Dechant, Georg; Apostolova, Galina

    2016-11-29

    SATB2 is a risk locus for schizophrenia and encodes a DNA-binding protein that regulates higher-order chromatin configuration. In the adult brain Satb2 is almost exclusively expressed in pyramidal neurons of two brain regions important for memory formation, the cerebral cortex and the CA1-hippocampal field. Here we show that Satb2 is required for key hippocampal functions since deletion of Satb2 from the adult mouse forebrain prevents the stabilization of synaptic long-term potentiation and markedly impairs long-term fear and object discrimination memory. At the molecular level, we find that synaptic activity and BDNF up-regulate Satb2, which itself binds to the promoters of coding and non-coding genes. Satb2 controls the hippocampal levels of a large cohort of miRNAs, many of which are implicated in synaptic plasticity and memory formation. Together, our findings demonstrate that Satb2 is critically involved in long-term plasticity processes in the adult forebrain that underlie the consolidation and stabilization of context-linked memory.

  6. Long-term increased carnitine palmitoyltransferase 1A expression in ventromedial hypotalamus causes hyperphagia and alters the hypothalamic lipidomic profile.

    Directory of Open Access Journals (Sweden)

    Paula Mera

    Full Text Available Lipid metabolism in the ventromedial hypothalamus (VMH has emerged as a crucial pathway in the regulation of feeding and energy homeostasis. Carnitine palmitoyltransferase (CPT 1A is the rate-limiting enzyme in mitochondrial fatty acid β-oxidation and it has been proposed as a crucial mediator of fasting and ghrelin orexigenic signalling. However, the relationship between changes in CPT1A activity and the intracellular downstream effectors in the VMH that contribute to appetite modulation is not fully understood. To this end, we examined the effect of long-term expression of a permanently activated CPT1A isoform by using an adeno-associated viral vector injected into the VMH of rats. Peripherally, this procedure provoked hyperghrelinemia and hyperphagia, which led to overweight, hyperglycemia and insulin resistance. In the mediobasal hypothalamus (MBH, long-term CPT1AM expression in the VMH did not modify acyl-CoA or malonyl-CoA levels. However, it altered the MBH lipidomic profile since ceramides and sphingolipids increased and phospholipids decreased. Furthermore, we detected increased vesicular γ-aminobutyric acid transporter (VGAT and reduced vesicular glutamate transporter 2 (VGLUT2 expressions, both transporters involved in this orexigenic signal. Taken together, these observations indicate that CPT1A contributes to the regulation of feeding by modulating the expression of neurotransmitter transporters and lipid components that influence the orexigenic pathways in VMH.

  7. Responses in colonic microbial community and gene expression of pigs to a long-term high resistant starch diet

    Directory of Open Access Journals (Sweden)

    Yue eSun

    2015-08-01

    Full Text Available Intake of raw potato starch (RPS has been associated with various intestinal health benefits, but knowledge of its mechanism in a long-term is limited. The aim of this study was to investigate the effects of long-term intake of RPS on microbial composition, genes expression profiles in the colon of pigs. Thirty-six Duroc × Landrace × Large White growing barrows were randomly allocated to corn starch (CS and RPS groups with a randomized block design. Each group consisted of six replicates (pens, with three pigs per pen. Pigs in the CS group were offered a corn/soybean-based diet, while pigs in the RPS group were put on a diet in which 230 g/kg (growing period or 280 g/kg (finishing period purified corn starch was replaced with purified RPS during a 100-day trial. Real-time PCR assay showed that RPS significantly decreased the number of total bacteria in the colonic digesta. MiSeq sequencing of the V3-V4 region of the 16S rRNA genes showed that RPS significantly decreased the relative abundance of Clostridium, Treponema, Oscillospira, Phascolarctobacterium, RC9 gut group, and S24-7-related operational taxonomic units (OTUs, and increased the relative abundance of Turicibacter, Blautia, Ruminococcus, Coprococcus, Marvinbryantia, and Ruminococcus bromii-related OTUs in colonic digesta and mucosa. Analysis of the colonic transcriptome profiles revealed that the RPS diet changed the colonic expression profile of the host genes mainly involved in immune response pathways. RPS significantly increased proinflammartory cytokine IL-1β gene expression and suppressed genes involved in lysosome. Our findings suggest that long-term intake of high resistant starch (RS diet may result in both positive and negative roles in gut health.

  8. [Inhibition of histone deacetylases in the chick brain modulates expression of c-Fos and ZENK transcription factors and facilitates establishment of long-term memory].

    Science.gov (United States)

    Toropova, K A; Anokhin, K V; Tiunova, A A

    2014-01-01

    The aim of the work was to examine the role of histone acetylation in memory consolidation in newborn chicks. We studied the effects of histone deacetylase inhibitor trichostatin A (TSA) on a "weak" memory for passive avoidance and on expression of two transcription factors c-Fos and ZENK known to play a role in neuronal plasticity in the chick brain. Intraventricular administration of trichostatin A prior to training produced a dose-dependent enhancement of memory when tested 24 hours after the training. It also increased neuronal expression of c-Fos and ZENK proteins: the density of ZENK immunopositive cells increased in the hippocampus and intermediate medial mesopallium and the density of c-Fos immunopositive cells increased in intermediate arcopallium and dorsocaudal nidopallium. Weak passive avoidance training did not produce further enhancement of c-Fos and ZENK expression in any of these brain areas. These data demonstrate possibility of facilitating long-term memory in day-old chicks by a histone deacetylases inhibitor, thus supporting the hypothesis on the role of histone acetylation in long-term memory formation. They also suggest that these effects might be mediated through modulation of transcriptional response in brain areas involved in consolidation of this form of memory.

  9. Long-term stability of β-galactosidase protein expression in the ...

    African Journals Online (AJOL)

    In this study, the adequacy of β-galactosidase (β-gal) as marker for models that requires durable and high level gene expression in the absence of selective pressure was investigated. Chinese hamster ovary (CHO) cells were transfected with expression vector pcDNA4/HisMax-TOPO/lacZ containing lacZ and zeocin ...

  10. Muscarinic Long-Term Enhancement of Tonic and Phasic GABAA Inhibition in Rat CA1 Pyramidal Neurons

    Science.gov (United States)

    Domínguez, Soledad; Fernández de Sevilla, David; Buño, Washington

    2016-01-01

    Acetylcholine (ACh) regulates network operation in the hippocampus by controlling excitation and inhibition in rat CA1 pyramidal neurons (PCs), the latter through gamma-aminobutyric acid type-A receptors (GABAARs). Although, the enhancing effects of ACh on GABAARs have been reported (Dominguez et al., 2014, 2015), its role in regulating tonic GABAA inhibition has not been explored in depth. Therefore, we aimed at determining the effects of the activation of ACh receptors on responses mediated by synaptic and extrasynaptic GABAARs. Here, we show that under blockade of ionotropic glutamate receptors ACh, acting through muscarinic type 1 receptors, paired with post-synaptic depolarization induced a long-term enhancement of tonic GABAA currents (tGABAA) and puff-evoked GABAA currents (pGABAA). ACh combined with depolarization also potentiated IPSCs (i.e., phasic inhibition) in the same PCs, without signs of interactions of synaptic responses with pGABAA and tGABAA, suggesting the contribution of two different GABAA receptor pools. The long-term enhancement of GABAA currents and IPSCs reduced the excitability of PCs, possibly regulating plasticity and learning in behaving animals. PMID:27833531

  11. MUSCARINIC LONG-TERM ENHANCEMENT OF TONIC AND PHASIC GABAA INHIBITION IN RAT CA1 PYRAMIDAL NEURONS

    Directory of Open Access Journals (Sweden)

    Soledad Dominguez

    2016-10-01

    Full Text Available ABSTRACTAcetylcholine (ACh regulates network operation in the hippocampus by controlling excitation and inhibition in rat CA1 pyramidal neurons (PCs, the latter through gamma-aminobutyric acid type-A receptors (GABAARs. Although, the enhancing effects of ACh on GABAARs have been reported (Dominguez et al., 2014; 2015, its role in regulating tonic GABAA inhibition has not been explored in depth. Therefore, we aimed at determining the effects of the activation of ACh receptors on responses mediated by synaptic and extrasynaptic GABAARs. Here, we show that under blockade of ionotropic glutamate receptors ACh, acting through muscarinic type 1 receptors, paired with postsynaptic depolarization induced a long-term enhancement of tonic GABAA currents (tGABAA and puff-evoked GABAA currents (pGABAA. ACh combined with depolarization also potentiated IPSCs (i.e., phasic inhibition in the same PCs, without signs of interactions of synaptic responses with pGABAA and tGABAA, suggesting the contribution of two different GABAA receptor pools. The long-term enhancement of GABAA currents and IPSCs reduced the excitability of PCs, possibly regulating plasticity and learning in behaving animals.

  12. Superior Long-Term Synaptic Memory Induced by Combining Dual Pharmacological Activation of PKA and ERK with an Enhanced Training Protocol

    Science.gov (United States)

    Liu, Rong-Yu; Neveu, Curtis; Smolen, Paul; Cleary, Leonard J.; Byrne, John H.

    2017-01-01

    Developing treatment strategies to enhance memory is an important goal of neuroscience research. Activation of multiple biochemical signaling cascades, such as the protein kinase A (PKA) and extracellular signal-regulated kinase (ERK) pathways, is necessary to induce long-term synaptic facilitation (LTF), a correlate of long-term memory (LTM).…

  13. 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

  14. Genome-Wide Temporal Expression Profiling in Caenorhabditis elegans Identifies a Core Gene Set Related to Long-Term Memory.

    Science.gov (United States)

    Freytag, Virginie; Probst, Sabine; Hadziselimovic, Nils; Boglari, Csaba; Hauser, Yannick; Peter, Fabian; Gabor Fenyves, Bank; Milnik, Annette; Demougin, Philippe; Vukojevic, Vanja; de Quervain, Dominique J-F; Papassotiropoulos, Andreas; Stetak, Attila

    2017-07-12

    The identification of genes related to encoding, storage, and retrieval of memories is a major interest in neuroscience. In the current study, we analyzed the temporal gene expression changes in a neuronal mRNA pool during an olfactory long-term associative memory (LTAM) in Caenorhabditis elegans hermaphrodites. Here, we identified a core set of 712 (538 upregulated and 174 downregulated) genes that follows three distinct temporal peaks demonstrating multiple gene regulation waves in LTAM. Compared with the previously published positive LTAM gene set (Lakhina et al., 2015), 50% of the identified upregulated genes here overlap with the previous dataset, possibly representing stimulus-independent memory-related genes. On the other hand, the remaining genes were not previously identified in positive associative memory and may specifically regulate aversive LTAM. Our results suggest a multistep gene activation process during the formation and retrieval of long-term memory and define general memory-implicated genes as well as conditioning-type-dependent gene sets.SIGNIFICANCE STATEMENT The identification of genes regulating different steps of memory is of major interest in neuroscience. Identification of common memory genes across different learning paradigms and the temporal activation of the genes are poorly studied. Here, we investigated the temporal aspects of Caenorhabditis elegans gene expression changes using aversive olfactory associative long-term memory (LTAM) and identified three major gene activation waves. Like in previous studies, aversive LTAM is also CREB dependent, and CREB activity is necessary immediately after training. Finally, we define a list of memory paradigm-independent core gene sets as well as conditioning-dependent genes. Copyright © 2017 the authors 0270-6474/17/376661-12$15.00/0.

  15. Sex-Specificity of Mineralocorticoid Target Gene Expression during Renal Development, and Long-Term Consequences

    Directory of Open Access Journals (Sweden)

    Laurence Dumeige

    2017-02-01

    Full Text Available Sex differences have been identified in various biological processes, including hypertension. The mineralocorticoid signaling pathway is an important contributor to early arterial hypertension, however its sex-specific expression has been scarcely studied, particularly with respect to the kidney. Basal systolic blood pressure (SBP and heart rate (HR were measured in adult male and female mice. Renal gene expression studies of major players of mineralocorticoid signaling were performed at different developmental stages in male and female mice using reverse transcription quantitative PCR (RT-qPCR, and were compared to those of the same genes in the lung, another mineralocorticoid epithelial target tissue that regulates ion exchange and electrolyte balance. The role of sex hormones in the regulation of these genes was also investigated in differentiated KC3AC1 renal cells. Additionally, renal expression of the 11 β-hydroxysteroid dehydrogenase type 2 (11βHSD2 protein, a regulator of mineralocorticoid specificity, was measured by immunoblotting and its activity was indirectly assessed in the plasma using liquid-chromatography coupled to mass spectrometry in tandem (LC-MSMS method. SBP and HR were found to be significantly lower in females compared to males. This was accompanied by a sex- and tissue-specific expression profile throughout renal development of the mineralocorticoid target genes serum and glucocorticoid-regulated kinase 1 (Sgk1 and glucocorticoid-induced leucine zipper protein (Gilz, together with Hsd11b2, Finally, the implication of sex hormones in this sex-specific expression profile was demonstrated in vitro, most notably for Gilz mRNA expression. We demonstrate a tissue-specific, sex-dependent and developmentally-regulated pattern of expression of the mineralocorticoid pathway that could have important implications in physiology and pathology.

  16. Consolidation power of extrinsic rewards: reward cues enhance long-term memory for irrelevant past events.

    Science.gov (United States)

    Murayama, Kou; Kitagami, Shinji

    2014-02-01

    Recent research suggests that extrinsic rewards promote memory consolidation through dopaminergic modulation processes. However, no conclusive behavioral evidence exists given that the influence of extrinsic reward on attention and motivation during encoding and consolidation processes are inherently confounded. The present study provides behavioral evidence that extrinsic rewards (i.e., monetary incentives) enhance human memory consolidation independently of attention and motivation. Participants saw neutral pictures, followed by a reward or control cue in an unrelated context. Our results (and a direct replication study) demonstrated that the reward cue predicted a retrograde enhancement of memory for the preceding neutral pictures. This retrograde effect was observed only after a delay, not immediately upon testing. An additional experiment showed that emotional arousal or unconscious resource mobilization cannot explain the retrograde enhancement effect. These results provide support for the notion that the dopaminergic memory consolidation effect can result from extrinsic reward.

  17. Expression of HSPs: an adaptive mechanism during long-term heat stress in goats ( Capra hircus)

    Science.gov (United States)

    Dangi, Satyaveer Singh; Gupta, Mahesh; Dangi, Saroj K.; Chouhan, Vikrant Singh; Maurya, V. P.; Kumar, Puneet; Singh, Gyanendra; Sarkar, Mihir

    2015-08-01

    Menacing global rise in surface temperature compelled more focus of research over understanding heat stress response mechanism of animals and mitigation of heat stress. Twenty-four goats divided into four groups ( n = 6) such as NHS (non-heat-stressed), HS (heat-stressed), HS + VC (heat-stressed administered with vitamin C), and HS + VE + Se (heat-stressed administered with vitamin E and selenium). Except NHS group, other groups were exposed to repeated heat stress (42 °C) for 6 h on 16 consecutive days. Blood samples were collected at the end of heat exposure on days 1, 6, 11, and 16. When groups compared between days, expression of all heat shock proteins (HSPs) showed a similar pattern as first peak on day 1, reached to basal level on the sixth day, and followed by second peak on day 16. The relative messenger RNA (mRNA) and protein expression of HSP 60, HSP70, and HSP90 was observed highest ( P < 0.05) in HS group, followed by antioxidant-administered group on days 1 and 16, which signifies that antioxidants have dampening effect on HSP expression. HSP105/110 expression was highest ( P < 0.05) on day 16. We conclude that HSP expression pattern is at least two-peak phenomenon, i.e., primary window of HSP protection on the first day followed by second window of protection on day 16. HSP60, HSP70, and HSP90 play an important role during the initial phase of heat stress acclimation whereas HSP105/110 joins this cascade at later phase. Antioxidants may possibly attenuate the HSP expression by reducing the oxidative stress.

  18. Long-Term Behavioral Recovery in Parkinsonian Rats by an HSV Vector Expressing Tyrosine Hydroxylase

    Science.gov (United States)

    Naegele, Janice R.; O’Malley, Karen L.; Geller, Alfred I.

    2006-01-01

    One therapeutic approach to treating Parkinson’s disease is to convert endogenous striatal cells into levo-3,4-dihydroxyphenylalanine (l-dopa)–producing cells. A defective herpes simplex virus type 1 vector expressing human tyrosine hydroxylase was delivered into the partially denervated striatum of 6-hydroxydopamine–lesioned rats, used as a model of Parkinson’s disease. Efficient behavioral and biochemical recovery was maintained for 1 year after gene transfer. Biochemical recovery included increases in both striatal tyrosine hydroxylase enzyme activity and in extracellular dopamine concentrations. Persistence of human tyrosine hydroxylase was revealed by expression of RNA and immunoreactivity. PMID:7669103

  19. Combining brain stimulation and video game to promote long-term transfer of learning and cognitive enhancement.

    Science.gov (United States)

    Looi, Chung Yen; Duta, Mihaela; Brem, Anna-Katharine; Huber, Stefan; Nuerk, Hans-Christoph; Cohen Kadosh, Roi

    2016-02-23

    Cognitive training offers the potential for individualised learning, prevention of cognitive decline, and rehabilitation. However, key research challenges include ecological validity (training design), transfer of learning and long-term effects. Given that cognitive training and neuromodulation affect neuroplasticity, their combination could promote greater, synergistic effects. We investigated whether combining transcranial direct current stimulation (tDCS) with cognitive training could further enhance cognitive performance compared to training alone, and promote transfer within a short period of time. Healthy adults received real or sham tDCS over their dorsolateral prefrontal cortices during two 30-minute mathematics training sessions involving body movements. To examine the role of training, an active control group received tDCS during a non-mathematical task. Those who received real tDCS performed significantly better in the game than the sham group, and showed transfer effects to working memory, a related but non-numerical cognitive domain. This transfer effect was absent in active and sham control groups. Furthermore, training gains were more pronounced amongst those with lower baseline cognitive abilities, suggesting the potential for reducing cognitive inequalities. All effects associated with real tDCS remained 2 months post-training. Our study demonstrates the potential benefit of this approach for long-term enhancement of human learning and cognition.

  20. Dual-tDCS Enhances Online Motor Skill Learning and Long-Term Retention in Chronic Stroke Patients

    Science.gov (United States)

    Lefebvre, S.; Laloux, P.; Peeters, A.; Desfontaines, P.; Jamart, J.; Vandermeeren, Y.

    2013-01-01

    Background: Since motor learning is a key component for stroke recovery, enhancing motor skill learning is a crucial challenge for neurorehabilitation. Transcranial direct current stimulation (tDCS) is a promising approach for improving motor learning. The aim of this trial was to test the hypothesis that dual-tDCS applied bilaterally over the primary motor cortices (M1) improves online motor skill learning with the paretic hand and its long-term retention. Methods: Eighteen chronic stroke patients participated in a randomized, cross-over, placebo-controlled, double bind trial. During separate sessions, dual-tDCS or sham dual-tDCS was applied over 30 min while stroke patients learned a complex visuomotor skill with the paretic hand: using a computer mouse to move a pointer along a complex circuit as quickly and accurately as possible. A learning index involving the evolution of the speed/accuracy trade-off was calculated. Performance of the motor skill was measured at baseline, after intervention and 1 week later. Results: After sham dual-tDCS, eight patients showed performance worsening. In contrast, dual-tDCS enhanced the amount and speed of online motor skill learning compared to sham (p skill learning both quantitatively and qualitatively, leading to successful long-term retention and generalization. The combination of motor skill learning and dual-tDCS is promising for improving post-stroke neurorehabilitation. PMID:23316151

  1. Post-learning stress enhances long-term memory and differentially influences memory in females depending on menstrual stage.

    Science.gov (United States)

    Zoladz, Phillip R; Peters, David M; Cadle, Chelsea E; Kalchik, Andrea E; Aufdenkampe, Rachael L; Dailey, Alison M; Brown, Callie M; Scharf, Amanda R; Earley, McKenna B; Knippen, Courtney L; Rorabaugh, Boyd R

    2015-09-01

    Most work has shown that post-learning stress enhances long-term memory; however, there have been recent inconsistencies in this literature. The purpose of the present study was to examine further the effects of post-learning stress on long-term memory and to explore any sex differences that may exist. Male and female participants learned a list of 42 words that varied in emotional valence and arousal level. Following encoding, participants completed a free recall assessment and then submerged their hand into a bath of ice cold (stress) or lukewarm (no stress) water for 3 min. The next day, participants were given free recall and recognition tests. Stressed participants recalled more words than non-stressed participants 24h after learning. Stress also enhanced female participants' recall of arousing words when they were in the follicular, but not luteal, phase. These findings replicate previous work examining post-learning stress effects on memory and implicate the involvement of sex-related hormones in such effects. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Enhancing long-term photostability of BiVO4 photoanodes for solar water splitting by tuning electrolyte composition

    Science.gov (United States)

    Lee, Dong Ki; Choi, Kyoung-Shin

    2018-01-01

    As the performance of photoelectrodes used for solar water splitting continues to improve, enhancing the long-term stability of the photoelectrodes becomes an increasingly crucial issue. In this study, we report that tuning the composition of the electrolyte can be used as a strategy to suppress photocorrosion during solar water splitting. Anodic photocorrosion of BiVO4 photoanodes involves the loss of V5+ from the BiVO4 lattice by dissolution. We demonstrate that the use of a V5+-saturated electrolyte, which inhibits the photooxidation-coupled dissolution of BiVO4, can serve as a simple yet effective method to suppress anodic photocorrosion of BiVO4. The V5+ species in the solution can also incorporate into the FeOOH/NiOOH oxygen-evolution catalyst layer present on the BiVO4 surface during water oxidation, further enhancing water-oxidation kinetics. The effect of the V5+ species in the electrolyte on both the long-term photostability of BiVO4 and the performance of the FeOOH/NiOOH oxygen-evolution catalyst layer is systematically elucidated.

  3. Long-term dietary restriction up-regulates activity and expression of ...

    Indian Academy of Sciences (India)

    T Majaw

    2017-04-18

    Apr 18, 2017 ... DR, where it promotes metabolic reprogramming indicative of a transcriptional shift that favors energy metabolism and increased protein turnover (Lewis et al. 1985; Tavernarakis and Driscoll 2002). It also enhances gluconeogenesis with an increasing pace of protein turnover and eliminates damaged.

  4. Long-term maintenance of human hematopoietic stem/progenitor cells by expression of BMI1

    NARCIS (Netherlands)

    Rizo, Aleksandra; Dontje, Bert; Vellenga, Edo; de Haan, Gerald; Schuringa, Jan Jacob

    2008-01-01

    The polycomb group (PcG) gene BMI1 has been identified as one of the key epigenetic regulators of cell fates during different stages of development in multiple murine tissues. In a clinically relevant model, we demonstrate that enforced expression of BMI1 in cord blood CD34(+) cells results in

  5. Effect of long-term actual spaceflight on the expression of key genes encoding serotonin and dopamine system

    Science.gov (United States)

    Popova, Nina; Shenkman, Boris; Naumenko, Vladimir; Kulikov, Alexander; Kondaurova, Elena; Tsybko, Anton; Kulikova, Elisabeth; Krasnov, I. B.; Bazhenova, Ekaterina; Sinyakova, Nadezhda

    The effect of long-term spaceflight on the central nervous system represents important but yet undeveloped problem. The aim of our work was to study the effect of 30-days spaceflight of mice on Russian biosatellite BION-M1 on the expression in the brain regions of key genes of a) serotonin (5-HT) system (main enzymes in 5-HT metabolism - tryptophan hydroxylase-2 (TPH-2), monoamine oxydase A (MAO A), 5-HT1A, 5-HT2A and 5-HT3 receptors); b) pivotal enzymes in DA metabolism (tyrosine hydroxylase, COMT, MAO A, MAO B) and D1, D2 receptors. Decreased expression of genes encoding the 5-HT catabolism (MAO A) and 5-HT2A receptor in some brain regions was shown. There were no differences between “spaceflight” and control mice in the expression of TPH-2 and 5-HT1A, 5-HT3 receptor genes. Significant changes were found in genetic control of DA system. Long-term spaceflight decreased the expression of genes encoding the enzyme in DA synthesis (tyrosine hydroxylase in s.nigra), DA metabolism (MAO B in the midbrain and COMT in the striatum), and D1 receptor in hypothalamus. These data suggested that 1) microgravity affected genetic control of 5-HT and especially the nigrostriatal DA system implicated in the central regulation of muscular tonus and movement, 2) the decrease in the expression of genes encoding key enzyme in DA synthesis, DA degradation and D1 receptor contributes to the movement impairment and dyskinesia produced by the spaceflight. The study was supported by Russian Foundation for Basic Research grant № 14-04-00173.

  6. The effects of test-enhanced learning on long-term retention in AAN annual meeting courses.

    Science.gov (United States)

    Larsen, Douglas P; Butler, Andrew C; Aung, Wint Y; Corboy, John R; Friedman, Deborah I; Sperling, Michael R

    2015-02-17

    We measured the long-term retention of knowledge gained through selected American Academy of Neurology annual meeting courses and compared the effects of repeated quizzing (known as test-enhanced learning) and repeated studying on that retention. Participants were recruited from 4 annual meeting courses. All participants took a pretest. This randomized, controlled trial utilized a within-subjects design in which each participant experienced 3 different postcourse activities with each activity performed on different material. Each key information point from the course was randomized in a counterbalanced fashion among participants to one of the 3 activities: repeated short-answer quizzing, repeated studying, and no further exposure to the materials. A final test covering all information points from the course was taken 5.5 months after the course. Thirty-five participants across the 4 courses completed the study. Average score on the pretest was 36%. Performance on the final test showed that repeated quizzing led to significantly greater long-term retention relative to both repeated studying (55% vs 46%; t[34] = 3.28, SEM = 0.03, p = 0.01, d = 0.49) and no further exposure (55% vs 44%; t[34] = 3.16, SEM = 0.03, p = 0.01, d = 0.58). Relative to the pretest baseline, repeated quizzing helped participants to retain almost twice as much of the knowledge acquired from the course compared to repeated studying or no further exposure. Whereas annual meeting continuing medical education (CME) courses lead to long-term gains in knowledge, when repeated quizzing is added, retention is significantly increased. CME planners may consider adding repeated quizzing to increase the impact of their courses. © 2015 American Academy of Neurology.

  7. Bupropion and sertraline enhance retrieval of recent and remote long-term memory in rats.

    Science.gov (United States)

    Barros, D M; Izquierdo, L A; Medina, J H; Izquierdo, I

    2002-05-01

    Wistar rats were trained in step-down inhibitory avoidance at the age of 3 months, and tested for retrieval either 1 day later or 3, 6, 9, 12, 15 or 19 months later, when the animals were 6, 9, 12, 15, 18 or 22 months old, respectively. Bupropion (20 or 60 mg/kg) and sertraline (3.3 or 10 mg/kg) given orally 6 or 3 h before retention testing, respectively, enhanced retrieval of this task at all training-test intervals, despite the fact that retrieval at the longest intervals was practically not seen in control animals. The effect cannot be explained by influences of the drugs on locomotor activity; the treatments had no effect on open field behaviour at the age of 3, 8 or 21 months. The findings may be relevant to the use of these drugs as cognitive enhancers in elderly subjects. Copyright 2002 Lippincott Williams & Wilkins.

  8. Repeated batch fermentation of immobilized E. coli expressing Vitreoscilla hemoglobin for long-term use.

    Science.gov (United States)

    Sar, Taner; Seker, Gamze; Erman, Ayse Gokce; Stark, Benjamin C; Yesilcimen Akbas, Meltem

    2017-09-03

    This study describes an efficient and reusable process for ethanol production from medium containing whey powder, using alginate immobilized ethanologenic E. coli strains either expressing (TS3) or not expressing (FBR5) Vitreoscilla hemoglobin. Reuseabilities of the FBR5 and TS3 strains were investigated regarding their ethanol production capacities over the course of 15 successive 96-h batch fermentations. The ethanol production was fairly stable over the entire duration of the experiment, with strain TS3 maintaining a substantial advantage over strain FBR5. Storage of both strains in 2 different solutions for up to 60 d resulted in only a modest loss of ethanol production, with strain TS3 consistently outperforming strain FBR5 by a substantial amount. Strains stored for 15 or 30 d maintained their abilities to produce ethanol without dimunition over the course of 8 successive batch fermentations; again strain TS3 maintained a substantial advantage over strain FBR5 throughout the entire experiment. Thus, immobilization is a useful strategy to maintain the advantage in ethanol productivity afforded by expression of Vitreoscilla hemoglobin over long periods of time and large numbers of repeated batch fermentations, including, as in this case, using media with food processing wastes as the carbon source.

  9. Accumulation of long-term transcriptionally active integrated retroviral vectors in active promoters and enhancers

    Czech Academy of Sciences Publication Activity Database

    Šenigl, Filip; Miklík, Dalibor; Auxt, Miroslav; Hejnar, Jiří

    2017-01-01

    Roč. 45, č. 22 (2017), s. 12752-12765 ISSN 0305-1048 R&D Projects: GA ČR(CZ) GA14-34873S; GA MŠk LO1419 Institutional support: RVO:68378050 Keywords : human-immunodeficiency-virus * dna methylation * site selection * human genome * avian-sarcoma * morphological reversion * hiv -1 integration * mlv integration * gene-expression * leukosis virus Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 10.162, year: 2016

  10. Comparative effectiveness of exercise with patterned sensory enhanced music and background music for long-term care residents.

    Science.gov (United States)

    O'Konski, Marjorie; Bane, Cynthia; Hettinga, Johanna; Krull, Katelyn

    2010-01-01

    The current study compared exercise performance and participant satisfaction for 2 conditions: Patterned Sensory Enhanced music (PSE) and big band background music. Residents of long-term care facilities in the Midwest (N = 45) attended a minimum of 3 sessions per condition and reported levels of satisfaction after each session. Observers blind to condition coded videotapes for number of repetitions, adherence to modeled movements, range of motion, and form. Significant differences were found for only 3/19 exercises and satisfaction levels did not differ between the 2 conditions. The results indicate that PSE may not be more effective than big band background music but that both types of music enhance exercise performance and participant enjoyment. PSE also provides consistency in number of repetitions led.

  11. Reduction of photo bleaching and long term archiving of chemically cleared GFP-expressing mouse brains.

    Directory of Open Access Journals (Sweden)

    Klaus Becker

    Full Text Available Tissue clearing allows microscopy of large specimens as whole mouse brains or embryos. However, lipophilic tissue clearing agents as dibenzyl ether limit storage time of GFP-expressing samples to several days and do not prevent them from photobleaching during microscopy. To preserve GFP fluorescence, we developed a transparent solid resin formulation, which maintains the specimens' transparency and provides a constant signal to noise ratio even after hours of continuous laser irradiation. If required, high-power illumination or long exposure times can be applied with virtually no loss in signal quality and samples can be archived for years.

  12. MiR-132 Regulates Rem Expression in Cardiomyocytes During Long-Term β-Adrenoceptor Agonism

    Directory of Open Access Journals (Sweden)

    Elba D. Carrillo

    2015-04-01

    Full Text Available Aims: To characterize the effects of long-term β-adrenergic receptor stimulation on Rem protein and mRNA expression in rat heart and possible involvement of miR-132. Methods: Adult rats were treated with isoproterenol (ISO, 150 µg.kg.h-1 for 2 d and Rem, miR-132, and α1c (the principal subunit of Cav1.2 channels were measured at protein and mRNA levels with western blot and quantitative reverse transcriptase polymerase chain reaction (qRT-PCR experiments, respectively. Ca2+ currents and intracellular Ca2+ signals were evaluated in isolated cardiomyocytes. Results: Systemic administration of ISO led to decreases in Rem protein and mRNA levels (down to 49%. Furthermore, levels of the microRNAs (miRs miR-132 and miR-214 were upregulated 5- and 9-fold, respectively. Transfection of miR-132, but not miR-214, into HEK293 cells reduced the expression of a luciferase reporter gene controlled by a conserved 3´-untranslated region (UTR of Rem by half. Chronic ISO administration also led to a 25% decrease in the amplitude of peak L-type Ca2+ currents, a 40% decrease in α1c subunit protein abundance at the membrane level, and a 60% decrease in expression of α1c channel subunit mRNA. Conclusions: These results suggest that Rem expression is down-regulated posttranscriptionally by miR-132 in response to long-term activation of β-adrenergic signaling, but this down-regulation does not produce a larger Ca2+ influx through Cav1.2 channels.

  13. Temperature during early development has long-term effects on microRNA expression in Atlantic cod.

    Science.gov (United States)

    Bizuayehu, Teshome Tilahun; Johansen, Steinar D; Puvanendran, Velmurugu; Toften, Hilde; Babiak, Igor

    2015-04-17

    Environmental temperature has serious implications in life cycle of aquatic ectotherms. Understanding the molecular mechanisms of temperature acclimation and adaptation of marine organisms is of the uttermost importance for ecology, fisheries, and aquaculture, as it allows modeling the effects of global warming on population dynamics. Regulatory molecules are major modulators of acclimation and adaptation; among them, microRNAs (miRNAs) are versatile and substantial contributors to regulatory networks of development and adaptive plasticity. However, their role in thermal plasticity is poorly known. We have asked whether the temperature and its shift during the early ontogeny (embryonic and larval development) affect the miRNA repertoire of Atlantic cod (Gadus morhua), and if thermal experience has long-term consequences in the miRNA profile. We characterized miRNA during different developmental stages and in juvenile tissues using next generation sequencing. We identified 389 putative miRNA precursor loci, 120 novel precursor miRNAs, and 281 mature miRNAs. Some miRNAs showed stage- or tissue-enriched expression and miRNAs, such as the miR-17 ~ 92 cluster, myomiRs (miR-206), neuromiRs (miR-9, miR-124), miR-130b, and miR-430 showed differential expression in different temperature regimes. Long-term effect of embryonic incubation temperature was revealed on expression of some miRNAs in juvenile pituitary (miR-449), gonad (miR-27c, miR-30c, and miR-200a), and liver (let-7 h, miR-7a, miR-22, miR-34c, miR-132a, miR-192, miR-221, miR-451, miR-2188, and miR-7550), but not in brain. Some of differentially expressed miRNAs in the liver were confirmed using LNA-based rt-qPCR. The effect of temperature on methylation status of selected miRNA promoter regions was mostly inconclusive. Temperature elevation by several degrees during embryonic and larval developmental stages significantly alters the miRNA profile, both short-term and long-term. Our results suggest that a further

  14. Distinctiveness enhances long-term event memory in non-human primates, irrespective of reinforcement.

    Science.gov (United States)

    Lewis, Amy; Call, Josep; Berntsen, Dorthe

    2017-08-01

    Non-human primates are capable of recalling events that occurred as long as 3 years ago, and are able to distinguish between similar events; akin to human memory. In humans, distinctiveness enhances memory for events, however, it is unknown whether the same occurs in non-human primates. As such, we tested three great ape species on their ability to remember an event that varied in distinctiveness. Across three experiments, apes witnessed a baiting event in which one of three identical containers was baited with food. After a delay of 2 weeks, we tested their memory for the location of the baited container. Apes failed to recall the baited container when the event was undistinctive (Experiment 1), but were successful when it was distinctive (Experiment 2), although performance was equally good in a less-distinctive condition. A third experiment (Experiment 3) confirmed that distinctiveness, independent of reinforcement, was a consistent predictor of performance. These findings suggest that distinctiveness may enhance memory for events in non-human primates in the same way as in humans, and provides further evidence of basic similarities between the ways apes and humans remember past events. © 2017 Wiley Periodicals, Inc.

  15. Physical activity enhances long-term quality of life in older adults: efficacy, esteem, and affective influences.

    Science.gov (United States)

    Elavsky, Steriani; McAuley, Edward; Motl, Robert W; Konopack, James F; Marquez, David X; Hu, Liang; Jerome, Gerald J; Diener, Ed

    2005-10-01

    Physical activity has been effective in enhancing quality of life (QOL) of older adults over relatively short periods of time. However, little is known about the long-term effects of physical activity and even less about the possible mediators of this relationship. We examined the mediating effects of psychological variables on the relationship between physical activity and global QOL (satisfaction with life) in older adults over a 4-year period. Participants (N = 174, M age = 66.7 years) completed a battery of psychosocial measures at 1 and 5 years following enrollment in a 6-month randomized controlled exercise trial. Panel analysis conducted within a covariance modeling framework indicated that physical activity was related to self-efficacy, physical self-esteem, and positive affect at 1 year, and in turn, greater levels of self-efficacy and positive affect were associated with higher levels of QOL. Analyses indicated that changes in physical activity over the 4-year period were related to increases in physical self-esteem and positive affect, but only positive affect directly influenced improvements in QOL. The findings lend support to the position that physical activity effects on QOL are in part mediated by intermediate psychological outcomes and that physical activity can have long-term effects on well-being.

  16. Enhancement of long-term stability of pentacene thin-film transistors encapsulated with transparent SnO{sub 2}

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Woo Jin [Department of Metallurgical Engineering, Yonsei University, Seoul 120-749 (Korea, Republic of); Koo, Won Hoe [Department of Metallurgical Engineering, Yonsei University, Seoul 120-749 (Korea, Republic of); Jo, Sung Jin [Department of Metallurgical Engineering, Yonsei University, Seoul 120-749 (Korea, Republic of); Kim, Chang Su [Department of Metallurgical Engineering, Yonsei University, Seoul 120-749 (Korea, Republic of); Baik, Hong Koo [Department of Metallurgical Engineering, Yonsei University, Seoul 120-749 (Korea, Republic of)]. E-mail: thinfilm@yonsei.ac.kr; Lee, Jiyoul [Institute of Physics and Applied Physics, Yonsei University, Seoul 120-749 (Korea, Republic of); Im, Seongil [Institute of Physics and Applied Physics, Yonsei University, Seoul 120-749 (Korea, Republic of)

    2005-12-15

    The long-term stability of pentacene thin-film transistors (TFTs) encapsulated with a transparent SnO{sub 2} thin-film prepared by ion beam-assisted deposition (IBAD) was investigated. After encapsulation process, our organic thin-film transistors (OTFTs) showed somewhat degraded field-effect mobility of 0.5 cm{sup 2}/(V s) that was initially 0.62 cm{sup 2}/(V s), when a buffer layer of thermally evaporated 100 nm SnO{sub 2} film had been deposited prior to IBAD process. However, the mobility was surprisingly sustained up to 1 month and then gradually degraded down to 0.35 cm{sup 2}/(V s) which was still three times higher than that of the OTFT without any encapsulation layer after 100 days in air ambient. The encapsulated OTFTs also exhibited superior on/off current ratio of over 10{sup 5} to that of the unprotected devices ({approx}10{sup 4}) which was reduced from {approx}10{sup 6} before aging. Therefore, the enhanced long-term stability of our encapsulated OTFTs should be attributed to well protection of permeation of H{sub 2}O and O{sub 2} into the devices by the IBAD SnO{sub 2} thin-film which could be used as an effective inorganic gas barrier for transparent organic electronic devices.

  17. Test-enhanced learning: taking memory tests improves long-term retention.

    Science.gov (United States)

    Roediger, Henry L; Karpicke, Jeffrey D

    2006-03-01

    Taking a memory test not only assesses what one knows, but also enhances later retention, a phenomenon known as the testing effect. We studied this effect with educationally relevant materials and investigated whether testing facilitates learning only because tests offer an opportunity to restudy material. In two experiments, students studied prose passages and took one or three immediate free-recall tests, without feedback, or restudied the material the same number of times as the students who received tests. Students then took a final retention test 5 min, 2 days, or 1 week later. When the final test was given after 5 min, repeated studying improved recall relative to repeated testing. However, on the delayed tests, prior testing produced substantially greater retention than studying, even though repeated studying increased students' confidence in their ability to remember the material. Testing is a powerful means of improving learning, not just assessing it.

  18. Enhanced long-term nitrogen removal and its quantitative molecular mechanism in tidal flow constructed wetlands.

    Science.gov (United States)

    Zhi, Wei; Yuan, Li; Ji, Guodong; He, Chunguang

    2015-04-07

    Tidal flow constructed wetlands (TF CWs) have recently been studied as a sustainable technology to achieve enhanced nitrogen removal; however, the underlying mechanisms responsible for removing ammonium (NH4(+)) and nitrate (NO3(-)) have not been compared and quantified at the molecular level (genes) in controlled TF CWs. In this study, two TF CWs T1 (treating NH4(+) wastewater) and T2 (treating NO3(-) wastewater) achieved high removal efficiencies for chemical oxygen demand (COD, 92 ± 2.7% and 95 ± 2.4%, respectively), NH4(+)/NO3(-) (76 ± 3.9% and 97 ± 2.2%, respectively), and total nitrogen (TN, 81 ± 3.5% and 93 ± 2.3%, respectively). Combined analyses revealed that the presence of simultaneous nitrification, anammox, and denitrification processes and the coupling of dissimilatory nitrate reduction to ammonium, ammonia oxidation, and anammox were the primary reason accounted for the robust treatment performance in T1 and T2, respectively. Results from stepwise regression analysis suggested that the NH4(+) removal rate in T1 was collectively controlled by amoA, nxrA, and anammox, while the NO3(-) removal rate in T2 was governed by nxrA and narG gene.

  19. Sustained photosynthetic performance of Coffea spp. under long-term enhanced [CO2].

    Science.gov (United States)

    Ramalho, José C; Rodrigues, Ana P; Semedo, José N; Pais, Isabel P; Martins, Lima D; Simões-Costa, Maria C; Leitão, António E; Fortunato, Ana S; Batista-Santos, Paula; Palos, Isabel M; Tomaz, Marcelo A; Scotti-Campos, Paula; Lidon, Fernando C; DaMatta, Fábio M

    2013-01-01

    Coffee is one of the world's most traded agricultural products. Modeling studies have predicted that climate change will have a strong impact on the suitability of current cultivation areas, but these studies have not anticipated possible mitigating effects of the elevated atmospheric [CO2] because no information exists for the coffee plant. Potted plants from two genotypes of Coffea arabica and one of C. canephora were grown under controlled conditions of irradiance (800 μmol m(-2) s(-1)), RH (75%) and 380 or 700 μL CO2 L(-1) for 1 year, without water, nutrient or root development restrictions. In all genotypes, the high [CO2] treatment promoted opposite trends for stomatal density and size, which decreased and increased, respectively. Regardless of the genotype or the growth [CO2], the net rate of CO2 assimilation increased (34-49%) when measured at 700 than at 380 μL CO2 L(-1). This result, together with the almost unchanged stomatal conductance, led to an instantaneous water use efficiency increase. The results also showed a reinforcement of photosynthetic (and respiratory) components, namely thylakoid electron transport and the activities of RuBisCo, ribulose 5-phosphate kinase, malate dehydrogenase and pyruvate kinase, what may have contributed to the enhancements in the maximum rates of electron transport, carboxylation and photosynthetic capacity under elevated [CO2], although these responses were genotype dependent. The photosystem II efficiency, energy driven to photochemical events, non-structural carbohydrates, photosynthetic pigment and membrane permeability did not respond to [CO2] supply. Some alterations in total fatty acid content and the unsaturation level of the chloroplast membranes were noted but, apparently, did not affect photosynthetic functioning. Despite some differences among the genotypes, no clear species-dependent responses to elevated [CO2] were observed. Overall, as no apparent sign of photosynthetic down-regulation was found, our

  20. Sustained Photosynthetic Performance of Coffea spp. under Long-Term Enhanced [CO2

    Science.gov (United States)

    Ramalho, José C.; Rodrigues, Ana P.; Semedo, José N.; Pais, Isabel P.; Martins, Lima D.; Simões-Costa, Maria C.; Leitão, António E.; Fortunato, Ana S.; Batista-Santos, Paula; Palos, Isabel M.; Tomaz, Marcelo A.; Scotti-Campos, Paula; Lidon, Fernando C.; DaMatta, Fábio M.

    2013-01-01

    Coffee is one of the world’s most traded agricultural products. Modeling studies have predicted that climate change will have a strong impact on the suitability of current cultivation areas, but these studies have not anticipated possible mitigating effects of the elevated atmospheric [CO2] because no information exists for the coffee plant. Potted plants from two genotypes of Coffea arabica and one of C. canephora were grown under controlled conditions of irradiance (800 μmol m-2 s-1), RH (75%) and 380 or 700 μL CO2 L-1 for 1 year, without water, nutrient or root development restrictions. In all genotypes, the high [CO2] treatment promoted opposite trends for stomatal density and size, which decreased and increased, respectively. Regardless of the genotype or the growth [CO2], the net rate of CO2 assimilation increased (34-49%) when measured at 700 than at 380 μL CO2 L-1. This result, together with the almost unchanged stomatal conductance, led to an instantaneous water use efficiency increase. The results also showed a reinforcement of photosynthetic (and respiratory) components, namely thylakoid electron transport and the activities of RuBisCo, ribulose 5-phosphate kinase, malate dehydrogenase and pyruvate kinase, what may have contributed to the enhancements in the maximum rates of electron transport, carboxylation and photosynthetic capacity under elevated [CO2], although these responses were genotype dependent. The photosystem II efficiency, energy driven to photochemical events, non-structural carbohydrates, photosynthetic pigment and membrane permeability did not respond to [CO2] supply. Some alterations in total fatty acid content and the unsaturation level of the chloroplast membranes were noted but, apparently, did not affect photosynthetic functioning. Despite some differences among the genotypes, no clear species-dependent responses to elevated [CO2] were observed. Overall, as no apparent sign of photosynthetic down-regulation was found, our data

  1. Sustained photosynthetic performance of Coffea spp. under long-term enhanced [CO2].

    Directory of Open Access Journals (Sweden)

    José C Ramalho

    Full Text Available Coffee is one of the world's most traded agricultural products. Modeling studies have predicted that climate change will have a strong impact on the suitability of current cultivation areas, but these studies have not anticipated possible mitigating effects of the elevated atmospheric [CO2] because no information exists for the coffee plant. Potted plants from two genotypes of Coffea arabica and one of C. canephora were grown under controlled conditions of irradiance (800 μmol m(-2 s(-1, RH (75% and 380 or 700 μL CO2 L(-1 for 1 year, without water, nutrient or root development restrictions. In all genotypes, the high [CO2] treatment promoted opposite trends for stomatal density and size, which decreased and increased, respectively. Regardless of the genotype or the growth [CO2], the net rate of CO2 assimilation increased (34-49% when measured at 700 than at 380 μL CO2 L(-1. This result, together with the almost unchanged stomatal conductance, led to an instantaneous water use efficiency increase. The results also showed a reinforcement of photosynthetic (and respiratory components, namely thylakoid electron transport and the activities of RuBisCo, ribulose 5-phosphate kinase, malate dehydrogenase and pyruvate kinase, what may have contributed to the enhancements in the maximum rates of electron transport, carboxylation and photosynthetic capacity under elevated [CO2], although these responses were genotype dependent. The photosystem II efficiency, energy driven to photochemical events, non-structural carbohydrates, photosynthetic pigment and membrane permeability did not respond to [CO2] supply. Some alterations in total fatty acid content and the unsaturation level of the chloroplast membranes were noted but, apparently, did not affect photosynthetic functioning. Despite some differences among the genotypes, no clear species-dependent responses to elevated [CO2] were observed. Overall, as no apparent sign of photosynthetic down

  2. Long-term efficacy and safety of ExPress implantation for treatment of open angle glaucoma

    Directory of Open Access Journals (Sweden)

    Geun Young Lee

    2017-09-01

    Full Text Available AIM: To compare the long-term efficacy and safety of ExPress implantation and standard trabeculectomy in patients with primary open angle glaucoma (POAG. METHODS: In this retrospective study, we compared 17 eyes treated by ExPress implantation with 23 eyes treated by trabeculectomy. Efficacy was assessed according to the relevant intraocular pressure (IOP values and success rates during the first year of follow-up. Postoperative corneal endothelial cell loss was also compared. RESULTS: The number of antiglaucoma medications and the IOP reduction were similar between the 2 groups during the follow-up period. Although the mean IOP was similar, the IOP-fluctuation rate during the early postoperative period was significantly lower in the ExPress group than in the trabeculectomy group (P=0.038. A Kaplan-Meier survival curve analysis showed no significant success-rate difference between the groups (P=0.810. The corneal endothelial cell loss rate, moreover, was significantly lower in the ExPress group (P=0.05. CONCLUSION: ExPress implantation compared with trabeculectomy showed similar IOP-reduction and success rates along with lower IOP fluctuation and endothelial cell loss rates. For this reason, it can be considered to be the treatment of choice for patients with advanced glaucoma or low corneal endothelial cell density.

  3. Startup and long term operation of enhanced biological phosphorus removal in continuous-flow reactor with granules.

    Science.gov (United States)

    Li, Dong; Lv, Yufeng; Zeng, Huiping; Zhang, Jie

    2016-07-01

    The startup and long term operation of enhanced biological phosphorus removal (EBPR) in a continuous-flow reactor (CFR) with granules were investigated in this study. Through reducing the settling time from 9min to 3min gradually, the startup of EBPR in a CFR with granules was successfully realized in 16days. Under continuous-flow operation, the granules with good phosphorus and COD removal performance were stably operated for more than 6months. And the granules were characterized with particle size of around 960μm, loose structure and good settling ability. During the startup phase, polysaccharides (PS) was secreted excessively by microorganisms to resist the influence from the variation of operational mode. Results of relative quantitative PCR indicated that granules dominated by polyphosphate-accumulating organisms (PAOs) were easier accumulated in the CFR because more excellent settling ability was needed in the system. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. 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

  5. Long-term effects of di-octyl phthalate on the expression of immune-related genes in Tegillarca granosa

    Science.gov (United States)

    Wang, Ji; Li, Ye; Dai, Juan; Su, Xiurong; Li, Chenghua; Shen, Lingling

    2016-05-01

    Di-octyl phthalate (DOP) is widely used as a plasticizer in the plastics industry. As a result, DOP is often found in marine water ecosystems where many species are exposed to it. Our objective was to evaluate the effect of long-term (14 d) DOP exposure (2.6, 7.8, or 31.2 mg/L) on the expression of immunerelated genes in Tegillarca granosa. The expression of small heat shock protein (sHSPs) and tissue inhibitor of metalloproteinase (TIMP) were highest in clams exposed to 31.2 mg/L DOP on days 7 and 14. The relative expression of Tg-ferritin, superoxide dismutase (SOD), and metallothionein (MT) increased initially then decreased as the concentration of DOP increased. The hemoglobin of T. granosa (Tg-HbI) exhibited two distinct expression patterns at two time points. Our results suggest that the immune response of T. granosa against DOP pollution varies depending on the dose. Additionally, we identified some immune-related genes that are promising candidates for biomarkers of DOP.

  6. Short- and long-term changes in sugarbeet (Beta vulgaris L. gene expression due to postharvest jasmonic acid treatment - Data

    Directory of Open Access Journals (Sweden)

    Lucilene Silva de Oliveira

    2017-04-01

    Full Text Available Jasmonic acid is a natural plant hormone that induces native defense responses in plants. Sugarbeet (Beta vulgaris L. root unigenes that were differentially expressed 2 and 60 days after a postharvest jasmonic acid treatment are presented. Data include changes in unigene expression relative to water-treated controls, unigene annotations against nonredundant (Nr, Swiss-Prot, Clusters of Orthologous Groups (COG, and Kyoto Encyclopedia of Genes and Genomes (KEGG protein databases, and unigene annotations with Gene Ontology (GO terms. Putative defense unigenes are compiled and annotated against the sugarbeet genome. Differential gene expression data were generated by RNA sequencing. Interpretation of the data is available in the research article, “Jasmonic acid causes short- and long-term alterations to the transcriptome and the expression of defense genes in sugarbeet roots” (K.K. Fugate, L.S. Oliveira, J.P. Ferrareze, M.D. Bolton, E.L. Deckard, F.L. Finger, 2017 [1]. Public dissemination of this dataset will allow further analyses of the data.

  7. Short- and long-term changes in sugarbeet (Beta vulgaris L.) gene expression due to postharvest jasmonic acid treatment - Data.

    Science.gov (United States)

    de Oliveira, Lucilene Silva; Fugate, Karen Klotz; Ferrareze, Jocleita Perruzo; Bolton, Melvin D; Deckard, Edward L; Finger, Fernando L

    2017-04-01

    Jasmonic acid is a natural plant hormone that induces native defense responses in plants. Sugarbeet (Beta vulgaris L.) root unigenes that were differentially expressed 2 and 60 days after a postharvest jasmonic acid treatment are presented. Data include changes in unigene expression relative to water-treated controls, unigene annotations against nonredundant (Nr), Swiss-Prot, Clusters of Orthologous Groups (COG), and Kyoto Encyclopedia of Genes and Genomes (KEGG) protein databases, and unigene annotations with Gene Ontology (GO) terms. Putative defense unigenes are compiled and annotated against the sugarbeet genome. Differential gene expression data were generated by RNA sequencing. Interpretation of the data is available in the research article, "Jasmonic acid causes short- and long-term alterations to the transcriptome and the expression of defense genes in sugarbeet roots" (K.K. Fugate, L.S. Oliveira, J.P. Ferrareze, M.D. Bolton, E.L. Deckard, F.L. Finger, 2017) [1]. Public dissemination of this dataset will allow further analyses of the data.

  8. Effects of long-term football training on the expression profile of genes involved in muscle oxidative metabolism.

    Science.gov (United States)

    Alfieri, A; Martone, D; Randers, M B; Labruna, G; Mancini, A; Nielsen, J J; Bangsbo, J; Krustrup, P; Buono, P

    2015-02-01

    We investigated whether long-term recreational football training affects the expression of health-related biochemical and molecular markers in healthy untrained subjects. Five untrained healthy men trained for 1 h 2.4 times/week for 12 weeks and 1.3 times/week for another 52 weeks. Blood samples and a muscle biopsy from the vastus lateralis were collected at T0 (pre intervention) and at T1 (post intervention). Gene expression was measured by RTqPCR on RNA extracted from muscle biopsies. The expression levels of the genes principally involved in energy metabolism (PPARγ, adiponectin, AMPKα1/α2, TFAM, NAMPT, PGC1α and SIRT1) were measured at T0 and T1. Up-regulation of PPARγ (p football training could be a useful tool to improve the expression of muscle molecular biomarkers that are correlated to oxidative metabolism in healthy males. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Improving the care of people with long-term conditions in primary care: protocol for the ENHANCE pilot trial.

    Science.gov (United States)

    Healey, Emma L; Jinks, Clare; Tan, Valerie A; Chew-Graham, Carolyn A; Lawton, Sarah A; Nicholls, Elaine; Finney, Andrew G; Porcheret, Mark; Cooper, Vince; Lewis, Martyn; Dziedzic, Krysia S; Wathall, Simon; Mallen, Christian D

    2015-01-01

    Long-term conditions (LTCs) are important determinants of quality of life and healthcare expenditure worldwide. Whilst multimorbidity is increasingly the norm in primary care, clinical guidelines and the delivery of care remain focused on single diseases, resulting in poorer clinical outcomes. Osteoarthritis, and anxiety and/or depression frequently co-occur with other LTCs, yet are seldom prioritized by the patient or clinician, resulting in higher levels of disability, poorer prognosis, and increased healthcare costs. To examine the feasibility and acceptability of an integrated approach to LTC management, tackling the under-diagnosis and under-management of osteoarthritis-related pain and anxiety and/or depression in older adults with other LTCs in primary care. The ENHANCE study is a pilot stepped-wedge cluster randomized controlled trial to test the feasibility and acceptability of a nurse-led ENAHNCE LTC review consultation for identifying, assessing, and managing joint pain, and anxiety and/or depression in patients attending LTC reviews. Specific objectives (process evaluation and research outcomes) will be achieved through a theoretically informed mixed-methods approach using participant self-reported questionnaires, a medical record review, an ENHANCE EMIS template, qualitative interviews, and audio recordings of the ENHANCE LTC review. Success of the pilot trial will be measured against the level of the primary care team engagement, assessment of training delivery, and degree of patient recruitment and retention. Patient satisfaction and treatment fidelity will also be explored. ISRCTN registry number: 12154418.

  10. Analysis of long-term cognitive-enhancing effects of bryostatin-1 on the rabbit (Oryctolagus cuniculus) nictitating membrane response.

    Science.gov (United States)

    Wang, Desheng; Darwish, Deya S; Schreurs, Bernard G; Alkon, Daniel L

    2008-05-01

    Previous work demonstrated that protein kinase C (PKC) is implicated in learning and memory. This study investigated whether: (i) PKC activated by bryostatin-1 (Bryo) just before or just after sessions of classical conditioning was capable of enhancing classical conditioning of the rabbit nictitating membrane response; (ii) improved behavioral performance matched the time course of PKC activation induced by Bryo; and (iii) vitamin E (Vit E) enhanced the efficacy of Bryo. Paired rabbits received daily trace conditioning with a tone conditioned stimulus and a corneal air puff unconditioned stimulus. Unpaired rabbits received the same stimuli but in an explicitly unpaired manner. After trace conditioning, all rabbits received daily delay conditioning, and then tone intensity testing. Rabbits pretreated with 10 microg/kg Bryo every other day before a relatively simple trace conditioning task showed more conditioned responses (CRs) during the first 10 trials of each trace conditioning session and a higher likelihood of a CR on the first trial of each trace conditioning session than rabbits pretreated with the vehicle control. Rabbits either posttreated daily with 10 microg/kg Bryo or pretreated with Vit E and subjected to a difficult trace conditioning task showed increased CRs relative to the vehicle control. Neither Bryo nor Vit E or their combination altered nonassociative responding or altered sensitivity to the conditioned stimulus or unconditioned stimulus. These findings demonstrate Bryo has long-term enhancing effects on classical conditioning of the rabbit nictitating membrane response.

  11. 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

  12. The role of serotonin in the enhancement of long-term memory resulting from predator detection in Lymnaea.

    Science.gov (United States)

    Il-Han, Jae; Janes, Tara; Lukowiak, Ken

    2010-11-01

    Serotonergic systems play important roles in modulating stress-induced arousal and vigilance behaviours. The pond snail, Lymnaea, shows multiple defensive vigilance behaviours in response to the stress associated with predator detection. Predator detection elicited by crayfish effluent (CE), increases the time to re-emerge from the shell and enhances the shadow withdrawal response. More importantly, in Lymnaea, CE enhances the ability to form long-term memory (LTM). We investigated the role of the serotonergic system in these anti-predator responses in Lymnaea. Using a serotonin-receptor antagonist, mianserin, we found that two defensive vigilance behaviours (e.g. increasing the time to re-emerge from their shell and shadow response) elicited by CE were not observed when the serotonergic system was disrupted. Also, methysergide, another serotonin antagonist, blocked the enhanced LTM formation after training in CE. Importantly, mianserin did not alter LTM formation in pond water (PW). These data suggest that a serotonergic system is activated only when Lymnaea detect a predator. When snails were trained in CE using a training procedure that in PW produces a 24-h LTM, a more persistent form of LTM (5 days) occurred. This more persistent form of LTM was abolished after mianserin treatment. Increasing 5-HT levels in the snail by the injection of 5-HT was also associated with enhanced LTM formation. Lastly, we tested whether the osphradium is implicated in CE detection and subsequent enhanced formation of LTM. Cutting the osphradial nerve to the CNS resulted in the loss of the ability to form enhanced LTM in CE. Together, these findings support the hypothesis that the serotonergic system plays a key role in modulating the predator-induced stress responses in Lymnaea.

  13. Fibrin glue is a candidate scaffold for long-term therapeutic protein expression in spontaneously differentiated adipocytes in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Aoyagi, Yasuyuki [Center for Advanced Medicine, Chiba University Hospital, Chiba University, Chiba (Japan); Department of Genome Research and Clinical Application, Graduate School of Medicine, Chiba University, Chiba (Japan); Kuroda, Masayuki, E-mail: kurodam@faculty.chiba-u.jp [Center for Advanced Medicine, Chiba University Hospital, Chiba University, Chiba (Japan); Department of Genome Research and Clinical Application, Graduate School of Medicine, Chiba University, Chiba (Japan); Asada, Sakiyo [Center for Advanced Medicine, Chiba University Hospital, Chiba University, Chiba (Japan); Department of Genome Research and Clinical Application, Graduate School of Medicine, Chiba University, Chiba (Japan); Tanaka, Shigeaki; Konno, Shunichi; Tanio, Masami; Aso, Masayuki [CellGenTech, Inc., Chiba (Japan); Okamoto, Yoshitaka [Center for Advanced Medicine, Chiba University Hospital, Chiba University, Chiba (Japan); Nakayama, Toshinori [Department of Immunology, Graduate School of Medicine, Chiba University, Chiba (Japan); Saito, Yasushi [Chiba University, Chiba (Japan); Bujo, Hideaki [Department of Genome Research and Clinical Application, Graduate School of Medicine, Chiba University, Chiba (Japan)

    2012-01-01

    Adipose tissue is expected to provide a source of cells for protein replacement therapies via auto-transplantation. However, the conditioning of the environment surrounding the transplanted adipocytes for their long-term survival and protein secretion properties has not been established. We have recently developed a preparation procedure for preadipocytes, ceiling culture-derived proliferative adipocytes (ccdPAs), as a therapeutic gene vehicle suitable for stable gene product secretion. We herein report the results of our evaluation of using fibrin glue as a scaffold for the transplanted ccdPAs for the expression of a transduced gene in a three-dimensional culture system. The ccdPAs secreted the functional protein translated from an exogenously transduced gene, as well as physiological adipocyte proteins, and the long viability of ccdPAs (up to 84 days) was dependent on the fibrinogen concentrations. The ccdPAs spontaneously accumulated lipid droplets, and their expression levels of the transduced exogenous gene with its product were maintained for at least 56 days. The fibrinogen concentration modified the adipogenic differentiation of ccdPAs and their exogenous gene expression levels, and the levels of exogenously transduced gene expression at the different fibrinogen concentrations were dependent on the extent of adipogenic differentiation in the gel. These results indicate that fibrin glue helps to maintain the high adipogenic potential of cultured adipocytes after passaging in a 3D culture system, and suggests that once they are successfully implanted at the transplantation site, the cells exhibit increased expression of the transduced gene with adipogenic differentiation.

  14. Long-term study on the impact of temperature on enhanced biological phosphorus and nitrogen removal in membrane bioreactor.

    Science.gov (United States)

    Sayi-Ucar, N; Sarioglu, M; Insel, G; Cokgor, E U; Orhon, D; van Loosdrecht, M C M

    2015-11-01

    The study involved experimental observation and performance evaluation of a membrane bioreactor system treating municipal wastewater for nutrient removal for a period 500 days, emphasizing the impact of high temperature on enhanced biological phosphorus removal (EBPR). The MBR system was operated at relatively high temperatures (24-41 °C). During the operational period, the total phosphorus (TP) removal gradually increased from 50% up to 95% while the temperature descended from 41 to 24 °C. At high temperatures, anaerobic volatile fatty acid (VFA) uptake occurred with low phosphorus release implying the competition of glycogen accumulating organisms (GAOs) with polyphosphate accumulating organisms (PAOs). Low dissolved oxygen conditions associated with high wastewater temperatures did not appreciable affected nitrification but enhanced nitrogen removal. Dissolved oxygen levels around 1.0 mgO2/L in membrane tank provided additional denitrification capacity of 6-7 mgN/L by activating simultaneous nitrification and denitrification. As a result, nearly complete removal of nitrogen could be achieved in the MBR system, generating a permeate with no appreciable nitrogen content. The gross membrane flux was 43 LMH corresponding to the specific permeability (K) of 413 LMH/bar at 39 °C in the MBR tank. The specific permeability increased by the factor of 43% at 39 °C compared to that of 25 °C during long-term operation. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Long-term motor improvement after stroke is enhanced by short-term treatment with the alpha-2 antagonist, atipamezole.

    Science.gov (United States)

    Beltran, Erik J; Papadopoulos, Catherine M; Tsai, Shih-Yen; Kartje, Gwendolyn L; Wolf, William A

    2010-07-30

    Drugs that increase central noradrenergic activity have been shown to enhance the rate of recovery of motor function in pre-clinical models of brain damage. Less is known about whether noradrenergic agents can improve the extent of motor recovery and whether such improvement can be sustained over time. This study was designed to determine if increasing central noradrenergic tone using atipamezole, an alpha-2 adrenoceptor antagonist, could induce a long-term improvement in motor performance in rats subjected to ischemic brain damage caused by permanent middle cerebral artery occlusion. The importance of pairing physical "rehabilitation" with enhanced noradrenergic activity was also investigated. Atipamezole (1 mg/kg, s.c.) or vehicle (sterile saline) was administered once daily on Days 2-8 post-operatively. Half of each drug group was housed under enriched environment conditions supplemented with daily focused activity sessions while the other half received standard housing with no focused activity. Skilled motor performance in forelimb reaching and ladder rung walking was assessed for 8 weeks post-operatively. Animals receiving atipamezole plus rehabilitation exhibited significantly greater motor improvement in both behavioral tests as compared to vehicle-treated animals receiving rehabilitation. Interestingly, animals receiving atipamezole without rehabilitation exhibited a significant motor improvement in the ladder rung walk test but not the forelimb reaching test. These results suggest that a short-term increase in noradrenergic activity can lead to sustained motor improvement following stroke, especially when paired with rehabilitation. Published by Elsevier B.V.

  16. Intermediate and Long-term Outcomes of Mitomycin C-enhanced Trabeculectomy as a First Glaucoma Procedure in Uveitic Glaucoma.

    Science.gov (United States)

    Almobarak, Faisal A; Alharbi, Ali H; Morales, Jose; Aljadaan, Ibrahim

    2017-05-01

    To evaluate the intermediate and long-term outcomes of mitomycin C-enhanced trabeculectomy as a first glaucoma procedure in uveitic glaucoma. Retrospective cohort study included 70 eyes of 50 patients with uveitic glaucoma who underwent mitomycin C-enhanced trabeculectomy as a first glaucoma procedure at King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia between 1996 and 2014. The main outcome measures were: the intraocular pressure (IOP), the number of antiglaucoma medications, the presence of visually threatening complications, and the need for further surgeries to control the IOP. Surgical outcome of each eye was classified as an absolute success, qualified success, or failure, based on the main outcome measures. The mean follow-up period was 77.0 months (±40.9). The IOP and number of antiglaucoma medications decreased significantly from a mean of 39.5 mm Hg (±8.9) and 3.7 (±0.8) to 14.4 mm Hg (±6.9) and 1 (±1.3) at the last follow-up, respectively (Pglaucoma, a significant number of patients needed further procedures to control the pressure. Thus, continuous monitoring of the pressure and inflammation are crucial.

  17. Variations in gene and protein expression in canine chondrodystrophic nucleus pulposus cells following long-term three-dimensional culture.

    Directory of Open Access Journals (Sweden)

    Munetaka Iwata

    Full Text Available Intervertebral disc (IVD degeneration greatly affects quality of life. The nucleus pulposus (NP of chondrodystrophic dog breeds (CDBs is similar to the human NP, because the cells disappear with age and are replaced by fibrochondrocyte-like cells. However, because IVD develops as early as within the first year of life, we used canines as a model to investigate in vitro the mechanisms underlying IVD degeneration. Specifically, we evaluated the potential of a three-dimensional (3D culture of healthy NP as an in vitro model system to investigate the mechanisms of IVD degeneration. Agarose hydrogels were populated with healthy NP cells from beagles after performing magnetic resonance imaging, and mRNA expression profiles and pericellular extracellular matrix (ECM protein distribution were determined. After 25 days of 3D culture, there was a tendency for redifferentiation into the native NP phenotype, and mRNA levels of Col2A1, COMP, and CK18 were not significantly different from those of freshly isolated cells. Our findings suggest that long-term 3D culture promoted chondrodystrophic NP redifferentiation through reconstruction of the pericellular microenvironment. Further, lipopolysaccharide (LPS induced expression of TNF-α, MMP3, MMP13, VEGF, and PGES mRNA in the 3D cultures, creating a molecular milieu that mimics that of degenerated NP. These results suggest that this in vitro model represents a reliable and cost-effective tool for evaluating new therapies for disc degeneration.

  18. Improving the care of people with long-term conditions in primary care: protocol for the ENHANCE pilot trial

    Directory of Open Access Journals (Sweden)

    Emma L. Healey

    2015-12-01

    Full Text Available Background: Long-term conditions (LTCs are important determinants of quality of life and healthcare expenditure worldwide. Whilst multimorbidity is increasingly the norm in primary care, clinical guidelines and the delivery of care remain focused on single diseases, resulting in poorer clinical outcomes. Osteoarthritis, and anxiety and/or depression frequently co-occur with other LTCs, yet are seldom prioritized by the patient or clinician, resulting in higher levels of disability, poorer prognosis, and increased healthcare costs. Objective: To examine the feasibility and acceptability of an integrated approach to LTC management, tackling the under-diagnosis and under-management of osteoarthritis-related pain and anxiety and/or depression in older adults with other LTCs in primary care. Design: The ENHANCE study is a pilot stepped-wedge cluster randomized controlled trial to test the feasibility and acceptability of a nurse-led ENHANCE LTC review consultation for identifying, assessing, and managing joint pain, and anxiety and/or depression in patients attending LTC reviews. Specific objectives (process evaluation and research outcomes will be achieved through a theoretically informed mixed-methods approach using participant self-reported questionnaires, a medical record review, an ENHANCE EMIS template, qualitative interviews, and audio recordings of the ENHANCE LTC review. Discussion: Success of the pilot trial will be measured against the level of the primary care team engagement, assessment of training delivery, and degree of patient recruitment and retention. Patient satisfaction and treatment fidelity will also be explored. ISRCTN registry number: 12154418. Journal of Comorbidity 2015;5(1:135–149

  19. Long-term exposure to triphenylphosphate alters hormone balance and HPG, HPI, and HPT gene expression in zebrafish (Danio rerio).

    Science.gov (United States)

    Liu, Xiaoshan; Jung, Dawoon; Jo, Areum; Ji, Kyunghee; Moon, Hyo-Bang; Choi, Kyungho

    2016-09-01

    With the global decline in the use of polybrominated diphenyl ethers, the demand for alternative flame retardants, such as triphenylphosphate (TPP), has increased substantially. Triphenylphosphate is now detected in various environments including aquatic ecosystems worldwide. However, studies on the toxicological consequences of chronic TPP exposure on aquatic organisms are scarce. The zebrafish model was used to investigate the effects of long-term TPP exposure on the endocrine system. Zebrafish embryos were exposed to 5 µg/L, 50 µg/L, or 500 µg/L TPP for 120 d, and hormonal and transcriptional responses were measured along the hypothalamic-pituitary-gonad (HPG) axis, the hypothalamic-pituitary-interrenal (HPI) axis, and the hypothalamic-pituitary-thyroid (HPT) axis. Exposure to TPP significantly increased plasma 17β-estradiol, but decreased 11-ketotestosterone in both sexes. Gene expression data support these changes. In the HPI axis, plasma cortisol and proopiomelanocortin (pomc) and mineralocorticoid receptor transcripts increased in females, but in males cortisol decreased whereas pomc increased (p HPG axis, but modulated the HPI, and HPT axes differently by sex, suggesting that both genomic and nongenomic responses might be involved. Environ Toxicol Chem 2016;35:2288-2296. © 2016 SETAC. © 2016 SETAC.

  20. Guilt, shame and expressed emotion in carers of people with long-term mental health difficulties: A systematic review.

    Science.gov (United States)

    Cherry, Mary Gemma; Taylor, Peter James; Brown, Stephen Lloyd; Rigby, Jake Wilfred; Sellwood, William

    2017-03-01

    Expressed emotion (EE) is a global index of familial emotional climate, whose primary components are emotional over-involvement (EOI) and critical comments (CC)/hostility. There is a strong theoretical rationale for hypothesising that carers' guilt and shame may be differentially associated with their EOI and CC/hostility respectively. This systematic review investigates the magnitude of these theorised associations in carers of people with long-term mental health difficulties. Electronic searches (conducted in May 2016 across Medline, CINAHL, Embase, PsycINFO and ProQuest) were supplemented with iterative hand searches. Ten papers, reporting data from eight studies, were included. Risk of bias was assessed using a standardised checklist. Relevant data were extracted and synthesised narratively. EOI was positively associated with both guilt and shame, whereas CC/hostility was positively associated with shame. The strength of associations varied depending on whether or not guilt and shame were assessed within the context of the caring relationship. Based on these data, an argument can be made for the refinement, development and evaluation of systemic and individual interventions designed to target carers' guilt and shame. However, more research is needed to clarify the strength of these associations and their direction of effect before firm conclusions can be drawn. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  1. The long-term effect of nitrite on the granule-based enhanced biological phosphorus removal system and the reversibility.

    Science.gov (United States)

    Zheng, Xiongliu; Sun, Peide; Lou, Juqing; Fang, Zhiguo; Guo, Maoxin; Song, Yingqi; Tang, Xiudi; Jiang, Tao

    2013-03-01

    This study investigated the long-term effect of nitrite on the granule-based enhanced biological phosphorus removal (EBPR) system and the reversibility from macro- to micro-scale. Nitrite was found to seriously deteriorate the EBPR performance and result in severe sludge bulking. The inhibited polysaccharides excretion could lead to breaking the stability and integrity of the granules. Therefore, the reduced particle size and granule disintegration were observed. In this study, granules with lower ratio of proteins to polysaccharides (1.76) had better structure and function than the higher (3.84). Experimental results demonstrated that the microbial community structure was largely changed due to the presence of nitrite. In comparison, glycogen accumulating organisms (GAOs) had stronger resistibility and higher recovery rate than poly-phosphate accumulating organisms (PAOs). Interestingly, the community composition was unable to recover (Dice coefficients, 33.0%), although good EBPR performance was achieved only by propagating other types of PAOs. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. CB2 Cannabinoid Receptor Knockout in Mice Impairs Contextual Long-Term Memory and Enhances Spatial Working Memory

    Directory of Open Access Journals (Sweden)

    Yong Li

    2016-01-01

    Full Text Available Neurocognitive effects of cannabinoids have been extensively studied with a focus on CB1 cannabinoid receptors because CB1 receptors have been considered the major cannabinoid receptor in the nervous system. However, recent discoveries of CB2 cannabinoid receptors in the brain demand accurate determination of whether and how CB2 receptors are involved in the cognitive effects of cannabinoids. CB2 cannabinoid receptors are primarily involved in immune functions, but also implicated in psychiatric disorders such as schizophrenia and depression. Here, we examined the effects of CB2 receptor knockout in mice on memory to determine the roles of CB2 receptors in modulating cognitive function. Behavioral assays revealed that hippocampus-dependent, long-term contextual fear memory was impaired whereas hippocampus-independent, cued fear memory was normal in CB2 receptor knockout mice. These mice also displayed enhanced spatial working memory when tested in a Y-maze. Motor activity and anxiety of CB2 receptor knockout mice were intact when assessed in an open field arena and an elevated zero maze. In contrast to the knockout of CB2 receptors, acute blockade of CB2 receptors by AM603 in C57BL/6J mice had no effect on memory, motor activity, or anxiety. Our results suggest that CB2 cannabinoid receptors play diverse roles in regulating memory depending on memory types and/or brain areas.

  3. Long-term moderate elevation of corticosterone facilitates avian food-caching behaviour and enhances spatial memory.

    Science.gov (United States)

    Pravosudov, Vladimir V

    2003-12-22

    It is widely assumed that chronic stress and corresponding chronic elevations of glucocorticoid levels have deleterious effects on animals' brain functions such as learning and memory. Some animals, however, appear to maintain moderately elevated levels of glucocorticoids over long periods of time under natural energetically demanding conditions, and it is not clear whether such chronic but moderate elevations may be adaptive. I implanted wild-caught food-caching mountain chickadees (Poecile gambeli), which rely at least in part on spatial memory to find their caches, with 90-day continuous time-release corticosterone pellets designed to approximately double the baseline corticosterone levels. Corticosterone-implanted birds cached and consumed significantly more food and showed more efficient cache recovery and superior spatial memory performance compared with placebo-implanted birds. Thus, contrary to prevailing assumptions, long-term moderate elevations of corticosterone appear to enhance spatial memory in food-caching mountain chickadees. These results suggest that moderate chronic elevation of corticosterone may serve as an adaptation to unpredictable environments by facilitating feeding and food-caching behaviour and by improving cache-retrieval efficiency in food-caching birds.

  4. Early Expressive Language Skills Predict Long-Term Neurocognitive Outcomes in Cochlear Implant Users: Evidence from the MacArthur-Bates Communicative Development Inventories.

    Science.gov (United States)

    Castellanos, Irina; Pisoni, David B; Kronenberger, William G; Beer, Jessica

    2016-08-01

    The objective of the present article was to document the extent to which early expressive language skills (measured using the MacArthur-Bates Communicative Development Inventories [CDI; Fenson et al., 2006]) predict long-term neurocognitive outcomes in a sample of early-implanted prelingually deaf cochlear implant (CI) users. The CDI was used to index the early expressive language skills of 32 pediatric CI users after an average of 1.03 years (SD = 0.56, range = 0.39-2.17) of CI experience. Long-term neurocognitive outcomes were assessed after an average of 11.32 (SD = 2.54, range = 7.08-16.52) years of CI experience. Measures of long-term neurocognitive outcomes were derived from gold-standard performance-based and questionnaire-based assessments of language, executive functioning, and academic skills. Analyses revealed that early expressive language skills, collected on average 1.03 years post cochlear implantation, predicted long-term language, executive functioning, and academic skills up to 16 years later. These findings suggest that early expressive language skills, as indexed by the CDI, are clinically relevant for identifying CI users who may be at high risk for long-term neurocognitive delays and disturbances.

  5. Genome-Wide Expression Analysis of Reactive Oxygen Species Gene Network in Mizuna Plants Grown in Long-Term Spaceflight

    Science.gov (United States)

    Sugimoto, Manabu; Gusev, Oleg; Wheeler, Raymond; Levinskikh, Margarita; Sychev, Vladimir; Bingham, Gail; Hummerick, Mary; Oono, Youko; Matsumoto, Takashi; Yazawa, Takayuki

    We have developed a plant growth system, namely Lada, which was installed in ISS to study and grow plants, including vegetables in a spaceflight environment. We have succeeded in cultivating Mizuna, tomato, pea, radish, wheat, rice, and barley in long-term spaceflight. Transcription levels of superoxide dismutase, glutamyl transferase, catalase, and ascorbate peroxidase were increased in the barley germinated and grown for 26 days in Lada, though the whole-plant growth and development of the barley in spaceflight were the same as in the ground control barley. In this study, we investigated the response of the ROS gene network in Mizuna, Brassica rapa var. nipposinica, cultivated under spaceflight condition. Seeds of Mizuna were sown in the root module of LADA aboard the Zvezda module of ISS and the seedlings were grown under 24h lighting in the leaf chamber. After 27 days of cultivation, the plants were harvested and stored at -80(°) C in MELFI aboard the Destiny module, and were transported to the ground at < -20(°) C in GLACIER aboard Space Shuttle. Ground control cultivation was carried out under the same conditions in LADA. Total RNA isolated from leaves was subjected to mRNA-Seq using next generation sequencing (NGS) technology. A total of 20 in 32 ROS oxidative marker genes were up-regulated, including high expression of four hallmarks, and preferentially expressed genes associated with ROS-scavenging including thioredoxin, glutaredoxin, and alternative oxidase genes. In the transcription factors of the ROS gene network, MEKK1-MKK4-MPK3, OXI1-MKK4-MPK3, and OXI1-MPK3 of MAP cascades, induction of WRKY22 by MEKK1-MKK4-MPK3 cascade, induction of WRKY25 and repression of Zat7 by Zat12 were suggested. These results revealed that the spaceflight environment induced oxidative stress and the ROS gene network activation in the space-grown Mizuna.

  6. Differentially expressed genes linked to natural variation in long-term memory formation in Cotesia parasitic wasps

    Directory of Open Access Journals (Sweden)

    Joke J. F. A. Van Vugt

    2015-09-01

    Full Text Available Even though learning and memory are universal traits in the Animal Kingdom, closely related species reveal substantial variation in learning rate and memory dynamics. To determine the genetic background of this natural variation, we studied two congeneric parasitic wasp species, Cotesia glomerata and C. rubecula, which lay their eggs in caterpillars of the large and small cabbage white butterfly. A successful egg laying event serves as an unconditioned stimulus in a classical conditioning paradigm, where plant odors become associated to the encounter of a suitable host caterpillar. Depending on the host species, the number of conditioning trials and the parasitic wasp species, three different types of transcription-dependent long-term memory (LTM and one type of transcription-independent, anesthesia-resistant memory (ARM can be distinguished. To identify transcripts underlying these differences in memory formation, we isolated mRNA from parasitic wasp heads at three different time points between induction and consolidation of each of the four memory types, and for each sample three biological replicates, where after strand-specific paired-end 100 bp deep sequencing. Transcriptomes were assembled de novo and differential expression was determined for each memory type and time point after conditioning, compared to unconditioned wasps. Most differentially expressed (DE genes and antisense transcripts were only DE in one of the LTM types. Among the DE genes that were DE in two or more LTM types, were many protein kinases and phosphatases, small GTPases, receptors and ion channels. Some genes were DE in opposing directions between any of the LTM memory types and ARM, suggesting that ARM in Cotesia requires the transcription of genes inhibiting LTM or vice versa. We discuss our findings in the context of neuronal functioning, including RNA splicing and transport, epigenetic regulation, neurotransmitter/peptide synthesis and antisense transcription. In

  7. Long-term expression of Fos-related antigen and transient expression of delta FosB associated with seizures in the rat hippocampus and striatum.

    Science.gov (United States)

    Bing, G; Wang, W; Qi, Q; Feng, Z; Hudson, P; Jin, L; Zhang, W; Bing, R; Hong, J S

    1997-01-01

    Systemic administration of kainic acid (KA), an analogue of glutamic acid, causes limbic seizures and pathophysiological changes in adult rats that are very similar to human temporal lobe epilepsy. One of the earliest changes in gene expression after treatment with KA is the induction of immediate-early genes. The fos and jun families are frequently studied immediate-early genes that are induced by KA. Several groups, including ours, have recently reported that a 35-kDa Fos-related antigen (FRA) is induced for a protracted time by various stimuli. It has been suggested that this FRA is delta FosB, which has a molecular mass of approximately 35 kDa. The present study characterizes the long-term expression of FRA and delta FosB after systemic treatment with KA. Immunocytochemistry and western blot analysis using an antibody that cross-reacts with all known FRAs showed that a 35-kDa FRA was induced at high levels in both the hippocampus and striatum for up to 1 month by KA. A semiquantitative PCR analysis showed that delta FosB was induced by KA, but its expression lasted for only 6 h. This result was also verified by northern blot analysis. These results suggested that the 35-kDa FRA with long-term elevated levels seen with western blot analysis and immunocytochemistry is a new species of the FRA and not delta FosB. The long-term expression of FRA in both the hippocampus and striatum may be associated with the pathophysiological changes after KA administration.

  8. The n-butanolic extract of Opuntia ficus-indica var. saboten enhances long-term memory in the passive avoidance task in mice.

    Science.gov (United States)

    Kim, Jong Min; Kim, Dong Hyun; Park, Se Jin; Park, Dong Hyun; Jung, Seo Yun; Kim, Hyoung Ja; Lee, Yong Sup; Jin, Changbae; Ryu, Jong Hoon

    2010-08-16

    Opuntia ficus-indica var. saboten Makino (Cactaceae) is used to treat burns, edema, dyspepsia, and asthma in traditional medicine. The present study investigated the beneficial effects of the n-butanolic extract of O. ficus-indica var. saboten (BOF) on memory performance in mice and attempts to uncover the mechanisms underlying its action. Memory performance was assessed with the passive avoidance task, and western blotting and immunohistochemistry were used to measure changes in protein expression and cell survival. After the oral administration of BOF for 7 days, the latency time in the passive avoidance task was significantly increased relative to vehicle-treated controls (P<0.05). Western blotting revealed that the expression levels of brain-derived neurotrophic factor (BDNF), phosphorylated cAMP response element binding-protein (pCREB), and phosphorylated extracellular signal-regulated kinase (pERK) 1/2 were significantly increased in hippocampal tissue after 7 days of BOF administration (P<0.05). Doublecortin and 5-bromo-2-deoxyuridine immunostaining also revealed that BOF significantly enhanced the survival of immature neurons, but did not affect neuronal cell proliferation in the subgranular zone of the hippocampal dentate gyrus. These results suggest that the subchronic administration of BOF enhances long-term memory, and that this effect is partially mediated by ERK-CREB-BDNF signaling and the survival of immature neurons. Copyright (c) 2010 Elsevier Inc. All rights reserved.

  9. [Influence of oxidative stress on the level of genes expression Tgfb1 and Hgf in rat liver upon long-term gastric hypochlorhydria and administration of multiprobiotic Symbiter].

    Science.gov (United States)

    Dvorshchenko, K O; Bernyk, O O; Dranytsyna, A S; Senin, S A; Ostapchenko, L I

    2013-01-01

    Free-radical processes upon long-term omeprazole-induced gastric hypochlorhydria in the rat liver were researched. Intensification of oxidative processes in the liver tissue upon gastric hypoacid state was established: overproduction of superoxide anion, hydrogen peroxide, the quantitative changes of lipid functional groups, increased level of lipid peroxidation products, and augmentation of xanthine oxidase activity. The expression of Tgfb1 gene increased, while the expression of Hgf gene was not detected upon long-term suppression of gastric acid secretion of hydrochloric acid by omeprazole that indicated possible development of liver fibrosis. Abovementioned parameters were only partially restored to control values in the case of simultaneous administration of multiprobiotic "Symbiter acidophilic" concentrated with omeprazole, thus indicating the ability of this preparation to counteract the development of oxidative damages in liver tissues upon long-term gastric hypoacidic conditions.

  10. Acute food deprivation enhances fear extinction but inhibits long-term depression in the lateral amygdala via ghrelin signaling.

    Science.gov (United States)

    Huang, Chiung-Chun; Chou, Dylan; Yeh, Che-Ming; Hsu, Kuei-Sen

    2016-02-01

    Fear memory-encoding thalamic input synapses to the lateral amygdala (T-LA) exhibit dynamic efficacy changes that are tightly correlated with fear memory strength. Previous studies have shown that auditory fear conditioning involves strengthening of synaptic strength, and conversely, fear extinction training leads to T-LA synaptic weakening and occlusion of long-term depression (LTD) induction. These findings suggest that the mechanisms governing LTD at T-LA synapses may determine the behavioral outcomes of extinction training. Here, we explored this hypothesis by implementing food deprivation (FD) stress in mice to determine its effects on fear extinction and LTD induction at T-LA synapses. We found that FD increased plasma acylated ghrelin levels and enhanced fear extinction and its retention. Augmentation of fear extinction by FD was blocked by pretreatment with growth hormone secretagogue receptor type-1a antagonist D-Lys(3)-GHRP-6, suggesting an involvement of ghrelin signaling. Confirming previous findings, two distinct forms of LTD coexist at thalamic inputs to LA pyramidal neurons that can be induced by low-frequency stimulation (LFS) or paired-pulse LFS (PP-LFS) paired with postsynaptic depolarization, respectively. Unexpectedly, we found that FD impaired the induction of PP-LFS- and group I metabotropic glutamate receptor agonist (S)-3,5-dihydroxyphenylglycine (DHPG)-induced LTD, but not LFS-induced LTD. Ghrelin mimicked the effects of FD to impair the induction of PP-LFS- and DHPG-induced LTD at T-LA synapses, which were blocked by co-application of D-Lys(3)-GHRP-6. The sensitivity of synaptic transmission to 1-naphthyl acetyl spermine was not altered by either FD or ghrelin treatment. These results highlight distinct features of fear extinction and LTD at T-LA synapses. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Long-term melatonin treatment reduces ovarian mass and enhances tissue antioxidant defenses during ovulation in the rat

    Directory of Open Access Journals (Sweden)

    L.G.A. Chuffa

    2011-03-01

    Full Text Available Melatonin regulates the reproductive cycle, energy metabolism and may also act as a potential antioxidant indoleamine. The present study was undertaken to investigate whether long-term melatonin treatment can induce reproductive alterations and if it can protect ovarian tissue against lipid peroxidation during ovulation. Twenty-four adult female Wistar rats, 60 days old (± 250-260 g, were randomly divided into two equal groups. The control group received 0.3 mL 0.9% NaCl + 0.04 mL 95% ethanol as vehicle, and the melatonin-treated group received vehicle + melatonin (100 µg·100 g body weight-1·day-1 both intraperitoneally daily for 60 days. All animals were killed by decapitation during the morning estrus at 4:00 am. Body weight gain and body mass index were reduced by melatonin after 10 days of treatment (P < 0.05. Also, a marked loss of appetite was observed with a fall in food intake, energy intake (melatonin 51.41 ± 1.28 vs control 57.35 ± 1.34 kcal/day and glucose levels (melatonin 80.3 ± 4.49 vs control 103.5 ± 5.47 mg/dL towards the end of treatment. Melatonin itself and changes in energy balance promoted reductions in ovarian mass (20.2% and estrous cycle remained extensive (26.7%, arresting at diestrus. Regarding the oxidative profile, lipid hydroperoxide levels decreased after melatonin treatment (6.9% and total antioxidant substances were enhanced within the ovaries (23.9%. Additionally, melatonin increased superoxide dismutase (21.3%, catalase (23.6% and glutathione-reductase (14.8% activities and the reducing power (10.2% GSH/GSSG ratio. We suggest that melatonin alters ovarian mass and estrous cyclicity and protects the ovaries by increasing superoxide dismutase, catalase and glutathione-reductase activities.

  12. Long-term effects of abscisic acid (ABA) on the grape berry phenylpropanoid pathway: Gene expression and metabolite content.

    Science.gov (United States)

    Villalobos-González, Luis; Peña-Neira, Alvaro; Ibáñez, Freddy; Pastenes, Claudio

    2016-08-01

    ABA has been proposed as the main signal triggering the onset of the ripening process in grapes, and modulating the secondary metabolism in grape berry skins. To determine the effect of ABA on secondary metabolism in berries, clusters of Carménère were sprayed with 0 μLL(-1) ABA; 50 μLL(-1) ABA and 100 μLL(-1) ABA during pre-véraison, and the gene expression of the transcription factors and enzymes of the phenylpropanoid pathway were assessed from véraison to 70 days after véraison (DAV). Additionally, flavonols, tannins and anthocyanins were assessed from véraison until harvest (110 DAV). ABA accelerated sugar and anthocyanin accumulation at véraison. The grape transcript abundance of VvDFR, VvANS, VvUFGT and VvMybA1, all peaking around véraison mimicked the concentration of ABA throughout the season. The highest anthocyanin concentration occurred 35 DAV for all treatments, but higher pigment concentrations were observed in ABA-treated berries at véraison and from 60 to 70 DAV to harvest. VvPAL was also increased by treatment at the higher concentration of ABA from véraison to 40 DAV. Regarding flavanol synthesis, VvLAR2 and VvMyb4A decreased from véraison until 40 DAV and then increased again until 70 DAV. Compared to the control, both ABA treatments resulted in a less-than-proportional reduction of the expression of both genes compared to the control and, after 40 DAV, in a more-than-proportional increase compared to the control, suggesting a long-term effect of the pre-véraison ABA spray on the berries. A concomitant increase in flavanols was observed in berries after 40 DAV, and this occurred at a higher extent in berries treated with the highest ABA concentration. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  13. Short term, high fat-feeding induced changes in white adipose tissue gene expression are highly predictive for long term changes

    NARCIS (Netherlands)

    Voigt, A.; Agnew, K.; Schothorst, van E.M.; Keijer, J.; Klaus, S.

    2013-01-01

    Scope - We aimed to evaluate the predictability of short-term (5 days) changes in epididymal white adipose tissue (eWAT) gene expression for long-term (12 weeks) changes induced by high-fat diet (HFD) feeding. Methods and results - Mice were fed semisynthetic diets containing 10 (low-fat diet) or 40

  14. Enhanced long-term fear memory and increased anxiety and depression-like behavior after exposure to an aversive event in mice lacking TIP39 signaling

    Science.gov (United States)

    Coutellier, Laurence; Usdin, Ted B.

    2011-01-01

    Exaggerated recall for fear-provoking events leads to abnormal behaviors. We hypothesized that tuberoinfundibular-peptide-of-39-residues (TIP39) modulates fear memory by limiting long-term consequences of aversive experiences. We now show that mice lacking TIP39 signaling display enhanced fear-recall, anxiety and depression-like behavior two weeks after a traumatic event. We suggest that TIP39 modulates long-term fear recall and that mice lacking TIP39 or its receptor are tools for investigating fear-related psychopathologies. PMID:21382418

  15. Long-term consequences of chronic fluoxetine exposure on the expression of myelination-related genes in the rat hippocampus

    NARCIS (Netherlands)

    Kroeze, Y.L.; Peeters, D.G.A.; Boulle, F.; Hove, D.L. van den; Bokhoven, H. van; Zhou, Huiqing; Homberg, J.R.

    2015-01-01

    The selective serotonin reuptake inhibitor (SSRI) fluoxetine is widely prescribed for the treatment of symptoms related to a variety of psychiatric disorders. After chronic SSRI treatment, some symptoms remediate on the long term, but the underlying mechanisms are not yet well understood. Here we

  16. CREB expression in the brains of two closely related parasitic wasp species that differ in long-term memory formation

    NARCIS (Netherlands)

    Berg, van den M.; Verbaarschot, P.G.H.; Hontelez, S.; Vet, L.E.M.; Dicke, M.; Smid, H.M.

    2010-01-01

    The cAMP/PKA signalling pathway and transcription factor cAMP response element-binding protein (CREB) play key roles in long-term memory (LTM) formation. We used two closely related parasitic wasp species, Cotesia glomerata and Cotesia rubecula, which were previously shown to be different in LTM

  17. Semantic congruency but not temporal synchrony enhances long-term memory performance for audio-visual scenes.

    Science.gov (United States)

    Meyerhoff, Hauke S; Huff, Markus

    2016-04-01

    Human long-term memory for visual objects and scenes is tremendous. Here, we test how auditory information contributes to long-term memory performance for realistic scenes. In a total of six experiments, we manipulated the presentation modality (auditory, visual, audio-visual) as well as semantic congruency and temporal synchrony between auditory and visual information of brief filmic clips. Our results show that audio-visual clips generally elicit more accurate memory performance than unimodal clips. This advantage even increases with congruent visual and auditory information. However, violations of audio-visual synchrony hardly have any influence on memory performance. Memory performance remained intact even with a sequential presentation of auditory and visual information, but finally declined when the matching tracks of one scene were presented separately with intervening tracks during learning. With respect to memory performance, our results therefore show that audio-visual integration is sensitive to semantic congruency but remarkably robust against asymmetries between different modalities.

  18. 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...

  19. Using corporate governance to enhance 'long-term situation awareness' and assist in the avoidance of organisation-induced disasters.

    Science.gov (United States)

    Siemieniuch, C E; Sinclair, M A

    2008-03-01

    This paper considers the issue of how corporate governance can and should deal with the long-term understanding of systems health-what we may call 'long-term situation awareness' (i.e. which evolves and is coherent over time) for organisational systems (and their component sub systems) in the engineering domain. Many characteristics affect long-term situation awareness-the rate of change to processes, pressures for greater efficiency from existing resources, changes in personnel, cultural changes and changes to the operational environment of the organisational systems. Many disasters (e.g. Chernobyl, Flixborough, Piper Alpha) have a causal path that indicates a loss of group situation awareness, over a long period of time. The problem of the gradual, slow drift over many years towards unsafe conduct of company operations is discussed and examples of possible consequences provided. A 'parable' from the world of manufacturing is used to exemplify the problem. The paper goes on to discuss some ways by which this problem could be addressed and longer-term system situational awareness increased; essentially by good corporate governance, knowledge management and ownership of processes. Links are made to the literature on these topics, and a route map to help organisations to gain the benefits is offered.

  20. A long-term period of observation a patients with moderate and advanced open-angle glaucoma after implantation glau- coma device Ex-PRESS

    Directory of Open Access Journals (Sweden)

    A. V. Kuroedov

    2012-01-01

    Full Text Available Purpose: to determine the long-term efficiency and safety of implantation Ex-PRESS open-angle glaucoma device to patients at advanced stage of POAG.Methods: Seven male patients underwent penetrating filtering surgery with implantation of the Ex-PRESS shunt over the lack of stabilization of visual functions on hypotensive drugs.Results: Average monitoring of patients was 19.96±9.73 months. IOP in postoperative period was 16.14±3.67 mm Hg (by Makla- kov. the reduction of IOP was 12.72 mm Hg (40.2%. Cell density didn’t differ from double (2879±87 cell/mm2 и 2798±67 cell/mm2, p>0.05.Conclusion: Long-term gradual reduction of IOP and safety of implantation Ex-PRESS glaucoma device may be a reason of choicethis type of surgery for patients at advanced stage.

  1. A long-term period of observation a patients with moderate and advanced open-angle glaucoma after implantation glau- coma device Ex-PRESS

    Directory of Open Access Journals (Sweden)

    A. V. Kuroedov

    2014-07-01

    Full Text Available Purpose: to determine the long-term efficiency and safety of implantation Ex-PRESS open-angle glaucoma device to patients at advanced stage of POAG.Methods: Seven male patients underwent penetrating filtering surgery with implantation of the Ex-PRESS shunt over the lack of stabilization of visual functions on hypotensive drugs.Results: Average monitoring of patients was 19.96±9.73 months. IOP in postoperative period was 16.14±3.67 mm Hg (by Makla- kov. the reduction of IOP was 12.72 mm Hg (40.2%. Cell density didn’t differ from double (2879±87 cell/mm2 и 2798±67 cell/mm2, p>0.05.Conclusion: Long-term gradual reduction of IOP and safety of implantation Ex-PRESS glaucoma device may be a reason of choicethis type of surgery for patients at advanced stage.

  2. Learning-Induced Gene Expression in the Hippocampus Reveals a Role of Neuron -Astrocyte Metabolic Coupling in Long Term Memory.

    Science.gov (United States)

    Tadi, Monika; Allaman, Igor; Lengacher, Sylvain; Grenningloh, Gabriele; Magistretti, Pierre J

    2015-01-01

    We examined the expression of genes related to brain energy metabolism and particularly those encoding glia (astrocyte)-specific functions in the dorsal hippocampus subsequent to learning. Context-dependent avoidance behavior was tested in mice using the step-through Inhibitory Avoidance (IA) paradigm. Animals were sacrificed 3, 9, 24, or 72 hours after training or 3 hours after retention testing. The quantitative determination of mRNA levels revealed learning-induced changes in the expression of genes thought to be involved in astrocyte-neuron metabolic coupling in a time dependent manner. Twenty four hours following IA training, an enhanced gene expression was seen, particularly for genes encoding monocarboxylate transporters 1 and 4 (MCT1, MCT4), alpha2 subunit of the Na/K-ATPase and glucose transporter type 1. To assess the functional role for one of these genes in learning, we studied MCT1 deficient mice and found that they exhibit impaired memory in the inhibitory avoidance task. Together, these observations indicate that neuron-glia metabolic coupling undergoes metabolic adaptations following learning as indicated by the change in expression of key metabolic genes.

  3. Learning-Induced Gene Expression in the Hippocampus Reveals a Role of Neuron -Astrocyte Metabolic Coupling in Long Term Memory.

    Directory of Open Access Journals (Sweden)

    Monika Tadi

    Full Text Available We examined the expression of genes related to brain energy metabolism and particularly those encoding glia (astrocyte-specific functions in the dorsal hippocampus subsequent to learning. Context-dependent avoidance behavior was tested in mice using the step-through Inhibitory Avoidance (IA paradigm. Animals were sacrificed 3, 9, 24, or 72 hours after training or 3 hours after retention testing. The quantitative determination of mRNA levels revealed learning-induced changes in the expression of genes thought to be involved in astrocyte-neuron metabolic coupling in a time dependent manner. Twenty four hours following IA training, an enhanced gene expression was seen, particularly for genes encoding monocarboxylate transporters 1 and 4 (MCT1, MCT4, alpha2 subunit of the Na/K-ATPase and glucose transporter type 1. To assess the functional role for one of these genes in learning, we studied MCT1 deficient mice and found that they exhibit impaired memory in the inhibitory avoidance task. Together, these observations indicate that neuron-glia metabolic coupling undergoes metabolic adaptations following learning as indicated by the change in expression of key metabolic genes.

  4. Learning-Induced Gene Expression in the Hippocampus Reveals a Role of Neuron -Astrocyte Metabolic Coupling in Long Term Memory

    KAUST Repository

    Tadi, Monika

    2015-10-29

    We examined the expression of genes related to brain energy metabolism and particularly those encoding glia (astrocyte)-specific functions in the dorsal hippocampus subsequent to learning. Context-dependent avoidance behavior was tested in mice using the step-through Inhibitory Avoidance (IA) paradigm. Animals were sacrificed 3, 9, 24, or 72 hours after training or 3 hours after retention testing. The quantitative determination of mRNA levels revealed learning-induced changes in the expression of genes thought to be involved in astrocyte-neuron metabolic coupling in a time dependent manner. Twenty four hours following IA training, an enhanced gene expression was seen, particularly for genes encoding monocarboxylate transporters 1 and 4 (MCT1, MCT4), alpha2 subunit of the Na/K-ATPase and glucose transporter type 1. To assess the functional role for one of these genes in learning, we studied MCT1 deficient mice and found that they exhibit impaired memory in the inhibitory avoidance task. Together, these observations indicate that neuron-glia metabolic coupling undergoes metabolic adaptations following learning as indicated by the change in expression of key metabolic genes.

  5. Aging and a long-term diabetes mellitus increase expression of 1 α-hydroxylase and vitamin D receptors in the rat liver.

    Science.gov (United States)

    Vuica, Ana; Ferhatović Hamzić, Lejla; Vukojević, Katarina; Jerić, Milka; Puljak, Livia; Grković, Ivica; Filipović, Natalija

    2015-12-01

    Diabetes mellitus (DM) is a metabolic disorder associated with serious liver complications. As a metabolic chronic disease, DM is very common in the elderly. Recent studies suggest ameliorating effects of vitamin D on metabolic and oxidative stress in the liver tissue in an experimental model of DM. The aim of this study was to investigate the expression of vitamin D receptors (VDRs) and 1α-hydroxylase, the key enzyme for the production of active vitamin D form (calcitriol) in the liver during long-term diabetes mellitus type 1 (DM1) in aging rats. We performed immunohistochemical analysis of liver expression of 1α-hydroxylase and VDRs during aging in long-term streptozotocin-induced DM1. 1α-Hydroxylase was identified in the monocyte/macrophage system of the liver. In addition to the nuclear expression, we also observed the expression of VDR in membranes of lipid droplets within hepatocytes. Aging and long-term DM1 resulted in significant increases in the number of 1α-hydroxylase immunoreactive cells, as well as the percentage of strongly positive VDR hepatocytes. In conclusion, the liver has the capacity for active vitamin D synthesis in its monocyte/macrophage system that is substantially increased in aging and long-term diabetes mellitus. These conditions are also characterized by significant increases in vitamin D receptor expression in hepatocytes. The present study suggests that VDR signaling system could be a potential target in prevention of liver complications caused by diabetes and aging. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Naringin Enhances CaMKII Activity and Improves Long-Term Memory in a Mouse Model of Alzheimer’s Disease

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    Lian-Feng Zhang

    2013-03-01

    Full Text Available The Amyloid-β (Aβ-induced impairment of hippocampal synaptic plasticity is an underlying mechanism of memory loss in the early stages of Alzheimer's disease (AD in human and mouse models. The inhibition of the calcium/calmodulin-dependent protein kinase II (CaMKII autophosphorylation plays an important role in long-term memory. In this study, we isolated naringin from Pomelo peel (a Citrus species and studied its effect on long-term memory in the APPswe/PS1dE9 transgenic mouse model of AD. Three-month-old APPswe/PS1dE9 transgenic mice were randomly assigned to a vehicle group, two naringin (either 50 or 100 mg/kg body weight/day groups, or an Aricept (2 mg/kg body weight/day group. After 16 weeks of treatment, we observed that treatment with naringin (100 mg/kg body weight/day enhanced the autophosphorylation of CaMKII, increased the phosphorylation of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic (AMPA receptor at a CaMKII-dependent site and improved long-term learning and memory ability. These findings suggest that the increase in CaMKII activity may be one of the mechanisms by which naringin improves long-term cognitive function in the APPswe/PS1dE9 transgenic mouse model of AD.

  7. Therapist-assisted, self-administered bibliotherapy to enhance parental competence: short- and long-term effects.

    Science.gov (United States)

    Hahlweg, Kurt; Heinrichs, Nina; Kuschel, Annett; Feldmann, Marit

    2008-09-01

    The efficacy of bibliotherapy has primarily been investigated in anxiety disorders, depression, or substance dependence. The efficacy of self-help books to increase parenting competence was only investigated in a few studies despite their broad dissemination in public. The aims of the study were to investigate the short- and long-term efficacy of a therapist assisted version of the Triple P self-help booklet (Sanders, Markie-Dadds, & Turner, 2003) for families with preschool-age children in Germany. Sixty-nine families were randomly assigned to either a therapist-assisted self-administered parent training (SDPT+T) or to a waitlist control group (WL). Parents in the SDPT+T received the 10 chapter self-help book and an accompanying video. A Triple P facilitator offered seven telephone consultations which aimed to support parents in skill implementation. After the post test, the WL parents were also offered the intervention. A follow-up assessment was conducted six months after post. Compared to waitlist controls, SDPT+T mothers reported significant short- and long-term reductions in child behavior problems as well as in dysfunctional parenting practices. Fathers reported only marginal changes. The study adds further empirical support of parenting self-help materials.

  8. A novel bio-mimicking, planar nano-edge microelectrode enables enhanced long-term neural recording

    Science.gov (United States)

    Wijdenes, Pierre; Ali, Hasan; Armstrong, Ryden; Zaidi, Wali; Dalton, Colin; Syed, Naweed I.

    2016-10-01

    Our inability to accurately monitor individual neurons and their synaptic activity precludes fundamental understanding of brain function under normal and various pathological conditions. However, recent breakthroughs in micro- and nano-scale fabrication processes have advanced the development of neuro-electronic hybrid technology. Among such devices are three-dimensional and planar electrodes, offering the advantages of either high fidelity or longer-term recordings respectively. Here, we present the next generation of planar microelectrode arrays with “nano-edges” that enable long-term (≥1 month) and high fidelity recordings at a resolution 15 times higher than traditional planar electrodes. This novel technology enables better understanding of brain function and offers a tremendous opportunity towards the development of future bionic hybrids and drug discovery devices.

  9. Genome-wide functional analysis of CREB/long-term memory-dependent transcription reveals distinct basal and memory gene expression programs.

    Science.gov (United States)

    Lakhina, Vanisha; Arey, Rachel N; Kaletsky, Rachel; Kauffman, Amanda; Stein, Geneva; Keyes, William; Xu, Daniel; Murphy, Coleen T

    2015-01-21

    Induced CREB activity is a hallmark of long-term memory, but the full repertoire of CREB transcriptional targets required specifically for memory is not known in any system. To obtain a more complete picture of the mechanisms involved in memory, we combined memory training with genome-wide transcriptional analysis of C. elegans CREB mutants. This approach identified 757 significant CREB/memory-induced targets and confirmed the involvement of known memory genes from other organisms, but also suggested new mechanisms and novel components that may be conserved through mammals. CREB mediates distinct basal and memory transcriptional programs at least partially through spatial restriction of CREB activity: basal targets are regulated primarily in nonneuronal tissues, while memory targets are enriched for neuronal expression, emanating from CREB activity in AIM neurons. This suite of novel memory-associated genes will provide a platform for the discovery of orthologous mammalian long-term memory components. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Effects of long-term exercise and low-level inhibition of GABAergic synapses on motor control and the expression of BDNF in the motor related cortex.

    Science.gov (United States)

    Inoue, Takahiro; Ninuma, Shuta; Hayashi, Masataka; Okuda, Akane; Asaka, Tadayoshi; Maejima, Hiroshi

    2018-01-01

    Objectives Brain-derived neurotrophic factor (BDNF) plays important roles in neuroplasticity in the brain. The objective of this study was to examine the effects of long-term exercise combined with low-level inhibition of GABAergic synapses on motor control and the expression of BDNF in the motor-related cortex. Methods ICR mice were divided into four groups based on the factors exercise and GABA A receptor inhibition. We administered the GABA A receptor antagonist bicuculline intraperitoneally (0.25 mg/kg). Mice exercised on a treadmill 5 days/week for 4 weeks. Following behavioral tests, BDNF expression in the motor cortex and cerebellar cortex was assayed using RT-PCR and ELISA. Results Exercise increased BDNF protein in the motor cortex and improved motor coordination in the rotarod test either in the presence or absence of bicuculline. BDNF mRNA expression in the motor cortex and muscle coordination in the wire hang test decreased after administration of bicuculline, whereas bicuculline administration increased mRNA and protein expression of BDNF in the cerebellum. Discussion The present study revealed that long-term exercise increased BDNF expression in the motor cortex and facilitated a transfer of motor learning from aerobic exercise to postural coordination. Thus, aerobic exercise is meaningful for conditioning motor learning to rehabilitate patients with central nervous system (CNS) disorders. However, long-term inhibition of GABA A receptors decreased the expression of cortical BDNF mRNA and decreased muscle coordination, despite the increase of BDNF in the cerebellum, suggesting that we have to consider the term of the inhibition of the GABAergic receptor for future clinical application to CNS patients.

  11. Expression of Gast, Cckbr, Reg1α genes in rat duodenal epithelial cells upon long-term gastric hypoacidity and after a multiprobiotic administration

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    Dranitsina A. S.

    2014-11-01

    Full Text Available Aim. Determination of the Cckbr, Gast and Reg1α genes expression in rat duodenal epithelial cells upon long- term hypoacidity and with the administration of the multiprobiotic Symbiter. Methods. The experiments were carried out on white non-strain male rats. The hypoacidic state was induced through intraperitoneal injection of omeprazole for 28 days. The level of genes expression was determined by semi-quantitative analysis with RT-PCR Results. The elevation of mRNA levels of the Cckbr and Gast genes in rat duodenal villus and crypt epitheliocytes, the increased expression of the Reg1A gene in crypt epithelial cells were shown as well as the appearance of the Reg1a gene expression in villus epitheliocytes upon hypoacidic conditions were shown. The content of mRNAs of the above mentioned genes decreased or remained at the control level upon the treatment of hypoacidic rats with the multiprobiotic Symbiter. Conclusions. Long-term gastric hypoacidity is accompanied by the changes in expression of the Cckbr, Gast and Reg1a genes in rat duodenum, whereas upon administration of the multiprobiotic Symbiter the pattern of studied gene expression did not changed in the most cases.

  12. Combining long term field experiments and nanoscale analysis to enhance process understanding of root litter stabilization by mineral interactions

    Science.gov (United States)

    Chabbi, Abad; Baumann, Karen; Remusat, Laurent; Barre, Pierre; Dignac, Marie-France; Rumpel, Cornelia

    2015-04-01

    Mineral interaction may affect the stabilisation of root litter directly or indirectly after microbial decomposition and transformation. The importance of both processes may vary within the soil profile. In this study we studied C stabilisation of isotopically labelled root litter (13C and 15N), which was incubated during 3 year in the field at different soil depth. Samples from this field experiment were recovered and subjected to nanoscale analyses in order to elucidate mineral interactions occurring in different parts of the soil profile. Our results showed enrichment of mineral associated organic matter in subsoil horizons. However, material derived from new plant litter may be stabilised at similar rates in top- and subsoil horizons. N-containing compounds are enriched in the mineral associated fraction of subsoil horizons, indicating enrichment of microbial derived material with depth. Nano scale analyses showed that indeed plant-derived material may be associated with metal oxides in topsoil horizons, whereas the mineral associated organic matter in subsoil horizons may consist of microbial cells. Interestingly, in contrast to short term laboratory analysis, decoupling of C and N through stabilisation with soil minerals was observed during this long term field experiment. Our results indicate that the nature of OM stabilised by mineral interactions is depth specific. Therefore, we suggest, that plant derived lignocellulosic material may be preserved by mineral interactions in topsoil given its incomplete degradation, thereby leading to the formation of functional groups and favouring adsorption to soil minerals. This is consistent with the higher state of lignin-degradation observed in topsoil horizons as compared to subsoil. At depth, where microorganisms are most likely energy limited, degradation of fresh plant litter may be complete, thereby diminishing the formation of lignocellulosic compounds capable of sorption onto metal oxides. As a result

  13. 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.

  14. 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.

  15. 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.

  16. Micronutrients on the Menu: Enhancing the Quality of Food in Long-term Care for Regular, Nontherapeutic Menus.

    Science.gov (United States)

    Lam, Ivy T; Keller, Heather H; Duizer, Lisa; Stark, Ken

    2015-06-01

    Micronutrient (vitamin and mineral) deficiencies may exacerbate prevalent health conditions occurring in long-term care (LTC) residents, and current food provision may potentiate this problem. A micronutrient-focused, food-first approach to menu planning may address this gap by emphasizing nutrient-dense foods. The objectives were to determine if: (i) selected LTC menus met micronutrient and Canada's Food Guide (CFG) recommendations, and (ii) recommendations can be met through food alone with strategic menu planning. Regular, nontherapeutic menus (week 1, all meals) from diverse LTC homes (n = 5) across Canada were analyzed for micronutrient content using Food Processor and CFG servings. Site dietitians confirmed menu analyses. Five super-menus were created and analyzed for comparison. The nutrient content of the menus varied significantly across homes. Micronutrients of greatest concern were (mean ± SD) vitamin D (8.90 ± 5.29 µg/d) and vitamin E (5.13 ± 1.74 mg/d). Folate, magnesium, and potassium were also below recommendations. Super-menus of equal food volume met recommendations for all micronutrients except vitamin D (56%), vitamin E (84%), and potassium (85%). Meeting most micronutrient recommendations is possible with creative and deliberate menu planning. Knowledge translation of best practices is needed.

  17. Toward a theory of multilevel evolution: long-term information integration shapes the mutational landscape and enhances evolvability.

    Science.gov (United States)

    Hogeweg, Paulien

    2012-01-01

    Most of evolutionary theory has abstracted away from how information is coded in the genome and how this information is transformed into traits on which selection takes place. While in the earliest stages of biological evolution, in the RNA world, the mapping from the genotype into function was largely predefined by the physical-chemical properties of the evolving entities (RNA replicators, e.g. from sequence to folded structure and catalytic sites), in present-day organisms, the mapping itself is the result of evolution. I will review results of several in silico evolutionary studies which examine the consequences of evolving the genetic coding, and the ways this information is transformed, while adapting to prevailing environments. Such multilevel evolution leads to long-term information integration. Through genome, network, and dynamical structuring, the occurrence and/or effect of random mutations becomes nonrandom, and facilitates rapid adaptation. This is what does happen in the in silico experiments. Is it also what did happen in biological evolution? I will discuss some data that suggest that it did. In any case, these results provide us with novel search images to tackle the wealth of biological data.

  18. 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.

  19. 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.

  20. Long-term physiological effects of enhanced O/sub 2/ release by inositol hexaphosphate-loaded erythrocytes

    Energy Technology Data Exchange (ETDEWEB)

    Teisseire, B.; Ropars, C.; Villereal, M.C.; Nicolau, C.

    1987-10-01

    A continuous lysing and resealing procedure with erythrocytes permitted incorporation in these cells of inositol hexaphosphate (InsP/sub 6/), a strong allosteric effector of Hb. This leads to significant rightward shifts of the HbO/sub 2/ dissociation curves with in vitro P/sub 50/, values increasing from 32.2 +/- 1.8 torr for control erythrocytes to 86 +/- 60 torr. The shape of the dissociation curve was still sigmoidal, although the Hill coefficient was decreased. The life span of InsP/sub 6/-loaded erythrocytes equaled that of control erythrocytes. Erythrocyte-survival studies were done using /sub 51/Cr labeling of cells. The long-term physiological effects of the InsP/sub 6/-loaded erythrocytes on piglets were increased O/sub 2/ release and reduced cardiac output. The reduced O/sub 2/ affinity of the InsP/sub 6/-loaded erythrocytes was still effective 20 days after transfusion in awake piglets. The electrolyte concentration appeared stable over the 5-day observation period except for a transient, but significant, hyperkalemia immediately after transfusion. The reductions in the O/sub 2/ affinity of Hb reported here are large compared with previously reported values. Introduction of InsP/sub 6/ into viable erythrocytes improves tissue oxygenation when, for any reason, normal blood flow is impaired.

  1. Effects of long-term infusion of sedatives on the cognitive function and expression level of RAGE in hippocampus of rats.

    Science.gov (United States)

    Wang, Junyan; Niu, Mengxuan; Bai, Shuancheng

    2016-08-01

    This study aims to investigate the effects of long-term infusion of midazolam, propofol, and lytic cocktail on the rat cognitive ability and expression of receptor for advanced glycation end products (RAGE) in the hippocampus. The correlation between cognitive function and RAGE protein expression level could provide basis for clinical application. Adult male Wistar rats were first treated with midazolam, propofol, lytic cocktail, and saline solution for 5 consecutive days, respectively, and then their behavioral performance in a Morris water maze was monitored to determine the effects of these sedatives on the cognition of spatial learning and memory. After the behavioral tests, the expression level of RAGE protein in the hippocampus of each rat was determined by ELISA and immunohistochemistry. Compared with the control rats, the sedative-treated rats showed impaired performance in the Morris water maze. These three sedatives rendered similar extents of impairment of learning and memory at the first day after the treatment (p  0.05). In addition, midazolam and propofol, but not lytic cocktail, caused significant upregulation of RAGE expression in the hippocampus. The upregulation of RAGE protein was further corroborated by the increment of RAGE-positive cells in the CA1 region of hippocampus from midazolam- and propofol-treated rats. The long-term treatment of propofol, midazolam, and lytic cocktail could impair cognition. The upregulation of RAGE protein in hippocampus might play a role in the midazolam- and propofol-caused cognitive dysfunction.

  2. Long-Term Effects of Ketogenic Diet on Subsequent Seizure-Induced Brain Injury During Early Adulthood: Relationship of Seizure Thresholds to Zinc Transporter-Related Gene Expressions.

    Science.gov (United States)

    Tian, Tian; Li, Li-Li; Zhang, Shu-Qi; Ni, Hong

    2016-12-01

    The divalent cation zinc is associated with cortical plasticity. However, the mechanism of zinc in the pathophysiology of cortical injury-associated neurobehavioral damage following neonatal seizures is uncertain. We have previously shown upregulated expression of ZnT-3; MT-3 in hippocampus of neonatal rats submitted to flurothyl-induced recurrent seizures, which was restored by pretreatment with ketogenic diet (KD). In this study, utilizing a novel "twist" seizure model by coupling early-life flurothyl-induced seizures with later exposure to penicillin, we further investigated the long-term effects of KD on cortical expression of zinc homeostasis-related genes in a systemic scale. Ten Sprague-Dawley rats were assigned each averagely into the non-seizure plus normal diet (NS + ND), non-seizure plus KD (NS + KD), recurrent seizures plus normal diet (RS + ND) and recurrent seizures plus KD (RS + KD) group. Recurrent seizures were induced by volatile flurothyl during P9-P21. During P23-P53, rats in NS + KD and RS + KD groups were dieted with KD. Neurological behavioral parameters of brain damage (plane righting reflex, cliff avoidance reflex, and open field test) were observed at P43. At P63, we examined seizure threshold using penicillin, then the cerebral cortex were evaluated for real-time RT-PCR and western blot study. The RS + ND group showed worse performances in neurological reflex tests and reduced latencies to myoclonic seizures induced by penicillin compared with the control, which was concomitant with altered expressions of ZnT-7, MT-1, MT-2, and ZIP7. Specifically, there was long-term elevated expression of ZIP7 in RS + ND group compared with that in NS + ND that was restored by chronic ketogenic diet (KD) treatment in RS + KD group, which was quite in parallel with the above neurobehavioral changes. Taken together, these findings indicate that the long-term altered expression of the metal transporter ZIP7 in adult cerebral cortex might

  3. Antenatal maternal long-term hypoxia: acclimatization responses with altered gene expression in ovine fetal carotid arteries.

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    Ravi Goyal

    Full Text Available In humans and other species, long-term hypoxia (LTH during pregnancy can lead to intrauterine growth restriction with reduced body/brain weight, dysregulation of cerebral blood flow (CBF, and other problems. To identify the signal transduction pathways and critical molecules, which may be involved in acclimatization to high altitude LTH, we conducted microarray with advanced bioinformatic analysis on carotid arteries (CA from the normoxic near-term ovine fetus at sea-level and those acclimatized to high altitude for 110+ days during gestation. In response to LTH acclimatization, in fetal CA we identified mRNA from 38 genes upregulated >2 fold (P2-fold (P<0.05. The major genes with upregulated mRNA were SLC1A3, Insulin-like growth factor (IGF binding protein 3, IGF type 2 receptor, transforming growth factor (TGF Beta-3, and genes involved in the AKT and BCL2 signal transduction networks. Most genes with upregulated mRNA have a common motif for Pbx/Knotted homeobox in the promoter region, and Sox family binding sites in the 3' un translated region (UTR. Genes with downregulated mRNA included those involved in the P53 pathway and 5-lipoxygenase activating proteins. The promoter region of all genes with downregulated mRNA, had a common 49 bp region with a binding site for DOT6 and TOD6, components of the RPD3 histone deacetylase complex RPD3C(L. We also identified miRNA complementary to a number of the altered genes. Thus, the present study identified molecules in the ovine fetus, which may play a role in the acclimatization response to high-altitude associated LTH.

  4. Ganzfeld stimulation or sleep enhance long term motor memory consolidation compared to normal viewing in saccadic adaptation paradigm.

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    Caroline Voges

    Full Text Available Adaptation of saccade amplitude in response to intra-saccadic target displacement is a type of implicit motor learning which is required to compensate for physiological changes in saccade performance. Once established trials without intra-saccadic target displacement lead to de-adaptation or extinction, which has been attributed either to extra-retinal mechanisms of spatial constancy or to the influence of the stable visual surroundings. Therefore we investigated whether visual deprivation ("Ganzfeld"-stimulation or sleep can partially maintain this motor learning compared to free viewing of the natural surroundings. Thirty-five healthy volunteers performed two adaptation blocks of 100 inward adaptation trials - interspersed by an extinction block - which were followed by a two-hour break with or without visual deprivation (VD. Using additional adaptation and extinction blocks short and long (4 weeks term memory of this implicit motor learning were tested. In the short term, motor memory tested immediately after free viewing was superior to adaptation performance after VD. In the long run, however, effects were opposite: motor memory and relearning of adaptation was superior in the VD conditions. This could imply independent mechanisms that underlie the short-term ability of retrieving learned saccadic gain and its long term consolidation. We suggest that subjects mainly rely on visual cues (i.e., retinal error in the free viewing condition which makes them prone to changes of the visual stimulus in the extinction block. This indicates the role of a stable visual array for resetting adapted saccade amplitudes. In contrast, visual deprivation (GS and sleep, might train subjects to rely on extra-retinal cues, e.g., efference copy or prediction to remap their internal representations of saccade targets, thus leading to better consolidation of saccadic adaptation.

  5. Optimised retroviral infection of human epidermal keratinocytes: long-term expression of transduced integrin gene following grafting on to SCID mice.

    Science.gov (United States)

    Levy, L; Broad, S; Zhu, A J; Carroll, J M; Khazaal, I; Péault, B; Watt, F M

    1998-07-01

    Previous attempts to achieve long-term gene expression in retrovirally transduced human epidermal keratinocytes in vivo have been largely unsuccessful. This has been variously attributed to a failure to target epidermal stem cells, suboptimal grafting conditions or inactivation of the retroviral vector. In an attempt to overcome these problems we expressed the chick beta 1 integrin subunit in primary human epidermal keratinocytes, which allowed us to monitor retroviral gene expression on a cell-by-cell basis. We describe optimised methods for selecting high-titre amphotropic packaging cells and for infecting keratinocytes in culture. When transduced cells were grafted into mice, graft survival was comparable in nude and SCID mice, but it was essential to combine the keratinocytes with a dermal substrate. Using these methods the majority of keratinocytes expressed the chick beta 1 integrin subunit for at least 16 weeks after grafting. We conclude that epidermal keratinocytes are attractive recipient cells for gene therapy.

  6. Long-term population dynamics and in situ physiology in activated sludge systems with enhanced biological phosphorus removal operated with and without nitrogen removal

    DEFF Research Database (Denmark)

    Lee, N.; Nielsen, P.H.; Aspegren, H.

    2003-01-01

    Quantitative fluorescence in situ hybridization (FISH) and the combination of FISH with microautoradiography (MAR) were used in order to study the long-term population dynamics (2.5 years) and the in situ physiology in two parallel activated sludge pilot systems with enhanced biological phosphorus...... and [H-3]-glucose uptake by activated sludge after different fixation and incubation procedures showed that a part of the observed P-33(i), uptake may have been caused by a combination of a biological and chemical or biologically induced chemical P adsorption....

  7. Nestin-Expressing Stem Cells Promote Nerve Growth in Long-Term 3-Dimensional Gelfoam®-Supported Histoculture.

    Directory of Open Access Journals (Sweden)

    Sumiyuki Mii

    Full Text Available We have previously reported that hair follicles contain multipotent stem cells which express nestin. The nestin-expressing cells form the hair follicle sensory nerve. In vitro, the nestin-expressing hair follicle cells can differentiate into neurons, Schwann cells, and other cell types. In the present study, the sciatic nerve was excised from transgenic mice in which the nestin promoter drives green fluorescent protein (ND-GFP mice. The ND-GFP cells of the sciatic nerve were also found to be multipotent as the ND-GFP cells in the hair follicle. When the ND-GFP cells in the mouse sciatic nerve cultured on Gelfoam® and were imaged by confocal microscopy, they were observed forming fibers extending the nerve. The fibers consisted of ND-GFP-expressing spindle cells, which co-expressed the neuron marker β-III tubulin, the immature Schwann-cell marker p75(NTR and TrkB which is associated with neurons. The fibers also contain nestin-negative spherical cells expressing GFAP, a Schwann-cell marker. The β-III tubulin-positive fibers had growth cones on their tips expressing F-actin, indicating they are growing axons. When the sciatic nerve from mice ubiquitously expressing red fluorescent protein (RFP was co-cultured on Gelfoam® with the sciatic nerve from ND-GFP transgenic mice, the interaction of nerves was observed. Proliferating nestin-expressing cells in the injured sciatic nerve were also observed in vivo. Nestin-expressing cells were also observed in posterior nerves but not in the spinal cord itself, when placed in 3-D Gelfoam® culture. The results of the present report suggest a critical function of nestin-expressing cells in peripheral nerve growth and regeneration.

  8. Long-term exposure to IL-1beta enhances Toll-IL-1 receptor-mediated inflammatory signaling in murine airway hyperresponsiveness

    DEFF Research Database (Denmark)

    Zhang, Yaping; Xu, Cang-Bao; Cardell, Lars-Olaf

    2009-01-01

    -1beta (IL-1beta), induce AHR. However, the underlying intracellular signaling mechanisms that lead to AHR remain elusive. In order to see if the Toll-IL-1 receptor-mediated inflammatory signal pathways are involved in the development of AHR, the present study was designed to use a real-time PCR...... mechanisms to the AHR, the anti-inflammatory drug dexamethasone, was used. Dexamethasone not only completely abolished the IL-1beta-induced AHR to bradykinin, but also abrogated the increased mRNA expression for inflammatory mediators, IL-6, IFN-gamma and Cox-2. In conclusion, long-term exposure of murine...

  9. Visual Input Enhancement via Essay Coding Results in Deaf Learners' Long-Term Retention of Improved English Grammatical Knowledge

    Science.gov (United States)

    Berent, Gerald P.; Kelly, Ronald R.; Schmitz, Kathryn L.; Kenney, Patricia

    2009-01-01

    This study explored the efficacy of visual input enhancement, specifically "essay enhancement", for facilitating deaf college students' improvement in English grammatical knowledge. Results documented students' significant improvement immediately after a 10-week instructional intervention, a replication of recent research. Additionally, the…

  10. Short- and long-term changes in sugarbeet (Beta vulgaris L.) gene expression after postharvest jasmonic acid treatment

    Science.gov (United States)

    Jasmonic acid is a natural plant hormone that induces native defense responses in plants. Sugarbeet (Beta vulgaris L.) root unigenes that were differentially expressed 2 and 60 days after a postharvest jasmonic acid treatment are presented. Data include changes in unigene expression relative to wate...

  11. Long-term chemiluminescence signal is produced in the course of luminol oxidation catalyzed by enhancer-independent peroxidase purified from Jatropha curcas leaves.

    Science.gov (United States)

    Duan, Peipei; Cai, Feng; Luo, Yongting; Chen, Yangxi; Zou, Shujuan

    2015-09-01

    Isoenzyme c of horseradish peroxidase (HRP-C) is widely used in enzyme immunoassay combined with chemiluminescence (CL) detection. For this application, HRP-C activity measurement is usually based on luminol oxidation in the presence of hydrogen peroxide (H2O2). However, this catalysis reaction was enhancer dependent. In this study, we demonstrated that Jatropha curcas peroxidase (JcGP1) showed high efficiency in catalyzing luminol oxidation in the presence of H2O2. Compared with HRP-C, the JcGP1-induced reaction was enhancer independent, which made the enzyme-linked immunosorbent assay (ELISA) simpler. In addition, the JcGP1 catalyzed reaction showed a long-term stable CL signal. We optimized the conditions for JcGP1 catalysis and determined the favorable conditions as follows: 50 mM Tris buffer (pH 8.2) containing 10 mM H2 O2, 14 mM luminol and 0.75 M NaCl. The optimum catalysis temperature was 30°C. The detection limit of JcGP1 under optimum condition was 0.2 pM. Long-term stable CL signal combined with enhancer-independent property indicated that JcGP1 might be a valuable candidate peroxidase for clinical diagnosis and enzyme immunoassay with CL detection. Copyright © 2014 John Wiley & Sons, Ltd.

  12. Short and long-term impact of lipectomy on expression profile of hepatic anabolic genes in rats: a high fat and high cholesterol diet-induced obese model.

    Directory of Open Access Journals (Sweden)

    Bey-Leei Ling

    Full Text Available OBJECTIVE: To understand the molecular basis of the short and long-term effects of an immediate shortage of energy storage caused by lipectomy on expression profile of genes involved in lipid and carbohydrate metabolism in high fat and high cholesterol diet-induced obese rats. METHODS: The hepatic mRNA levels of enzymes, regulator and transcription factors involved in glucose and lipid metabolism were analyzed by quantitative real time polymerase chain reaction (RT-qPCR ten days and eight weeks after lipectomy in obese rats. Body and liver weights and serum biochemical parameters, adiponectin, leptin and insulin were determined. RESULTS: No significant difference was observed on the food intake between the lipectomized and sham-operated groups during the experimental period. Ten days after the operation, the lipectomized animals showed significant higher triacylglycerol, glucose and insulin levels, a lower adiponectin concentration than the sham-operated rats, along with significant higher hepatic mRNA levels of hepatocyte nuclear factor 4α (HNF4α and the enzymes involved in lipogenesis, sterol biosynthesis and gluconeogenesis. The results of immunohistochemical (IHC analysis also confirmed increased levels of lipogenic enzymes in the liver of lipectomized versus sham-operated animals. The lipectomized group had a significantly lower adiponectin/leptin ratio that was positively correlated to the level of LDL (r = 0.823, P<0.05 and negatively to glucose and insulin (r = -0.821 and -0.892 respectively, P<0.05. Eight weeks after the operation, the lipectomized animals revealed significant higher body and liver weights, weight gain, liver to body weight ratio, hepatic triacylglycerol and serum insulin level. CONCLUSIONS: In response to lipectomy a short term enhancement of the expression of hepatic anabolic genes involved in lipid and carbohydrate metabolism was triggered that might eventually lead to the final extra weight gain. These

  13. Dual-Function Au@Y2O3:Eu3+Smart Film for Enhanced Power Conversion Efficiency and Long-Term Stability of Perovskite Solar Cells.

    Science.gov (United States)

    Kim, Chang Woo; Eom, Tae Young; Yang, In Seok; Kim, Byung Su; Lee, Wan In; Kang, Yong Soo; Kang, Young Soo

    2017-07-28

    In the present study, a dual-functional smart film combining the effects of wavelength conversion and amplification of the converted wave by the localized surface plasmon resonance has been investigated for a perovskite solar cell. This dual-functional film, composed of Au nanoparticles coated on the surface of Y 2 O 3 :Eu 3+ phosphor (Au@Y 2 O 3 :Eu 3+ ) nanoparticle monolayer, enhances the solar energy conversion efficiency to electrical energy and long-term stability of photovoltaic cells. Coupling between the Y 2 O 3 :Eu 3+ phosphor monolayer and ultraviolet solar light induces the latter to be converted into visible light with a quantum yield above 80%. Concurrently, the Au nanoparticle monolayer on the phosphor nanoparticle monolayer amplifies the converted visible light by up to 170%. This synergy leads to an increased solar light energy conversion efficiency of perovskite solar cells. Simultaneously, the dual-function film suppresses the photodegradation of perovskite by UV light, resulting in long-term stability. Introducing the hybrid smart Au@Y 2 O 3 :Eu 3+ film in perovskite solar cells increases their overall solar-to-electrical energy conversion efficiency to 16.1% and enhances long-term stability, as compared to the value of 15.2% for standard perovskite solar cells. The synergism between the wavelength conversion effect of the phosphor nanoparticle monolayer and the wave amplification by the localized surface plasmon resonance of the Au nanoparticle monolayer in a perovskite solar cell is comparatively investigated, providing a viable strategy of broadening the solar spectrum utilization.

  14. Cloning, phylogenetic analysis and expression of somatolactin and its receptor in Cichlasoma dimerus: their role in long-term background color acclimation.

    Science.gov (United States)

    Cánepa, Maximiliano M; Zhu, Yong; Fossati, Mariana; Stiller, John W; Vissio, Paula G

    2012-03-01

    Somatolactin (SL) and SL receptor (SLR) belong to the growth hormone and cytokine type I receptor superfamilies, respectively. However, further research is required to define the duplications and functions of SL and its receptors in basal vertebrates including environmental background color adaptation in fish. In the present study, we cloned and sequenced SL and its putative receptor (SLR), classified and compared the sequences phylogenetically, and determined SL and SLR mRNA expression levels during long-term background color exposure in Cichlasoma dimerus, a freshwater South American cichlid. Our results show that C. dimerus SL and SLR share high sequence similarity with homologous from other perciform fish. Phylogenetic analysis indicates that C. dimerus SL belongs to the SLα clade sub-group. C. dimerus SLR is clearly a member of the GHR1 receptor subgroup, which includes the experimentally validated SLR from salmonids. Higher transcript levels of SLα in the pituitary and SLR in the epidermis and dermis cells of fish scales were observed in fish following long-term black background color exposure compared to those exposed to a white background. A higher number of melanophores was also observed in fish exposed for 10days to a black background compared to those exposed to a white background. These changes were concomitant to differences in SL or SLR transcript levels found in fish exposed to these two different background colors. Our results suggest, for the first time, that SLR is expressed in fish scales, and that there is an increase in SL in the pituitary and the putative SLR in likely target cells, i.e., melanophores, in long-term black background exposure in C. dimerus. Copyright © 2011 Elsevier Inc. All rights reserved.

  15. Long-term activation of group I metabotropic glutamate receptors increases functional TRPV1-expressing neurons in mouse dorsal root ganglia

    Directory of Open Access Journals (Sweden)

    Takayoshi eMasuoka

    2016-03-01

    Full Text Available Damaged tissues release glutamate and other chemical mediators for several hours. These chemical mediators contribute to modulation of pruritus and pain. Herein, we investigated the effects of long-term activation of excitatory glutamate receptors on functional expression of transient receptor potential vaniloid type 1 (TRPV1 in dorsal root ganglion (DRG neurons and then on thermal pain behavior. In order to detect the TRPV1-mediated responses in cultured DRG neurons, we monitored intracellular calcium responses to capsaicin, a TRPV1 agonist, with Fura-2. Long-term (4 h treatment with glutamate receptor agonists (glutamate, quisqualate or DHPG increased the proportion of neurons responding to capsaicin through activation of metabotropic glutamate receptor mGluR1, and only partially through the activation of mGluR5; engagement of these receptors was evident in neurons responding to allylisothiocyanate (AITC, a transient receptor potential ankyrin type 1 (TRPA1 agonist. Increase in the proportion was suppressed by phospholipase C, protein kinase C, mitogen/extracellular signal-regulated kinase, p38 mitogen-activated protein kinase or transcription inhibitors. Whole-cell recording was performed to record TRPV1-mediated membrane current; TRPV1 current density significantly increased in the AITC-sensitive neurons after the quisqualate treatment. To elucidate the physiological significance of this phenomenon, a hot plate test was performed. Intraplantar injection of quisqualate or DHPG induced heat hyperalgesia that lasted for 4 h post injection. This chronic hyperalgesia was attenuated by treatment with either mGluR1 or mGluR5 antagonists. These results suggest that long-term activation of mGluR1/5 by peripherally released glutamate may increase the number of neurons expressing functional TRPV1 in DRG, which may be strongly associated with chronic hyperalgesia.

  16. Helios expression and Foxp3 TSDR methylation of IFNy+ and IFNy- Treg from kidney transplant recipients with good long-term graft function.

    Directory of Open Access Journals (Sweden)

    Karina Trojan

    Full Text Available There is circumstantial evidence that IFNy+ Treg might have clinical relevance in transplantation. IFNy+ Treg express IFNy receptors and are induced by IFNy. In the present study we investigated in kidney transplant recipients with good long-term stable graft function the absolute cell counts of IFNy+ Treg subsets and whether their expression of Foxp3 is stable or transient.Helios expression determined by eight-color-fluorescence flow cytometry and methylation status of the Foxp3 Treg specific demethylation region (TSDR served as indicators for stability of Foxp3 expression. Methylation status was investigated in enriched IFNy+ and IFNy- Treg preparations originating from peripheral blood using high resolution melt analysis. A total of 136 transplant recipients and 52 healthy controls were studied.Proportions of IFNy+ Treg were similar in patients and healthy controls (0.05% and 0.04% of all CD4+ lymphocytes; p = n.s.. Patients also had similar absolute counts of IFNy producing Helios+ and Helios- Treg (p = n.s.. Most of the IFNy+ and IFNy- Treg in transplant recipients had a methylated Foxp3 TSDR, however, there was a sizeable proportion of IFNy+ and IFNy- Treg with demethylated Foxp3 TSDR. Male and female patients showed more frequently methylated IFNy+ and IFNy- Treg than male and female controls (all p<0.05.Kidney transplant recipients with good long-term stable graft function have similar levels of IFNy+ Treg as healthy controls. IFNy+ and IFNy- Treg subsets in patients consist of cells with stable and cells with transient Foxp3 expression; however, patients showed more frequently methylated IFNy+ and IFNy- Treg than controls. The data show increased levels of Treg subsets with stable as well as transient Foxp3 expression in patients with stable allograft acceptance compared to healthy controls.

  17. Visual input enhancement via essay coding results in deaf learners' long-term retention of improved English grammatical knowledge.

    Science.gov (United States)

    Berent, Gerald P; Kelly, Ronald R; Schmitz, Kathryn L; Kenney, Patricia

    2009-01-01

    This study explored the efficacy of visual input enhancement, specifically essay enhancement, for facilitating deaf college students' improvement in English grammatical knowledge. Results documented students' significant improvement immediately after a 10-week instructional intervention, a replication of recent research. Additionally, the results of delayed assessment documented students' significant retention of that improvement five and a half months beyond the instructional intervention period. Essay enhancement served to highlight, via a coding procedure, students' successful and unsuccessful production of discourse-required target grammatical structures. The procedure converted students' written communicative output into enhanced input for inducing noticing of grammatical form and, through essay revision, establishing form-meaning connections leading to acquisition. With its optimal design characteristics supported by theoretical and empirical research, essay enhancement is a highly effective methodology that can be easily implemented as primary or supplementary English instruction for deaf students. The results of this study hold great promise for facilitating deaf students' English language and literacy development and have broad implications for second-language research, teaching, and learning.

  18. AAV-mediated expression of CNTF promotes long-term survival and regeneration of adult rat retinal ganglion cells

    NARCIS (Netherlands)

    Leaver, Simone G; Cui, Qi; Plant, Giles W; Arulpragasam, A.; Hisheh, S; Verhaagen, J; Harvey, Alan R

    We compared the effects of intravitreal injection of bi-cistronic adeno-associated viral (AAV-2) vectors encoding enhanced green fluorescent protein (GFP) and either ciliary neurotrophic factor (CNTF), brain-derived neurotrophic factor (BDNF) or growth-associated protein-43 (GAP43) on adult retinal

  19. 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.

  20. Stable immediate early gene expression patterns in medial prefrontal cortex and striatum after long-term cocaine self-administration

    NARCIS (Netherlands)

    Gao, Ping; Limpens, Jules H W; Spijker, Sabine; Vanderschuren, Louk J M J; Voorn, Pieter

    The transition from casual to compulsive drug use is thought to occur as a consequence of repeated drug taking leading to neuroadaptive changes in brain circuitry involved in emotion and cognition. At the basis of such neuroadaptations lie changes in the expression of immediate early genes (IEGs)

  1. Genetically engineered red cells expressing single domain camelid antibodies confer long-term protection against botulinum neurotoxin.

    Science.gov (United States)

    Huang, Nai-Jia; Pishesha, Novalia; Mukherjee, Jean; Zhang, Sicai; Deshycka, Rhogerry; Sudaryo, Valentino; Dong, Min; Shoemaker, Charles B; Lodish, Harvey F

    2017-09-04

    A short half-life in the circulation limits the application of therapeutics such as single-domain antibodies (VHHs). We utilize red blood cells to prolong the circulatory half-life of VHHs. Here we present VHHs against botulinum neurotoxin A (BoNT/A) on the surface of red blood cells by expressing chimeric proteins of VHHs with Glycophorin A or Kell. Mice whose red blood cells carry the chimeric proteins exhibit resistance to 10,000 times the lethal dose (LD50) of BoNT/A, and transfusion of these red blood cells into naive mice affords protection for up to 28 days. We further utilize an improved CD34+ culture system to engineer human red blood cells that express these chimeric proteins. Mice transfused with these red blood cells are resistant to highly lethal doses of BoNT/A. We demonstrate that engineered red blood cells expressing VHHs can provide prolonged prophylactic protection against bacterial toxins without inducing inhibitory immune responses and illustrates the potentially broad translatability of our strategy for therapeutic applications.The therapeutic use of single-chain antibodies (VHHs) is limited by their short half-life in the circulation. Here the authors engineer mouse and human red blood cells to express VHHs against botulinum neurotoxin A (BoNT/A) on their surface and show that an infusion of these cells into mice confers long lasting protection against a high dose of BoNT/A.

  2. Long-term effects of sulphide on the enhanced biological removal of phosphorus : The symbiotic role of Thiothrix caldifontis

    NARCIS (Netherlands)

    Rubio Rincon, F.J.; Welles, L.; Lopez Vazquez, Carlos; Nierychlo, M.; Abbas, B.A.; Geleijnse, M.A.A.; Nielsen, PH; van Loosdrecht, Mark C.M.; Brdanovic, Damir

    Thiothrix caldifontis was the dominant microorganism (with an estimated bio-volume of 65 ± 3%) in a lab-scale enhanced biological phosphorus removal (EBPR) system containing 100 mg of sulphide per litre in the influent. After a gradual exposure to the presence of sulphide, the EBPR system initially

  3. Criterion 6: Maintenance and enhancement of long-term multiple socioeconomic benefits to meet the needs of societies

    Science.gov (United States)

    Stephen R. Shifley; Francisco X. Aguilar; Nianfu Song; Susan I. Stewart; David J. Nowak; Dale D. Gormanson; W. Keith Moser; Sherri Wormstead; Eric J. Greenfield

    2012-01-01

    Forests provide an array of products and services that maintain and enhance benefits to our society and economy. Benefits derived from forests may be categorized into wood products, nontimber products and services, and ecosystem services. The value and volume of these products and services indicate the importance of forests for a wide variety of uses.Tracking values,...

  4. Long-term alterations of cytokines and growth factors expression in irradiated tissues and relation with histological severity scoring.

    Directory of Open Access Journals (Sweden)

    Patrice Gallet

    Full Text Available PURPOSE: Beside its efficacy in cancer treatment, radiotherapy induces degeneration of healthy tissues within the irradiated area. The aim of this study was to analyze the variations of proinflammatory (IL-1α, IL-2, IL-6, TNF-α, IFN-γ, profibrotic (TGF-β1, proangiogneic (VEGF and stem cell mobilizing (GM-CSF cytokines and growth factors in an animal model of radiation-induced tissue degeneration. MATERIALS AND METHODS: 24 rats were irradiated unilaterally on the hindlimb at a monodose of 30 Gy. Six weeks (n=8, 6 months (n=8 and 1 year (n=8 after irradiation the mediators expression in skin and muscle were analyzed using Western blot and the Bio-Plex® protein array (BPA technology. Additional histological severity for fibrosis, inflammation, vascularity and cellularity alterations scoring was defined from histology and immnunohistochemistry analyses. RESULTS: A significant increase of histological severity scoring was found in irradiated tissue. Skin tissues were more radio-sensitive than muscle. A high level of TGF-β1 expression was found throughout the study and a significant relation was evidenced between TGF-β1 expression and fibrosis scoring. Irradiated tissue showed a chronic inflammation (IL-2 and TNF-α significantly increased. Moreover a persistent expression of GM-CSF and VEGF was found in all irradiated tissues. The vascular score was related to TGF-β1 expression and the cellular alterations score was significantly related with the level of IL-2, VEGF and GM-CSF. CONCLUSION: The results achieved in the present study underline the complexity and multiplicity of radio-induced alterations of cytokine network. It offers many perspectives of development, for the comprehension of the mechanisms of late injuries or for the histological and molecular evaluation of the mode of action and the efficacy of rehabilitation techniques.

  5. Long-Term Enrichment Enhances the Cognitive Behavior of the Aging Neurogranin Null Mice without Affecting Their Hippocampal LTP

    Science.gov (United States)

    Huang, Freesia L.; Huang, Kuo-Ping; Boucheron, Catherine

    2007-01-01

    Neurogranin (Ng), a PKC substrate, is abundantly expressed in brain regions important for cognitive functions. Deletion of Ng caused severe deficits in spatial learning and LTP in the hippocampal CA1 region of mice. These Ng-/- mice also exhibit deficits in the amplification of their hippocampal signaling pathways critical for learning and memory.…

  6. Dilemmas in providing resilience-enhancing social services to long-term social assistance clients. A qualitative study of Swedish social workers

    Science.gov (United States)

    2012-01-01

    Background Long-term recipients of social assistance face barriers to social and economic inclusion, and have poorer health and more limited opportunities for improving their health than many other groups in the population. During recent decades there have been changes in Swedish social policy, with cutbacks in public benefits and a re-emphasis on means-tested policies. In this context, it is important to investigate the necessary conditions for social workers to offer social assistance and services, as well as the mediating role of social workers between public policies and their clients. Swedish social services aim to promote social inclusion by strengthening the individual´s own resources. We investigated the issues that arise when providing social services to long-term social assistance clients within the framework of resilience, which focuses on the processes leading to positive functioning in adverse conditions. Methods Interviews were conducted with 23 social workers in Stockholm and analysed by qualitative content analysis. Results The main theme to emerge from the interviews concerned the constraints that the social workers faced in providing social services to social assistance clients. The first subtheme focused on dilemmas in the interaction between social workers and clients resulting from the dual role of exercising authority and supporting and building trust with clients. Working conditions of social workers also played a crucial role. The second subtheme addressed the impact of the societal context, such as labour market opportunities and coordination between authorities. Conclusions Overall, we found that social workers to a great extent tried to find individual solutions to structural problems. To provide resilience-enhancing social services to long-term social assistance clients with varying obstacles and needs requires a constructive working environment, supportive societal structures and inter-sectoral cooperation between different authorities

  7. Critical thinking: Reported enhancers and barriers by nurses in long-term care: implications for staff development.

    Science.gov (United States)

    Raterink, Ginger

    2011-01-01

    Nursing acknowledges critical thinking as an important guide to clinical decision making. Agreement on how to define, teach, and evaluate this skill is lacking. The purpose of this study was to evaluate critical thinking in practice using a survey that asked nurses to evaluate work-related factors that enhance or pose barriers to the use of critical thinking in practice. Results indicated that enhancers and barriers to practice included teamwork, staffing patterns, and staff and administrator support. A relationship with patients was the most satisfying factor, whereas paperwork was the least. Staff development educators must consider the work environment aspects that affect performance and create the life long learning needed for increased competency in practice.

  8. Transient Notch Activation Induces Long-Term Gene Expression Changes Leading to Sick Sinus Syndrome in Mice.

    Science.gov (United States)

    Qiao, Yun; Lipovsky, Catherine; Hicks, Stephanie; Bhatnagar, Somya; Li, Gang; Khandekar, Aditi; Guzy, Robert; Woo, Kel Vin; Nichols, Colin G; Efimov, Igor R; Rentschler, Stacey

    2017-08-18

    Notch signaling programs cardiac conduction during development, and in the adult ventricle, injury-induced Notch reactivation initiates global transcriptional and epigenetic changes. To determine whether Notch reactivation may stably alter atrial ion channel gene expression and arrhythmia inducibility. To model an injury response and determine the effects of Notch signaling on atrial electrophysiology, we transiently activate Notch signaling within adult myocardium using a doxycycline-inducible genetic system (inducible Notch intracellular domain [iNICD]). Significant heart rate slowing and frequent sinus pauses are observed in iNICD mice when compared with controls. iNICD mice have structurally normal atria and preserved sinus node architecture, but expression of key transcriptional regulators of sinus node and atrial conduction, including Nkx2-5 (NK2 homeobox 5), Tbx3, and Tbx5 are dysregulated. To determine whether the induced electrical changes are stable, we transiently activated Notch followed by a prolonged washout period and observed that, in addition to decreased heart rate, atrial conduction velocity is persistently slower than control. Consistent with conduction slowing, genes encoding molecular determinants of atrial conduction velocity, including Scn5a (Nav1.5) and Gja5 (connexin 40), are persistently downregulated long after a transient Notch pulse. Consistent with the reduction in Scn5a transcript, Notch induces global changes in the atrial action potential, including a reduced dVm/dtmax. In addition, programmed electrical stimulation near the murine pulmonary vein demonstrates increased susceptibility to atrial arrhythmias in mice where Notch has been transiently activated. Taken together, these results suggest that transient Notch activation persistently alters ion channel gene expression and atrial electrophysiology and predisposes to an arrhythmogenic substrate. Our data provide evidence that Notch signaling regulates transcription factor and ion

  9. Kootenai River Wildlife Habitat Enhancement Project : Long-term Bighorn Sheep/Mule Deer Winter and Spring Habitat Improvement Project : Wildlife Mitigation Project, Libby Dam, Montana : Management Plan.

    Energy Technology Data Exchange (ETDEWEB)

    Yde, Chis

    1990-06-01

    The Libby hydroelectric project, located on the Kootenai River in northwestern Montana, resulted in several impacts to the wildlife communities which occupied the habitats inundated by Lake Koocanusa. Montana Department of Fish, Wildlife and Parks, in cooperation with the other management agencies, developed an impact assessment and a wildlife and wildlife habitat mitigation plan for the Libby hydroelectric facility. In response to the mitigation plan, Bonneville Power Administration funded a cooperative project between the Kootenai National Forest and Montana Department of Fish, Wildlife and Parks to develop a long-term habitat enhancement plan for the bighorn sheep and mule deer winter and spring ranges adjacent to Lake Koocanusa. The project goal is to rehabilitate 3372 acres of bighorn sheep and 16,321 acres of mule deer winter and spring ranges on Kootenai National Forest lands adjacent to Lake Koocanusa and to monitor and evaluate the effects of implementing this habitat enhancement work. 2 refs.

  10. 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.

  11. Differences in gene expression in the hippocampus of aged rats are associated with better long-term memory performance in a passive avoidance test.

    Science.gov (United States)

    Di Stefano, Giuseppina; Casoli, Tiziana; Platano, Daniela; Fattoretti, Patrizia; Balietti, Marta; Giorgetti, Belinda; Bertoni-Freddari, Carlo; Lattanzio, Fabrizia; Aicardi, Giorgio

    2010-01-01

    Microarray analysis was used to identify genes differentially expressed in the hippocampus of aged rats showing diverse long-term (3 and 6 h) spatial-associative memory performance in a single-trial inhibitory avoidance task. The transcription of 43 genes (including genes functionally linked to signal transduction, cell growth and differentiation, translation, energy metabolism, and nucleic acid processing) was significantly upregulated in good- versus bad-performing animals, whereas that of 18 genes (including genes functionally linked to transcription, cell growth and differentiation, apoptosis, and protein transport) was significantly downregulated in good- versus bad-performing animals. The differential expression of 14 of these genes was confirmed by real-time polymerase chain reaction.

  12. The long term oral regulation of blood glucose in diabetic patients by using of Escherichia coli Nissle 1917 expressing CTB-IGF-1 hybrid protein.

    Science.gov (United States)

    Bazi, Zahra; Jalili, Mahsa; Hekmatdoost, Azita

    2013-11-01

    Regarding to the high prevalence and comorbidities of chronic high blood glucose in diabetic patients and the limited efficacy and current painful treatments. It is necessary to improve new treatments that are non-invasive and long-term for controlling blood glucose. Recent studies have shown that the healthy microflora in different body organs can perform as the gene vectors for expressing different types of gene therapies in situ. We have proposed that by constructing a recombinant Escherichia coli Nissle 1917 that expresses CTB-IGF-1 hybrid gene under control of ompC glucose sensitive promoter, the intestinal glucose level can be regulated. This method in comparison with other methods is a non-invasive way to control the blood glucose orally and it can be used for all types of diabetes. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. Prenatal nutrition and the risk of adult obesity: Long-term effects of nutrition on epigenetic mechanisms regulating gene expression.

    Science.gov (United States)

    Navarro, Estanislau; Funtikova, Anna N; Fíto, Montserrat; Schröder, Helmut

    2017-01-01

    Solid epidemiological evidence indicates that part of the risk of obesity in adulthood could be programmed during prenatal development by the quality of maternal nutrition. Nevertheless, the molecular mechanisms involved are mostly unknown, which hinders our capacity to develop effective intervention policies. Here, we discuss the hypothesis that mechanisms underlying prenatal programming of adult risk are epigenetic and sensitive to environmental cues such as nutrition. While the information encoded in DNA is essentially stable, regulatory epigenetic mechanisms include reversible, covalent modifications of DNA and chromatin, such as methylation, acetylation etc. It is known that dietary availability of methyl donors has an impact on the patterns of gene expression by affecting DNA methylation at regulatory regions, a likely basis for reprogramming developmental plasticity. The Agouti and Axin-fused genes, as well as the embryonic growth factor IGF2/H19 locus are examples of diet-induced modulation of phenotypic traits by affecting methylation of gene-regulatory regions. Recent work has evidenced an unsuspected role for chromatin as metabolic sensor. Chromatin is susceptible to a number of post-translational modifications that modulate gene expression, among them the GlcNAcylation of histone proteins and other epigenetic regulators. Intracellular levels of the precursor molecule UDP-GlcNAc, and hence the degree of global chromatin GlcNAcylation, depend on the energetic state of the cell, making GlcNAcylation a functional link between nutrition and regulation of gene expression. Dietary interference with these regulatory mechanisms could effectively counteract the early-life programming of adult risk. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Carprofen neither reduces postoperative facial expression scores in rabbits treated with buprenorphine nor alters long term bone formation after maxillary sinus grafting.

    Science.gov (United States)

    Hedenqvist, Patricia; Trbakovic, Amela; Thor, Andreas; Ley, Cecilia; Ekman, Stina; Jensen-Waern, Marianne

    2016-08-01

    In connection with bilateral maxillary sinus augmentation, the acute effects of the nonsteroidal anti-inflammatory drug carprofen on facial expressions and long-term effects on bone formation were evaluated in 18 male New Zealand White rabbits. A 10×10mm bone window was drilled in the maxilla, the sinus membrane elevated and a titanium mini-implant inserted. One of two test materials was randomly inserted unilaterally and bovine bone chips (control) on the contralateral side in the created space. Rabbits were randomly allocated to receive buprenorphine plus carprofen (n=9) or buprenorphine plus saline (n=9) postoperatively. Buprenorphine was administered subcutaneously every 6h for 3days in a tapered dose (0.05-0.01mg/kg) and carprofen (5mg/kg) or saline administered subcutaneously 1h before, and daily for 4days postoperatively. To assess pain, clinical examination, body weight recording and scoring of facial expressions from photos taken before, and 6-13h after surgery were performed. Twelve weeks after surgery the rabbits were euthanized and sections of maxillary bones and sinuses were analysed with histomorphometry and by qualitative histology. Carprofen had no effect on mean facial expression scores, which increased from 0.0 to 3.6 (carprofen) and 4.3 (saline), of a maximum of 8.0. Neither did carprofen have an effect on bone formation or implant incorporation, whereas the test materials had. In conclusion, treatment with 5mg/kg carprofen once daily for 5days did not reduce facial expression scores after maxillary sinus augmentation in buprenorphine treated rabbits and did not affect long term bone formation. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Long-term treadmill exercise improves spatial memory of male appswe/ps1de9 mice by regulation of BDNF expression and microglia activation

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    JY Xiong

    2015-11-01

    Full Text Available Increasing evidence suggests that physical activity could delay or attenuate the symptoms of Alzheimer’s disease (AD. But the underlying mechanisms are still not fully understood. To investigate the effect of long-term treadmill exercise on the spatial memory of AD mice and the possible role of β-amyloid, brain-derived neurotrophic factor (BDNF and microglia in the effect, male APPswe/PS1dE9 AD mice aged 4 months were subjected to treadmill exercise for 5 months with 6 sessions per week and gradually increased load. A Morris water maze was used to evaluate the spatial memory. Expression levels of β-amyloid, BDNF and Iba-1 (a microglia marker in brain tissue were detected by immunohistochemistry. Sedentary AD mice and wildtype C57BL/6J mice served as controls. The results showed that 5-month treadmill exercise significantly decreased the escape latencies (P 0.05. The study suggested that long-term treadmill exercise could improve the spatial memory of the male APPswe/PS1dE9 AD mice. The increase in BDNF-positive cells and decrease in activated microglia might underpin the beneficial effect.

  16. Increase of long-term 'diabesity' risk, hyperphagia, and altered hypothalamic neuropeptide expression in neonatally overnourished 'small-for-gestational-age' (SGA) rats.

    Science.gov (United States)

    Schellong, Karen; Neumann, Uta; Rancourt, Rebecca C; Plagemann, Andreas

    2013-01-01

    Epidemiological data have shown long-term health adversity in low birth weight subjects, especially concerning the metabolic syndrome and 'diabesity' risk. Alterations in adult food intake have been suggested to be causally involved. Responsible mechanisms remain unclear. By rearing in normal (NL) vs. small litters (SL), small-for-gestational-age (SGA) rats were neonatally exposed to either normal (SGA-in-NL) or over-feeding (SGA-in-SL), and followed up into late adult age as compared to normally reared appropriate-for-gestational-age control rats (AGA-in-NL). SGA-in-SL rats displayed rapid neonatal weight gain within one week after birth, while SGA-in-NL growth caught up only at juvenile age (day 60), as compared to AGA-in-NL controls. In adulthood, an increase in lipids, leptin, insulin, insulin/glucose-ratio (all pSGA-in-SL as compared to both SGA-in-NL and AGA-in-NL rats (pSGA-in-SL rats (pSGA-in-SL regarding Npy/Pomc expression (pSGA rats developed increased 'diabesity' risk only if exposed to neonatal overfeeding. Hypothalamic malprogramming towards decreased anorexigenic activity was involved into the pathophysiology of this neonatally acquired adverse phenotype. Neonatal overfeeding appears to be a critical long-term risk factor in 'small-for-gestational-age babies'.

  17. Increase of Long-Term ‘Diabesity’ Risk, Hyperphagia, and Altered Hypothalamic Neuropeptide Expression in Neonatally Overnourished ‘Small-For-Gestational-Age’ (SGA) Rats

    Science.gov (United States)

    Schellong, Karen; Neumann, Uta; Rancourt, Rebecca C.; Plagemann, Andreas

    2013-01-01

    Background Epidemiological data have shown long-term health adversity in low birth weight subjects, especially concerning the metabolic syndrome and ‘diabesity’ risk. Alterations in adult food intake have been suggested to be causally involved. Responsible mechanisms remain unclear. Methods and Findings By rearing in normal (NL) vs. small litters (SL), small-for-gestational-age (SGA) rats were neonatally exposed to either normal (SGA-in-NL) or over-feeding (SGA-in-SL), and followed up into late adult age as compared to normally reared appropriate-for-gestational-age control rats (AGA-in-NL). SGA-in-SL rats displayed rapid neonatal weight gain within one week after birth, while SGA-in-NL growth caught up only at juvenile age (day 60), as compared to AGA-in-NL controls. In adulthood, an increase in lipids, leptin, insulin, insulin/glucose-ratio (all pSGA-in-SL as compared to both SGA-in-NL and AGA-in-NL rats (pSGA-in-SL rats (pSGA-in-SL regarding Npy/Pomc expression (pSGA rats developed increased ‘diabesity’ risk only if exposed to neonatal overfeeding. Hypothalamic malprogramming towards decreased anorexigenic activity was involved into the pathophysiology of this neonatally acquired adverse phenotype. Neonatal overfeeding appears to be a critical long-term risk factor in ‘small-for-gestational-age babies’. PMID:24265718

  18. Changes in heart rate variability are associated with expression of short-term and long-term contextual and cued fear memories.

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    Jun Liu

    Full Text Available Heart physiology is a highly useful indicator for measuring not only physical states, but also emotional changes in animals. Yet changes of heart rate variability during fear conditioning have not been systematically studied in mice. Here, we investigated changes in heart rate and heart rate variability in both short-term and long-term contextual and cued fear conditioning. We found that while fear conditioning could increase heart rate, the most significant change was the reduction in heart rate variability which could be further divided into two distinct stages: a highly rhythmic phase (stage-I and a more variable phase (stage-II. We showed that the time duration of the stage-I rhythmic phase were sensitive enough to reflect the transition from short-term to long-term fear memories. Moreover, it could also detect fear extinction effect during the repeated tone recall. These results suggest that heart rate variability is a valuable physiological indicator for sensitively measuring the consolidation and expression of fear memories in mice.

  19. A microfluidic device for temporally controlled gene expression and long-term fluorescent imaging in unperturbed dividing yeast cells.

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    Gilles Charvin

    Full Text Available BACKGROUND: Imaging single cells with fluorescent markers over multiple cell cycles is a powerful tool for unraveling the mechanism and dynamics of the cell cycle. Over the past ten years, microfluidic techniques in cell biology have emerged that allow for good control of growth environment. Yet the control and quantification of transient gene expression in unperturbed dividing cells has received less attention. METHODOLOGY/PRINCIPAL FINDINGS: Here, we describe a microfluidic flow cell to grow Saccharomyces Cerevisiae for more than 8 generations (approximately 12 hrs starting with single cells, with controlled flow of the growth medium. This setup provides two important features: first, cells are tightly confined and grow in a remarkably planar array. The pedigree can thus be determined and single-cell fluorescence measured with 3 minutes resolution for all cells, as a founder cell grows to a micro-colony of more than 200 cells. Second, we can trigger and calibrate rapid and transient gene expression using reversible administration of inducers that control the GAL1 or MET3 promoters. We then show that periodic 10-20 minutes gene induction pulses can drive many cell division cycles with complete coherence across the cell cluster, with either a G1/S trigger (cln1 cln2 cln3 MET3-CLN2 or a mitotic trigger (cdc20 GALL-CDC20. CONCLUSIONS/SIGNIFICANCE: In addition to evident cell cycle applications, this device can be used to directly measure the amount and duration of any fluorescently scorable signal-transduction or gene-induction response over a long time period. The system allows direct correlation of cell history (e.g., hysteresis or epigenetics or cell cycle position with the measured response.

  20. Long term operation of continuous-flow system with enhanced biological phosphorus removal granules at different COD loading.

    Science.gov (United States)

    Li, Dong; Lv, Yufeng; Zeng, Huiping; Zhang, Jie

    2016-09-01

    In this study, a continuous-flow system with enhanced biological phosphorus removal (EBPR) granules was operated at different COD concentrations (200, 300 and 400mgL(-)(1)) to investigate the effect of COD loading on this system. The results showed that when the COD concentration in influent was increased to 400mgL(-)(1), the anaerobic COD removal efficiency and total phosphorus removal efficiency reduced obviously and the settling ability of granules deteriorated due to the proliferation of filamentous bacteria. Moreover, high COD loading inhibited the EPS secretion and destroyed the stability of granules. Results of high-through pyrosequencing indicated that filamentous bacteria had a competitive advantage over polyphosphate-accumulating organisms (PAOs) at high COD loading. The performance of system, settling ability of granules and proportion of PAOs gradually recovered to the initial level after the COD concentration was reduced to 200mgL(-)(1) on day 81. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Spontaneous liver fibrosis induced by long term dietary vitamin D deficiency in adult mice is related to chronic inflammation and enhanced apoptosis.

    Science.gov (United States)

    Zhu, Longdong; Kong, Ming; Han, Yuan-Ping; Bai, Li; Zhang, Xiaohui; Chen, Yu; Zheng, Sujun; Yuan, Hong; Duan, Zhongping

    2015-05-01

    Epidemiological studies have revealed an association between vitamin D deficiency and various chronic liver diseases. However, it is not known whether lack of vitamin D can induce spontaneous liver fibrosis in an animal model. To study this, mice were fed either a control diet or a vitamin D deficient diet (VDD diet). For the positive control, liver fibrosis was induced with carbon tetrachloride. Here we show, for the first time, that liver fibrosis spontaneously developed in mice fed the VDD diet. Long-term administration of a VDD diet resulted in necro-inflammation and liver fibrosis. Inflammatory mediators including tumor necrosis factor-α, interleulin-1, interleukin-6, Toll-like-receptor 4, and monocyte chemotactic protein-1 were up-regulated in the livers of the mice fed the VDD diet. Conversely, the expression of Th2/M2 markers such as IL-10, IL-13, arginase 1, and heme oxygenase-1 were down-regulated in the livers of mice fed the VDD diet. Transforming growth factor-β1 and matrix metalloproteinase 13, which are important for fibrosis, were induced in the livers of mice fed the VDD diet. Moreover, the VDD diet triggered apoptosis in the parenchymal cells, in agreement with the increased levels of Fas and FasL, and decreased Bcl2 and Bclx. Thus, long-term vitamin D deficiency can provoke chronic inflammation that can induce liver apoptosis, which consequently activates hepatic stellate cells to initiate liver fibrosis.

  2. Long-term rugby practice enhances bone mass and metabolism in relation with physical fitness and playing position.

    Science.gov (United States)

    Elloumi, Mohamed; Ben Ounis, Omar; Courteix, Daniel; Makni, Emna; Sellami, Saleheddine; Tabka, Zouhair; Lac, Gérard

    2009-01-01

    We attempted to clarify whether rugby was able to enhance bone mineral density (BMD) and content (BMC) of weight-bearing bones by modifying bone remodelling in relation to physical fitness in male rugby players compared to controls. 22 male international rugby players aged 20-31 years (forwards, n = 12 and backs, n = 10) were compared to 14 age-matched controls of the same ethnic origin aged 21-33 years. BMD and BMC were measured by DEXA and bone metabolism was evaluated by specific makers. Physical fitness level was analysed in parallel. Both forwards and backs exhibited significantly higher BMD (+15%, +6%, respectively) and BMC (+36%, +18%, respectively) for whole body and all examined sites, regions and segments than controls, with more pronounced difference at forwards. The difference between both groups of rugby players and controls noted for BMD became more pronounced for BMC (+52% for lower limbs). BMD and BMC values were higher in forwards than backs at total body (+9, +16%) and at stressed sites such as spine (+12%, +13%), pelvis (+10%, +11%), upper (+17% for BMC) and lower limbs (+9%, +18%). Athletes, especially forwards, presented higher concentrations of OC and CTX resulting in positive values of the uncoupling index. Total body lean mass as well as muscular strength strongly correlated with total and stressed regional sites such as spine, pelvis, and lower limbs BMD and BMC (r = 0.59, p Rugby participation is associated with improved physical fitness, enhanced axial and appendicular bone mass and increased bone turnover in adult athletes. Moreover, the positive bone adaptation of these athletes may be related to an increase of bone remodelling rate in favour of bone formation, especially in forwards.

  3. Long-term safety and stability of angiogenesis induced by balanced single-vector co-expression of PDGF-BB and VEGF164 in skeletal muscle

    Science.gov (United States)

    Gianni-Barrera, Roberto; Burger, Maximilian; Wolff, Thomas; Heberer, Michael; Schaefer, Dirk J.; Gürke, Lorenz; Mujagic, Edin; Banfi, Andrea

    2016-01-01

    Therapeutic angiogenesis by growth factor delivery is an attractive treatment strategy for ischemic diseases, yet clinical efficacy has been elusive. The angiogenic master regulator VEGF-A can induce aberrant angiogenesis if expressed above a threshold level. Since VEGF remains localized in the matrix around expressing cells, homogeneous dose distribution in target tissues is required, which is challenging. We found that co-expression of the pericyte-recruiting factor PDGF-BB at a fixed ratio with VEGF from a single bicistronic vector ensured normal angiogenesis despite heterogeneous high VEGF levels. Taking advantage of a highly controlled gene delivery platform, based on monoclonal populations of transduced myoblasts, in which every cell stably produces the same amount of each factor, here we rigorously investigated a) the dose-dependent effects, and b) the long-term safety and stability of VEGF and PDGF-BB co-expression in skeletal muscle. PDGF-BB co-expression did not affect the normal angiogenesis by low and medium VEGF doses, but specifically prevented vascular tumors by high VEGF, yielding instead normal and mature capillary networks, accompanied by robust arteriole formation. Induced angiogenesis persisted unchanged up to 4 months, while no tumors appeared. Therefore, PDGF-BB co-expression is an attractive strategy to improve safety and efficacy of therapeutic angiogenesis by VEGF gene delivery. PMID:26882992

  4. Estradiol attenuates ischemia-induced death of hippocampal neurons and enhances synaptic transmission in aged, long-term hormone-deprived female rats.

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    Tomoko Inagaki

    Full Text Available Transient global forebrain ischemia causes selective, delayed death of hippocampal CA1 pyramidal neurons, and the ovarian hormone 17β-estradiol (E2 reduces neuronal loss in young and middle-aged females. The neuroprotective efficacy of E2 after a prolonged period of hormone deprivation is controversial, and few studies examine this issue in aged animals given E2 treatment after induction of ischemia.The present study investigated the neuroprotective effects of E2 administered immediately after global ischemia in aged female rats (15-18 months after 6 months of hormone deprivation. We also used electrophysiological methods to assess whether CA1 synapses in the aging hippocampus remain responsive to E2 after prolonged hormone withdrawal. Animals were ovariohysterectomized and underwent 10 min global ischemia 6 months later. A single dose of E2 (2.25 µg infused intraventricularly after reperfusion significantly increased cell survival, with 45% of CA1 neurons surviving vs 15% in controls. Ischemia also induced moderate loss of CA3/CA4 pyramidal cells. Bath application of 1 nM E2 onto brain slices derived from non-ischemic aged females after 6 months of hormone withdrawal significantly enhanced excitatory transmission at CA1 synapses evoked by Schaffer collateral stimulation, and normal long-term potentiation (LTP was induced. The magnitude of LTP and of E2 enhancement of field excitatory postsynaptic potentials was indistinguishable from that recorded in slices from young rats.The data demonstrate that 1 acute post-ischemic infusion of E2 into the brain ventricles is neuroprotective in aged rats after 6 months of hormone deprivation; and 2 E2 enhances synaptic transmission in CA1 pyramidal neurons of aged long-term hormone deprived females. These findings provide evidence that the aging hippocampus remains responsive to E2 administered either in vivo or in vitro even after prolonged periods of hormone withdrawal.

  5. Altered mRNA expression after long-term soleus electrical stimulation training in humans with paralysis.

    Science.gov (United States)

    Adams, Christopher M; Suneja, Manish; Dudley-Javoroski, Shauna; Shields, Richard K

    2011-01-01

    In humans, spinal cord injury (SCI) induces deleterious changes in skeletal muscle that may be prevented or reversed by electrical stimulation muscle training. The molecular mechanisms underlying muscle stimulation training remain unknown. We studied two unique SCI subjects whose right soleus received >6 years of training (30 minutes/day, 5 days/week). Training preserved torque, fatigue index, contractile speed, and cross-sectional area in the trained leg, but not the untrained leg. Training decreased 10 mRNAs required for fast-twitch contractions and mRNA that encodes for myostatin, an autocrine/paracrine hormone that inhibits muscle growth. Conversely, training increased 69 mRNAs that mediate the slow-twitch, oxidative phenotype, including PGC-1α, a transcriptional coactivator that inhibits muscle atrophy. When we discontinued right soleus training, training-induced effects diminished slowly, with some persisting for >6 months. Training of paralyzed muscle induces localized and long-lasting changes in skeletal muscle mRNA expression that improve muscle mass and function. Copyright © 2010 Wiley Periodicals, Inc.

  6. Ebi/AP-1 suppresses pro-apoptotic genes expression and permits long-term survival of Drosophila sensory neurons.

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    Young-Mi Lim

    Full Text Available Sensory organs are constantly exposed to physical and chemical stresses that collectively threaten the survival of sensory neurons. Failure to protect stressed neurons leads to age-related loss of neurons and sensory dysfunction in organs in which the supply of new sensory neurons is limited, such as the human auditory system. Transducin β-like protein 1 (TBL1 is a candidate gene for ocular albinism with late-onset sensorineural deafness, a form of X-linked age-related hearing loss. TBL1 encodes an evolutionarily conserved F-box-like and WD40 repeats-containing subunit of the nuclear receptor co-repressor/silencing mediator for retinoid and thyroid hormone receptor and other transcriptional co-repressor complexes. Here we report that a Drosophila homologue of TBL1, Ebi, is required for maintenance of photoreceptor neurons. Loss of ebi function caused late-onset neuronal apoptosis in the retina and increased sensitivity to oxidative stress. Ebi formed a complex with activator protein 1 (AP-1 and was required for repression of Drosophila pro-apoptotic and anti-apoptotic genes expression. These results suggest that Ebi/AP-1 suppresses basal transcription levels of apoptotic genes and thereby protects sensory neurons from degeneration.

  7. Global gene expression analysis of the response of physic nut (Jatropha curcas L.) to medium- and long-term nitrogen deficiency.

    Science.gov (United States)

    Kuang, Qi; Zhang, Sheng; Wu, Pingzhi; Chen, Yaping; Li, Meiru; Jiang, Huawu; Wu, Guojiang

    2017-01-01

    Jatropha curcas L. is an important biofuel plant with excellent tolerance of barren environments. However, studies on the regulatory mechanisms that operate in this plant in response to nitrogen (N) shortage are scarce. In this study, genome-wide transcriptional profiles of the roots and leaves of 8-week old physic nut seedlings were analyzed after 2 and 16 days of N starvation. Enrichment results showed that genes associated with N metabolism, processing and regulation of RNA, and transport predominated among those showing alterations in expression. Genes encoding transporter families underwent major changes in expression in both roots and leaves; in particular, those with roles in ammonia, amino acid and peptide transport were generally up-regulated after long-term starvation, while AQUAPORIN genes, whose products function in osmoregulation, were down-regulated. We also found that ASPARA-GINASE B1 and SARCOSINE OXIDASE genes were up-regulated in roots and leaves after 2 and 16 d N starvation. Genes associated with ubiquitination-mediated protein degradation were significantly up-regulated. In addition, genes in the JA biosynthesis pathway were strongly activated while expression of those in GA signaling was inhibited in leaves. We showed that four major classes of genes, those with roles in N uptake, N reutilization, C/N ratio balance, and cell structure and synthesis, were particularly influenced by long-term N limitation. Our discoveries may offer clues to the molecular mechanisms that regulate N reallocation and reutilization so as to maintain or increase plant performance even under adverse environmental conditions.

  8. Polyvinylidene fluoride/siloxane nanofibrous membranes for long-term continuous CO2 -capture with large absorption-flux enhancement.

    Science.gov (United States)

    Lin, Yi-Feng; Wang, Chi-Sen; Ko, Chia-Chieh; Chen, Chien-Hua; Chang, Kai-Shiun; Tung, Kuo-Lun; Lee, Kueir-Rarn

    2014-02-01

    In a CO2 membrane contactor system, CO2 passes through a hydrophobic porous membrane in the gas phase to contact the amine absorbent in the liquid phase. Consequently, additional CO2 gas is absorbed by amine absorbents. This study examines highly porous polyvinylidene fluoride (PVDF)/siloxane nanofibrous layers that are modified with hydrophobic fluoroalkylsilane (FAS) functional groups and successfully coated onto a macroporous Al2 O3 membrane. The performance of these materials in a membrane contactor system for CO2 absorption is also investigated. Compared with pristine PVDF nanofibrous membranes, the PVDF/siloxane nanofibrous membranes exhibit greater solvent resistance and mechanical strength, making them more suitable for use in CO2 capture by the membrane contactor. The PVDF/siloxane nanofibrous layer in highly porous FAS-modified membranes can prevent the wetting of the membrane by the amine absorbent; this extends the periods of continuous CO2 absorption and results in a high CO2 absorption flux with a minimum of 500 % enhancement over that of the uncoated membranes. This study suggests the potential use of an FAS-modified PVDF/siloxane nanofibrous membrane in a membrane contactor system for CO2 absorption. The resulting hydrophobic membrane contactor also demonstrates the potential for large-scale CO2 absorption during post-combustion processes in power plants. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Muscle tension induced after learning enhances long-term narrative and visual memory in healthy older adults.

    Science.gov (United States)

    Nielson, Kristy A; Wulff, Laura L; Arentsen, Timothy J

    2014-03-01

    Arousing events are better remembered than mundane events. Indeed, manipulation of arousal, such as by muscle tension, can influence memory even when it occurs shortly after learning. Indeed, our founding study showed this approach can raise delayed memory performance in older adults to a level comparable to that of unaided young adults. Yet, systematic studies, especially those investigating different modalities or types of memory, have not been done. This study investigated the effects of a brief bout of isometric exercise via handgrip on narrative and visuospatial episodic memory in healthy elders. Forty-seven participants completed the Logical Memory subtest of the Wechsler Memory Scales III (LM) and the Benton Visual Retention Test (BVRT), followed alternately by no treatment and by moderately squeezing a sand-filled latex ball for 1-min (counterbalanced order and test forms). Isometric exercise significantly increased both positive and negative affect ratings. Retention was tested 2 weeks later. Delayed recall and recognition of LM was enhanced by arousal relative to control, as was recognition of the BVRT. The results extend past findings that muscle tension induced after learning modulates memory consolidation, extending findings in elders to suggest that a simple form of isometric exercise can have practical effects, such as aiding memory for stories and images. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Using single-walled carbon nanotubes nonwoven films as scaffolds to enhance long-term cell proliferation in vitro.

    Science.gov (United States)

    Meng, Jie; Song, Li; Meng, Jie; Kong, Hua; Zhu, Guangjin; Wang, Chaoying; Xu, Lianghua; Xie, Sishen; Xu, Haiyan

    2006-11-01

    Carbon nanotubes have attracted intensive interests in biomedical research in recent years. In this study, a novel type of carbon nanotubes material so called nonwoven single-walled carbon nanotubes (SWNTs) with nanotopographic structure and macroscopic volume was used as cell growing scaffold. The morphology and surface chemistry of nonwoven SWNTs were observed and characterized through scanning electron microscopy and X-ray photoelectron spectroscopy, respectively. The cells were cultivated in nonwoven SWNTs and in other types of substrate as control. The cells growth behaviors including adhesion, proliferation, and cytoskeletal development was investigated by using cell viability assay and confocal observation. The experimental results indicated that nonwoven SWNTs exhibited significant enhancement to the cells adhesion and proliferation in at least 3 weeks. Numerous and highly organized cytoskeletal structures were observed when the cells were cultured in nonwoven SWNTs. Furthermore, an obvious promotional influence of the cells cultivated in nonwoven SWNTs scaffold upon the proliferation of those growing in the other kind of substrate through cell-cell communication had been found. The results obtained in this work are of significance to in vitro cell amplification in large scale, tissue regeneration, or guided repair, as well as biomedical device application.

  11. Long-term effects of sulphide on the enhanced biological removal of phosphorus: The symbiotic role of Thiothrix caldifontis.

    Science.gov (United States)

    Rubio-Rincón, F J; Welles, L; Lopez-Vazquez, C M; Nierychlo, M; Abbas, B; Geleijnse, M; Nielsen, P H; van Loosdrecht, M C M; Brdjanovic, D

    2017-06-01

    Thiothrix caldifontis was the dominant microorganism (with an estimated bio-volume of 65 ± 3%) in a lab-scale enhanced biological phosphorus removal (EBPR) system containing 100 mg of sulphide per litre in the influent. After a gradual exposure to the presence of sulphide, the EBPR system initially dominated by Candidatus Accumulibacter phosphatis Clade I (98 ± 3% bio-volume) (a known polyphosphate accumulating organism, PAO) became enriched with T. caldifontis. Throughout the different operating conditions studied, practically 100% phosphate removal was always achieved. The gradual increase of the sulphide content in the medium (added to the anaerobic stage of the alternating anaerobic-aerobic sequencing batch reactor) and the adjustment of the aerobic hydraulic retention time played a major role in the enrichment of T. caldifontis. T. caldifontis exhibited a mixotrophic metabolism by storing carbon anaerobically as poly-β-hydroxy-alkanoates (PHA) and generating the required energy through the hydrolysis of polyphosphate. PHA was used in the aerobic period as carbon and energy source for growth, polyphosphate, and glycogen formation. Apparently, extra energy was obtained by the initial accumulation of sulphide as an intracellular sulphur, followed by its gradual oxidation to sulphate. The culture enriched with T. caldifontis was able to store approximately 100 mg P/g VSS. This research suggests that T. caldifontis could behave like PAO with a mixotrophic metabolism for phosphorus removal using an intracellular sulphur pool as energy source. These findings can be of major interest for the biological removal of phosphorus from wastewaters with low organic carbon concentrations containing reduced S-compounds like those (pre-)treated in anaerobic systems or from anaerobic sewers. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  12. Long-term effects of gestational nicotine exposure and food-restriction on gene expression in the striatum of adolescent rats.

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    Nicholas E Ilott

    Full Text Available Gestational exposure to environmental toxins such as nicotine may result in detectable gene expression changes in later life. To investigate the direct toxic effects of prenatal nicotine exposure on later brain development, we have used transcriptomic analysis of striatal samples to identify gene expression differences between adolescent Lister Hooded rats exposed to nicotine in utero and controls. Using an additional group of animals matched for the reduced food intake experienced in the nicotine group, we were also able to assess the impact of imposed food-restriction on gene expression profiles. We found little evidence for a role of gestational nicotine exposure on altered gene expression in the striatum of adolescent offspring at a significance level of p0.5|, although we cannot exclude the possibility of nicotine-induced changes in other brain regions, or at other time points. We did, however, find marked gene expression differences in response to imposed food-restriction. Food-restriction resulted in significant group differences for a number of immediate early genes (IEGs including Fos, Fosb, Fosl2, Arc, Junb, Nr4a1 and Nr4a3. These genes are associated with stress response pathways and therefore may reflect long-term effects of nutritional deprivation on the development of the stress system.

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

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    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.

  14. Response of aboveground carbon balance to long-term, experimental enhancements in precipitation seasonality is contingent on plant community type in cold-desert rangelands

    Science.gov (United States)

    McAbee, Kathryn; Reinhardt, Keith; Germino, Matthew; Bosworth, Andrew

    2017-01-01

    Semi-arid rangelands are important carbon (C) pools at global scales. However, the degree of net C storage or release in water-limited systems is a function of precipitation amount and timing, as well as plant community composition. In northern latitudes of western North America, C storage in cold-desert ecosystems could increase with boosts in wintertime precipitation, in which climate models predict, due to increases in wintertime soil water storage that enhance summertime productivity. However, there are few long-term, manipulative field-based studies investigating how rangelands will respond to altered precipitation amount or timing. We measured aboveground C pools and fluxes at leaf, soil, and ecosystem scales over a single growing season in plots that had 200 mm of supplemental precipitation added in either winter or summer for the past 21 years, in shrub- and exotic-bunchgrass-dominated garden plots. At our cold-desert site (298 mm precipitation during the study year), we hypothesized that increased winter precipitation would stimulate the aboveground C uptake and storage relative to ambient conditions, especially in plots containing shrubs. Our hypotheses were generally supported: ecosystem C uptake and long-term biomass accumulation were greater in winter- and summer-irrigated plots compared to control plots in both vegetation communities. However, substantial increases in the aboveground biomass occurred only in winter-irrigated plots that contained shrubs. Our findings suggest that increases in winter precipitation will enhance C storage of this widespread ecosystem, and moreso in shrub- compared to grass-dominated communities.

  15. 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

  16. Response of aboveground carbon balance to long-term, experimental enhancements in precipitation seasonality is contingent on plant community type in cold-desert rangelands.

    Science.gov (United States)

    McAbee, Kathryn; Reinhardt, Keith; Germino, Matthew J; Bosworth, Andrew

    2017-03-01

    Semi-arid rangelands are important carbon (C) pools at global scales. However, the degree of net C storage or release in water-limited systems is a function of precipitation amount and timing, as well as plant community composition. In northern latitudes of western North America, C storage in cold-desert ecosystems could increase with boosts in wintertime precipitation, in which climate models predict, due to increases in wintertime soil water storage that enhance summertime productivity. However, there are few long-term, manipulative field-based studies investigating how rangelands will respond to altered precipitation amount or timing. We measured aboveground C pools and fluxes at leaf, soil, and ecosystem scales over a single growing season in plots that had 200 mm of supplemental precipitation added in either winter or summer for the past 21 years, in shrub- and exotic-bunchgrass-dominated garden plots. At our cold-desert site (298 mm precipitation during the study year), we hypothesized that increased winter precipitation would stimulate the aboveground C uptake and storage relative to ambient conditions, especially in plots containing shrubs. Our hypotheses were generally supported: ecosystem C uptake and long-term biomass accumulation were greater in winter- and summer-irrigated plots compared to control plots in both vegetation communities. However, substantial increases in the aboveground biomass occurred only in winter-irrigated plots that contained shrubs. Our findings suggest that increases in winter precipitation will enhance C storage of this widespread ecosystem, and moreso in shrub- compared to grass-dominated communities.

  17. Long-term omega-3 supplementation modulates behavior, hippocampal fatty acid concentration, neuronal progenitor proliferation and central TNF-α expression in 7 month old unchallenged mice

    Directory of Open Access Journals (Sweden)

    Trent eGrundy

    2014-11-01

    Full Text Available Dietary polyunsaturated fatty acid (PUFA manipulation is being investigated as a potential therapeutic supplement to reduce the risk of developing age-related cognitive decline (ARCD. Animal studies suggest that high omega (Ω-3 and low Ω-6 dietary content reduces cognitive decline by decreasing central nervous system (CNS inflammation and modifying neuroimmune activity. However, no previous studies have investigated the long term effects of Ω-3 and Ω-6 dietary levels in healthy aging mice leaving the important question about the preventive effects of Ω-3 and Ω-6 on behavior and underlying molecular pathways unaddressed. We aimed to investigate the efficacy of long-term Ω-3 and Ω-6 PUFA dietary supplementation in mature adult C57BL/6 mice. We measured the effect of low, medium and high Ω-3:Ω-6 dietary ratio, given from the age of 3 to 7 months, on anxiety and cognition-like behavior, hippocampal tissue expression of TNF-α, markers of neuronal progenitor proliferation and gliogenesis and serum cytokine concentration. Our results show that a higher Ω-3:Ω-6 PUFA diet ratio increased hippocampal PUFA, increased anxiety, improved hippocampal dependent spatial memory and reduced hippocampal TNF-α levels compared to a low Ω-3:Ω-6 diet. Furthermore, serum TNF-α concentration was reduced in the higher Ω-3:Ω-6 PUFA ratio supplementation group while expression of the neuronal progenitor proliferation markers KI67 and doublecortin (DCX was increased in the dentate gyrus as opposed to the low Ω-3:Ω-6 group. Conversely, Ω-3:Ω-6 dietary PUFA ratio had no significant effect on astrocyte or microglia number or cell death in the dentate gyrus. These results suggest that supplementation of PUFAs may delay ageing effects on cognitive function in unchallenged mature adult C57BL/6 mice. This effect is possibly induced by increasing neuronal progenitor proliferation and reducing TNF-α.

  18. Long-term omega-3 supplementation modulates behavior, hippocampal fatty acid concentration, neuronal progenitor proliferation and central TNF-α expression in 7 month old unchallenged mice.

    Science.gov (United States)

    Grundy, Trent; Toben, Catherine; Jaehne, Emily J; Corrigan, Frances; Baune, Bernhard T

    2014-01-01

    Dietary polyunsaturated fatty acid (PUFA) manipulation is being investigated as a potential therapeutic supplement to reduce the risk of developing age-related cognitive decline (ARCD). Animal studies suggest that high omega (Ω)-3 and low Ω-6 dietary content reduces cognitive decline by decreasing central nervous system (CNS) inflammation and modifying neuroimmune activity. However, no previous studies have investigated the long term effects of Ω-3 and Ω-6 dietary levels in healthy aging mice leaving the important question about the preventive effects of Ω-3 and Ω-6 on behavior and underlying molecular pathways unaddressed. We aimed to investigate the efficacy of long-term Ω-3 and Ω-6 PUFA dietary supplementation in mature adult C57BL/6 mice. We measured the effect of low, medium, and high Ω-3:Ω-6 dietary ratio, given from the age of 3-7 months, on anxiety and cognition-like behavior, hippocampal tissue expression of TNF-α, markers of neuronal progenitor proliferation and gliogenesis and serum cytokine concentration. Our results show that a higher Ω-3:Ω-6 PUFA diet ratio increased hippocampal PUFA, increased anxiety, improved hippocampal dependent spatial memory and reduced hippocampal TNF-α levels compared to a low Ω-3:Ω-6 diet. Furthermore, serum TNF-α concentration was reduced in the higher Ω-3:Ω-6 PUFA ratio supplementation group while expression of the neuronal progenitor proliferation markers KI67 and doublecortin (DCX) was increased in the dentate gyrus as opposed to the low Ω-3:Ω-6 group. Conversely, Ω-3:Ω-6 dietary PUFA ratio had no significant effect on astrocyte or microglia number or cell death in the dentate gyrus. These results suggest that supplementation of PUFAs may delay aging effects on cognitive function in unchallenged mature adult C57BL/6 mice. This effect is possibly induced by increasing neuronal progenitor proliferation and reducing TNF-α.

  19. Long-term omega-3 supplementation modulates behavior, hippocampal fatty acid concentration, neuronal progenitor proliferation and central TNF-α expression in 7 month old unchallenged mice

    Science.gov (United States)

    Grundy, Trent; Toben, Catherine; Jaehne, Emily J.; Corrigan, Frances; Baune, Bernhard T.

    2014-01-01

    Dietary polyunsaturated fatty acid (PUFA) manipulation is being investigated as a potential therapeutic supplement to reduce the risk of developing age-related cognitive decline (ARCD). Animal studies suggest that high omega (Ω)-3 and low Ω-6 dietary content reduces cognitive decline by decreasing central nervous system (CNS) inflammation and modifying neuroimmune activity. However, no previous studies have investigated the long term effects of Ω-3 and Ω-6 dietary levels in healthy aging mice leaving the important question about the preventive effects of Ω-3 and Ω-6 on behavior and underlying molecular pathways unaddressed. We aimed to investigate the efficacy of long-term Ω-3 and Ω-6 PUFA dietary supplementation in mature adult C57BL/6 mice. We measured the effect of low, medium, and high Ω-3:Ω-6 dietary ratio, given from the age of 3–7 months, on anxiety and cognition-like behavior, hippocampal tissue expression of TNF-α, markers of neuronal progenitor proliferation and gliogenesis and serum cytokine concentration. Our results show that a higher Ω-3:Ω-6 PUFA diet ratio increased hippocampal PUFA, increased anxiety, improved hippocampal dependent spatial memory and reduced hippocampal TNF-α levels compared to a low Ω-3:Ω-6 diet. Furthermore, serum TNF-α concentration was reduced in the higher Ω-3:Ω-6 PUFA ratio supplementation group while expression of the neuronal progenitor proliferation markers KI67 and doublecortin (DCX) was increased in the dentate gyrus as opposed to the low Ω-3:Ω-6 group. Conversely, Ω-3:Ω-6 dietary PUFA ratio had no significant effect on astrocyte or microglia number or cell death in the dentate gyrus. These results suggest that supplementation of PUFAs may delay aging effects on cognitive function in unchallenged mature adult C57BL/6 mice. This effect is possibly induced by increasing neuronal progenitor proliferation and reducing TNF-α. PMID:25484856

  20. 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...

  1. 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...

  2. 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...

  3. Long-term colonization of the cystic fibrosis lung by Burkholderia cepacia complex bacteria: epidemiology, clonal variation, and genome-wide expression alterations.

    Science.gov (United States)

    Coutinho, Carla P; Dos Santos, Sandra C; Madeira, Andreia; Mira, Nuno P; Moreira, Ana S; Sá-Correia, Isabel

    2011-01-01

    Long-term respiratory infections with Burkholderia cepacia complex (Bcc) bacteria in cystic fibrosis (CF) patients generally lead to a more rapid decline in lung function and, in some cases, to a fatal necrotizing pneumonia known as the "cepacia syndrome." Bcc bacteria are ubiquitous in the environment and are recognized as serious opportunistic pathogens that are virtually impossible to eradicate from the CF lung, posing a serious clinical threat. The epidemiological survey of Bcc bacteria involved in respiratory infections at the major Portuguese CF Treatment Center at Santa Maria Hospital, in Lisbon, has been carried out by our research group for the past 16 years, covering over 500 clinical isolates where B. cepacia and B. cenocepacia are the predominant species, with B. stabilis, B. contaminans, B. dolosa, and B. multivorans also represented. The systematic and longitudinal study of this CF population during such an extended period of time represents a unique case-study, comprehending 41 Bcc-infected patients (29 pediatric and 12 adult) of whom around 70% have been persistently colonized between 7 months and 9 years. During chronic infection, the CF airways represent an evolving ecosystem, with multiple phenotypic variants emerging from the clonal population and becoming established in the patients' airways as the result of genetic adaptation. Understanding the evolutionary mechanisms involved is crucial for an improved therapeutic outcome of chronic infections in CF. This review focuses on our contribution to the understanding of these adaptive mechanisms based on extensive phenotypic, genotypic, and genome-wide expression approaches of selected Bcc clonal variants obtained during long-term colonization of the CF airways.

  4. Long-term electromagnetic field treatment enhances brain mitochondrial function of both Alzheimer's transgenic mice and normal mice: a mechanism for electromagnetic field-induced cognitive benefit?

    Science.gov (United States)

    Dragicevic, N; Bradshaw, P C; Mamcarz, M; Lin, X; Wang, L; Cao, C; Arendash, G W

    2011-06-30

    We have recently reported that long-term exposure to high frequency electromagnetic field (EMF) treatment not only prevents or reverses cognitive impairment in Alzheimer's transgenic (Tg) mice, but also improves memory in normal mice. To elucidate the possible mechanism(s) for these EMF-induced cognitive benefits, brain mitochondrial function was evaluated in aged Tg mice and non-transgenic (NT) littermates following 1 month of daily EMF exposure. In Tg mice, EMF treatment enhanced brain mitochondrial function by 50-150% across six established measures, being greatest in cognitively-important brain areas (e.g. cerebral cortex and hippocampus). EMF treatment also increased brain mitochondrial function in normal aged mice, although the enhancement was not as robust and less widespread compared to that of Tg mice. The EMF-induced enhancement of brain mitochondrial function in Tg mice was accompanied by 5-10 fold increases in soluble Aβ1-40 within the same mitochondrial preparations. These increases in mitochondrial soluble amyloid-β peptide (Aβ) were apparently due to the ability of EMF treatment to disaggregate Aβ oligomers, which are believed to be the form of Aβ causative to mitochondrial dysfunction in Alzheimer's disease (AD). Finally, the EMF-induced mitochondrial enhancement in both Tg and normal mice occurred through non-thermal effects because brain temperatures were either stable or decreased during/after EMF treatment. These results collectively suggest that brain mitochondrial enhancement may be a primary mechanism through which EMF treatment provides cognitive benefit to both Tg and NT mice. Especially in the context that mitochondrial dysfunction is an early and prominent characteristic of Alzheimer's pathogenesis, EMF treatment could have profound value in the disease's prevention and treatment through intervention at the mitochondrial level. Copyright © 2011 IBRO. All rights reserved.

  5. Caffeine suppresses exercise-enhanced long-term and location memory in middle-aged rats: Involvement of hippocampal Akt and CREB signaling.

    Science.gov (United States)

    Cechella, José L; Leite, Marlon R; da Rocha, Juliana T; Dobrachinski, Fernando; Gai, Bibiana M; Soares, Félix A A; Bresciani, Guilherme; Royes, Luiz F F; Zeni, Gilson

    2014-11-05

    The cognitive function decline is closely related with brain changes generated by age. The ability of caffeine and exercise to prevent memory impairment has been reported in animal models and humans. The purpose of the present study was to investigate whether swimming exercise and caffeine administration enhance memory in middle-aged Wistar rats. Male Wistar rats (18months) received caffeine at a dose of 30mg/kg, 5days per week by a period of 4weeks. Animals were subjected to swimming training with a workload (3% of body weight, 20min per day for 4weeks). After 4weeks, the object recognition test (ORT) and the object location test (OLT) were performed. The results of this study demonstrated that caffeine suppressed exercise-enhanced long-term (ORT) and spatial (OLT) memory in middle-aged and this effect may be related to a decrease in hippocampal p-CREB signaling. This study also provided evidence that the effects of this protocol on memory were not accompanied by alterations in the levels of activated Akt. The [(3)H] glutamate uptake was reduced in hippocampus of rats administered with caffeine and submitted to swimming protocol. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  6. Damage to the vestibular inner ear causes long-term changes in neuronal nitric oxide synthase expression in the rat hippocampus.

    Science.gov (United States)

    Zheng, Y; Horii, A; Appleton, I; Darlington, C L; Smith, P F

    2001-01-01

    The vestibular inner ear detects head acceleration and initiates compensatory eye movement and postural reflexes that help keep the visual image of the world stable on the retina, and maintain balance, during unexpected head movement. The most primitive vestibular systems are estimated to have evolved more than 500 million years ago and in mammalian and submammalian species the vestibular reflexes are mediated by basic brainstem pathways (see Wilson and Melvill Jones, 1979 for review). Although the contributions of the vestibular system to higher cognitive function have generally received less attention than its reflexive roles, vestibular sensory information is transmitted to higher centres in the brain and humans with vestibular damage are known to experience debilitating perceptual illusions (see Curthoys and Halmagyi, 1995; Berthoz, 1996 for reviews). Increasing behavioural and neurophysiological evidence suggests that the hippocampus uses information from the vestibular inner ear in order to build up maps of space that can be used in the development of spatial memory during learning tasks (McNaughton et al., 1991; Chapuis et al., 1992; Wiener and Berthoz, 1993; O'Mara et al., 1994; Wiener et al., 1995; Gavrilov et al., 1995; Stackman and Taube, 1996; Vitte et al., 1996; Taube et al., 1996; Save et al., 1998; Peruch et al., 1999; Cuthbert et al., 2000; Russell et al., 2000). However, to date, there has been no indication of the long-term neurochemical effects of the loss of vestibular input on hippocampal function. Since nitric oxide has been implicated in the mechanisms of hippocampal synaptic plasticity associated with the development of short-term memory (e.g. Schuman and Madison, 1991; Schuman et al., 1994; Arancio et al., 1996; Wu et al., 1997; Lu et al., 1999), we examined whether changes occur in the activity and expression of the enzymes responsible for nitric oxide production (nitric oxide synthases) in subregions of the rat hippocampus at different

  7. Role of cognitive enhancer therapy in Alzheimer's disease with concomitant cerebral white matter disease: findings from a long-term naturalistic study.

    Science.gov (United States)

    Ng, Kok Pin; Ng, Aloysius; Assam, Pryseley; Heng, Esther; Kandiah, Nagaendran

    2014-09-01

    Evidence is lacking for cognitive enhancer therapy in patients with Alzheimer's disease (AD) and concomitant cerebrovascular disease (mixed AD) as such patients would have been excluded from clinical trials. Earlier studies of mixed AD have focused on large vessel cerebrovascular disease. The influence of small vessel cerebrovascular disease (svCVD) in the form of white matter hyperintensity (WMH) on treatment outcomes in mixed AD has not been addressed. In this long-term naturalistic study, we evaluated the effectiveness of cognitive enhancers in patients with mixed AD with svCVD. We conducted a retrospective analysis of a prospective clinical database from a memory clinic of a tertiary hospital. Magnetic resonance imaging WMH was used as a marker of svCVD. Demographic, cognitive, and treatment data were analysed. Linear mixed models with patient-specific random effects were used to evaluate cognitive outcomes over time while adjusting for confounders. Patients with mixed AD (n = 137) or AD without svCVD (pure AD) (n = 28) were studied over a median duration of 28.7 months. Patients with mixed AD had a higher prevalence of hypertension (62.8 vs. 35.7 %, p = 0.011). The majority (75.2 %) of the study sample were managed with monotherapy. Mini Mental State Examination (MMSE) scores decreased over time (-0.04, p = 0.007), and the decrease was similar for both diagnosis groups (-0.03, p = 0.246). Annual estimated mean MMSE decline was 0.84 for pure AD and 0.48 for mixed AD. Similar trends were observed with Montreal Cognitive Assessment (MoCA) scores, with annual estimated mean reduction of 0.72 and 0.48 for pure AD and mixed AD, respectively. Cognitive enhancers are effective in slowing the rate of cognitive decline in patients with AD with svCVD. These findings would need to be confirmed in randomized clinical trials.

  8. 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 ...

  9. Long-Term Over-Expression of Neuropeptide Y in Hypothalamic Paraventricular Nucleus Contributes to Adipose Tissue Insulin Resistance Partly via the Y5 Receptor.

    Directory of Open Access Journals (Sweden)

    Min Long

    Full Text Available Intracerebroventricular injection and overexpression of Neuropeptide Y (NPY in the paraventricular nucleus (PVN has been shown to induce obesity and glucose metabolism disorder in rodents; however, the underlying mechanisms are still unclear. The aim of this study was to investigate the mechanism contributing to glucose metabolic disturbance induced by NPY. Recombinant lentiviral NPY vectors were injected into the PVN of rats fed a high fat (HFD or low-fat diet. 8 weeks later, in vivo intravenous glucose tolerance tests and euglycemic-hyperinsulinemic clamp revealed that insulin resistance of adipose tissue were induced by NPY overexpression with or without HFD. NPY increased food intake, but did not change blood glucose, glycated hemoglobin A1c (HbA1c or lipid levels. However, NPY decreased the expression of pGSK3β, PI3K p85 and pAKTSer473 in adipose tissue of rats. In vitro, 3T3-L1 adipocytes were treated with NPY, NPY Y1 and Y5 receptor antagonists. Glucose consumption and 2-deoxy-D-[3H] glucose uptake were partly inhibited by NPY, while a decrease in PI3K-AKT pathway signaling and a decreased expression of pGSK3α and pGSK3β were observed. Nevertheless, a Y5 receptor antagonist (L-152,804 reversed the effects of NPY on glucose uptake and consumption. These data suggest that long-term over-expression of NPY in PVN contributes to the establishment of adipose tissue insulin resistance, at least partly via the Y5 Receptor.

  10. Long-term Neuroglial Cocultures as a Brain Aging Model: Hallmarks of Senescence, MicroRNA Expression Profiles, and Comparison With In Vivo Models.

    Science.gov (United States)

    Bigagli, Elisabetta; Luceri, Cristina; Scartabelli, Tania; Dolara, Piero; Casamenti, Fiorella; Pellegrini-Giampietro, Domenico E; Giovannelli, Lisa

    2016-01-01

    Our purpose was to evaluate long-term neuroglial cocultures as a model for investigating senescence in the nervous system and to assess its similarities with in vivo models. To this aim, we maintained the cultures from 15 days in vitro (mature cultures) up to 27 days in vitro (senescent cultures), measuring senescence-associated, neuronal, dendritic, and astrocytic markers. Whole microRNA expression profiles were compared with those measured in the cortex of 18- and 24-month-old C57Bl/6J aged mice and of transgenic TgCRND8 mice, a model of amyloid-β deposition. Neuroglial cocultures displayed features of cellular senescence (increased senescence-associated-β-galactosidase activity, oxidative stress, γ-H2AX expression, IL-6 production, astrogliosis) that were concentration dependently counteracted by the antiaging compound resveratrol (1-5 µM). Among the 1,080 microRNAs analyzed, 335 were downregulated or absent in 27 compared with 15 days in vitro and resveratrol reversed this effect. A substantial overlapping was found between age-associated changes in microRNA expression profiles in vitro and in TgCRND8 mice but not in physiologically aged mice, indicating that this culture model displays more similarities with pathological than physiological brain aging. Our results demonstrate that neuroglial cocultures aged in vitro can be useful for investigating the cellular and molecular mechanisms of brain aging and for preliminary testing of protective compounds. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  11. Acute and long-term effects of adolescent methylphenidate on decision-making and dopamine receptor mRNA expression in the orbitofrontal cortex.

    Science.gov (United States)

    Amodeo, Leslie R; Jacobs-Brichford, Eliza; McMurray, Matthew S; Roitman, Jamie D

    2017-05-01

    Though commonly used as a treatment for ADHD, the psychostimulant methylphenidate (MPH) is also misused and abused in adolescence in both clinical and general populations. Although MPH acts via pathways activated by other drugs of abuse, the short- and long-term effects of MPH on reward processing in learning and decision-making are not clearly understood. We examined the effect of adolescent MPH treatment on a battery of reward-directed behaviors both in adolescence during its administration and in adulthood after its discontinuation. We further measured whether MPH had lasting effects on dopamine receptor mRNA expression in orbitofrontal cortex (OFC) that may correspond with behavior. Long-Evans rats were injected with MPH (0, 1, 2.5, or 5mg/kg IP) twice daily from middle to late adolescence (PD38-57). During adolescence, the high dose of MPH reduced preference for large rewards in a Reward Magnitude Discrimination task, but did not affect preference for smaller-sooner rewards in a Delay Discounting task. In adulthood, after discontinuation of MPH, animals previously treated with the moderate dose of MPH showed improved acquisition, but not reversal, in a Reversal Learning task. MPH exposure did not increase preference for large-risky rewards in a Risk task in adulthood. We then quantified mRNA expression of D1, D2, and D3 receptors in the OFC using qPCR. MPH increased mRNA expression of dopamine D3 receptor subtype, but not D1 or D2. Overall, these results indicate that MPH has both immediate and lasting effects on reward-dependent learning and decisions, as well as dopaminergic function in rodents. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Long-term expression and repeated administration of AAV type 1, 2 and 5 vectors in skeletal muscle of immunocompetent adult mice.

    Science.gov (United States)

    Rivière, C; Danos, O; Douar, A M

    2006-09-01

    Adeno-associated viral (AAV) vectors promote long-term gene transfer into muscle in many animal species. Increased expression levels may be obtained by using alternative serotypes in combination with repeated administrations. Here we compared AAV vectors based on serotypes 1, 2 and 5 in immunocompetent mice and assessed the feasibility of multiple administrations of either identical (readministration) or different (cross-administration) serotype-based vectors. A 1-year-long dose-response study confirmed the superiority of recombinant (r)AAV1, achieving transduction levels 5 to 10-fold higher than rAAV2 and rAAV5 in mouse skeletal muscle, respectively. Repeated administration demonstrated that increased gene transfer level was achieved with a second injection of rAAV1 following the first administration of rAAV2 or rAAV5. A readministration study with a vector encoding a different gene allowed the evaluation of gene expression from the second vector only. All three rAAVs were inhibited when the animals were previously exposed to the same serotype. In contrast, no significant change in gene expression from the second vector was observed in cross-administration. A humoral immune response was elicited against the viral capsid for all three serotypes following the initial exposure. Neutralizing antibody (NAB) levels correlated with the vector dose injected. No significant cross-reactivity of NAB from a given serotype toward another was observed in vitro. These data provide the first direct comparative evaluation of re- and cross-administration of rAAV1, rAAV2 and rAAV5 in muscle, and further indicate that rAAV1 is capable of transducing muscle tissue when cross-administered.

  13. 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.

  14. Circular siRNAs for Reducing Off-Target Effects and Enhancing Long-Term Gene Silencing in Cells and Mice.

    Science.gov (United States)

    Zhang, Liangliang; Liang, Duanwei; Chen, Changmai; Wang, Yuan; Amu, Gubu; Yang, Jiali; Yu, Lijia; Dmochowski, Ivan J; Tang, Xinjing

    2018-03-02

    Circular non-coding RNAs are found to play important roles in biology but are still relatively unexplored as a structural motif for chemically regulating gene function. Here, we investigated whether small interfering RNA (siRNA) with a circular structure can circumvent off-target gene silencing, a problem often observed with standard linear duplex siRNA. In the present work, we, for the first time, synthesized a series of circular siRNAs by cyclizing two ends of a single-stranded RNA (sense or antisense strand) to construct circular siRNAs that were more resistant to enzymatic degradation. Gene silencing of GFP and luciferase was successfully achieved using these circular siRNAs with circular sense strand RNAs and their complementary linear antisense strand RNAs. The off-target effect of sense strand RNAs was evaluated and no cross off-target effects were observed. In addition, we successfully achieved longer gene-silencing efficiency in mice with circular siRNAs than with linear siRNAs. These results indicate the promise of circular siRNAs for overcoming off-target effects of siRNAs and enhancing the possible long-term effect of siRNA gene silencing in basic research and drug development. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  15. Growth enhancement of Picea abies trees under long-term, low-dose N addition is due to morphological more than to physiological changes.

    Science.gov (United States)

    Krause, Kim; Cherubini, Paolo; Bugmann, Harald; Schleppi, Patrick

    2012-12-01

    Human activities have drastically increased nitrogen (N) inputs into natural and near-natural terrestrial ecosystems such that critical loads are now being exceeded in many regions of the world. This implies that these ecosystems are shifting from natural N limitation to eutrophication or even N saturation. This process is expected to modify the growth of forests and thus, along with management, to affect their carbon (C) sequestration. However, knowledge of the physiological mechanisms underlying tree response to N inputs, especially in the long term, is still lacking. In this study, we used tree-ring patterns and a dual stable isotope approach (δ(13)C and δ(18)O) to investigate tree growth responses and the underlying physiological reactions in a long-term, low-dose N addition experiment (+23 kg N ha(-1) a(-1)). This experiment has been conducted for 14 years in a mountain Picea abies (L.) Karst. forest in Alptal, Switzerland, using a paired-catchment design. Tree stem C sequestration increased by ∼22%, with an N use efficiency (NUE) of ca. 8 kg additional C in tree stems per kg of N added. Neither earlywood nor latewood δ(13)C values changed significantly compared with the control, indicating that the intrinsic water use efficiency (WUE(i)) (A/g(s)) did not change due to N addition. Further, the isotopic signal of δ(18)O in early- and latewood showed no significant response to the treatment, indicating that neither stomatal conductance nor leaf-level photosynthesis changed significantly. Foliar analyses showed that needle N concentration significantly increased in the fourth to seventh treatment year, accompanied by increased dry mass and area per needle, and by increased tree height growth. Later, N concentration and height growth returned to nearly background values, while dry mass and area per needle remained high. Our results support the hypothesis that enhanced stem growth caused by N addition is mainly due to an increased leaf area index (LAI

  16. Persistence of Amygdala-Hippocampal Connectivity and Multi-Voxel Correlation Structures During Awake Rest After Fear Learning Predicts Long-Term Expression of Fear

    NARCIS (Netherlands)

    Hermans, E.J.; Kanen, J.W.; Tambini, A.; Fernandez, G.; Davachi, L.; Phelps, E.A.

    2017-01-01

    After encoding, memories undergo a process of consolidation that determines long-term retention. For conditioned fear, animal models postulate that consolidation involves reactivations of neuronal assemblies supporting fear learning during postlearning "offline" periods. However, no human studies to

  17. 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.

  18. Viral-mediated Zif268 expression in the prefrontal cortex protects against gonadectomy-induced working memory, long-term memory, and social interaction deficits in male rats.

    Science.gov (United States)

    Dossat, Amanda M; Jourdi, Hussam; Wright, Katherine N; Strong, Caroline E; Sarkar, Ambalika; Kabbaj, Mohamed

    2017-01-06

    In humans, some males experience reductions in testosterone levels, as a natural consequence of aging or in the clinical condition termed hypogonadism, which are associated with impaired cognitive performance and mood disorder(s). Some of these behavioral deficits can be reversed by testosterone treatment. Our previous work in rats reported that sex differences in the expression of the transcription factor Zif268, a downstream target of testosterone, within the medial prefrontal cortex (mPFC) mediates sex differences in social interaction. In the present study, we aimed to examine the effects of gonadectomy (GNX) in male rats on mPFC Zif268 expression, mood and cognitive behaviors. We also examined whether reinstitution of Zif268 in GNX rats will correct some of the behavioral deficits observed following GNX. Our results show that GNX induced a downregulation of Zif268 protein in the mPFC, which was concomitant with impaired memory in the y-maze and spontaneous object recognition test, reduced social interaction time, and depression-like behaviors in the forced swim test. Reinstitution of mPFC Zif268, using a novel adeno-associated-viral (AAV) construct, abrogated GNX-induced working memory and long-term memory impairments, and reductions in social interaction time, but not GNX-induced depression-like behaviors. These findings suggest that mPFC Zif268 exerts beneficial effects on memory and social interaction, and could be a potential target for novel treatments for behavioral impairments observed in hypogonadal and aged men with declining levels of gonadal hormones. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  19. Enhancing hepatic fibrosis in spontaneously hypertensive rats fed a choline-deficient diet: a follow-up report on long-term effects of oxidative stress in non-alcoholic fatty liver disease.

    Science.gov (United States)

    Yamamoto, Hiroya; Kanno, Keishi; Ikuta, Takuya; Arihiro, Koji; Sugiyama, Akiko; Kishikawa, Nobusuke; Tazuma, Susumu

    2016-05-01

    We previously reported a model of non-alcoholic fatty liver disease (NAFLD) using spontaneously hypertensive rats (SHRs), fed a choline-deficient (CD) diet for 5 weeks, that hepatic steatosis but not fibrosis is developed through oxidative stress. To determine the relationship between hypertension and hepatic fibrosis in NAFLD, we examined whether long-term CD diet leads to hepatic fibrosis through oxidative stress. Eight-week-old male SHR and normotensive Wistar Kyoto rats (WKYs) were fed a CD diet for 5 or 20 weeks, then liver histology and hepatic expression of genes related to lipid metabolism, fibrosis, and oxidative stress were assessed. Oxidative stress was assessed by hepatic thiobarbituric acid reactive substance (TBARS) levels. After 5 weeks on CD diet, prominent hepatic steatosis and decrease in expression of genes for lipid metabolism were observed in SHRs as compared with WKYs. SHRs on a CD diet demonstrated a downregulated expression of genes for antioxidants, along with significant increases in hepatic TBARS. After 20 weeks on CD diet, SHRs demonstrated severe liver fibrosis and upregulated expressions of genes for fibrosis when compared with WKY. Hypertension precipitated hepatic steatosis, and further, acts as an enhancer in NAFLD progression to liver fibrosis through oxidative stress. © 2016 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

  20. Early calcium increase triggers the formation of olfactory long-term memory in honeybees.

    Science.gov (United States)

    Perisse, Emmanuel; Raymond-Delpech, Valérie; Néant, Isabelle; Matsumoto, Yukihisa; Leclerc, Catherine; Moreau, Marc; Sandoz, Jean-Christophe

    2009-06-16

    Synaptic plasticity associated with an important wave of gene transcription and protein synthesis underlies long-term memory processes. Calcium (Ca2+) plays an important role in a variety of neuronal functions and indirect evidence suggests that it may be involved in synaptic plasticity and in the regulation of gene expression correlated to long-term memory formation. The aim of this study was to determine whether Ca2+ is necessary and sufficient for inducing long-term memory formation. A suitable model to address this question is the Pavlovian appetitive conditioning of the proboscis extension reflex in the honeybee Apis mellifera, in which animals learn to associate an odor with a sucrose reward. By modulating the intracellular Ca2+ concentration ([Ca2+]i) in the brain, we show that: (i) blocking [Ca2+]i increase during multiple-trial conditioning selectively impairs long-term memory performance; (ii) conversely, increasing [Ca2+]i during single-trial conditioning triggers long-term memory formation; and finally, (iii) as was the case for long-term memory produced by multiple-trial conditioning, enhancement of long-term memory performance induced by a [Ca2+]i increase depends on de novo protein synthesis. Altogether our data suggest that during olfactory conditioning Ca2+ is both a necessary and a sufficient signal for the formation of protein-dependent long-term memory. Ca2+ therefore appears to act as a switch between short- and long-term storage of learned information.

  1. Randomized-controlled trial of mindfulness-based cancer recovery versus supportive expressive group therapy among distressed breast cancer survivors (MINDSET): long-term follow-up results.

    Science.gov (United States)

    Carlson, Linda E; Tamagawa, Rie; Stephen, Joanne; Drysdale, Elaine; Zhong, Lihong; Speca, Michael

    2016-07-01

    Mindfulness-based cancer recovery (MBCR) and supportive expressive group therapy (SET) are two well-validated psychosocial interventions, but they have not been directly compared, and little is known about long-term outcomes. This comparative effectiveness study measured the effects of these two interventions immediately following the groups and for 1 year thereafter in distressed breast cancer survivors. Two hundred fifty-two distressed Stage I-III breast cancer survivors were randomized into either MBCR or SET. Women completed questionnaires addressing mood, stress symptoms, quality of life, social support, spirituality and post-traumatic growth before and after the interventions, and 6 and 12 months later. Immediately following the intervention, women in MBCR reported greater reduction in mood disturbance (primarily fatigue, anxiety and confusion) and stress symptoms including tension, sympathetic arousal and cognitive symptoms than those in SET. They also reported increased emotional and functional quality of life, emotional, affective and positive social support, spirituality (feelings of peace and meaning in life) and post-traumatic growth (appreciation for life and ability to see new possibilities) relative to those in SET, who also improved to a lesser degree on many outcomes. Effect sizes of the time × group interactions were small to medium, and most benefits were maintained over 12 months of follow-up. This study is the first and largest to demonstrate sustained benefits of MBCR in distressed breast cancer survivors relative to an active control. MBCR was superior to SET for improving psychological well-being with lasting benefits over 1 year, suggesting these women gained long-lasting and efficacious tools to cope with cancer. Registered on clinicaltrials.gov number NCT00390169, October 2006. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  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 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

  4. Long-term enhanced winter soil frost alters growing season CO2 fluxes through its impact on vegetation development in a boreal peatland.

    Science.gov (United States)

    Zhao, Junbin; Peichl, Matthias; Nilsson, Mats B

    2017-08-01

    At high latitudes, winter climate change alters snow cover and, consequently, may cause a sustained change in soil frost dynamics. Altered winter soil conditions could influence the ecosystem exchange of carbon dioxide (CO2 ) and, in turn, provide feedbacks to ongoing climate change. To investigate the mechanisms that modify the peatland CO2 exchange in response to altered winter soil frost, we conducted a snow exclusion experiment to enhance winter soil frost and to evaluate its short-term (1-3 years) and long-term (11 years) effects on CO2 fluxes during subsequent growing seasons in a boreal peatland. In the first 3 years after initiating the treatment, no significant effects were observed on either gross primary production (GPP) or ecosystem respiration (ER). However, after 11 years, the temperature sensitivity of ER was reduced in the treatment plots relative to the control, resulting in an overall lower ER in the former. Furthermore, early growing season GPP was also lower in the treatment plots than in the controls during periods with photosynthetic photon flux density (PPFD) ≥800 μmol m-2  s-1 , corresponding to lower sedge leaf biomass in the treatment plots during the same period. During the peak growing season, a higher GPP was observed in the treatment plots under the low light condition (i.e. PPFD 400 μmol m-2  s-1 ) compared to the control. As Sphagnum moss maximizes photosynthesis at low light levels, this GPP difference between the plots may have been due to greater moss photosynthesis, as indicated by greater moss biomass production, in the treatment plots relative to the controls. Our study highlights the different responses to enhanced winter soil frost among plant functional types which regulate CO2 fluxes, suggesting that winter climate change could considerably alter the growing season CO2 exchange in boreal peatlands through its effect on vegetation development. © 2017 John Wiley & Sons Ltd.

  5. Long-Term Memory for Place Learning Is Facilitated by Expression of cAMP Response Element-Binding Protein in the Dorsal Hippocampus

    Science.gov (United States)

    Brightwell, Jennifer J.; Smith, Clayton A.; Neve, Rachael L.; Colombo, Paul J.

    2007-01-01

    Extensive research has shown that the hippocampus is necessary for consolidation of long-term spatial memory in rodents. We reported previously that rats using a place strategy to solve a cross maze task showed sustained phosphorylation of hippocampus cyclic AMP response element-binding protein (CREB), a transcription factor implicated in…

  6. Long-term progressive motor skill training enhances corticospinal excitability for the ipsilateral hemisphere and motor performance of the untrained hand

    DEFF Research Database (Denmark)

    Christiansen, Lasse; Larsen, Malte Nejst; Grey, Michael James

    2017-01-01

    It is well-established that unilateral motor practice can lead to increased performance in the opposite non-trained hand. Here, we test the hypothesis that progressively increasing task difficulty during long-term skill training with the dominant right hand increase performance and corticomotor e...

  7. Long-term progressive motor skill training enhances corticospinal excitability for the ipsilateral hemisphere and motor performance of the untrained hand

    DEFF Research Database (Denmark)

    Christiansen, Lasse; Larsen, Malte Nejst; Grey, Michael James

    2017-01-01

    It is well established that unilateral motor practice can lead to increased performance in the opposite non-trained hand. Here, we test the hypothesis that progressively increasing task difficulty during long-term skill training with the dominant right hand increase performance and corticomotor e...

  8. Activation of nicotinic α(7) acetylcholine receptor enhances long term potentation in wild type mice but not in APP(swe)/PS1ΔE9 mice

    DEFF Research Database (Denmark)

    Söderman, Andreas; Mikkelsen, Jens D; West, Mark J

    2011-01-01

    Amyloid β (Aβ) plays a central role in Alzheimer's disease (AD) and binds to the nicotinic α(7) receptor (α(7) nAChR). Little is known about the degree to which the binding of Aβ to the α(7) nAChR influences the role of this receptor in long-term potentiation (LTP), however. We have studied the e...

  9. Hungry Horse Dam Wildlife Habitat Enhancement Project: Long-Term Habitat Management Plan, Elk and Mule Deer Winter Range Enhancement, Firefighter Mountain and Spotted Bear Winter Ranges.

    Energy Technology Data Exchange (ETDEWEB)

    Casey, Daniel; Malta, Patrick

    1990-06-01

    Project goals are to rehabilitate 1120 acres of big game (elk and mule deer, Odocoileus hemionus) winter range on the Hungry Horse and Spotted Bear Districts of Flathead National Forest lands adjacent to Hungry Horse Reservoir. This project represents the initial phase of implementation toward the mitigation goal. A minimum of 547 acres Trust-funded enhancements are called for in this plan. The remainder are part of the typical Forest Service management activities for the project area. Monitor and evaluate the effects of project implementation on the big game forage base and elk and mule deer populations in the project area. Monitor enhancement success to determine effective acreage to be credited against mitigation goal. Additional enhancement acreage will be selected elsewhere in the Flathead Forest or other lands adjacent'' to the reservoir based on progress toward the mitigation goal as determined through monitoring. The Wildlife Mitigation Trust Fund Advisory Committee will serve to guide decisions regarding future enhancement efforts. 7 refs.

  10. Implementing a social network intervention designed to enhance and diversify support for people with long-term conditions. A qualitative study.

    Science.gov (United States)

    Kennedy, Anne; Vassilev, Ivaylo; James, Elizabeth; Rogers, Anne

    2016-02-29

    For people with long-term conditions, social networks provide a potentially central means of mobilising, mediating and accessing support for health and well-being. Few interventions address the implementation of improving engagement with and through social networks. This paper describes the development and implementation of a web-based tool which comprises: network mapping, user-centred preference elicitation and need assessment and facilitated engagement with resources. The study aimed to determine whether the intervention was acceptable, implementable and acted to enhance support and to add to theory concerning social networks and engagement with resources and activities. A longitudinal design with 15 case studies used ethnographic methods comprising video, non-participant observation of intervention delivery and qualitative interviews (baseline, 6 and 12 months). Participants were people with type 2 diabetes living in a marginalised island community. Facilitators were local health trainers and care navigators. Analysis applied concepts concerning implementation of technology for self-management support to explain how new practices of work were operationalised and how the technology impacted on relationships fit with everyday life and allowed for visual feedback. Most participants reported identifying and taking up new activities as a result of using the tool. Thematic analysis suggested that workability of the tool was predicated on disruption and reconstruction of networks, challenging/supportive facilitation and change and reflection over time concerning network support. Visualisation of the network enabled people to mobilise support and engage in new activities. The tool aligned synergistically with the facilitators' role of linking people to local resources. The social network tool works through a process of initiating positive disruption of established self-management practice through mapping and reflection on personal network membership and support. This

  11. Impact of protein supplementation and exercise in preventing changes in gene expression profiling in woman muscles after long-term bedrest as revealed by microarray analysis.

    Science.gov (United States)

    Chopard, Angele; Lecunff, Martine; Danger, Richard; Teusan, Raluca; Jasmin, Bernard J.; Marini, Jean-Francois; Leger, Jean

    Long duration space flights have a dramatic impact on human physiology and under such a condition, skeletal muscles are known to be one of the most affected systems. A thorough understanding of the basic mechanisms leading to muscle impairment under microgravity, which causes significant loss of muscle mass as well as structural disorders, is necessary for the development of efficient space flight countermeasures. This study was conducted under the aegis of the European Space Agency (ESA), the National Aeronautics and Space Administration of the USA (NASA), the Canadian Space Agency (CSA), and the French "Centre National d'Etudes Spatiales" (CNES). It gave us the opportunity to investigate for the first time the effects of prolonged disuse (long-term bedrest, LTBR) on the transcriptome of different muscle types in healthy women (control, n=8), as well as the potential beneficial impact of protein supplementation (nutrition, n=8) and a combined resistance and aerobic exercise training program (exercise, n=8). Pre- (LTBR -8) and post- (LTBR +59) biopsies were obtained from vastus lateralis (VL) and soleus (SOL) muscles from each subject. Skeletal muscle gene expression profiles were obtained using a custom made microarray containing 6681 muscle-relevant genes. 555 differentiallyexpressed and statistically-significant genes were identified in control group following 60 days of LTBR, including 348 specific for SOL, 83 specific for VL, and 124 common for the two types of muscle (p<0.05). After LTBR, both muscle types exhibited a consistent decrease in pathways involved in fatty acid oxidation, ATP synthesis, and oxidative phosphorylation (p<0.05). However, the postural SOL muscle exhibited a higher level of changes with mRNA encoding proteins involved in protein synthesis and activation of protein degradation (mainly ubiquitinproteasome components) (p<0.05). Major changes in muscle function, such as those involved in calcium signaling and muscle structure including

  12. A training program to enhance recognition of depression in nursing homes, assisted living, and other long-term care settings: Description and evaluation.

    Science.gov (United States)

    Abrams, Robert C; Nathanson, Mark; Silver, Stephanie; Ramirez, Mildred; Toner, John A; Teresi, Jeanne A

    2017-01-01

    Low levels of symptom recognition by staff have been "gateway" barriers to the management of depression in long-term care. The study aims were to refine a depression training program for front-line staff in long-term care and provide evaluative knowledge outcome data. Three primary training modules provide an overview of depression symptoms; a review of causes and situational and environmental contributing factors; and communication strategies, medications, and clinical treatment strategies. McNemar's chi-square tests and paired t-tests were used to examine change in knowledge. Data were analyzed for up to 143 staff members, the majority from nursing. Significant changes (p depressive disorder.

  13. 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.

  14. 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.

  15. 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 ...

  16. Long-term omeprazole and esomeprazole treatment does not significantly increase gastric epithelial cell proliferation and epithelial growth factor receptor expression and has no effect on apoptosis and p53 expression.

    Science.gov (United States)

    Hritz, Istvan; Herszenyi, Laszlo; Molnar, Bela; Tulassay, Zsolt; Pronai, Laszlo

    2005-08-14

    To study the effect of proton pump inhibitor (PPI) treatment on patients with reflux esophagitis and its in vivo effect on apoptosis, p53- and epidermal growth factor receptor (EGFR) expression. After informed consent was obtained, gastric biopsies of the antrum were taken from patients with reflux oesophagitis prior to and after 6 mo of 20 mg omeprazole (n = 14) or 40 mg esomeprazole (n = 12) therapy. Patients did not take any other medications known to affect the gastric mucosa. All patients were Helicobacter pylori negative as confirmed by rapid urease test and histology, respectively. Cell proliferation, apoptosis, EGFR, and p53 expression were measured by immunohistochemical techniques. At least 600 glandular epithelial cells were encountered and results were expressed as percentage of total cells counted. Was considered statistically significant. Although there was a trend towards increase of cell proliferation and EGFR expression both in omeprazole and esomeprazole treated group, the difference was not statistically significant. Neither apoptosis nor p53 expression was affected. Long-term PPI treatment does not significantly increase gastric epithelial cell proliferation and EGFR expression and has no effect on apoptosis and p53 expression.

  17. 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.

  18. Improved long-term expression from helper virus-free HSV-1 vectors packaged using combinations of mutated HSV-1 proteins that include the UL13 protein kinase and specific components of the VP16 transcriptional complex

    Directory of Open Access Journals (Sweden)

    Geller Alfred I

    2009-06-01

    Full Text Available Abstract Background Herpes Simplex Virus (HSV-1 gene expression is thought to shut off recombinant gene expression from HSV-1 vectors; however, in a helper virus-free HSV-1 vector system, a number of promoters support only short-term expression. These results raise the paradox that recombinant gene expression remains short-term even in the absence of almost all (~99% of the HSV-1 genome, HSV-1 genes, and HSV-1 gene expression. To resolve this paradox, we hypothesized that specific proteins in the HSV-1 virus particle shut off recombinant gene expression. In two earlier studies, we examined the effects on recombinant gene expression of packaging vectors using specific mutated HSV-1 proteins. We found that vectors packaged using mutated UL13 (a protein kinase, or VP16, or UL46 and/or UL47 (components of the VP16 transcriptional complex supported improved long-term expression, and vectors packaged using mutated UL46 and/or UL47 also supported improved gene transfer (numbers of cells at 4 days. These results suggested the hypothesis that specific proteins in the HSV-1 particle act by multiple pathways to reduce recombinant gene expression. To test this hypothesis, we examined combinations of mutated proteins that included both UL13 and specific components of the VP16 transcriptional complex. Results A HSV-1 vector containing a neuronal-specific promoter was packaged using specific combinations of mutated proteins, and the resulting vector stocks were tested in the rat striatum. For supporting long-term expression, the preferred combination of mutated HSV-1 proteins was mutated UL13, UL46, and UL47. Vectors packaged using this combination of mutated proteins supported a higher efficiency of gene transfer and high levels expression for 3 months, the longest time examined. Conclusion Vector particles containing this combination of mutated HSV-1 proteins improve recombinant gene expression. Implications of these results for strategies to further improve

  19. Improved long-term expression from helper virus-free HSV-1 vectors packaged using combinations of mutated HSV-1 proteins that include the UL13 protein kinase and specific components of the VP16 transcriptional complex.

    Science.gov (United States)

    Liu, Meng; Wang, Xiaodan; Geller, Alfred I

    2009-06-16

    Herpes Simplex Virus (HSV-1) gene expression is thought to shut off recombinant gene expression from HSV-1 vectors; however, in a helper virus-free HSV-1 vector system, a number of promoters support only short-term expression. These results raise the paradox that recombinant gene expression remains short-term even in the absence of almost all (approximately 99%) of the HSV-1 genome, HSV-1 genes, and HSV-1 gene expression. To resolve this paradox, we hypothesized that specific proteins in the HSV-1 virus particle shut off recombinant gene expression. In two earlier studies, we examined the effects on recombinant gene expression of packaging vectors using specific mutated HSV-1 proteins. We found that vectors packaged using mutated UL13 (a protein kinase), or VP16, or UL46 and/or UL47 (components of the VP16 transcriptional complex) supported improved long-term expression, and vectors packaged using mutated UL46 and/or UL47 also supported improved gene transfer (numbers of cells at 4 days). These results suggested the hypothesis that specific proteins in the HSV-1 particle act by multiple pathways to reduce recombinant gene expression. To test this hypothesis, we examined combinations of mutated proteins that included both UL13 and specific components of the VP16 transcriptional complex. A HSV-1 vector containing a neuronal-specific promoter was packaged using specific combinations of mutated proteins, and the resulting vector stocks were tested in the rat striatum. For supporting long-term expression, the preferred combination of mutated HSV-1 proteins was mutated UL13, UL46, and UL47. Vectors packaged using this combination of mutated proteins supported a higher efficiency of gene transfer and high levels expression for 3 months, the longest time examined. Vector particles containing this combination of mutated HSV-1 proteins improve recombinant gene expression. Implications of these results for strategies to further improve long-term expression are discussed

  20. A relationship between reduced nucleus accumbens shell and enhanced lateral hypothalamic orexin neuronal activation in long-term fructose bingeing behavior.

    Directory of Open Access Journals (Sweden)

    Jacki M Rorabaugh

    Full Text Available Fructose accounts for 10% of daily calories in the American diet. Fructose, but not glucose, given intracerebroventricularly stimulates homeostatic feeding mechanisms within the hypothalamus; however, little is known about how fructose affects hedonic feeding centers. Repeated ingestion of sucrose, a disaccharide of fructose and glucose, increases neuronal activity in hedonic centers, the nucleus accumbens (NAc shell and core, but not the hypothalamus. Rats given glucose in the intermittent access model (IAM display signatures of hedonic feeding including bingeing and altered DA receptor (R numbers within the NAc. Here we examined whether substituting fructose for glucose in this IAM produces bingeing behavior, alters DA Rs and activates hedonic and homeostatic feeding centers. Following long-term (21-day exposure to the IAM, rats given 8-12% fructose solutions displayed fructose bingeing but unaltered DA D1R or D2R number. Fructose bingeing rats, as compared to chow bingeing controls, exhibited reduced NAc shell neuron activation, as determined by c-Fos-immunoreactivity (Fos-IR. This activation was negatively correlated with orexin (Orx neuron activation in the lateral hypothalamus/perifornical area (LH/PeF, a brain region linking homeostatic to hedonic feeding centers. Following short-term (2-day access to the IAM, rats exhibited bingeing but unchanged Fos-IR, suggesting only long-term fructose bingeing increases Orx release. In long-term fructose bingeing rats, pretreatment with the Ox1R antagonist SB-334867 (30 mg/kg; i.p. equally reduced fructose bingeing and chow intake, resulting in a 50% reduction in calories. Similarly, in control rats, SB-334867 reduced chow/caloric intake by 60%. Thus, in the IAM, Ox1Rs appear to regulate feeding based on caloric content rather than palatability. Overall, our results, in combination with the literature, suggest individual monosaccharides activate distinct neuronal circuits to promote feeding behavior

  1. Physiological, Molecular and Genetic Mechanisms of Long-Term Habituation

    Energy Technology Data Exchange (ETDEWEB)

    Calin-Jageman, Robert J

    2009-09-12

    Work funded on this grant has explored the mechanisms of long-term habituation, a ubiquitous form of learning that plays a key role in basic cognitive functioning. Specifically, behavioral, physiological, and molecular mechanisms of habituation have been explored using a simple model system, the tail-elicited siphon-withdrawal reflex (T-SWR) in the marine mollusk Aplysia californica. Substantial progress has been made on the first and third aims, providing some fundamental insights into the mechanisms by which memories are stored. We have characterized the physiological correlates of short- and long-term habituation. We found that short-term habituation is accompanied by a robust sensory adaptation, whereas long-term habituation is accompanied by alterations in sensory and interneuron synaptic efficacy. Thus, our data indicates memories can be shifted between different sites in a neural network as they are consolidated from short to long term. At the molecular level, we have accomplished microarray analysis comparing gene expression in both habituated and control ganglia. We have identified a network of putatively regulated transcripts that seems particularly targeted towards synaptic changes (e.g. SNAP25, calmodulin) . We are now beginning additional work to confirm regulation of these transcripts and build a more detailed understanding of the cascade of molecular events leading to the permanent storage of long-term memories. On the third aim, we have fostered a nascent neuroscience program via a variety of successful initiatives. We have funded over 11 undergraduate neuroscience scholars, several of whom have been recognized at national and regional levels for their research. We have also conducted a pioneering summer research program for community college students which is helping enhance access of underrepresented groups to life science careers. Despite minimal progress on the second aim, this project has provided a) novel insight into the network mechanisms by

  2. 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.

  3. Latexin Inactivation Enhances Survival and Long-Term Engraftment of Hematopoietic Stem Cells and Expands the Entire Hematopoietic System in Mice

    Directory of Open Access Journals (Sweden)

    Yi Liu

    2017-04-01

    Full Text Available Natural genetic diversity offers an important yet largely untapped resource to decipher the molecular mechanisms regulating hematopoietic stem cell (HSC function. Latexin (Lxn is a negative stem cell regulatory gene identified on the basis of genetic diversity. By using an Lxn knockout mouse model, we found that Lxn inactivation in vivo led to the physiological expansion of the entire hematopoietic hierarchy. Loss of Lxn enhanced the competitive repopulation capacity and survival of HSCs in a cell-intrinsic manner. Gene profiling of Lxn-null HSCs showed altered expression of genes enriched in cell-matrix and cell-cell interactions. Thrombospondin 1 (Thbs1 was a potential downstream target with a dramatic downregulation in Lxn-null HSCs. Enforced expression of Thbs1 restored the Lxn inactivation-mediated HSC phenotypes. This study reveals that Lxn plays an important role in the maintenance of homeostatic hematopoiesis, and it may lead to development of safe and effective approaches to manipulate HSCs for clinical benefit.

  4. 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.

  5. Protein-pacing caloric-restriction enhances body composition similarly in obese men and women during weight loss and sustains efficacy during long-term weight maintenance

    DEFF Research Database (Denmark)

    Arciero, Paul J; Edmonds, Rohan; He, Feng

    2016-01-01

    /day) in obese adults. Less is known whether obese men and women respond similarly to P-CR during weight loss (WL) and whether a modified P-CR (mP-CR) is more efficacious than a HH diet during long-term (52 week) weight maintenance (WM). The purposes of this study were to evaluate the efficacy of: (1) P......) completed WM. mP-CR regained significantly less body weight (6%), TBF (12%), and ABF (17%) compared to HH (p weight loss, body composition and biomarkers, and maintains these changes for 52-weeks compared to a traditional HH diet.......Short-Term protein-pacing (P; ~6 meals/day, >30% protein/day) and caloric restriction (CR, ~25% energy deficit) improves total (TBF), abdominal (ABF) and visceral (VAT) fat loss, energy expenditure, and biomarkers compared to heart healthy (HH) recommendations (3 meals/day, 15% protein...

  6. Enhancement of denitrifying phosphorus removal and microbial community of long-term operation in an anaerobic anoxic oxic-biological contact oxidation system.

    Science.gov (United States)

    Zhang, Miao; Yang, Qing; Zhang, Jianhua; Wang, Cong; Wang, Shuying; Peng, Yongzhen

    2016-10-01

    A two-sludge system consisting of anaerobic anoxic oxic-biological contact oxidation (A(2)/O-BCO) was developed to treat domestic wastewater with a low carbon/nitrogen (COD/TN) ratio (around 3.21) by shortening sludge retention time (SRT) for phosphorus accumulating organisms (PAOs) in the A(2)/O reactor and prolonging SRT for nitrifiers in the BCO reactor. Specifically, the BCO reactor was composed of three stages in series (N1, N2 and N3), so that simultaneous nitrogen and phosphorus removals by denitrifying PAOs (DNPAOs) was achieved in the A(2)/O reactor with [Formula: see text] as the electron acceptor from the BCO reactor. Long term operational tests (600 days) were conducted with various operational parameters [e.g., hydraulic retention time (HRTs), nitrate recycling ratio (Rs), volume ratio (Vs)] to examine the denitrifying phosphorus removal performance. The system exhibited the highest removal of TN and [Formula: see text] at the HRTs of 8 h, Rs of 300% and Vs of 2:4:1. The optimal TN and [Formula: see text] removals were 80.30% and 96.61% at low COD/TN of 3.21. The species diversity and microbial community examined by the Illumina MiSeq method demonstrated the fact of two-sludge system, and the improved community structure by long-term optimization was prominent comparing with the seed sludge. Additionally, Accumulibacter and Dechloromonas were the dominant functional PAOs with 25.74% in the A(2)/O reactor, while nitrifiers (including Nitrosomonas and Nitrospira) were gradually enriched with 13.10%, 21.33%, and 31.10% in the three stages of the BCO reactor. Copyright © 2016 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  7. Long-term multi-species Lactobacillus and Bifidobacterium dietary supplement enhances memory and changes regional brain metabolites in middle-aged rats.

    Science.gov (United States)

    O'Hagan, Caroline; Li, Jia V; Marchesi, Julian R; Plummer, Sue; Garaiova, Iveta; Good, Mark A

    2017-10-01

    Ageing is associated with changes in the gut microbiome that may contribute to age-related changes in cognition. Previous work has shown that dietary supplements with multi-species live microorganisms can influence brain function, including induction of hippocampal synaptic plasticity and production of brain derived neurotrophic factor, in both young and aged rodents. However, the effect of such dietary supplements on memory processes has been less well documented, particularly in the context of aging. The main aim of the present study was to examine the impact of a long-term dietary supplement with a multi-species live Lactobacillus and Bifidobacteria mixture (Lactobacillus acidophilus CUL60, L. acidophilus CUL21, Bifidobacterium bifidum CUL20 and B. lactis CUL34) on tests of memory and behavioural flexibility in 15-17-month-old male rats. Following behavioural testing, the hippocampus and prefrontal cortex was extracted and analysed ex vivo using (1)H nuclear magnetic resonance ((1)H NMR) spectroscopy to examine brain metabolites. The results showed a small beneficial effect of the dietary supplement on watermaze spatial navigation and robust improvements in long-term object recognition memory and short-term memory for object-in-place associations. Short-term object novelty and object temporal order memory was not influenced by the dietary supplement in aging rats. (1)H NMR analysis revealed diet-related regional-specific changes in brain metabolites; which indicated changes in several pathways contributing to modulation of neural signaling. These data suggest that chronic dietary supplement with multi-species live microorganisms can alter brain metabolites in aging rats and have beneficial effects on memory. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. A 33 kDa protein band is enhanced during long-term adaptation of EUE cells to a hypertonic medium.

    Science.gov (United States)

    Giuliani, A; Ferraretto, A; Fuhrman Conti, A M; De Grada, L; Fraschini, A; Pellicciari, C; Manfredi Romanini, M G

    1991-04-01

    A cell line derived from human embryonic epithelium (EUE cells) shows an enhanced expression of a 33 kDa protein when adapted to grow in a hypertonic medium containing 0.246 M NaCl (1.8 x the isotonic concentration). The maximum amount of this protein, followed by SDS-PAGE electrophoresis, was found after 4 days of adaptation; thereafter, the protein band remained fairly constant up to 30 days. When the cells were transferred back to a medium containing 0.137 M NaCl (isotonic medium), the protein pattern reverted to that of control cells. This protein is mainly localized in the cytosol, although a small part is associated with the 150,000 g pellet and needs detergents to be extracted. The molecular weight and the cellular location suggest a possible analogy with the so-called amphitropic proteins, that are known to interact with both the epidermal growth factor receptor and hydrophobic structures, such as the membrane phospholipids and the cytoskeletal components.

  9. Effects of long-term environmental enrichment on anxiety, memory, hippocampal plasticity and overall brain gene expression in C57BL6 mice

    Directory of Open Access Journals (Sweden)

    Melanie Hüttenrauch

    2016-08-01

    Full Text Available There is ample evidence that physical activity exerts positive effects on a variety of brain functions by facilitating neuroprotective processes and influencing neuroplasticity. Accordingly, numerous studies have shown that continuous exercise can successfully diminish or prevent the pathology of neurodegenerative diseases such as Alzheimer’s disease in transgenic mouse models. However, the long-term effect of physical activity on brain health of aging WT mice has not been studied in detail yet. Here, we show that prolonged physical and cognitive stimulation, mediated by an enriched environment (EE paradigm for a duration of eleven months, leads to reduced anxiety and improved spatial reference memory in C57BL6 wildtype (WT mice. While the number of CA1 pyramidal neurons remained unchanged between standard housed (SH and EE mice, the number of dentate gyrus (DG neurons, as well as the CA1 and DG volume were significantly increased in EE mice. A whole-brain deep sequencing transcriptome analysis, carried out to better understand the molecular mechanisms underlying the observed effects, revealed an up-regulation of a variety of genes upon EE, mainly associated with synaptic plasticity and transcription regulation. The present findings corroborate the impact of continuous physical activity as a potential prospective route in the prevention of age-related cognitive decline and neurodegenerative disorders.

  10. Long-term changes in collagen formation expressed by serum carboxyterminal propeptide of type-I procollagen and relation to left ventricular function after acute myocardial infarction

    DEFF Research Database (Denmark)

    Poulsen, S H; Høst, N B; Egstrup, K

    2001-01-01

    and prognosis following acute myocardial infarction (AMI). Forty-eight consecutive patients with their first AMI and 15 control subjects were studied. Patients with AMI were stratified according to the changes in s-PICP levels between days 1 and 90 (DeltaPICP) and divided into group I with microg/l...... or group II with >16.0 microg/l. Patients in group II were characterized by LV dilatation, no improvement in ejection fraction and development of impaired diastolic filling from day 1 to 360, findings which were in contrast to group I. Cox regression analysis identified changes in s-PICP of >16.0 microg/l......The purpose of this study was to investigate the long-term sequential changes in serum levels of the carboxyterminal propeptide of type-I procollagen (s-PICP), which is a marker of type-I collagen synthesis, and to assess its clinical value in relation to left ventricular (LV) function...

  11. Sharpened cortical tuning and enhanced cortico-cortical communication contribute to the long-term neural mechanisms of visual motion perceptual learning.

    Science.gov (United States)

    Chen, Nihong; Bi, Taiyong; Zhou, Tiangang; Li, Sheng; Liu, Zili; Fang, Fang

    2015-07-15

    Much has been debated about whether the neural plasticity mediating perceptual learning takes place at the sensory or decision-making stage in the brain. To investigate this, we trained human subjects in a visual motion direction discrimination task. Behavioral performance and BOLD signals were measured before, immediately after, and two weeks after training. Parallel to subjects' long-lasting behavioral improvement, the neural selectivity in V3A and the effective connectivity from V3A to IPS (intraparietal sulcus, a motion decision-making area) exhibited a persistent increase for the trained direction. Moreover, the improvement was well explained by a linear combination of the selectivity and connectivity increases. These findings suggest that the long-term neural mechanisms of motion perceptual learning are implemented by sharpening cortical tuning to trained stimuli at the sensory processing stage, as well as by optimizing the connections between sensory and decision-making areas in the brain. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Below-ground carbon allocation in mature beech and spruce trees following long-term, experimentally enhanced O{sub 3} exposure in Southern Germany

    Energy Technology Data Exchange (ETDEWEB)

    Andersen, Christian P., E-mail: Andersen.christian@epa.go [US Environmental Protection Agency, Western Ecology Division, 200 SW 35th St., Corvallis, OR 97333 (United States); Ritter, Wilma [Ecophysiology of Plants, Department of Ecology and Ecosystem Management, Technische Universitaet Muenchen, Am Hochanger 13, 85354 Freising (Germany); Gregg, Jillian [Terrestrial Ecosystems Research Associates, 200 SW 35th St., Corvallis, OR 97333 (United States); Matyssek, Rainer; Grams, Thorsten E.E. [Ecophysiology of Plants, Department of Ecology and Ecosystem Management, Technische Universitaet Muenchen, Am Hochanger 13, 85354 Freising (Germany)

    2010-08-15

    Canopies of adult European beech (Fagus sylvatica) and Norway spruce (Picea abies) were labeled with CO{sub 2} depleted in {sup 13}C to evaluate carbon allocation belowground. One-half the trees were exposed to elevated O{sub 3} for 6 yrs prior to and during the experiment. Soil-gas sampling wells were placed at 8 and 15 cm and soil CO{sub 2} was sampled during labeling in mid-late August, 2006. In beech, {delta}{sup 13}CO{sub 2} at both depths decreased approximately 50 h after labeling, reflecting rapid translocation of fixed C to roots and release through respiration. In spruce, label was detected in fine-root tissue, but there was no evidence of label in {delta}{sup 13}CO{sub 2}. The results show that C fixed in the canopy rapidly reaches respiratory pools in beech roots, and suggest that spruce may allocate very little of recently-fixed carbon into root respiration during late summer. A change in carbon allocation belowground due to long-term O{sub 3} exposure was not observed. - Below-ground carbon allocation in mature beech and spruce exposed to ozone.

  13. Enhancing Knowledge and InterProfessional care for Heart Failure (EKWIP-HF) in long-term care: a pilot study.

    Science.gov (United States)

    Heckman, George A; Boscart, Veronique M; Huson, Kelsey; Costa, Andrew; Harkness, Karen; Hirdes, John P; Stolee, Paul; McKelvie, Robert S

    2018-01-01

    Heart failure (HF) affects 20% of long-term care (LTC) residents and is associated with significant morbidity, acute care visits, and mortality. Barriers to HF management are staff knowledge gaps and ineffective interprofessional (IP) communication. This pilot study assessed the acceptability, feasibility, and impact of an intervention to (1) improve HF knowledge; (2) improve IP communication; and (3) integrate improved knowledge and communication processes into work routines. The intervention provides multimodal IP education about HF in LTC, including specialist-supported bedside teaching. It was piloted on single units in two facilities. A mixed-methods repeated-measures approach was used to collect qualitative and quantitative process and outcome data at baseline and 6 months post-intervention. Results were similar at both sites. Participants developed optimized IP communication to promote HF care. Results indicate a perceived increase in staff confidence and self-efficacy, strengthened assessment and clinical proficiency skills, and more effective IP collaboration. Staff deemed the intervention useful and feasible. This pilot study suggests that a novel intervention in which HF-specific knowledge is applied by LTC staff to improve IP collaboration in their own work place is acceptable and feasible and has a favourable preliminary impact on staff knowledge and IP communication.

  14. 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

  15. Long-term intermittent multiple micronutrient supplementation enhances hemoglobin and micronutrient status more than iron + folic acid supplementation in Bangladeshi rural adolescent girls with nutritional anemia.

    Science.gov (United States)

    Ahmed, Faruk; Khan, Moududur R; Akhtaruzzaman, Mohammad; Karim, Rezaul; Williams, Gail; Torlesse, Harriet; Darnton-Hill, Ian; Dalmiya, Nita; Banu, Cadi P; Nahar, Badrun

    2010-10-01

    Previous short-term supplementation studies showed no additional hematologic benefit of multiple micronutrients (MMN) compared with iron + folic acid (IFA) in adolescent girls. This study examines whether long-term once- or twice-weekly supplementation of MMN can improve hemoglobin (Hb) and micronutrient status more than twice-weekly IFA supplementation in anemic adolescent girls in Bangladesh. Anemic girls (n = 324) aged 11-17 y attending rural schools were given once- or twice-weekly MMN or twice-weekly IFA, containing 60 mg iron/dose in both supplements, for 52 wk in a randomized double-blind trial. Blood samples were collected at baseline and 26 and 52 wk. Intent to treat analysis showed no significant difference in the Hb concentration between treatments at either 26 or 52 wk. However, after excluding girls with hemoglobinopathy and adjustment for baseline Hb, a greater increase in Hb was observed with twice-weekly MMN at 26 wk (P = 0.045). Although all 3 treatments effectively reduced iron deficiency, once-weekly MMN produced significantly lower serum ferritin concentrations than the other treatments at both 26 and 52 wk. Both once- and twice-weekly MMN significantly improved riboflavin, vitamin A, and vitamin C status compared with IFA. Overall, once-weekly MMN was less efficacious than twice-weekly MMN in improving iron, riboflavin, RBC folic acid, and vitamin A levels. Micronutrient supplementation beyond 26 wk was likely important in sustaining improved micronutrient status. These findings highlight the potential usefulness of MMN intervention in this population and have implications for programming.

  16. Long-term manure amendments and chemical fertilizers enhanced soil organic carbon sequestration in a wheat (Triticum aestivum L.)-maize (Zea mays L.) rotation system.

    Science.gov (United States)

    Zhang, Shuiqing; Huang, Shaomin; Li, Jianwei; Guo, Doudou; Lin, Shan; Lu, Guoan

    2017-06-01

    The carbon sequestration potential is affected by cropping system and management practices, but soil organic carbon (SOC) sequestration potential under fertilizations remains unclear in north China. This study examined SOC change, total C input to soil and, via integration of these estimates over years, carbon sequestration efficiency (CSE, the ratio of SOC change over C input) under no fertilization (control), chemical nitrogen fertilizer alone (N) or combined with phosphorus and potassium fertilizers (NP, NK, PK and NPK), or chemical fertilizers combined with low or high (1.5×) manure input (NPKM and 1.5NPKM). Results showed that, as compared with the initial condition, SOC content increased by 0.03, 0.06, 0.05, 0.09, 0.16, 0.26, 0.47 and 0.68 Mg C ha(-1) year(-1) under control, N, NK, PK, NP, NPK, NPKM and 1.5NPKM treatments respectively. Correspondingly, the C inputs of wheat and maize were 1.24, 1.34, 1.55, 1.33, 2.72, 2.96, 2.97 and 3.15 Mg ha(-1) year(-1) respectively. The long-term fertilization-induced CSE showed that about 11% of the gross C input was transformed into SOC pool. Overall, this study demonstrated that decade-long manure input combined with chemical fertilizers can maintain high crop yield and lead to SOC sequestration in north China. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  17. Protein-Pacing Caloric-Restriction Enhances Body Composition Similarly in Obese Men and Women during Weight Loss and Sustains Efficacy during Long-Term Weight Maintenance.

    Science.gov (United States)

    Arciero, Paul J; Edmonds, Rohan; He, Feng; Ward, Emery; Gumpricht, Eric; Mohr, Alex; Ormsbee, Michael J; Astrup, Arne

    2016-07-30

    Short-Term protein-pacing (P; ~6 meals/day, >30% protein/day) and caloric restriction (CR, ~25% energy deficit) improves total (TBF), abdominal (ABF) and visceral (VAT) fat loss, energy expenditure, and biomarkers compared to heart healthy (HH) recommendations (3 meals/day, 15% protein/day) in obese adults. Less is known whether obese men and women respond similarly to P-CR during weight loss (WL) and whether a modified P-CR (mP-CR) is more efficacious than a HH diet during long-term (52 week) weight maintenance (WM). The purposes of this study were to evaluate the efficacy of: (1) P-CR on TBF, ABF, resting metabolic rate (RMR), and biomarkers between obese men and women during WL (weeks 0-12); and (2) mP-CR compared to a HH diet during WM (weeks 13-64). During WL, men (n = 21) and women (n = 19) were assessed for TBF, ABF, VAT, RMR, and biomarkers at weeks 0 (pre) and 12 (post). Men and women had similar reductions (p weight (10%), TBF (19%), ABF (25%), VAT (33%), glucose (7%-12%), insulin (40%), leptin (>50%) and increase in % lean body mass (9%). RMR (kcals/kg bodyweight) was unchanged and respiratory quotient decreased 9%. Twenty-four subjects (mP-CR, n = 10; HH, n = 14) completed WM. mP-CR regained significantly less body weight (6%), TBF (12%), and ABF (17%) compared to HH (p weight loss, body composition and biomarkers, and maintains these changes for 52-weeks compared to a traditional HH diet.

  18. Dietary advanced glycated end-products and medicines influence the expression of SIRT1 and DDOST in peripheral mononuclear cells from long-term type 1 diabetes patients.

    Science.gov (United States)

    Santos-Bezerra, Daniele P; Machado-Lima, Adriana; Monteiro, Maria Beatriz; Admoni, Sharon N; Perez, Ricardo V; Machado, Cleide G; Shimizu, Maria Heloíza; Cavaleiro, Ana M; Thieme, Karina; Queiroz, Márcia S; Machado, Ubiratan F; Giannella-Neto, Daniel; Passarelli, Marisa; Corrêa-Giannella, Maria Lúcia

    2018-01-01

    Quantitative polymerase chain reaction was employed to quantify expression of two genes coding for advanced glycation end-product receptors [RAGE ( AGER) and AGER1 ( DDOST)] and of the gene coding the deacetylase SIRT1 ( SIRT1) in peripheral blood mononuclear cells from type 1 diabetes patients without [Group A, n = 35; 28.5 (24-39) years old; median (interquartile interval)] or with at least one microvascular complication [Group B, n = 117; 34.5 (30-42) years old]; 31 healthy controls were also included. In a subgroup of 48 patients, daily advanced glycation end-products intake before blood collection was assessed. Lower expression of DDOST was found in patients than in controls after adjustment for sex, age, use of statins, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. Higher expressions of AGER, DDOST and SIRT1 were observed in Group A. Stratifying by complications, AGER and DDOST expressions were higher in those without retinopathy and without diabetic kidney disease, respectively, compared to patients with these complications. Patients using statins or angiotensin receptor blockers presented higher expression of DDOST. Expression of SIRT1 was higher in patients consuming ≥12,872 KU daily of advanced glycation end-products. Although AGER, DDOST and SIRT1 are differently expressed in peripheral blood mononuclear cells from type 1 diabetes patients with and without microvascular complications, they are also influenced by dietary advanced glycation end-products and by statins and angiotensin receptor blockers.

  19. ER-alpha-cDNA as part of a bicistronic transcript gives rise to high frequency, long term, receptor expressing cell clones.

    Directory of Open Access Journals (Sweden)

    Michal Shenfeld

    Full Text Available Within the large group of Estrogen Receptor alpha (ERα-negative breast cancer patients, there is a subgroup carrying the phenotype ERα(-, PR(-, and Her2(-, named accordingly "Triple-Negative" (TN. Using cell lines derived from this TN group, we wished to establish cell clones, in which ERα is ectopically expressed, forming part of a synthetic lethality screening system. Initially, we generated cell transfectants expressing a mono-cistronic ERα transcription unit, adjacent to a separate dominant selectable marker transcription unit. However, the yield of ERα expressing colonies was rather low (5-12.5%, and only about half of these displayed stable ectopic ERα expression over time. Generation and maintenance of such cell clones under minimal exposure to the ERα ligand, did not improve yield or expression stability. Indeed, other groups have also reported grave difficulties in obtaining ectopic expression of ERα in ERα-deficient breast carcinoma cells. We therefore switched to transfecting these cell lines with pERα-IRES, a plasmid vector encoding a bicistronic translation mRNA template: ERα Open Reading Frame (ORF being upstream followed by a dominant-positive selectable marker (hygro(R ORF, directed for translation from an Internal Ribosome Entry Site (IRES. Through usage of this bicistronic vector linkage system, it was possible to generate a very high yield of ERα expressing cell clones (50-100%. The stability over time of these clones was also somewhat improved, though variations between individual cell clones were evident. Our successful experience with ERα in this system may serve as a paradigm for other genes where ectopic expression meets similar hardships.

  20. Preexisting High Expression of Matrix Metalloproteinase-2 in Tunica Media of Saphenous Vein Conduits Is Associated with Unfavorable Long-Term Outcomes after Coronary Artery Bypass Grafting

    Directory of Open Access Journals (Sweden)

    Bartlomiej Perek

    2013-01-01

    Full Text Available Introduction. Migration of the smooth muscle cells (SMCs to the tunica media in the saphenous vein (SV transplants is facilitated by matrix metalloproteinases (MMPs. The aim of this study was to identify any associations between expression of MMP-2 or endogenous tissue inhibitors (TIMP-2 and TIMP-3 in the SV segments and late failure of the SV grafts. Methods. Two hundred consecutive patients with a mean age of 63.1 ± 8.9 years who underwent primary isolated venous CABG were examined. Patients were retrospectively split into two subgroups, with the SV graft disease (SVGD (+; or without it (SVGD (−; . In the SV segments, immunohistochemical analysis of the expression of the MMP-2, TIMP-2, and -3 was performed. Results. In the SVGD (+ patients, tissue expression of MMP-2 was stronger, whereas that of both TIMPs was weaker than in the SVGD (− patients. In majority of the SV segments obtained from the SVGD (− individuals, a balance in MMP and TIMP expressions was found, whereas an upregulation of MMP-2 expression was usually noted in the SVGD (+ subjects. Conclusion. The strong expression of MMP-2 accompanied by reduced immunostaining of both TIMPs is associated with the development of the SV graft disease and unfavorable CABG outcomes.

  1. Postnatal overfeeding causes early shifts in gene expression in the heart and long-term alterations in cardiometabolic and oxidative parameters.

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    Ahmed Habbout

    Full Text Available BACKGROUND: Postnatal overfeeding (OF in rodents induces a permanent moderate increase in body weight in adulthood. However, the repercussions of postnatal OF on cardiac gene expression, cardiac metabolism and nitro-oxidative stress are less well known. METHODOLOGY/PRINCIPAL FINDINGS: Immediately after birth, litters of C57BL/6 mice were either maintained at 10 (normal-fed group, NF, or reduced to 3 in order to induce OF. At weaning, mice of both groups received a standard diet. The cardiac gene expression profile was determined at weaning and cardiac metabolism and oxidative stress were assessed at 7 months. The cardiac expression of several genes, including members of the extracellular matrix and apelin pathway, was modified in juvenile OF mice. In adult mice, OF led to an increase in body weight (+30% and to significant increases in plasma cholesterol, insulin and leptin levels. Myocardial oxidative stress, SOD and catalase activity and mRNA expression were increased in OF mice. In vivo, diastolic and systolic blood pressures were significantly higher and LV shortening and ejection fraction were decreased in OF mice. Ex vivo, after 30 min of ischemia, hearts isolated from OF mice showed lower functional recovery and larger infarct size (31% vs. 54%, p<0.05. Increases in collagen deposition and expression/activity of matrix-metalloproteinase-2 were observed in adult OF mouse hearts. Moreover, an increase in the expression of SOCS-3 and a decrease in STAT-3 phosphorylation were observed in ventricular tissues from OF mice. CONCLUSIONS/SIGNIFICANCE: Our study emphasizes that over-nutrition during the immediate postnatal period in mice leads to early changes in cardiac gene expression, which may permanently modify the heart's structural organization and metabolism and could contribute to a greater susceptibility to myocardial ischemia-reperfusion injury.

  2. Serotonin transporter gene expression predicts the worsening of suicidal ideation and suicide attempts along a long-term follow-up of a Major Depressive Episode.

    Science.gov (United States)

    Consoloni, Julia-Lou; Ibrahim, El Chérif; Lefebvre, Marie-Noëlle; Zendjidjian, Xavier; Olié, Emilie; Mazzola-Pomietto, Pascale; Desmidt, Thomas; Samalin, Ludovic; Llorca, Pierre-Michel; Abbar, Mocrane; Lopez-Castroman, Jorge; Haffen, Emmanuel; Baumstarck, Karine; Naudin, Jean; Azorin, Jean-Michel; El-Hage, Wissam; Courtet, Philippe; Belzeaux, Raoul

    2017-12-26

    The quest for biomarkers in suicidal behaviors has been elusive so far, despite their potential utility in clinical practice. One of the most robust biological findings in suicidal behaviors is the alteration of the serotonin transporter function in suicidal individuals. Our main objective was to investigate the predictive value of the serotonin transporter gene expression (SLC6A4) for suicidal ideation and as secondary, for suicide attempts in individuals with a major depressive episode (MDE). A 30-week prospective study was conducted on 148 patients with a MDE and 100 healthy controls including 4 evaluation times (0, 2, 8 and 30 weeks). Blood samples and clinical data were collected and SLC6A4 mRNA levels were measured from peripheral blood mononuclear cells using RT-qPCR. We first demonstrated the stability and reproducibility of SLC6A4 mRNA expression measures over time in healthy controls (F=0.658; p=0.579; η 2 =0.008; ICC=0.91, 95% CI [0.87-0.94]). Baseline SLC6A4 expression level (OR=0.563 [0.340-0.932], p=0.026) as well as early changes in SLC6A4 expression between baseline and the 2 nd week (β=0.200, p=0.042) predicted the worsening of suicidal ideation (WSI) in the following 8 weeks. Moreover, changes in SLC6A4 expression between the 2 nd and 8 th weeks predicted the occurrence of a suicide attempt within 30 weeks (OR=10.976 [1.438-83.768], p=0.021). Altogether, the baseline level and the changes in SLC6A4 mRNA expression during a MDE might predict the WSI and the occurrence of suicidal attempts and could be a useful biomarker in clinical practice. Copyright © 2017 Elsevier B.V. and ECNP. All rights reserved.

  3. Hypovascular hypointense nodules on hepatobiliary phase without T2 hyperintensity on gadoxetic acid-enhanced MR images in patients with chronic liver disease: long-term outcomes and risk factors for hypervascular transformation

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Yong Seek [Chonbuk National University Medical School and Hospital, Department of Radiology, Jeonju-si, Chonbuk (Korea, Republic of); Song, Ji Soo; Lee, Hyun Kyung; Han, Young Min [Chonbuk National University Medical School and Hospital, Department of Radiology, Jeonju-si, Chonbuk (Korea, Republic of); Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Research Institute of Clinical Medicine, Chonbuk (Korea, Republic of)

    2016-10-15

    To evaluate the long-term outcomes and imaging features associated with hypervascularization of hypovascular nodules that show T2 iso-/hypointensity and hypointensity on hepatobiliary phase (HBP) of gadoxetic acid-enhanced magnetic resonance (MR) images in patients with chronic liver disease. Sixty patients and 114 nodules, which were hypovascular and iso-/hypointense on T2-weighted images and hypointense on HBP of gadoxetic acid-enhanced MRI, were included. We evaluated the effect of baseline clinical features, baseline MR features and growth rate on subsequent hypervascularization. Twenty-seven nodules in 21 patients transformed to hypervascular hepatocellular carcinoma (HCC). Using multivariate Cox analysis, T1 hyperintensity (hazard ratio [HR] = 2.69, P = 0.021), previous history of HCC (HR = 2.64, P = 0.021), and initial nodule size (HR = 1.09, P = 0.046) were identified to be associated with hypervascularization. The growth rate of nodules was a more powerful determinant of subsequent hypervascularization than baseline clinical and MR features. At long-term follow-up after >3 years, only one nodule with T1 isointensity showed hypervascularization. Careful follow-up or diagnostic procedures, such as biopsy, should be considered for up to 3 years after detection of hypointense nodules on HBP with T1 hyperintensity or a higher growth rate. (orig.)

  4. 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.

  5. Gene Expression Changes in Long-Term In Vitro Human Blood-Brain Barrier Models and Their Dependence on a Transwell Scaffold Material

    Directory of Open Access Journals (Sweden)

    Joel D. Gaston

    2017-01-01

    Full Text Available Disruption of the blood-brain barrier (BBB is the hallmark of many neurovascular disorders, making it a critically important focus for therapeutic options. However, testing the effects of either drugs or pathological agents is difficult due to the potentially damaging consequences of altering the normal brain microenvironment. Recently, in vitro coculture tissue models have been developed as an alternative to animal testing. Despite low cost, these platforms use synthetic scaffolds which prevent normal barrier architecture, cellular crosstalk, and tissue remodeling. We created a biodegradable electrospun gelatin mat “biopaper” (BP as a scaffold material for an endothelial/astrocyte coculture model allowing cell-cell contact and crosstalk. To compare the BP and traditional models, we investigated the expression of 27 genes involved in BBB permeability, cellular function, and endothelial junctions at different time points. Gene expression levels demonstrated higher expression of transcripts involved in endothelial junction formation, including TJP2 and CDH5, in the BP model. The traditional model had higher expression of genes associated with extracellular matrix-associated proteins, including SPARC and COL4A1. Overall, the results demonstrate that the BP coculture model is more representative of a healthy BBB state, though both models have advantages that may be useful in disease modeling.

  6. Long-term rescue of rat retinal ganglion cells and visual function by AAV-mediated BDNF expression after acute elevation of intraocular pressure.

    Science.gov (United States)

    Ren, Ruotong; Li, Ying; Liu, Zhiping; Liu, Kegao; He, Shigang

    2012-02-27

    To evaluate the ability of increased expression of brain-derived neurotrophic factor (BDNF) using adenoassociated viral (AAV) vector to prevent the loss of rat retinal ganglion cells (RGCs) and visual function after acute elevation of intraocular pressure (IOP). AAV vectors (expressing BDNF or GFP) were injected into the vitreous 6 hours after a transient IOP elevation to 130 mm Hg for 45 minutes. Protective effects were evaluated by counting RGCs retrogradely labeled with fluorogold (FG) from the superior colliculus, measuring the amplitude and the latency of the P1 component of the visual evoked potential (VEP), and observing the visual acuity and contrast sensitivity in awake and behaving animals. RGC numbers decreased continuously to 9 weeks after the elevation of IOP. FG-positive RGC loss was significantly decreased in the retinas treated with AAV-BDNF at 3, 6, and 9 weeks after the insult, with corresponding improvements in VEP parameters. Supplementing BDNF protein once to compensate for the slow onset of AAV-mediated gene expression rescued a larger number of RGCs and the parameters of the VEP. Visual acuity and contrast sensitivity were significantly improved in all treated groups, with the largest improvement in the combined-therapy group, and were maintained for up to 70 weeks. The authors further demonstrated that BDNF rescued the RGCs by activating TrkB receptors through both autocrine and paracrine mechanisms. AAV-mediated BDNF expression in the rat retina achieved a sustained rescue of RGCs and visual function after an acute elevation of IOP.

  7. Early postnatal maternal separation causes alterations in the expression of β3-adrenergic receptor in rat adipose tissue suggesting long-term influence on obesity

    Energy Technology Data Exchange (ETDEWEB)

    Miki, Takanori, E-mail: mikit@med.kagawa-u.ac.jp [Department of Anatomy and Neurobiology, Faculty of Medicine, Kagawa University (Japan); Liu, Jun-Qian; Ohta, Ken-ichi; Suzuki, Shingo [Department of Anatomy and Neurobiology, Faculty of Medicine, Kagawa University (Japan); Kusaka, Takashi [Department of Pediatrics, Faculty of Medicine, Kagawa University (Japan); Warita, Katsuhiko [Department of Anatomy and Neurobiology, Faculty of Medicine, Kagawa University (Japan); Yokoyama, Toshifumi [Department of Bioresource and Agrobiosciences, Graduate School of Science and Technology, Kobe University (Japan); Jamal, Mostofa [Department of Forensic Medicine, Faculty of Medicine, Kagawa University (Japan); Ueki, Masaaki [Department of Anesthesia, Nishiwaki Municipal Hospital (Japan); Yakura, Tomiko; Tamai, Motoki [Department of Anatomy and Neurobiology, Faculty of Medicine, Kagawa University (Japan); Sumitani, Kazunori [Department of Medical Education, Faculty of Medicine, Kagawa University (Japan); Hosomi, Naohisa [Department of Clinical Neuroscience and Therapeutics, Hiroshima University Graduate School of Biomedical Sciences (Japan); Takeuchi, Yoshiki [Department of Anatomy and Neurobiology, Faculty of Medicine, Kagawa University (Japan)

    2013-12-06

    Highlights: •High-fat diet intake following maternal separation did not cause body weight gain. •However, levels of metabolism-related molecules in adipose tissue were altered. •Increased levels of prohibitin mRNA in white fat were observed. •Attenuated levels of β3-adrenergic receptor mRNA were observed in brown fat. •Such alterations in adipose tissue may contribute to obesity later in life. -- Abstract: The effects of early postnatal maternal deprivation on the biological characteristics of the adipose tissue later in life were investigated in the present study. Sprague–Dawley rats were classified as either maternal deprivation (MD) or mother-reared control (MRC) groups. MD was achieved by separating the rat pups from their mothers for 3 h each day during the 10–15 postnatal days. mRNA levels of mitochondrial uncoupling protein 1 (UCP-1), β3-adrenergic receptor (β3-AR), and prohibitin (PHB) in the brown and white adipose tissue were determined using real-time RT-PCR analysis. UCP-1, which is mediated through β3-AR, is closely involved in the energy metabolism and expenditure. PHB is highly expressed in the proliferating tissues/cells. At 10 weeks of age, the body weight of the MRC and MD rats was similar. However, the levels of the key molecules in the adipose tissue were substantially altered. There was a significant increase in the expression of PHB mRNA in the white adipose tissue, while the β3-AR mRNA expression decreased significantly, and the UCP-1 mRNA expression remained unchanged in the brown adipose tissue. Given that these molecules influence the mitochondrial metabolism, our study indicates that early postnatal maternal deprivation can influence the fate of adipose tissue proliferation, presumably leading to obesity later in life.

  8. Long-term effects of early adolescent stress: dysregulation of hypothalamic-pituitary-adrenal axis and central corticotropin releasing factor receptor 1 expression in adult male rats.

    Science.gov (United States)

    Li, Chuting; Liu, Yuan; Yin, Shiping; Lu, Cuiyan; Liu, Dexiang; Jiang, Hong; Pan, Fang

    2015-07-15

    Post-traumatic stress disorder (PTSD) is a stress-related mental disorder caused by traumatic experiences. Studies have found that exposure to early stressful events is a risk factor for developing PTSD. However, a limited number of studies have explored the effects of traumatic stress in early adolescence on behavior, hypothalamic-pituitary-adrenal (HPA) axis function, central corticotropin releasing factor receptor 1 (CRFR1) expression and the relative vulnerability of PTSD in adulthood. The current study aims to explore these issues using inescapable electric foot shock to induce a PTSD model in early adolescent rats. Meanwhile, running on a treadmill for six weeks and administration of the antagonist with 3.2mg/kg/day of CP-154, 526 for 14 consecutive days were used as therapeutic measures. Presently, the stress (S) group showed more anxiety and depression in the open field (OF) test and elevated plus maze (EPM) test, memory damage in the Y maze test, decreased basal CORT level, increased DEX negative feedback inhibition and exacerbated and longer-lasting reaction to CRH challenge in the DEX/CRH test compared with the control group. Central CRFR1 expression was also changed in the S group, as evidenced by the increased CRFR1 expression in the hypothalamus, amygdala and the prefrontal cortex (PFC). However, treadmill exercise alleviated early adolescent stress-induced behavior abnormalities and improved the functional state of the HPA axis, performing a more powerful effect than the CRFR1 antagonist CP-154, 526. Additionally, this study revealed that the alteration of central CRFR1 expression might play an important role in etiology of PTSD in adulthood. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Alterations of physiology and gene expression due to long-term magnesium-deficiency differ between leaves and roots of Citrus reticulata.

    Science.gov (United States)

    Jin, Xiao-Lin; Ma, Cui-Lan; Yang, Lin-Tong; Chen, Li-Song

    2016-07-01

    Seedlings of Ponkan (Citrus reticulata) were irrigated with nutrient solution containing 0 (Mg-deficiency) or 1mM MgSO4 (control) every two day for 16 weeks. Thereafter, we examined magnesium (Mg)-deficiency-induced changes in leaf and root gas exchange, total soluble proteins and gene expression. Mg-deficiency lowered leaf CO2 assimilation, and increased leaf dark respiration. However, Mg-deficient roots had lower respiration. Total soluble protein level was not significantly altered by Mg-deficiency in roots, but was lower in Mg-deficient leaves than in controls. Using cDNA-AFLP, we obtained 70 and 71 differentially expressed genes from leaves and roots. These genes mainly functioned in signal transduction, stress response, carbohydrate and energy metabolism, cell transport, cell wall and cytoskeleton metabolism, nucleic acid, and protein metabolisms. Lipid metabolism (Ca(2+) signals)-related Mg-deficiency-responsive genes were isolated only from roots (leaves). Although little difference existed in the number of Mg-deficiency-responsive genes between them both, most of these genes only presented in Mg-deficient leaves or roots, and only four genes were shared by them both. Our data clearly demonstrated that Mg-deficiency-induced alterations of physiology and gene expression greatly differed between leaves and roots. In addition, we focused our discussion on the causes for photosynthetic decline in Mg-deficient leaves and the responses of roots to Mg-deficiency. Copyright © 2016 Elsevier GmbH. All rights reserved.

  10. Helper-dependent adenoviral vector-mediated long-term expression of human apolipoprotein A-I reduces atherosclerosis in apo E-deficient mice.

    Science.gov (United States)

    Pastore, Lucio; Belalcazar, L Maria; Oka, Kazuhiro; Cela, Racel; Lee, Brendan; Chan, Lawrence; Beaudet, Arthur L

    2004-03-03

    Apolipoprotein A-I (APOA-I) is the major protein component of high-density lipoproteins (HDL). It has been shown that over-expression of human APOA-I increases HDL cholesterol and decreases atherosclerosis. We constructed a helper-dependent adenoviral (HD-Ad) vector that contains the entire human APOA-I gene (hgAI). Intravenous delivery of 1x10(13) viral particles/kg of this vector was followed by high levels of human APOA-I expression (up to 200 mg/dl) in the absence of detectable hepatic toxicity. We treated apo E-deficient mice with the hgAI vector and fed them either with a high-fat diet or with regular chow. As a control, two groups of mice were treated with PBS. The apo E-deficient mice treated with the hgAI vector showed supraphysiological levels of expression of human APOA-I at week 4 and high levels of HDL cholesterol compared to the control groups. Analysis of aortic atherosclerotic lesions 20 weeks after treatment, showed a significant reduction of lesion size in the treated mice with both diets. In conclusion, liver-directed gene transfer of human APOA-I using a HD-Ad vector resulted in a reduction of the development of atherosclerosis with the absence of significant toxicity.

  11. Modulation of innate immunity and gene expressions in white shrimp Litopenaeus vannamei following long-term starvation and re-feeding

    Science.gov (United States)

    Lin, Yong-Chin; Chen, Jiann-Chu; C. Man, Siti Nursafura; W. Morni, Wan Zabidii; N.A. Suhaili, Awangku Shahrir; Cheng, Sha-Yen; Hsu, Chih-Hung

    2012-01-01

    The survival rate, weight loss, immune parameters, resistance against Vibrio alginolyticus and white-spot syndrome virus (WSSV), and expressions of lipopolysaccharide- and ß-glucan-binding protein (LGBP), peroxinectin (PX), prophenoloxidase-activating enzyme (ppA), prophenoloxidase (proPO) I, proPO II, α2-macroglobulin (α2-M), integrin ß, heat shock protein 70 (HSP70), cytosolic manganese superoxide dismutase (cytMnSOD), mitochondrial manganese superoxide dismutase (mtMnSOD), and extracellular copper and zinc superoxide dismutase (ecCuZnSOD) were examined in the white shrimp Litopenaeus vannamei (8.18 ± 0.86 g body weight) which had been denied food (starved) for up to 14–28 days. Among shrimp which had been starved for 7, 14, 21, and 28 days, 100%, 90%, 71%, and 59% survived, and they lost 3.2%, 7.3%, 9.2%, and 10.4% of their body weight, respectively. Hyaline cells (HCs), granular cells (GCs, including semi-granular cells), the total haemocyte count (THC), phenoloxidase (PO) activity, respiratory bursts (RBs), and SOD activity significantly decreased in shrimp which had been starved for 1, 1, 1, 5, 14, and 3 days, respectively. The expression of integrin ß significantly decreased after 0.5–5 days of starvation, whereas the expressions of LGBP, PX, proPO I, proPO II, ppA, and α2-M increased after 0.5–1 days. Transcripts of all genes except ecCuZnSOD decreased to the lowest level after 5 days, and tended to background values after 7 and 14 days. Cumulative mortality rates of 7-day-starved shrimp challenged with V. alginolyticus and WSSV were significantly higher than those of challenged control-shrimp for 1–7 and 1–4 days, respectively. In another experiment, immune parameters of shrimp which had been starved for 7 and 14 days and then received normal feeding (at 5% of their body weight daily) were examined after 3, 6, and 12 h, and 1, 3, and 5 days. All immune parameters of 7-day-starved shrimp were able to return to their baseline values

  12. Long-term effects of subacute ruminal acidosis (SARA) on milk quality and hepatic gene expression in lactating goats fed a high-concentrate diet.

    Science.gov (United States)

    Dong, Haibo; Wang, Shaoqing; Jia, Yuanyuan; Ni, Yingdong; Zhang, Yuanshu; Zhuang, Su; Shen, Xiangzhen; Zhao, Ruqian

    2013-01-01

    The mechanism underlying the decline in milk quality during periods of feeding high-concentrate diets to dairy ruminants is not well documented. The aim of this study was to investigate the metabolic changes in the liver that contribute to the input of substrate precursors to the mammary gland after feeding a high-concentrate diet to lactating goats for a long period. Eight mid-lactating goats with rumen cannulas were randomly assigned to two groups. For 9 weeks, the treatment group was fed a high-concentrate diet (60% concentrate of dry matter, HC) and the control group was fed a low-concentrate diet (40% concentrate of dry matter, LC). Ruminal fluid, plasma, and liver tissues were sampled, microarray techniques and real-time polymerase chain reaction were used to evaluate metabolic parameters and gene expression in liver. Feeding a 60%-concentrate diet for 9 weeks resulted in a significant decrease in rumen pH. Changes in fat and protein content also occurred, which negatively affected milk quality. Plasma levels of leptin (p = 0.058), non-esterified fatty acid (p = 0.071), and glucose (p = 0.014) increased markedly in HC group. Plasma cortisol concentration was significantly elevated in the treatment group (p<0.05). Expression of the glucocorticoid receptor protein gene was significantly down-regulated (p<0.05) in the liver. The expression of genes for interleukin 1β, serum amyloid A, C-reactive protein, and haptoglobin mRNA was significantly increased (p<0.05) in the HC group. GeneRelNet analysis showed that gene expression involved in inflammatory responses and the metabolism of lipids, protein, and carbohydrate were significantly altered by feeding a high-concentrate diet for 9 weeks. Activation of the acute phase response and the inflammatory response may contribute to nutrient partitioning and re-distribution of energy in the liver, and ultimately lead to a decline in milk quality.

  13. Long-term effects of subacute ruminal acidosis (SARA on milk quality and hepatic gene expression in lactating goats fed a high-concentrate diet.

    Directory of Open Access Journals (Sweden)

    Haibo Dong

    Full Text Available PURPOSE: The mechanism underlying the decline in milk quality during periods of feeding high-concentrate diets to dairy ruminants is not well documented. The aim of this study was to investigate the metabolic changes in the liver that contribute to the input of substrate precursors to the mammary gland after feeding a high-concentrate diet to lactating goats for a long period. EXPERIMENTAL DESIGN: Eight mid-lactating goats with rumen cannulas were randomly assigned to two groups. For 9 weeks, the treatment group was fed a high-concentrate diet (60% concentrate of dry matter, HC and the control group was fed a low-concentrate diet (40% concentrate of dry matter, LC. Ruminal fluid, plasma, and liver tissues were sampled, microarray techniques and real-time polymerase chain reaction were used to evaluate metabolic parameters and gene expression in liver. RESULTS: Feeding a 60%-concentrate diet for 9 weeks resulted in a significant decrease in rumen pH. Changes in fat and protein content also occurred, which negatively affected milk quality. Plasma levels of leptin (p = 0.058, non-esterified fatty acid (p = 0.071, and glucose (p = 0.014 increased markedly in HC group. Plasma cortisol concentration was significantly elevated in the treatment group (p<0.05. Expression of the glucocorticoid receptor protein gene was significantly down-regulated (p<0.05 in the liver. The expression of genes for interleukin 1β, serum amyloid A, C-reactive protein, and haptoglobin mRNA was significantly increased (p<0.05 in the HC group. GeneRelNet analysis showed that gene expression involved in inflammatory responses and the metabolism of lipids, protein, and carbohydrate were significantly altered by feeding a high-concentrate diet for 9 weeks. CONCLUSIONS: Activation of the acute phase response and the inflammatory response may contribute to nutrient partitioning and re-distribution of energy in the liver, and ultimately lead to a decline in milk quality.

  14. Long-term exposure to IL-1beta enhances Toll-IL-1 receptor-mediated inflammatory signaling in murine airway hyperresponsiveness

    DEFF Research Database (Denmark)

    Zhang, Yaping; Xu, Cang-Bao; Cardell, Lars-Olaf

    2009-01-01

    -time PCR-based cDNA array. The key gene expressions that were altered were verified by immunohistochemistry using confocal microscopy. Tracheal ring segment contractile responsiveness to the inflammatory mediator bradykinin was monitored using a sensitive myograph system. The results showed that after...... array, a sensitive and powerful tool, consisting of 84 genes related to Toll-IL-1 receptor signal pathways. Murine tracheal segments were organ cultured for four days in the presence and absence of IL-1beta. The Toll-IL-1 receptor-mediated inflammatory signal gene profile was studied using the real...

  15. Long-term untreated streptozotocin-diabetes leads to increased expression and elevated activity of prostaglandin H2 synthase in blood platelets.

    Science.gov (United States)

    Siewiera, Karolina; Kassassir, Hassan; Talar, Marcin; Wieteska, Lukasz; Watala, Cezary

    2016-01-01

    In diabetes-related states of chronic hyperglycaemia elevated concentrations of glucose may alter the functioning of platelet enzymes involved in arachidonic acid metabolism, including prostaglandin H2 synthase (cyclooxygenase) (PGHS, COX). Therefore, the principal aim of this study was to assess the effects of experimental chronic hyperglycaemia on platelet PGHS-1 (COX-1) expression and activity. Blood platelet activation and reactivity were assessed in Sprague-Dawley rats with the 5-month streptozotocin (STZ) diabetes. The PGHS-1 abundance in platelets was evaluated with flow cytometry and Western blotting, while its activity monitored using a high resolution respirometry and the peroxidase fluorescent assay. The production of prostaglandin E2 (PGE2) and thromboxane B2 (TXB2) in platelets were assayed immunoenzymatically. Circulating platelets from diabetic were characterised by increased size, elevated 'priming' and altered reactivity, compared to non-diabetic animals. Both Western blot analysis and flow cytometry revealed significantly elevated expressions of platelet PGHS-1 in STZ-diabetic rats (p platelet PGHS-1-related arachidonic acid metabolism in diabetic vs. non-diabetic animals, with the use of polarographic (p platelet PGHS-1 abundance. Therefore, our results further contribute to the explanation of the increased metabolism of arachidonic acid observed in diabetes.

  16. Effects of long-term theophylline exposure on recovery of respiratory function and expression of adenosine A1 mRNA in cervical spinal cord hemisected adult rats.

    Science.gov (United States)

    Nantwi, Kwaku D; Basura, Gregory J; Goshgarian, Harry G

    2003-07-01

    Our lab has previously shown that when administered acutely, the methylxanthine theophylline can activate a latent respiratory motor pathway to restore function to the hemidiaphragm paralyzed by an ipsilateral C2 spinal cord hemisection. The recovery is mediated by the antagonism of CNS adenosine A1 receptors. The objective of the present study was to assess quantitatively recovery after chronic theophylline administration, the effects of weaning from the drug, and the effects of the drug on adenosine A1 receptor mRNA expression in adult rats subjected to a C2 hemisection. Rats subjected to a left C2 hemisection received theophylline orally for 3, 7, 12, or 30 days and were classified as 3D, 7D, 12D, or 30D respectively. Separate groups of 3D animals were weaned from drug administration for 7, 12, and 30 days before assessment of respiratory recovery. Additional groups of 7D and 12D animals were also weaned from drug administration for 7 and 12 days prior to assessment. Sham-operated controls received theophylline vehicle for similar periods. Quantitative assessment of recovered respiratory activity was conducted under standardized electrophysiologic recording conditions approximately 18 h after each drug application period. Serum theophylline analysis was conducted at the end of electrophysiologic recordings. Adenosine A1 receptor mRNA expression in the phrenic nucleus was assessed with in situ hybridization and immunohistochemistry. Chronic theophylline induced a dose-dependent effect on respiratory recovery over a serum theophylline range of 1.2-1.9 microg/ml. Recovery was characterized as respiratory-related activity in the left phrenic nerve and expressed as a percentage of activity in the homolateral nerve in noninjured animals under similar recording conditions. Recovered activity was 34.13 +/- 2.07, 55.89 +/- 2.96, 74.78 +/- 1.93, and 79.12 +/- 1.75% respectively in the 3D, 7D, 12D, and 30D groups. Theophylline-induced recovered activity persisted for as

  17. Navigating Long-Term Care

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    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.

  18. Effects of Long-Term Exposure to 60 GHz Millimeter-Wavelength Radiation on the Genotoxicity and Heat Shock Protein (Hsp Expression of Cells Derived from Human Eye

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    Shin Koyama

    2016-08-01

    Full Text Available Human corneal epithelial (HCE-T and human lens epithelial (SRA01/04 cells derived from the human eye were exposed to 60 gigahertz (GHz millimeter-wavelength radiation for 24 h. There was no statistically significant increase in the micronucleus (MN frequency in cells exposed to 60 GHz millimeter-wavelength radiation at 1 mW/cm2 compared with sham-exposed controls and incubator controls. The MN frequency of cells treated with bleomycin for 1 h provided positive controls. The comet assay, used to detect DNA strand breaks, and heat shock protein (Hsp expression also showed no statistically significant effects of exposure. These results indicate that exposure to millimeter-wavelength radiation has no effect on genotoxicity in human eye cells.

  19. [Long-term drinking purified water may aggravate the inhibition of NMDA expression and spatial learning ability induced by lead on rat].

    Science.gov (United States)

    Chen, Qiang; Shu, Wei-qun; Zeng, Hui; Luo, Jiao-hua; Fu, Wen-juan

    2008-06-01

    To compare brain lead accumulation and neurotoxicity induced by lead under drinking purified water and tap water on rat. All 104 male weaning SD rats were randomly divided into eight groups, matched-four pairs according to drinking water: tap water, purified water, tap water with lead 50 mg/L(lead acetate water-solution), purified water with lead 50 mg/L, tap water with lead 200 mg/L, purified water with lead 200 mg/L, tap water with lead 800 mg/L. All were fed with normal food and environmental cognitions kept consistent Morris water maze(including Place Navigation, Spatial Probe Test, Visible Platform Trial) was measured to test rat spatial learning at the 12 and 24 week. At the end of the experiment (28 week), rats were killed and the lead of brain and blood was measured by Graphite furnace atomic absorption spectrometric method; the NR1, NR2A, NR2B of NMDAR (N-methyl-D-aspartame receptor) in hippocampus were analyzed by RT-PCR. Under the same lead exposure, no significant differences were observed in blood lead, however, brain lead level showed higher in drinking purified water group than that in tap water group. Expression of NR1, NR2A and NR2B in hippocampus of the rats drinking purified water was lower than those drinking tap water, especially at low lead exposure (50 mg/L) (P water maze, place navigation test's escape latency showed significantly prolonged at the rats drinking purified water as compared with those drinking tap water on the pairs of 50 mg/L and 200 mg/L pb2+ groups (P water, drinking purified water might increase the accumulation of brain lead, lower NR1, NR2A, NR2B expression and delay the spatial learning and memory ability under chronic lead exposure in water.

  20. Few-layer antimonene decorated microfiber: ultra-short pulse generation and all-optical thresholding with enhanced long term stability

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    Song, Yufeng; Liang, Zhiming; Jiang, Xiantao; Chen, Yunxiang; Li, Zhongjun; Lu, Lu; Ge, Yanqi; Wang, Ke; Zheng, Jilin; Lu, Shunbin; Ji, Jianhua; Zhang, Han

    2017-12-01

    Antimonene, a new type of mono/few-layer two-dimensional (2D) mono-elemental material purely consisting of antimony similar as graphene and phosphorene, has been theoretically predicted with excellent optical response and enhanced stability. Herein, we experimentally investigated the broadband nonlinear optical response of highly stable few-layer antimonene (FLA) by performing an open-aperture Z-scan laser measurement. Thanks to the direct bandgap and resonant absorption at the telecommunication band, we demonstrated the feasibility of FLA-decorated microfiber not only as an optical saturable absorber for ultrafast photonics operation, but also as a stable all-optical pulse thresholder that can effectively suppress the transmission noise, boost the signal-to-noise ratio (SNR), and reshape the deteriorated input signal. Our findings, as the first prototypic device of absorption of antimonene, might facilitate the development of antimonene-based optical communication technologies towards high stability and practical applications in the future.

  1. Transcriptional regulation of long-term memory in the marine snail Aplysia

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    Lee Yong-Seok

    2008-06-01

    Full Text Available Abstract Whereas the induction of short-term memory involves only covalent modifications of constitutively expressed preexisting proteins, the formation of long-term memory requires gene expression, new RNA, and new protein synthesis. On the cellular level, transcriptional regulation is thought to be the starting point for a series of molecular steps necessary for both the initiation and maintenance of long-term synaptic facilitation (LTF. The core molecular features of transcriptional regulation involved in the long-term process are evolutionally conserved in Aplysia, Drosophila, and mouse, and indicate that gene regulation by the cyclic AMP response element binding protein (CREB acting in conjunction with different combinations of transcriptional factors is critical for the expression of many forms of long-term memory. In the marine snail Aplysia, the molecular mechanisms that underlie the storage of long-term memory have been extensively studied in the monosynaptic connections between identified sensory neuron and motor neurons of the gill-withdrawal reflex. One tail shock or one pulse of serotonin (5-HT, a modulatory transmitter released by tail shocks, produces a transient facilitation mediated by the cAMP-dependent protein kinase leading to covalent modifications in the sensory neurons that results in an enhancement of transmitter release and a strengthening of synaptic connections lasting minutes. By contrast, repeated pulses of 5-hydroxytryptamine (5-HT induce a transcription- and translation-dependent long-term facilitation (LTF lasting more than 24 h and trigger the activation of a family of transcription factors in the presynaptic sensory neurons including ApCREB1, ApCREB2 and ApC/EBP. In addition, we have recently identified novel transcription factors that modulate the expression of ApC/EBP and also are critically involved in LTF. In this review, we examine the roles of these transcription factors during consolidation of LTF induced

  2. Long-Term Suppression of Hepatitis B Virus Replication by Short Hairpin RNA Expression Using the Scaffold/Matrix Attachment Region-Based Replicating Vector System pEPI-1▿

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    Jenke, Andreas C. W.; Wilhelm, Andreas D.; Orth, Valerie; Lipps, Hans Joachim; Protzer, Ulrike; Wirth, Stefan

    2008-01-01

    Since the emergence of viral resistance of hepatitis B virus (HBV) during treatment is becoming an important issue even with newer drugs, there is a need for alternative treatment options such as, for example, RNA interference (RNAi) technology. While short-term suppression of HBV replication is easily achieved with small interfering RNA oligonucleotides, this is not the case for long-term suppression due to the lack of an optimal vector system. Based on the nonviral scaffold/matrix attachment region (S/MAR)-based vector system pEPI-1, which is free of common side effects and is stably retained as an episome even in the absence of selection, we designed a short hairpin RNA (shRNA) expression vector called pEPI-RNAi for HBV suppression. HBV-replicating HepG2.2.15 cells were transfected with pEPI-RNAi, and the intracellular status of the plasmid was followed by PCR and Southern analysis. HBV replication was measured on the DNA, RNA, and protein level. HBV RNA expression was reduced by almost 85% 3 months posttransfection with pEPI-RNAi. At 8 months posttransfection in the absence of antibiotic selection pressure, the suppression level was still 70% and the vector was retained as an episome. The reduction of total intracellular HBV DNA at this point was 77%, showing a marked suppression of HBV DNA replication. At a comparable level, secretion of viral antigens, as well as progeny HBV virions, was inhibited. The S/MAR-based vector system pEPI-1 allows long-term suppression of HBV replication by the expression of suitable shRNAs. Due to its unique properties compared to commonly used vectors, it provides an interesting option for the treatment of chronically HBV-infected individuals. PMID:18474581

  3. Long-term feeding of hydroalcoholic extract powder of Lepidium meyenii (maca) enhances the steroidogenic ability of Leydig cells to alleviate its decline with ageing in male rats.

    Science.gov (United States)

    Yoshida, K; Ohta, Y; Kawate, N; Takahashi, M; Inaba, T; Hatoya, S; Morii, H; Takahashi, K; Ito, M; Tamada, H

    2017-03-10

    This study examined whether feeding hydroalcoholic extract of Lepidium meyenii (maca) to 8-week-old (sexually maturing) or 18-week-old (mature) male rats for more than a half year affects serum testosterone concentration and testosterone production by Leydig cells cultured with hCG, 22R-hydroxycholesterol or pregnenolone. Testosterone concentration was determined in the serum samples obtained before and 6, 12, 18 and 24 weeks after the feeding, and it was significantly increased only at the 6 weeks in the group fed with the maca extract to maturing rats when it was compared with controls. Testosterone production by Leydig cells significantly increased when cultured with hCG by feeding the maca extract to maturing rats for 27 weeks (35 weeks of age) and when cultured with 22R-hydroxycholesterol by feeding it to mature rats for 30 weeks (48 weeks of age). Overall testosterone production by cultured Leydig cells decreased to about a half from 35 to 48 weeks of age. These results suggest that feeding the maca extract for a long time to male rats may enhance the steroidogenic ability of Leydig cells to alleviate its decline with ageing, whereas it may cause only a transient increase in blood testosterone concentration in sexually maturing male rats. © 2017 Blackwell Verlag GmbH.

  4. Acute escitalopram treatment inhibits REM sleep rebound and activation of MCH-expressing neurons in the lateral hypothalamus after long term selective REM sleep deprivation.

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    Kátai, Zita; Adori, Csaba; Kitka, Tamás; Vas, Szilvia; Kalmár, Lajos; Kostyalik, Diána; Tóthfalusi, László; Palkovits, Miklós; Bagdy, György

    2013-08-01

    Selective rapid eye movement sleep (REMS) deprivation using the platform-on-water ("flower pot") method causes sleep rebound with increased REMS, decreased REMS latency, and activation of the melanin-concentrating hormone (MCH) expressing neurons in the hypothalamus. MCH is implicated in the pathomechanism of depression regarding its influence on mood, feeding behavior, and REMS. We investigated the effects of the most selective serotonin reuptake inhibitor escitalopram on sleep rebound following REMS deprivation and, in parallel, on the activation of MCH-containing neurons. Escitalopram or vehicle (10 mg/kg, intraperitoneally) was administered to REMS-deprived (72 h) or home cage male Wistar rats. During the 3-h-long "rebound sleep", electroencephalography was recorded, followed by an MCH/Fos double immunohistochemistry. During REMS rebound, the time spent in REMS and the number of MCH/Fos double-labeled neurons in the lateral hypothalamus increased markedly, and REMS latency showed a significant decrease. All these effects of REMS deprivation were significantly attenuated by escitalopram treatment. Besides the REMS-suppressing effects, escitalopram caused an increase in amount of and decrease in latency of slow wave sleep during the rebound. These results show that despite the high REMS pressure caused by REMS deprivation procedure, escitalopram has the ability to suppress REMS rebound, as well as to diminish the activation of MCH-containing neurons, in parallel. Escitalopram caused a shift from REMS to slow wave sleep during the rebound. Furthermore, these data point to the potential connection between the serotonergic system and MCH in sleep regulation, which can be relevant in depression and in other mood disorders.

  5. Long-term survival and concomitant gene expression of ribozyme-transduced CD4+ T-lymphocytes in HIV-infected patients.

    Science.gov (United States)

    Macpherson, Janet L; Boyd, Maureen P; Arndt, Allison J; Todd, Alison V; Fanning, Gregory C; Ely, Julie A; Elliott, Fiona; Knop, Alison; Raponi, Mitch; Murray, John; Gerlach, Wayne; Sun, Lun-Quan; Penny, Ronald; Symonds, Geoff P; Carr, Andrew; Cooper, David A

    2005-05-01

    An anti-HIV-1 tat ribozyme, termed Rz2, has been shown to inhibit HIV-1 infection/replication and to decrease HIV-1-induced pathogenicity in T-lymphocyte cell lines and normal peripheral blood T-lymphocytes. We report here the results of a phase I gene transfer clinical trial using Rz2. Apheresis was used to obtain a peripheral blood cell population from each of four HIV-negative donors. After enrichment for CD4+ T-lymphocytes, ex vivo expansion and genetic manipulation (approximately equal aliquots of the cells were transduced with the ribozyme-containing (RRz2) and the control (LNL6) retroviral vector), these cells were infused into the corresponding HIV-1-positive twin recipient. Marking was assessed over an initial 24-week period and in total over an approximate 4-year period. The gene transfer procedure was shown to be safe, and technically feasible. Both RRz2- and LNL6-gene-containing peripheral blood mononuclear cells (PBMC) were detected at all time points examined to 4 years. There was concomitant gene construct expression in the absence of the need for ex vivo peripheral blood cell stimulation and there was no evidence of immune elimination of the neoR T-lymphocytes nor of silencing of the Moloney murine leukemia virus long terminal repeat. The proof of principle results reported here demonstrate safety and feasibility of this type of gene transfer approach. While not specifically tested, T-lymphocytes containing an anti-HIV gene construct may impact on HIV-1 viral load and CD4+ T-lymphocyte count, potentially representing a new therapeutic modality for HIV-1 infection. Copyright (c) 2005 John Wiley & Sons, Ltd.

  6. Impact of AtNHX1, a vacuolar Na+/H+ antiporter, upon gene expression during short- and long-term salt stress in Arabidopsis thaliana

    Directory of Open Access Journals (Sweden)

    Blumwald Eduardo

    2007-04-01

    Full Text Available Abstract Background AtNHX1, the most abundant vacuolar Na+/H+ antiporter in Arabidopsis thaliana, mediates the transport of Na+ and K+ into the vacuole, influencing plant development and contributing to salt tolerance. In this report, microarray expression profiles of wild type plants, a T-DNA insertion knockout mutant of AtNHX1 (nhx1, and a 'rescued' line (NHX1::nhx1 were exposed to both short (12 h and 48 h and long (one and two weeks durations of a non-lethal salt stress to identify key gene transcripts associated with the salt response that are influenced by AtNHX1. Results 147 transcripts showed both salt responsiveness and a significant influence of AtNHX1. Fifty-seven of these genes showed an influence of the antiporter across all salt treatments, while the remaining genes were influenced as a result of a particular duration of salt stress. Most (69% of the genes were up-regulated in the absence of AtNHX1, with the exception of transcripts encoding proteins involved with metabolic and energy processes that were mostly down-regulated. Conclusion While part of the AtNHX1-influenced transcripts were unclassified, other transcripts with known or putative roles showed the importance of AtNHX1 to key cellular processes that were not necessarily limited to the salt stress response; namely calcium signaling, sulfur metabolism, cell structure and cell growth, as well as vesicular trafficking and protein processing. Only a small number of other salt-responsive membrane transporter transcripts appeared significantly influenced by AtNHX1.

  7. Intensive cognitive training in schizophrenia enhances working memory and associated prefrontal cortical efficiency in a manner that drives long-term functional gains.

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    Subramaniam, Karuna; Luks, Tracy L; Garrett, Coleman; Chung, Cleo; Fisher, Melissa; Nagarajan, Srikantan; Vinogradov, Sophia

    2014-10-01

    We investigated whether intensive computerized cognitive training in schizophrenia could improve working memory performance and increase signal efficiency of associated middle frontal gyri (MFG) circuits in a functionally meaningful manner. Thirty schizophrenia participants and 13 healthy comparison participants underwent fMRI scanning during a letter N-back working memory task. Schizophrenia participants were then randomly assigned to either 80 h (16 weeks) of cognitive training or a computer games control condition. After this intervention, participants completed a second fMRI N-back scanning session. At baseline, during 2-back working memory trials, healthy participants showed the largest and most significant activation in bilateral MFG, which correlated with task performance. Schizophrenia participants showed impaired working memory, hypoactivation in left MFG, and no correlation between bilateral MFG signal and task performance. After training, schizophrenia participants improved their 2-back working memory performance and showed increased activation in left MFG. They also demonstrated a significant association between enhanced task performance and right MFG signal, similar to healthy participants. Both task performance and brain activity in right MFG after training predicted better generalized working memory at 6-month follow-up. Furthermore, task performance and brain activity within bilateral MFG predicted better occupational functioning at 6-month follow-up. No such findings were observed in the computer games control participants. Working memory impairments in schizophrenia and its underlying neural correlates in MFG can be improved by intensive computerized cognitive training; these improvements generalize beyond the trained task and are associated with enduring effects on cognition and functioning 6 months after the intervention. Published by Elsevier Inc.

  8. Enhanced and long term immunogenicity of a Her-2/neu multi-epitope vaccine conjugated to the carrier CRM197 in conjunction with the adjuvant Montanide.

    Science.gov (United States)

    Tobias, Joshua; Jasinska, Joanna; Baier, Karin; Kundi, Michael; Ede, Nicholas; Zielinski, Christoph; Wiedermann, Ursula

    2017-02-09

    We previously identified three short single peptides (P4, P6 and P7) representing different B-cell epitopes on the extracellular domain of Her-2/neu for a vaccine that was tested in a phase-I clinical trial. Here we describe the improvement of the multi peptide vaccine by fusing the single peptides to a hybrid peptide P467. After coupling to either virosomes or to diphtheria toxoid CRM197 (CRM), the hybrid peptide was tested in different concentrations in combination with either Montanide or Aluminium hydroxide (Alum) in preclinical studies. Already low amount (10 μg) of P467 conjugated to CRM led to faster onset of high antibody levels compared to the P467-virosome. The formulation P467-CRM-Montanide induced higher serum IgG antibody titers, compared with P467-CRM-Alum, as examined by ELISA using recombinant Her-2/neu or Her-2/neu natively expressed on the tumor cell line SK-BR-3. Compared to P467-CRM-Alum, higher in vitro production of IL-2 and IFNγ in the Montanide-immunized mice was induced after re-stimulation of splenocytes with CRM but also with P467, indicating a clear Th1-biased response. In contrast to the single B cell peptides, the hybrid peptide led to T cell proliferation and cytokine production as CD4 T cell epitopes were generated in the fusion region of the single peptides P4 and P6 or P6 and P7. Additionally, a significantly higher proportion IFNγ-producing CD8+ T cells was found in the P467-CRM-Montanide immunized mice, probably by Montanide-driven bystander activation. Importantly, anti-P467 IgG antibodies exhibited anti-tumor properties and the combination of anti-P467 specific IgG with Herceptin® was found to inhibit the proliferation of Her-2/neu-overexpressing cell line SK-BR-3 in a significantly higher capacity than Herceptin® alone. Fusion of the B cell peptides has led to additional generation of CD4 T cell epitopes, and this P467-multi epitope vaccine was found to induce polyclonal antibody responses with anti

  9. HDAC3 Is a Critical Negative Regulator of Long-Term Memory Formation

    Science.gov (United States)

    McQuown, Susan C.; Barrett, Ruth M.; Matheos, Dina P.; Post, Rebecca J.; Rogge, George A.; Alenghat, Theresa; Mullican, Shannon E.; Jones, Steven; Rusche, James R.; Lazar, Mitchell A.; Wood, Marcelo A.

    2011-01-01

    Gene expression is dynamically regulated by chromatin modifications on histone tails, such as acetylation. In general, histone acetylation promotes transcription, whereas histone deacetylation negatively regulates transcription. The interplay between histone acetyl-transerases and histone deacetylases (HDACs) is pivotal for the regulation of gene expression required for long-term memory processes. Currently, very little is known about the role of individual HDACs in learning and memory. We examined the role of HDAC3 in long-term memory using a combined genetic and pharmacologic approach. We used HDAC3–FLOX genetically modified mice in combination with adeno-associated virus-expressing Cre recombinase to generate focal homozygous deletions of Hdac3 in area CA1 of the dorsal hippocampus. To complement this approach, we also used a selective inhibitor of HDAC3, RGFP136 [N-(6-(2-amino-4-fluorophenylamino)-6-oxohexyl)-4-methylbenzamide]. Immunohistochemistry showed that focal deletion or intrahippocampal delivery of RGFP136 resulted in increased histone acetylation. Both the focal deletion of HDAC3 as well as HDAC3 inhibition via RGFP136 significantly enhanced long-term memory in a persistent manner. Next we examined expression of genes implicated in long-term memory from dorsal hippocampal punches using quantitative reverse transcription-PCR. Expression of nuclear receptor subfamily 4 group A, member 2 (Nr4a2) and c-fos was significantly increased in the hippocampus of HDAC3–FLOX mice compared with wild-type controls. Memory enhancements observed in HDAC3–FLOX mice were abolished by intrahippocampal delivery of Nr4a2 small interfering RNA, suggesting a mechanism by which HDAC3 negatively regulates memory formation. Together, these findings demonstrate a critical role for HDAC3 in the molecular mechanisms underlying long-term memory formation. PMID:21228185

  10. Hypovascular hypointense nodules on hepatobiliary phase without T2 hyperintensity on gadoxetic acid-enhanced MR images in patients with chronic liver disease: long-term outcomes and risk factors for hypervascular transformation.

    Science.gov (United States)

    Kim, Yong Seek; Song, Ji Soo; Lee, Hyun Kyung; Han, Young Min

    2016-10-01

    To evaluate the long-term outcomes and imaging features associated with hypervascularization of hypovascular nodules that show T2 iso-/hypointensity and hypointensity on hepatobiliary phase (HBP) of gadoxetic acid-enhanced magnetic resonance (MR) images in patients with chronic liver disease. Sixty patients and 114 nodules, which were hypovascular and iso-/hypointense on T2-weighted images and hypointense on HBP of gadoxetic acid-enhanced MRI, were included. We evaluated the effect of baseline clinical features, baseline MR features and growth rate on subsequent hypervascularization. Twenty-seven nodules in 21 patients transformed to hypervascular hepatocellular carcinoma (HCC). Using multivariate Cox analysis, T1 hyperintensity (hazard ratio [HR] = 2.69, P = 0.021), previous history of HCC (HR = 2.64, P = 0.021), and initial nodule size (HR = 1.09, P = 0.046) were identified to be associated with hypervascularization. The growth rate of nodules was a more powerful determinant of subsequent hypervascularization than baseline clinical and MR features. At long-term follow-up after >3 years, only one nodule with T1 isointensity showed hypervascularization. Careful follow-up or diagnostic procedures, such as biopsy, should be considered for up to 3 years after detection of hypointense nodules on HBP with T1 hyperintensity or a higher growth rate. • T1 hyperintensity is a baseline MR predictive factor for subsequent hypervascularization. • A higher growth rate is a more powerful determinant of subsequent hypervascularization. • Management of patients with these predictive factors requires more attention.

  11. Long-term stable expression of human apolipoprotein A-I mediated by helper-dependent adenovirus gene transfer inhibits atherosclerosis progression and remodels atherosclerotic plaques in a mouse model of familial hypercholesterolemia.

    Science.gov (United States)

    Belalcazar, L Maria; Merched, Aksam; Carr, Boyd; Oka, Kazuhiro; Chen, Kuang-Hua; Pastore, Lucio; Beaudet, Arthur; Chan, Lawrence

    2003-06-03

    Epidemiologic studies and transgenic mouse experiments indicate that high plasma HDL and apolipoprotein (apo) A-I protect against atherosclerosis. We used helper-dependent adenovirus (HD-Ad) gene transfer to examine the effect of long-term hepatic apoA-I expression on atherosclerotic lesion progression and remodeling in a mouse model of familial hypercholesterolemia. We treated LDL receptor-deficient (LDLR-/-) mice maintained on a high-cholesterol diet for 6 weeks with either a HD-Ad containing human apoA-I gene (HD-Ad-AI) or saline (control). HD-Ad-AI treatment did not affect plasma liver enzymes but induced the appearance of plasma human apoA-I at or above human levels for the duration of the study. Substantial amounts of human apoA-I existed in lipid-free plasma. Compared with controls, HDLs from treated mice were larger and had a greater inhibitory effect on tumor necrosis factor-alpha-induced vascular cellular adhesion molecule-1 expression in cultured endothelial cells. Twenty-four weeks after injection, aortic atherosclerotic lesion area in saline-treated mice progressed approximately 700%; the rate of progression was reduced by >50% by HD-Ad-AI treatment. The lesions in HD-Ad-AI-treated mice contained human apoA-I that colocalized mainly with macrophages; they also contained less lipid, fewer macrophages, and less vascular cellular adhesion molecule-1 immunostaining but more smooth muscle cells (alpha-actin staining) and collagen. HD-Ad-AI treatment of LDLR-/- mice leads to long-term overexpression of apoA-I, retards atherosclerosis progression, and remodels the lesions to a more stable-appearing phenotype. HD-Ad-mediated transfer of apoA-I may be a useful clinical approach for protecting against atherosclerosis progression and stabilizing atherosclerotic lesions associated with dyslipidemia in human patients.

  12. Prophylactic Subacute Administration of Zinc Increases CCL2, CCR2, FGF2, and IGF-1 Expression and Prevents the Long-Term Memory Loss in a Rat Model of Cerebral Hypoxia-Ischemia

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    Victor Manuel Blanco-Alvarez

    2015-01-01

    Full Text Available Prophylactic subacute administration of zinc decreases lipoperoxidation and cell death following a transient cerebral hypoxia-ischemia, thus suggesting neuroprotective and preconditioning effects. Chemokines and growth factors are also involved in the neuroprotective effect in hypoxia-ischemia. We explored whether zinc prevents the cerebral cortex-hippocampus injury through regulation of CCL2, CCR2, FGF2, and IGF-1 expression following a 10 min of common carotid artery occlusion (CCAO. Male rats were grouped as follows: (1 Zn96h, rats injected with ZnCl2 (one dose every 24 h during four days; (2 Zn96h + CCAO, rats treated with ZnCl2 before CCAO; (3 CCAO, rats with CCAO only; (4 Sham group, rats with mock CCAO; and (5 untreated rats. The cerebral cortex-hippocampus was dissected at different times before and after CCAO. CCL2/CCR2, FGF2, and IGF-1 expression was assessed by RT-PCR and ELISA. Learning in Morris Water Maze was achieved by daily training during 5 days. Long-term memory was evaluated on day 7 after learning. Subacute administration of zinc increased expression of CCL2, CCR2, FGF2, and IGF-1 in the early and late phases of postreperfusion and prevented the CCAO-induced memory loss in the rat. These results might be explained by the induction of neural plasticity because of the expression of CCL2 and growth factors.

  13. Prophylactic Subacute Administration of Zinc Increases CCL2, CCR2, FGF2, and IGF-1 Expression and Prevents the Long-Term Memory Loss in a Rat Model of Cerebral Hypoxia-Ischemia

    Science.gov (United States)

    Blanco-Alvarez, Victor Manuel; Soto-Rodriguez, Guadalupe; Gonzalez-Barrios, Juan Antonio; Martinez-Fong, Daniel; Torres-Soto, Maricela; Aguilar-Peralta, Ana Karina; Gonzalez-Vazquez, Alejandro; Tomás-Sanchez, Constantino; Limón, I. Daniel; Eguibar, Jose R.; Ugarte, Araceli; Hernandez-Castillo, Jeanett

    2015-01-01

    Prophylactic subacute administration of zinc decreases lipoperoxidation and cell death following a transient cerebral hypoxia-ischemia, thus suggesting neuroprotective and preconditioning effects. Chemokines and growth factors are also involved in the neuroprotective effect in hypoxia-ischemia. We explored whether zinc prevents the cerebral cortex-hippocampus injury through regulation of CCL2, CCR2, FGF2, and IGF-1 expression following a 10 min of common carotid artery occlusion (CCAO). Male rats were grouped as follows: (1) Zn96h, rats injected with ZnCl2 (one dose every 24 h during four days); (2) Zn96h + CCAO, rats treated with ZnCl2 before CCAO; (3) CCAO, rats with CCAO only; (4) Sham group, rats with mock CCAO; and (5) untreated rats. The cerebral cortex-hippocampus was dissected at different times before and after CCAO. CCL2/CCR2, FGF2, and IGF-1 expression was assessed by RT-PCR and ELISA. Learning in Morris Water Maze was achieved by daily training during 5 days. Long-term memory was evaluated on day 7 after learning. Subacute administration of zinc increased expression of CCL2, CCR2, FGF2, and IGF-1 in the early and late phases of postreperfusion and prevented the CCAO-induced memory loss in the rat. These results might be explained by the induction of neural plasticity because of the expression of CCL2 and growth factors. PMID:26355725

  14. The long-term lasting effectiveness on self-efficacy, attribution style, expression of emotions and quality of life of a body awareness program for chronic a-specific psychosomatic symptoms.

    Science.gov (United States)

    Landsman-Dijkstra, Jeanet J A; van Wijck, Ruud; Groothoff, Johan W

    2006-01-01

    A 3-day residential body awareness program (BAP) was developed to teach people with chronic a-specific psychosomatic symptoms (CAPS) to react adequately to disturbances of the balance between a daily workload and the capacity to deal with it. The long-term effects of the program on body awareness, psychological factors, psychosomatic symptoms and quality of life for people with CAPS are presented in this study. A pre-post design is used with post-measures 2 and 12 months after the program, without controls (n = 122). Mean age is 42.5 (S.D. = 9.0) and 60% is female. The results showed an increase of body awareness, self-efficacy, expression of emotions and quality of life. Stress-related symptoms decreased and the attribution style was found to be less depressive. Participants achieved significantly higher levels of functioning at 2 months which increased significantly more at 12 months. The majority of the measured changes can be interpreted as clinically relevant outcomes with medium-to-large effect sizes. Spouses of the participants also confirm the found effects. Evaluation of the BAP gives evidence to conclude that this program leads to the theoretically expected long-term effects in CAPS. Participants react more adequately to disturbances between daily workload and the capacity to deal with this load. Two and 12 months after the 3-day program, they are more capable of self-management in coping with stress and psychosomatic symptoms. This article sheds new light on the difficulties that individuals with psychosomatic symptoms and their professional interventionists encounter when attempting to manage the chronicity of the problems. By paying more attention to learning self-management by increasing body awareness and self-efficacy, patient educators may be able to increase their effectiveness.

  15. Long-term fenofibrate treatment impaired glucose-stimulated insulin secretion and up-regulated pancreatic NF-kappa B and iNOS expression in monosodium glutamate-induced obese rats: Is that a latent disadvantage?

    Directory of Open Access Journals (Sweden)

    Liu Shuai-nan

    2011-10-01

    Full Text Available Abstract Background Fenofibrate, a PPAR alpha agonist, has been widely used in clinics as lipid-regulating agent. PPAR alpha is known to be expressed in many organs including pancreatic beta cells and regulate genes involved in fatty acid metabolism. Some reports based on cell lines or animals have provided evidences that PPAR alpha agonists may affect (increased or suppressed beta cell insulin secretion, and several studies are producing interesting but still debated results. Methods In this research, we investigated the long term effects of fenofibrate on beta cell function in a metabolic syndrome animal model, monosodium glutamate (MSG induced obese rats. Obese MSG rats were administered by gavage with fenofibrate at a dose of 100 mg/kg for 12 weeks. Oral glucose tolerance and insulin tolerance tests were performed to evaluate glucose metabolism and insulin sensitivity. We have used the hyperglycemic clamp technique to evaluate the capacity of beta cell insulin secretion. This technique provides an unbiased approach to understand the beta cell function in vivo. The changes of gene and protein expression in the pancreas and islets were also analyzed by Real-Time-PCR, Western blot and immunostaining. Results Fenofibrate reduced the plasma lipid levels within a few days, and showed no beneficial effects on glucose homeostasis or insulin sensitivity in obese MSG rats. But the animals treated with fenofibrate exhibited significantly decreased fasting plasma insulin and impaired insulin secretory response to glucose stimulation. Further studies confirmed that fenofibrate increased MDA level and decreased total ATPase activity in pancreatic mitochondrion, accompanied by the upregulation of iNOS and NF-kappa B and TNF alpha expression in pancreatic islets of obese MSG rats. Conclusions Long-term fenofibrate treatment disrupted beta cell function, and impaired glucose-stimulated insulin secretion in obese MSG rats, perhaps to some extent associated

  16. Detection and Quantization of the Expression of Two mu-Opioid Receptor Splice Variants mRNA (hMOR-1A and hMOR-1O in Peripheral Blood Lymphocytes of Long-Term Abstinent Former Opioid Addicts

    Directory of Open Access Journals (Sweden)

    N Vousooghi, Pharm

    2012-05-01

    Full Text Available

    Background and Objectives

    The mu-Opioid receptor (MOR exerts a critical role on effects of opiodis. The objective of this study is to find a peripheral bio-marker in addiction studies through quantization of the expression of two MOR splice variants mRNA (hMOR-1A and hMOR-1O in peripheral blood lymphocytes (PBLs of long-term abstinent former opioids addicts.

    Methods

    In this case-control study, case and control people were male and divided in two groups: people who gave up addiction to opioids (case and healthy individuals without history of addiction (control. The mRNA expression in PBLs of participants was detected and measured by real-time Polymerase Chain Reaction (PCR using SYBR Green Dye.

    Results

    The hMOR-1A mRNA expression in PBLs of abstinent group was significantly reduced and reached to 0.33 of the control group (p<0.001. Similar results were obtained for the other splice variant with the mRNA expression of hMOR-1O in PBLs of abstinent group reaching to 0.38 of that of the control group (p < 0.001.

    Conclusion

    mRNA expression deficiency of two mu-opioid receptor splice variants, hMOR-1A and nMOR-1O, seams to be a risk factor making individuals vulnerable to drug addiction. Based on this analysis measuring the amount of mRNA expression of these two splice variants in PBLs can serve as a peripheral bio-marker for detecting people at risk.

  17. Long-term memory, sleep, and the spacing effect.

    Science.gov (United States)

    Bell, Matthew C; Kawadri, Nader; Simone, Patricia M; Wiseheart, Melody

    2014-01-01

    Many studies have shown that memory is enhanced when study sessions are spaced apart rather than massed. This spacing effect has been shown to have a lasting benefit to long-term memory when the study phase session follows the encoding session by 24 hours. Using a spacing paradigm we examined the impact of sleep and spacing gaps on long-term declarative memory for Swahili-English word pairs by including four spacing delay gaps (massed, 12 hours same-day, 12 hours overnight, and 24 hours). Results showed that a 12-hour spacing gap that includes sleep promotes long-term memory retention similar to the 24-hour gap. The findings support the importance of sleep to the long-term benefit of the spacing effect.

  18. Long-term trends in the abundance and community structure of ...

    African Journals Online (AJOL)

    Long-term trends in the abundance and community structure of Coastal Zooplankton in the Southern Benguela system, 1951–1996. ... to the long-term increase in zooplankton is the observed long-term intensification of coastal upwelling, which could enhance primary and secondary production, and increase advective input ...

  19. Long-term topical oestrogen treatment of sun-exposed facial skin in post-menopausal women does not improve facial wrinkles or skin elasticity, but induces matrix metalloproteinase-1 expression.

    Science.gov (United States)

    Yoon, Hyun-Sun; Lee, Se-Rah; Chung, Jin Ho

    2014-01-01

    It is controversial whether treatment with oestrogen stimulates collagen production or accumulation in sun-exposed skin. The aim of this study was to determine the effect of long-term treatment with topical oestrogen on photoaged facial skin, with regard to wrinkle severity, and expression of procollagen and matrix metalloproteinase-1 enzyme. Two groups of 40 post-menopausal women applied either 1 g of 1% oestrone or vehicle cream once daily to the face for 24 weeks. Visiometer R1-R5 values (skin wrinkles) and Cutometer values (skin elasticity) were not significantly improved in the oestrone group after 24 weeks of treatment. Type I procollagen immunostaining did not increase in the oestrone group compared with the control group. However, levels of matrix metalloproteinase-1 mRNA increased robustly (10.3 times) in oestrone-treated skin compared with vehicle-treated skin. Thus, treatment with topical oestrogen may be deleterious in ultraviolet-induced skin ageing, at least in part, through induction of matrix metalloproteinase-1 (MMP-1) expression in human skin.

  20. 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.

  1. Adverse event reporting in Czech long-term care facilities.

    Science.gov (United States)

    Hěib, Zdenřk; Vychytil, Pavel; Marx, David

    2013-04-01

    To describe adverse event reporting processes in long-term care facilities in the Czech Republic. Prospective cohort study involving a written questionnaire followed by in-person structured interviews with selected respondents. Long-term care facilities located in the Czech Republic. Staff of 111 long-term care facilities (87% of long-term care facilities in the Czech Republic). None. Sixty-three percent of long-term health-care facilities in the Czech Republic have adverse event-reporting processes already established, but these were frequently very immature programs sometimes consisting only of paper recording of incidents. Compared to questionnaire responses, in-person interview responses only partially tended to confirm the results of the written survey. Twenty-one facilities (33%) had at most 1 unconfirmed response, 31 facilities (49%) had 2 or 3 unconfirmed responses and the remaining 11 facilities (17%) had 4 or more unconfirmed responses. In-person interviews suggest that use of a written questionnaire to assess the adverse event-reporting process may have limited validity. Staff of the facilities we studied expressed an understanding of the importance of adverse event reporting and prevention, but interviews also suggested a lack of knowledge necessary for establishing a good institutional reporting system in long-term care.

  2. 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

  3. 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…

  4. 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...

  5. Sugar metabolism, chip color, invertase activity, and gene expression during long-term cold storage of potato (Solanum tuberosum) tubers from wild-type and vacuolar invertase silencing lines of Katahdin.

    Science.gov (United States)

    Wiberley-Bradford, Amy E; Busse, James S; Jiang, Jiming; Bethke, Paul C

    2014-11-16

    Storing potato tubers at low temperatures minimizes sprouting and disease but can cause an accumulation of reducing sugars in a process called cold-induced sweetening. Tubers with increased amounts of reducing sugars produce dark-colored, bitter-tasting fried products with elevated amounts of acrylamide, a possible carcinogen. Vacuolar invertase (VInv), which converts sucrose produced by starch breakdown to glucose and fructose, is the key determinant of reducing sugar accumulation during cold-induced sweetening. In this study, wild-type tubers and tubers in which VInv expression was reduced by RNA interference were used to investigate time- and temperature-dependent changes in sugar contents, chip color, and expression of VInv and other genes involved in starch metabolism in tubers during long-term cold storage. VInv activities and tuber reducing sugar contents were much lower, and tuber sucrose contents were much higher, in transgenic than in wild-type tubers stored at 3-9°C for up to eight months. Large differences in VInv mRNA accumulation were not observed at later times in storage, especially at temperatures below 9°C, so differences in invertase activity were likely established early in the storage period and maintained by stability of the invertase protein. Sugar contents, chip color, and expression of several of the studied genes, including AGPase and GBSS, were affected by storage temperature in both wild-type and transgenic tubers. Though transcript accumulation for other sugar-metabolism genes was affected by storage temperature and duration, it was essentially unaffected by invertase silencing and altered sugar contents. Differences in stem- and bud-end sugar contents in wild-type and transgenic tubers suggested different compartmentalization of sucrose at the two ends of stored tubers. VInv silencing significantly reduced cold-induced sweetening in stored potato tubers, likely by means of differential VInv expression early in storage. Transgenic

  6. The Impact of Short and Long-Term Exercise on the Expression of Arc and AMPARs During Evolution of the 6-Hydroxy-Dopamine Animal Model of Parkinson's Disease.

    Science.gov (United States)

    Garcia, P C; Real, C C; Britto, L R

    2017-04-01

    The loss of nigral dopaminergic neurons typical in Parkinson's disease (PD) is responsible for hyperexcitability of medium spiny neurons resulting in abnormal corticostriatal glutamatergic synaptic drive. Considering the neuroprotective effect of exercise, the changes promoted by exercise on AMPA-type glutamate receptors (AMPARs), and the role of activity-regulated cytoskeleton-associated protein (Arc) in the AMPARs trafficking, we studied the impact of short and long-term treadmill exercise during evolution of the unilateral 6-hydroxy-dopamine (6-OHDA) animal model of PD. Wistar rats were divided into sedentary and exercised groups, with and without lesion by 6-OHDA and followed up to 4 months. The exercised groups were subjected to a moderate treadmill exercise 3×/week. We measured the proteins tyrosine hydroxylase (TH), Arc, GluA1, and GluA2/3 in the striatum, substantia nigra, and motor cortex. Our results showed a higher reduction of TH expression in all sedentary groups when compared to all exercised groups in striatum and substantia nigra. In general, larger changes occurred in the striatum in the first and third months after training. After 1 month of exercise, there was significant increase of GluA2/3 with concomitant reduction of GluA1 and Arc. As a balanced system, these changes were reversed in the third month, showing an increase of Arc and GluA1 and decrease of GluA2/3. Similar results for GluAs and Arc were observed in the motor cortex of the exercised animals. These modifications may be relevant for corticostriatal circuits in PD, since the exercise-dependent plasticity can modulate GluAs expression and maybe neuronal excitability.

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

    Science.gov (United States)

    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

  8. Long term water integration in interconnected ramets of ...

    African Journals Online (AJOL)

    Buffalograss (Buchloë dactyloides) is known for its drought resistant character. Natural resources are patchily distributed and resource sharing between interconnected ramets can enhance the performance of the whole genet. In order to examine whether there exists long term water integration between interconnected ...

  9. Long-Term Retardation of Uranium in the KURT Environment

    Energy Technology Data Exchange (ETDEWEB)

    Baik, Min Hoon [KAERI, Daejeon (Korea, Republic of); Shin, Joo Do [KARA, Seoul (Korea, Republic of); Park, Tae Jin [KAERI, Daejeon (Korea, Republic of)

    2016-05-15

    One of possibilities resolving this issue is to study the migration and retardation processes of radionuclides in the subsurface environments by using naturally occurring radionuclides as analogues of radioactive waste. To date, however, the long-term behavior of radionuclides in a granitic groundwater system is not yet fully understood. The ubiquitous presence of uranium (U) in rocks makes it an ideal natural analogue for studying the behaviors of radionuclides in a deep geological repository for the final disposal of HLW. In this study, long-term retardation behavior of natural uranium was investigated using granite rock samples taken from the KURT (KAERI Underground Research Tunnel), located in Daejeon city. The distribution of uranium and its binding mechanism in granite samples were investigated using the sequential chemical extraction (SCE) technique combined with X-ray diffraction (XRD) and ICP-MS methods. In this study, the long-term retardation of uranium in the KURT environment was investigated using SCE and EPMA techniques combined with ICP-MS and XRD. Results showed that long-term interaction of rock with groundwater can change U species and mineralize dissolved U, which can consequently contribute to the retardation of U in the fractured granitic rock environment. This study will help us to understand the long-term behavior of radionuclides migrating through the fractured granite rock and then enhance the reliability of the safety assessment for a HLW repository.

  10. Rectal epithelial cell mitosis and expression of macrophage migration inhibitory factor are increased 3 years after Roux-en-Y gastric bypass (RYGB) for morbid obesity: implications for long-term neoplastic risk following RYGB.

    Science.gov (United States)

    Kant, Prashant; Sainsbury, Anita; Reed, Karen R; Pollard, Stephen G; Scott, Nigel; Clarke, Alan R; Coletta, P Louise; Hull, Mark A

    2011-07-01

    Rectal epithelial cell mitosis and crypt size, as well as expression of proinflammatory genes including macrophage migration inhibitory factor (MIF), are increased 6 months after Roux-en-Y gastric bypass (RYGB) in morbidly obese patients. Tests were carried out to determine whether these putative colorectal cancer risk biomarkers remained elevated long term after RYGB, and the mechanistic basis, as well as the functional consequences, of Mif upregulation in intestinal epithelial cells was investigated. Rectal mucosa and blood were obtained a median of 3 years after RYGB from the original cohort of patients with RYGB (n = 19) for crypt microdissection, real-time PCR, immunohistochemistry for MIF and immunoassay of proinflammatory markers. Immunohistochemistry for Mif and bromodeoxyuridine labelling were performed on AhCre⁺ mouse and Apc(Min/⁺) mouse (with and without functional Mif alleles) intestine, respectively. Rectal epithelial cell mitosis and crypt size remained elevated 3 years after RYGB compared with preoperative values (1.7- and 1.5-fold, respectively; p < 0.05). There was a 40-fold (95% CI 13 to 125) increase in mucosal MIF transcript levels at 3 years associated with increased epithelial cell MIF protein levels. Conditional Apc loss in AhCre⁺ mice led to increased epithelial cell Mif content. Mif deficiency in Apc(Min/⁺) mice was associated with a combined defect in intestinal epithelial cell proliferation and migration, which was reflected by the longitudinal clinical data. Mucosal abnormalities persist 3 years after RYGB and include elevation of the protumorigenic cytokine MIF, which is upregulated following Apc loss and which contributes to intestinal epithelial cell homeostasis. These observations should prompt clinical studies of colorectal neoplastic risk after RYGB.

  11. Long-term In Vitro Treatment of Human Glioblastoma Cells with Temozolomide Increases Resistance In Vivo through Up-regulation of GLUT Transporter and Aldo-Keto Reductase Enzyme AKR1C Expression

    Directory of Open Access Journals (Sweden)

    Benjamin Le Calvé

    2010-09-01

    Full Text Available Glioblastoma (GBM is the most frequent malignant glioma. Treatment of GBM patients is multimodal with maximum surgical resection, followed by concurrent radiation and chemotherapy with the alkylating drug temozolomide (TMZ. The present study aims to identify genes implicated in the acquired resistance of two human GBM cells of astrocytic origin, T98G and U373, to TMZ. Resistance to TMZ was induced by culturing these cells in vitro for months with incremental TMZ concentrations up to 1 mM. Only partial resistance to TMZ has been achieved and was demonstrated in vivo in immunocompromised mice bearing orthotopic U373 and T98G xenografts. Our data show that long-term treatment of human astroglioma cells with TMZ induces increased expression of facilitative glucose transporter/solute carrier GLUT/SLC2A family members, mainly GLUT-3, and of the AKR1C family of proteins. The latter proteins are phase 1 drug-metabolizing enzymes involved in the maintenance of steroid homeostasis, prostaglandin metabolism, and metabolic activation of polycyclic aromatic hydrocarbons. GLUT-3 has been previously suggested to exert roles in GBM neovascularization processes, and TMZ was found to exert antiangiogenic effects in experimental gliomas. AKR1C1 was previously shown to be associated with oncogenic potential, with proproliferative effects similar to AKR1C3 in the latter case. Both AKR1C1 and AKR1C2 proteins are involved in cancer pro-proliferative cell chemoresistance. Selective targeting of GLUT-3 in GBM and/or AKR1C proteins (by means of jasmonates, for example could thus delay the acquisition of resistance to TMZ of astroglioma cells in the context of prolonged treatment with this drug.

  12. 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...

  13. 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...

  14. 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...

  15. 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.

  16. 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...

  17. 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). ...

  18. 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.

  19. Changing the culture of long-term care through narrative care: Individual, interpersonal, and institutional dimensions.

    Science.gov (United States)

    Villar, Feliciano; Serrat, Rodrigo

    2017-01-01

    Interest in the practice of narrative care with older adults is continuing to grow (Kenyon & Randall, 2015). Significant attention has been paid thus far to various formal interventions or programs that enhance the narrative development of individuals in later life by helping them to express and explore their unique life story. Comparatively little, however, has been paid to the many informal opportunities for practicing narrative care in long term settings that occur amidst everyday interpersonal interactions - e.g., staff-resident interactions in nursing homes. Even less attention has been paid to the importance of cultivating an overarching institutional narrative that provides a supportive context for the practice of narrative care in general. This paper will contribute to discussions of "person-centered care" by arguing the need to change the culture of long-term care so that narrative care is practiced on all three levels at once: individual, interpersonal, and institutional. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. 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.

  1. 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...

  2. The long-term lasting effectiveness on self-efficacy, attribution style, expression of emotions and quality of life of a body awareness program for chronic a-specific psychosomatic symptoms

    NARCIS (Netherlands)

    Landsman-Dijkstra, Jeanet J. A.; van Wijck, R; Groothoff, JW

    Objective: A 3-day residential body awareness program (BAP) was developed to teach people with chronic a-specific psychosomatic symptoms (CAPS) to react adequately to disturbances of the balance between a daily workload and the capacity to deal with it. The long-term effects of the program on body

  3. 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.

  4. Nutritional deficit and Long Term Potentiation alterations

    Directory of Open Access Journals (Sweden)

    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.

  5. 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.

  6. A Putative Biochemical Engram of Long-Term Memory.

    Science.gov (United States)

    Li, Liying; Sanchez, Consuelo Perez; Slaughter, Brian D; Zhao, Yubai; Khan, Mohammed Repon; Unruh, Jay R; Rubinstein, Boris; Si, Kausik

    2016-12-05

    How a transient experience creates an enduring yet dynamic memory remains an unresolved issue in studies of memory. Experience-dependent aggregation of the RNA-binding protein CPEB/Orb2 is one of the candidate mechanisms of memory maintenance. Here, using tools that allow rapid and reversible inactivation of Orb2 protein in neurons, we find that Orb2 activity is required for encoding and recall of memory. From a screen, we have identified a DNA-J family chaperone, JJJ2, which facilitates Orb2 aggregation, and ectopic expression of JJJ2 enhances the animal's capacity to form long-term memory. Finally, we have developed tools to visualize training-dependent aggregation of Orb2. We find that aggregated Orb2 in a subset of mushroom body neurons can serve as a "molecular signature" of memory and predict memory strength. Our data indicate that self-sustaining aggregates of Orb2 may serve as a physical substrate of memory and provide a molecular basis for the perduring yet malleable nature of memory. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. 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...

  8. 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...

  9. 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...

  10. Long-term melatonin treatment delays ovarian aging.

    Science.gov (United States)

    Tamura, Hiroshi; Kawamoto, Mai; Sato, Shun; Tamura, Isao; Maekawa, Ryo; Taketani, Toshiaki; Aasada, Hiromi; Takaki, Eiichi; Nakai, Akira; Reiter, Russel J; Sugino, Norihiro

    2017-03-01

    Ovarian aging is characterized by gradual declines in oocyte quantity and quality. Melatonin is considered an anti-aging agent due to its cytoprotective actions as an antioxidant. This study examined whether long-term melatonin treatment would delay ovarian aging in mice. Female ICR mice (10 weeks old) were given melatonin-containing water (100 μg/mL; melatonin) or water only until 43 weeks of age. Their oocytes were recovered from the oviduct, and in vitro fertilization was performed. The ovaries were used for a histological analysis of the number of follicles. The mRNA expression of the aging-related sirtuin genes (SIRT1, SIRT3) and the autophagy-related gene (LC3) and the telomere length of the ovarian chromosomes were analyzed. Transcriptome changes in the ovaries were also characterized using microarray. The number of ovulated oocytes decreased with age; however, it was greater in melatonin-treated mice than that from control animals. The decreased fertilization rate and blastocyst rate during aging also were higher in the melatonin-treated mice than in the controls, as were the numbers of primordial, primary, and antral follicles. The mRNA expression of SIRT1 and LC3 and telomere length were enhanced due to melatonin treatment. Seventy-eight genes that were downregulated during aging and upregulated by melatonin were identified by a microarray analysis. Forty of these 78 genes were ribosome-related genes, and a free radical scavenging network was identified. The present results indicate that melatonin delays ovarian aging by multiple mechanisms including antioxidant action, maintaining telomeres, stimulating SIRT expression and ribosome function, and by reducing autophagy. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. NLRP3 inflammasome activation contributes to long-term behavioral alterations in mice injected with lipopolysaccharide.

    Science.gov (United States)

    Zhu, Wei; Cao, Feng-Sheng; Feng, Jun; Chen, Hua-Weng; Wan, Jie-Ru; Lu, Qing; Wang, Jian

    2017-02-20

    Lipopolysaccharide (LPS) might affect the central nervous system by causing neuroinflammation, which subsequently leads to brain damage and dysfunction. In this study, we evaluated the role of nod-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome activation in long-term behavioral alterations of 8-week-old male C57BL/6 mice injected intraperitoneally with LPS (5mg/kg). At different time points after injection, we assessed locomotor function with a 24-point neurologic deficit scoring system and the rotarod test; assessed recognition memory with the novel object recognition test; and assessed emotional abnormality (anhedonia and behavioral despair) with the tail suspension test, forced swim test, and sucrose preference test. We also assessed protein expression of NLRP3, apoptosis-associated speck-like protein (ASC), and caspase-1 p10 in hippocampus by Western blotting; measured levels of interleukin (IL)-1β, IL-18, tumor necrosis factor α (TNFα), and IL-10 in hippocampus; measured TNFα and IL-1β in serum by ELISA; and evaluated microglial activity in hippocampus by Iba1 immunofluorescence. We found that LPS-injected mice displayed long-term depression-like behaviors and recognition memory deficit; elevated expression of NLRP3, ASC, and caspase-1 p10; increased levels of IL-1β, IL-18, and TNFα; decreased levels of IL-10; and increased microglial activation. These effects were blocked by the NLRP3 inflammasome inhibitor Ac-Tyr-Val-Ala-Asp-chloromethylketone. The results demonstrate proof of concept that NLRP3 inflammasome activation contributes to long-term behavioral alterations in LPS-exposed mice, probably through enhanced inflammation, and that NLRP3 inflammasome inhibition might alleviate peripheral and brain inflammation and thereby ameliorate long-term behavioral alterations in LPS-exposed mice. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  12. Epigenetic mechanisms linking early nutrition to long term health.

    Science.gov (United States)

    Lillycrop, Karen A; Burdge, Graham C

    2012-10-01

    Traditionally it has been widely accepted that our genes together with adult lifestyle factors determine our risk of developing non-communicable diseases such as type 2 diabetes mellitus, cardiovascular disease and obesity in later life. However, there is now substantial evidence that the pre and early postnatal environment plays a key role in determining our susceptible to such diseases in later life. Moreover the mechanism by which the environment can alter long term disease risk may involve epigenetic processes. Epigenetic processes play a central role in regulating tissue specific gene expression and hence alterations in these processes can induce long-term changes in gene expression and metabolism which persist throughout the lifecourse. This review will focus on how nutritional cues in early life can alter the epigenome, producing different phenotypes and altered disease susceptibilities. Copyright © 2012 Elsevier Ltd. All rights reserved.

  13. Sevoflurane Inhalation Accelerates the Long-Term Memory Consolidation via Small GTPase Overexpression in the Hippocampus of Mice in Adolescence.

    Science.gov (United States)

    Nakamura, Emi; Kinoshita, Hiroyuki; Feng, Guo-Gang; Hayashi, Hisaki; Satomoto, Maiko; Sato, Motohiko; Fujiwara, Yoshihiro

    2016-01-01

    Sevoflurane exposure impairs the long-term memory in neonates. Whether the exposure to animals in adolescence affects the memory, however, has been unclear. A small hydrolase enzyme of guanosine triphosphate (GTPase) rac1 plays a role in the F-actin dynamics related to the synaptic plasticity, as well as superoxide production via reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation. The current study was designed to examine whether sevoflurane exposure to mice in early adolescence modifies the long-term learning ability concomitantly with the changes in F-actin constitution as well as superoxide production in the hippocampus according to the levels of rac1 protein expression. Four-week-old mice were subjected to the evaluation of long-term learning ability for three days. On day one, each mouse was allowed to enter a dark chamber for five min to acclimatization. On day two, the procedure was repeated with the addition of an electric shock as soon as a mouse entered the dark chamber. All mice subsequently inhaled 2 L/min air with (Sevoflurane group) and without (Control group) 2.5% sevoflurane for three hours. On day three, each mouse was placed on the platform and retention time, which is the latency to enter the dark chamber, was examined. The brain removed after the behavior test, was used for analyses of immunofluorescence, Western immunoblotting and intracellular levels of superoxide. Sevoflurane exposure significantly prolonged retention time, indicating the enhanced long-term memory. Sevoflurane inhalation augmented F-actin constitution coexisting with the rac1 protein overexpression in the hippocampus whereas it did not alter the levels of superoxide. Sevoflurane exposure to 4-week-old mice accelerates the long-term memory concomitantly with the enhanced F-actin constitution coexisting with the small GTPase rac1 overexpression in the hippocampus. These results suggest that sevoflurane inhalation may amplify long-term memory

  14. 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.

  15. 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…

  16. 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...

  17. 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...

  18. 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…

  19. 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

  20. 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

  1. 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.

  2. 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.

  3. Science and society: the role of long-term studies in environmental stewardship

    Science.gov (United States)

    Charles T. Driscoll; Kathleen F. Lambert; F. Stuart Chapin; David J. Nowak; Thomas A. Spies; Frederick J. Swanson; David B. Kittredge; Clarisse M. Hart

    2012-01-01

    Long-term research should play a crucial role in addressing grand challenges in environmental stewardship. We examine the efforts of five Long Term Ecological Research Network sites to enhance policy, management, and conservation decisions for forest ecosystems. In these case studies, we explore the approaches used to inform policy on atmospheric deposition, public...

  4. Cloning and expression analysis of myostatin, fibroblast growth factor 6, insulin-like growth factor I and II in liver and muscle of sea bass (Dicentrarchus labrax, L. during long-term fasting and refeeding

    Directory of Open Access Journals (Sweden)

    M. Saroglia

    2010-04-01

    Full Text Available The exceptionally fast growth that fish experience after periods of fasting has been called “compensatory growth”. This phenomenon has been studied in intensive aquaculture as a means of enhancing growth rates, but the mechanisms by which food intake activates an increase in somatic growth, and especially in muscle growth, are complex and not yet fully understood. In the present paper, we describe the molecular cloning and sequencing of sea bass (Dicentrarchus labrax myostatin (MSTN and fibroblast growth factor 6 (FGF6, which have been shown to be major genetic determinants of skeletal muscle growth, together with insulin-like growth factor I (IGFI and IGF-II, which are potent mitogens known to play important roles in growth and development. We then report the pattern of expression of the four aforementioned genes, in liver and myotomal muscle in response to prolonged fasting and refeeding. Nutritional status significantly influenced the expression of IGF-I, IGF-II and MSTN, whereas the muscular FGF6 expression levels were not affected by the feeding status of the animals. Taken together these data indicate that IGF-I, IGF-II and MSTN are involved in the sea bass muscle compensatory growth induced by refeeding, whereas FGF6 probably has not a role in this phenomenon.

  5. PV plasticity sustained through D1/5 dopamine signaling required for long-term memory consolidation.

    Science.gov (United States)

    Karunakaran, Smitha; Chowdhury, Ananya; Donato, Flavio; Quairiaux, Charles; Michel, Christoph M; Caroni, Pico

    2016-03-01

    Long-term consolidation of memories depends on processes occurring many hours after acquisition. Whether this involves plasticity that is specifically required for long-term consolidation remains unclear. We found that learning-induced plasticity of local parvalbumin (PV) basket cells was specifically required for long-term, but not short/intermediate-term, memory consolidation in mice. PV plasticity, which involves changes in PV and GAD67 expression and connectivity onto PV neurons, was regulated by cAMP signaling in PV neurons. Following induction, PV plasticity depended on local D1/5 dopamine receptor signaling at 0-5 h to regulate its magnitude, and at 12-14 h for its continuance, ensuring memory consolidation. D1/5 dopamine receptor activation selectively induced DARPP-32 and ERK phosphorylation in PV neurons. At 12-14 h, PV plasticity was required for enhanced sharp-wave ripple densities and c-Fos expression in pyramidal neurons. Our results reveal general network mechanisms of long-term memory consolidation that requires plasticity of PV basket cells induced after acquisition and sustained subsequently through D1/5 receptor signaling.

  6. 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...

  7. 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...

  8. Samish Indian Nation Long-Term Strategic Energy Plan

    Energy Technology Data Exchange (ETDEWEB)

    Christine Woodward; B. Beckley; K. Hagen

    2005-06-30

    The Tribes strategic energy planning effort is divided into three phases: (1) Completing an Energy Resource Assessment; (2) Developing a Long-Term Strategic Energy Plan; and (3) Preparing a Strategic Energy Implementation Plan for the Samish Homelands. The Samish Indian Nation developed a comprehensive Strategic Energy plan to set policy for future development on tribal land that consists of a long-term, integrated, systems approach to providing a framework under which the Samish Community can use resources efficiently, create energy-efficient infrastructures, and protect and enhance quality of life. Development of the Strategic Energy plan will help the Samish Nation create a healthy community that will sustain current and future generations by addressing economic, environmental, and social issues while respecting the Samish Indian Nation culture and traditions.

  9. 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 ...

  10. 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.

  11. 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.

  12. 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.

  13. 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....

  14. 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.

  15. Recombinant self-complementary adeno-associated virus serotype vector-mediated hematopoietic stem cell transduction and lineage-restricted, long-term transgene expression in a murine serial bone marrow transplantation model.

    Science.gov (United States)

    Maina, Njeri; Han, Zongchao; Li, Xiaomiao; Hu, Zhongbo; Zhong, Li; Bischof, Daniela; Weigel-Van Aken, Kirsten A; Slayton, William B; Yoder, Mervin C; Srivastava, Arun

    2008-04-01

    Although conventional recombinant single-stranded adeno-associated virus serotype 2 (ssAAV2) vectors have been shown to efficiently transduce numerous cells and tissues such as brain and muscle, their ability to transduce primary hematopoietic stem cells (HSCs) has been reported to be controversial. We have previously documented that among the ssAAV serotype 1 through 5 vectors, ssAAV1 vectors are more efficient in transducing primary murine HSCs, but that viral second-strand DNA synthesis continues to be a rate-limiting step. In the present studies, we evaluated the transduction efficiency of several novel serotype vectors (AAV1, AAV7, AAV8, and AAV10) and documented efficient transduction of HSCs in a murine serial bone marrow transplantation model. Self-complementary AAV (scAAV) vectors were found to be more efficient than ssAAV vectors, and the use of hematopoietic cell-specific enhancers/promoters, such as the human beta-globin gene DNase I-hypersensitive site 2 enhancer and promoter (HS2-betap) from the beta-globin locus control region (LCR), and the human parvovirus B19 promoter at map unit 6 (B19p6), allowed sustained transgene expression in an erythroid lineage-restricted manner in both primary and secondary transplant recipient mice. The proviral AAV genomes were stably integrated into progenitor cell chromosomal DNA, and did not lead to any overt hematological abnormalities in mice. These studies demonstrate the feasibility of the use of novel scAAV vectors for achieving high-efficiency transduction of HSCs as well as erythroid lineage-restricted expression of a therapeutic gene for the potential gene therapy of beta-thalassemia and sickle cell disease.

  16. 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...

  17. 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.

  18. 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

  19. 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

  20. 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.

  1. 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.

  2. Murine model of long-term obstructive jaundice.

    Science.gov (United States)

    Aoki, Hiroaki; Aoki, Masayo; Yang, Jing; Katsuta, Eriko; Mukhopadhyay, Partha; Ramanathan, Rajesh; Woelfel, Ingrid A; Wang, Xuan; Spiegel, Sarah; Zhou, Huiping; Takabe, Kazuaki

    2016-11-01

    With the recent emergence of conjugated bile acids as signaling molecules in cancer, a murine model of obstructive jaundice by cholestasis with long-term survival is in need. Here, we investigated the characteristics of three murine models of obstructive jaundice. C57BL/6J mice were used for total ligation of the common bile duct (tCL), partial common bile duct ligation (pCL), and ligation of left and median hepatic bile duct with gallbladder removal (LMHL) models. Survival was assessed by Kaplan-Meier method. Fibrotic change was determined by Masson-Trichrome staining and Collagen expression. Overall, 70% (7 of 10) of tCL mice died by day 7, whereas majority 67% (10 of 15) of pCL mice survived with loss of jaundice. A total of 19% (3 of 16) of LMHL mice died; however, jaundice continued beyond day 14, with survival of more than a month. Compensatory enlargement of the right lobe was observed in both pCL and LMHL models. The pCL model demonstrated acute inflammation due to obstructive jaundice 3 d after ligation but jaundice rapidly decreased by day 7. The LHML group developed portal hypertension and severe fibrosis by day 14 in addition to prolonged jaundice. The standard tCL model is too unstable with high mortality for long-term studies. pCL may be an appropriate model for acute inflammation with obstructive jaundice, but long-term survivors are no longer jaundiced. The LHML model was identified to be the most feasible model to study the effect of long-term obstructive jaundice. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. 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....

  4. 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.

  5. 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.

  6. 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....

  7. 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.

  8. 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.

  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. Does physical activity counselling enhance the effects of a pedometer-based intervention over the long-term: 12-month findings from the Walking for Wellbeing in the west study

    Directory of Open Access Journals (Sweden)

    Fitzsimons Claire F

    2012-03-01

    Full Text Available Abstract Background Pedometers provide a simple, cost effective means of motivating individuals to increase walking yet few studies have considered if short term changes in walking behaviour can be maintained in the long-term. The role of physical activity consultations in such interventions is unclear. The purpose of this study was to assess the sustainability of pedometer-based interventions and empirically examine the role of physical activity consultations using long-term results of a community-based walking study. Methods 79 low active Scottish men and women (63 women and 16 men from the Walking for Wellbeing in the West intervention study were randomly assigned to receive either: Group 1; pedometer-based walking programme plus physical activity consultations or Group 2; pedometer-based walking programme and minimal advice. Step counts (Omron HJ-109E Step-O-Meter pedometer, 7 day recall of physical activity (IPAQ long, mood (PANAS and quality of life (EuroQol EQ-5D were assessed pre-intervention and 12, 24 and 48 weeks after receiving the intervention. Body mass, body mass index and waist and hip circumference were assessed pre-intervention and 12 and 24 weeks after receiving the intervention. Analyses were performed on an intention to treat basis (baseline value carried forward for missing data using mixed-factorial ANOVAs and follow-up t-tests. Results A significant main effect of time (p M = 6941, SD = 3047 and 12 weeks (M = 9327, SD = 4136, t(78 = - 6.52, p d = 0.66; pre-intervention and 24 weeks (M = 8804, SD = 4145, t(78 = - 4.82, p d = 0.52; and pre-intervention and 48 weeks (M = 8450, SD = 3855, t(78 = - 4.15, p d = 0.44. Significant effects were found for several variables of self-reported physical activity, mood and quality of life and are discussed. No other significant effects in health related outcomes were found. Conclusion Both interventions successfully increased and maintained step counts over 12 months. Physical activity

  13. Loss of FMRP Impaired Hippocampal Long-Term Plasticity and Spatial Learning in Rats

    Directory of Open Access Journals (Sweden)

    Yonglu Tian

    2017-08-01

    Full Text Available Fragile X syndrome (FXS is a neurodevelopmental disorder caused by mutations in the FMR1 gene that inactivate expression of the gene product, the fragile X mental retardation 1 protein (FMRP. In this study, we used clustered regularly interspaced short palindromic repeats (CRISPR/CRISPR-associated protein 9 (Cas9 technology to generate Fmr1 knockout (KO rats by disruption of the fourth exon of the Fmr1 gene. Western blotting analysis confirmed that the FMRP was absent from the brains of the Fmr1 KO rats (Fmr1exon4-KO. Electrophysiological analysis revealed that the theta-burst stimulation (TBS–induced long-term potentiation (LTP and the low-frequency stimulus (LFS–induced long-term depression (LTD were decreased in the hippocampal Schaffer collateral pathway of the Fmr1exon4-KO rats. Short-term plasticity, measured as the paired-pulse ratio, remained normal in the KO rats. The synaptic strength mediated by the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR was also impaired. Consistent with previous reports, the Fmr1exon4-KO rats demonstrated an enhanced 3,5-dihydroxyphenylglycine (DHPG–induced LTD in the present study, and this enhancement is insensitive to protein translation. In addition, the Fmr1exon4-KO rats showed deficits in the probe trial in the Morris water maze test. These results demonstrate that deletion of the Fmr1 gene in rats specifically impairs long-term synaptic plasticity and hippocampus-dependent learning in a manner resembling the key symptoms of FXS. Furthermore, the Fmr1exon4-KO rats displayed impaired social interaction and macroorchidism, the results consistent with those observed in patients with FXS. Thus, Fmr1exon4-KO rats constitute a novel rat model of FXS that complements existing mouse models.

  14. Loss of FMRP Impaired Hippocampal Long-Term Plasticity and Spatial Learning in Rats.

    Science.gov (United States)

    Tian, Yonglu; Yang, Chaojuan; Shang, Shujiang; Cai, Yijun; Deng, Xiaofei; Zhang, Jian; Shao, Feng; Zhu, Desheng; Liu, Yunbo; Chen, Guiquan; Liang, Jing; Sun, Qiang; Qiu, Zilong; Zhang, Chen

    2017-01-01

    Fragile X syndrome (FXS) is a neurodevelopmental disorder caused by mutations in the FMR1 gene that inactivate expression of the gene product, the fragile X mental retardation 1 protein (FMRP). In this study, we used clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) technology to generate Fmr1 knockout (KO) rats by disruption of the fourth exon of the Fmr1 gene. Western blotting analysis confirmed that the FMRP was absent from the brains of the Fmr1 KO rats (Fmr1exon4-KO ). Electrophysiological analysis revealed that the theta-burst stimulation (TBS)-induced long-term potentiation (LTP) and the low-frequency stimulus (LFS)-induced long-term depression (LTD) were decreased in the hippocampal Schaffer collateral pathway of the Fmr1exon4-KO rats. Short-term plasticity, measured as the paired-pulse ratio, remained normal in the KO rats. The synaptic strength mediated by the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) was also impaired. Consistent with previous reports, the Fmr1exon4-KO rats demonstrated an enhanced 3,5-dihydroxyphenylglycine (DHPG)-induced LTD in the present study, and this enhancement is insensitive to protein translation. In addition, the Fmr1exon4-KO rats showed deficits in the probe trial in the Morris water maze test. These results demonstrate that deletion of the Fmr1 gene in rats specifically impairs long-term synaptic plasticity and hippocampus-dependent learning in a manner resembling the key symptoms of FXS. Furthermore, the Fmr1exon4-KO rats displayed impaired social interaction and macroorchidism, the results consistent with those observed in patients with FXS. Thus, Fmr1exon4-KO rats constitute a novel rat model of FXS that complements existing mouse models.

  15. Zif268/Egr1 gain of function facilitates hippocampal synaptic plasticity and long-term spatial recognition memory.

    Science.gov (United States)

    Penke, Zsuzsa; Morice, Elise; Veyrac, Alexandra; Gros, Alexandra; Chagneau, Carine; LeBlanc, Pascale; Samson, Nathalie; Baumgärtel, Karsten; Mansuy, Isabelle M; Davis, Sabrina; Laroche, Serge

    2014-01-05

    It is well established that Zif268/Egr1, a member of the Egr family of transcription factors, is critical for the consolidation of several forms of memory; however, it is as yet uncertain whether increasing expression of Zif268 in neurons can facilitate memory formation. Here, we used an inducible transgenic mouse model to specifically induce Zif268 overexpression in forebrain neurons and examined the effect on recognition memory and hippocampal synaptic transmission and plasticity. We found that Zif268 overexpression during the establishment of memory for objects did not change the ability to form a long-term memory of objects, but enhanced the capacity to form a long-term memory of the spatial location of objects. This enhancement was paralleled by increased long-term potentiation in the dentate gyrus of the hippocampus and by increased activity-dependent expression of Zif268 and selected Zif268 target genes. These results provide novel evidence that transcriptional mechanisms engaging Zif268 contribute to determining the strength of newly encoded memories.

  16. Chronic unpredictable stress during adolescence causes long-term anxiety.

    Science.gov (United States)

    Chaby, L E; Cavigelli, S A; Hirrlinger, A M; Caruso, M J; Braithwaite, V A

    2015-02-01

    Exposure to stress during adolescence can cause long-term changes in behavior and cognition. Anxiety diagnoses rise during adolescence and are increased by adverse experiences. Currently, it is unknown how long stress during adolescence alters anxiety in adulthood. We found that rats exposed to chronic unpredictable stress during adolescence expressed altered behavior 6.5 months later; showing increased anxiety in a feeding test in a novel environment. Although behavioral changes indicative of anxiety were detected in late adulthood, the basal levels of fecal corticoid metabolites in prior-stressed rats did not differ from unstressed, control rats. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Long-term response to nivolumab and acute renal failure in a patient with metastatic papillary renal-cell carcinoma and a PD-L1 tumor expression increased with sunitinib therapy: A case report.

    Directory of Open Access Journals (Sweden)

    Juan Ruiz-Bañobre

    2016-11-01

    Full Text Available Introduction: Papillary renal-cell carcinoma, which represents around 20% of renal cell carcinomas, is a heterogeneous disease that includes different tumor types with several clinical and molecular phenotypes. Nivolumab, a fully human IgG4 programmed cell death protein 1 immune checkpoint inhibitor antibody, has shown not only an overall survival advantage when compared to everolimus, but also a relatively good side-effect profile among patients with previously treated advanced or metastatic renal-cell carcinoma. Case report: We describe a case of a young man diagnosed with papillary renal-cell carcinoma that achieved a durable response to nivolumab despite a temporary suspension of the treatment due to a renal function side effect. To our knowledge, it is the first renal failure secondary to nivolumab in a metastatic renal-cell carcinoma patient.Concluding Remarks: Nivolumab is a promising drug in patients with metastatic papillary renal-cell carcinoma and long-term responses can be achieved. In case of acute renal failure secondary to this treatment, temporary therapy suspension and a low dose of systemic corticosteroids can recover renal function without a negative impact on treatment efficacy.

  18. Characterization of vascular smooth muscle cell phenotype in long-term culture.

    Science.gov (United States)

    Absher, M; Woodcock-Mitchell, J; Mitchell, J; Baldor, L; Low, R; Warshaw, D

    1989-02-01

    Studies of bovine carotid artery smooth muscle cells, during long-term in vitro subcultivation (up to 100 population doublings), have revealed phenotypic heterogeneity among cells, as characterized by differences in proliferative behavior, cell morphology, and contractile-cytoskeletal protein profiles. In vivo, smooth muscle cells were spindle-shaped and expressed desmin and alpha-smooth muscle actin (50% of total actin) as their predominant cytoskeletal and contractile proteins. Within 24 h of culture, vimentin rather than desmin was the predominant intermediate filament protein, with little change in alpha-actin content. Upon initial subcultivation, all cells were flattened and fibroblastic in appearance with a concomitant fivefold reduction in alpha-actin content, whereas the beta and gamma nonmuscle actins predominated. In three out of four cell lines studied, fluctuations in proliferative activity were observed during the life span of the culture. These spontaneous fluctuations in proliferation were accompanied by coordinated changes in morphology and contractile-cytoskeletal protein profiles. During periods of enhanced proliferation a significant proportion of cells reverted to their original spindle-shaped morphology with a simultaneous increase in alpha-actin content (20 to 30% of total actin). These results suggest that in long-term culture smooth muscle cells undergo spontaneous modulations in cell phenotype and may serve as a useful model for studying the regulation of intracellular protein expression.

  19. 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...

  20. [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.

  1. 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...

  2. 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...

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. Transforming service employees and climate: a multilevel, multisource examination of transformational leadership in building long-term service relationships.

    Science.gov (United States)

    Liao, Hui; Chuang, Aichia

    2007-07-01

    This longitudinal field study integrates the theories of transformational leadership (TFL) and relationship marketing to examine how TFL influences employee service performance and customer relationship outcomes by transforming both (at the micro level) the service employees' attitudes and (at the macro level) the work unit's service climate. Results revealed that, at the individual level, managers' TFL was positively related to employee service performance, which, in turn, positively predicted customers' expressed intention to maintain a long-term service relationship with the service employee and manager-reported number of the employee's long-term customers measured 9 months later. In addition, the relationship between TFL and employee service performance was partially mediated by employee self-efficacy. Furthermore, store-level TFL was positively associated with store-level service climate, and service climate further enhanced the relationship between individual-level TFL and employee service performance.

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

    Directory of Open Access Journals (Sweden)

    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.

  10. 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....

  11. 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...

  12. Long-term NMDAR antagonism correlates reduced astrocytic glutamate uptake with anxiety-like phenotype

    Directory of Open Access Journals (Sweden)

    Eduardo R Zimmer

    2015-06-01

    Full Text Available The role of glutamate N-methyl-D-Aspartate receptor (NMDAR hypofunction has been extensively studied in schizophrenia; however, less is known about its role in anxiety disorders. Recently, it was demonstrated that astrocytic GLT-1 blockade leads to an anxiety-like phenotype. Although astrocytes are capable of modulating NMDAR activity through glutamate uptake transporters, the relationship between astrocytic glutamate uptake and the development of an anxiety phenotype remains poorly explored. Here, we aimed to investigative whether long-term antagonism of NMDAR impacts anxiety-related behaviors and astrocytic glutamate uptake. Memantine, an NMDAR antagonist, was administered daily for 24 days to healthy adult CF-1 mice by oral gavage at doses of 5, 10 or 20 mg/kg. The mice were submitted to a sequential battery of behavioral tests (open field, light-dark box and elevated plus-maze tests. We then evaluated glutamate uptake activity and the immunocontents of glutamate transporters in the frontoparietal cortex and hippocampus. Our results demonstrated that long-term administration of memantine induces anxiety-like behavior in mice in the light-dark box and elevated plus-maze paradigms. Additionally, the administration of memantine decreased glutamate uptake activity in both the frontoparietal cortex and hippocampus without altering the immunocontent of either GLT-1 or GLAST. Remarkably, the memantine-induced reduction in glutamate uptake was correlated with enhancement of an anxiety-like phenotype. In conclusion, long-term NMDAR antagonism with memantine induces anxiety-like behavior that is associated with reduced glutamate uptake activity but that is not dependent on GLT-1 or GLAST protein expression. Our study suggests that NMDAR and glutamate uptake hypofunction may contribute to the development of conditions that fall within the category of anxiety disorders.

  13. 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

  14. Human Engineered Heart Muscles Engraft and Survive Long-Term in a Rodent Myocardial Infarction Model

    Science.gov (United States)

    Riegler, Johannes; Tiburcy, Malte; Ebert, Antje; Tzatzalos, Evangeline; Raaz, Uwe; Abilez, Oscar J.; Shen, Qi; Kooreman, Nigel G.; Neofytou, Evgenios; Chen, Vincent C.; Wang, Mouer; Meyer, Tim; Tsao, Philip S.; Connolly, Andrew J.; Couture, Larry A.; Gold, Joseph D.; Zimmermann, Wolfram H.; Wu, Joseph C.

    2015-01-01

    Rational Tissue engineering approaches may improve survival and functional benefits from human embryonic stem cell-derived cardiomyocte (ESC-CM) transplantation, thereby potentially preventing dilative remodelling and progression to heart failure. Objective Assessment of transport stability, long term survival, structural organisation, functional benefits, and teratoma risk of engineered heart muscle (EHM) in a chronic myocardial infarction (MI) model. Methods and Results We constructed EHMs from ESC-CMs and released them for transatlantic shipping following predefined quality control criteria. Two days of shipment did not lead to adverse effects on cell viability or contractile performance of EHMs (n=3, P=0.83, P=0.87). After ischemia/reperfusion (I/R) injury, EHMs were implanted onto immunocompromised rat hearts at 1 month to simulate chronic ischemia. Bioluminescence imaging (BLI) showed stable engraftment with no significant cell loss between week 2 and 12 (n=6, P=0.67), preserving up to 25% of the transplanted cells. Despite high engraftment rates and attenuated disease progression (change in ejection fraction for EHMs −6.7±1.4% vs control −10.9±1.5%, n>12, P=0.05), we observed no difference between EHMs containing viable or non-viable human cardiomyocytes in this chronic xenotransplantation model (n>12, P=0.41). Grafted cardiomyocytes showed enhanced sarcomere alignment and increased connexin 43 expression at 220 days after transplantation. No teratomas or tumors were found in any of the animals (n=14) used for long-term monitoring. Conclusions EHM transplantation led to high engraftment rates, long term survival, and progressive maturation of human cardiomyocytes. However, cell engraftment was not correlated with functional improvements in this chronic MI model. Most importantly, the safety of this approach was demonstrated by the lack of tumor or teratoma formation. PMID:26291556

  15. [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.

  16. 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

  17. 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.

  18. 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.

  19. 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...

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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

  7. 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 ...

  8. 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.

  9. Scientific Understanding from Long Term Observations: Insights from the Long Term Ecological Research (LTER) Program

    Science.gov (United States)

    Gosz, J.

    2001-12-01

    The network dedicated to Long Term Ecological Research (LTER) in the United States has grown to 24 sites since it was formed in 1980. Long-term research and monitoring are performed on parameters thatare basic to all ecosystems and are required to understand patterns, processes, and relationship to change. Collectively, the sites in the LTER Network provide opportunities to contrast marine, coastal, and continental regions, the full range of climatic gradients existing in North America, and aquatic and terrestrial habitats in a range of ecosystem types. The combination of common core areas and long-term research and monitoring in many habitats have allowed unprecedented abilities to understand and compare complex temporal and spatial dynamics associated with issues like climate change, effects of pollution, biodiversity and landuse. For example, McMurdo Dry Valley in the Antarctic has demonstrated an increase in glacier mass since 1993 which coincides with a period of cooler than normal summers and more than average snowfall. In contrast, the Bonanza Creek and Toolik Lake sites in Alaska have recorded a warming period unprecedented in the past 200 years. Nitrogen deposition effects have been identified through long-term watershed studies on biogeochemical cycles, especially at Coweeta Hydrological Lab, Harvard Forest, and the Hubbard Brook Experimental Forest. In aquatic systems, such as the Northern Temperate Lakes site, long-term data revealed time lags in effects of invaders and disturbance on lake communities. Biological recovery from an effect such as lake acidification was shown to lag behind chemical recovery. The long-term changes documented over 2 decades have been instrumental in influencing management practices in many of the LTER areas. In Puerto Rico, the Luquillo LTER demonstrated that dams obstruct migrations of fish and freshwater shrimp and water abstraction at low flows can completely obliterate downstream migration of juveniles and damage

  10. Orlistat for the long-term treatment of obesity.

    Science.gov (United States)

    Harp, J B

    1999-02-01

    Orlistat, a potent gastrointestinal lipase inhibitor, is a member of a new class of drugs designed for the long-term treatment of obesity. When given with a fat-containing meal, orlistat reduces dietary fat absorption by approximately 30%, which equates to a decrease in caloric absorption of approximately 200 kilocalories per day. A 2-year European study found a mean decrease in body weight of 10.2% (10.3 kg) in the orlistat group compared to 6.1% (6.1 kg) in the placebo group at 1 year. Additionally, 9.3% of the orlistat group versus 2.1% of the placebo group lost >20% of their initial weight. Serum lipids and diabetes control are also improved by orlistat. Related to orlistat's mechanism of action, side effects include oily spotting, flatulence and frequent loose stools, but not frank diarrhea or intestinal malabsorption. Vitamin D and beta-carotene levels decreased, but remained within the normal range. In summary, orlistat is the first example of a new class of antiobesity drugs that enhances weight loss and weight maintenance by interfering with dietary fat absorption. Orlistat has tolerable gastrointestinal side effects and no major drug toxicity. Orlistat is a viable adjunct to lifestyle interventions used in the long-term management of obesity. (c) 1999 Prous Science. All rights reserved.

  11. Facilitating change among nursing assistants in long term care.

    Science.gov (United States)

    Aubry, Francois; Etheridge, Francis; Couturier, Yves

    2012-11-09

    In this article, the authors consider the implementation of change in long term care organizations (LTCOs) and present their study describing the process by which new nursing assistants are informally integrated into LTCOs in Quebec, Canada. The study method included 23 in-depth interviews with nursing assistants in two long term care centres. The findings enabled the authors to describe the informal process by which new nursing assistants are integrated into LTCOs and the manner in which informal work strategies enhance the work of nursing care, thus enabling the nursing assistants to manage heavy workloads. The authors discuss whether this teamwork is a deterrent to change or a lever for change and address issues regarding the collective structure of nursing assistant teams. Implications for practice include a Five-Step Innovation Plan. In conclusion, the authors propose that organizational change among nursing assistants in a LTCO is best accomplished when the leaders consider the nursing assistants' strong sense of community to be a change engine rather than a change obstacle.

  12. Association Between Long-term Alcohol Consumption and Undercarboxylated Osteocalcin.

    Science.gov (United States)

    Teraoka, Atsushi

    2015-10-01

    The Japanese Ministry of Health, Labour and Welfare has focused on enhancing knowldge about the association between alcohol consumption and health, such as early detection of alcohol abuse, the appropriate actions to be taken after detection, and prevention of teenage drinking. They believe that it is necessary to develop and improve the methods for early detection of alcohol-related problems in an easy and effective way. Given this context, we hypothsized that simultaneous determination of osteocalcin (OC) and undercarboxylated osteocalcin ucOC), bone metabolic markers, would facilitate research on the effects of alcohol drinking. We divided volunteers into a group of long-term drinkers (heavy drinking for 20 years or more) and a group of social drinkers (moderate and controlled drinkers), and determined blood DC, ucOC, bone-specific alkaline phosphatase (BAP), and tartrate-resistant acid phosphatase isoform 5b (TRACP-5b) levels, as bone metabolic markers, and glutamic-oxaloacetic transaminase (GOT), mitochondrial GOT (m-GOT), glutamic pyruvic transaminase (GPT), and γ-glutamyl transpeptidase (γ-GTP) levels, as biochemical markers. In addition, we determined the levels of free and bound ethanol and methanol in urine as markers of alcohol abuse and dependence. The group of long-term drinkers showed significantly higher levels of OC and ucOC than the group of social drinkers (p alcohol dependence.

  13. The histone deacetylase HDAC4 regulates long-term memory in Drosophila.

    Directory of Open Access Journals (Sweden)

    Helen L Fitzsimons

    Full Text Available A growing body of research indicates that pharmacological inhibition of histone deacetylases (HDACs correlates with enhancement of long-term memory and current research is concentrated on determining the roles that individual HDACs play in cognitive function. Here, we investigate the role of HDAC4 in long-term memory formation in Drosophila. We show that overexpression of HDAC4 in the adult mushroom body, an important structure for memory formation, resulted in a specific impairment in long-term courtship memory, but had no affect on short-term memory. Overexpression of an HDAC4 catalytic mutant also abolished LTM, suggesting a mode of action independent of catalytic activity. We found that overexpression of HDAC4 resulted in a redistribution of the transcription factor MEF2 from a relatively uniform distribution through the nucleus into punctate nuclear bodies, where it colocalized with HDAC4. As MEF2 has also been implicated in regulation of long-term memory, these data suggest that the repressive effects of HDAC4 on long-term memory may be through interaction with MEF2. In the same genetic background, we also found that RNAi-mediated knockdown of HDAC4 impairs long-term memory, therefore we demonstrate that HDAC4 is not only a repressor of long-term memory, but also modulates normal memory formation.

  14. 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.

  15. 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.

  16. 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

  17. 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.

  18. 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

  19. Local over-expression of VEGF-DΔNΔC in the uterine arteries of pregnant sheep results in long-term changes in uterine artery contractility and angiogenesis.

    Directory of Open Access Journals (Sweden)

    Vedanta Mehta

    Full Text Available The normal development of the uteroplacental circulation in pregnancy depends on angiogenic and vasodilatory factors such as vascular endothelial growth factor (VEGF. Reduced uterine artery blood flow (UABF is a common cause of fetal growth restriction; abnormalities in angiogenic factors are implicated. Previously we showed that adenovirus (Ad-mediated VEGF-A165 expression in the pregnant sheep uterine artery (UtA increased nitric oxide synthase (NOS expression, altered vascular reactivity and increased UABF. VEGF-D is a VEGF family member that promotes angiogenesis and vasodilatation but, in contrast to VEGF-A, does not increase vascular permeability. Here we examined the effect of Ad.VEGF-DΔNΔC vector encoding a fully processed form of VEGF-D, on the uteroplacental circulation.UtA transit-time flow probes and carotid artery catheters were implanted in mid-gestation pregnant sheep (n = 5 to measure baseline UABF and maternal haemodynamics respectively. 7-14 days later, after injection of Ad.VEGF-DΔNΔC vector (5×10(11 particles into one UtA and an Ad vector encoding β-galactosidase (Ad.LacZ contralaterally, UABF was measured daily until scheduled post-mortem examination at term. UtAs were assessed for vascular reactivity, NOS expression and endothelial cell proliferation; NOS expression was studied in ex vivo transduced UtA endothelial cells (UAECs.At 4 weeks post-injection, Ad.VEGF-DΔNΔC treated UtAs showed significantly lesser vasoconstriction (Emax144.0 v/s 184.2, p = 0.002. There was a tendency to higher UABF in Ad.VEGF-DΔNΔC compared to Ad.LacZ transduced UtAs (50.58% v/s 26.94%, p = 0.152. There was no significant effect on maternal haemodynamics. An increased number of proliferating endothelial cells and adventitial blood vessels were observed in immunohistochemistry. Ad.VEGF-DΔNΔC expression in cultured UAECs upregulated eNOS and iNOS expression.Local over-expression of VEGF-DΔNΔC in the UtAs of pregnant mid

  20. Local over-expression of VEGF-DΔNΔC in the uterine arteries of pregnant sheep results in long-term changes in uterine artery contractility and angiogenesis.

    Science.gov (United States)

    Mehta, Vedanta; Abi-Nader, Khalil N; Shangaris, Panicos; Shaw, S W Steven; Filippi, Elisa; Benjamin, Elizabeth; Boyd, Michael; Peebles, Donald M; Martin, John; Zachary, Ian; David, Anna L

    2014-01-01

    The normal development of the uteroplacental circulation in pregnancy depends on angiogenic and vasodilatory factors such as vascular endothelial growth factor (VEGF). Reduced uterine artery blood flow (UABF) is a common cause of fetal growth restriction; abnormalities in angiogenic factors are implicated. Previously we showed that adenovirus (Ad)-mediated VEGF-A165 expression in the pregnant sheep uterine artery (UtA) increased nitric oxide synthase (NOS) expression, altered vascular reactivity and increased UABF. VEGF-D is a VEGF family member that promotes angiogenesis and vasodilatation but, in contrast to VEGF-A, does not increase vascular permeability. Here we examined the effect of Ad.VEGF-DΔNΔC vector encoding a fully processed form of VEGF-D, on the uteroplacental circulation. UtA transit-time flow probes and carotid artery catheters were implanted in mid-gestation pregnant sheep (n = 5) to measure baseline UABF and maternal haemodynamics respectively. 7-14 days later, after injection of Ad.VEGF-DΔNΔC vector (5×10(11) particles) into one UtA and an Ad vector encoding β-galactosidase (Ad.LacZ) contralaterally, UABF was measured daily until scheduled post-mortem examination at term. UtAs were assessed for vascular reactivity, NOS expression and endothelial cell proliferation; NOS expression was studied in ex vivo transduced UtA endothelial cells (UAECs). At 4 weeks post-injection, Ad.VEGF-DΔNΔC treated UtAs showed significantly lesser vasoconstriction (Emax144.0 v/s 184.2, p = 0.002). There was a tendency to higher UABF in Ad.VEGF-DΔNΔC compared to Ad.LacZ transduced UtAs (50.58% v/s 26.94%, p = 0.152). There was no significant effect on maternal haemodynamics. An increased number of proliferating endothelial cells and adventitial blood vessels were observed in immunohistochemistry. Ad.VEGF-DΔNΔC expression in cultured UAECs upregulated eNOS and iNOS expression. Local over-expression of VEGF-DΔNΔC in the UtAs of pregnant mid

  1. A multicenter, open-label, long-term safety and tolerability study of DFN-02, an intranasal spray of sumatriptan 10?mg plus permeation enhancer DDM, for the acute treatment of episodic migraine

    OpenAIRE

    Munjal, Sagar; Brand-Schieber, Elimor; Allenby, Kent; Spierings, Egilius L.H.; Cady, Roger K.; Rapoport, Alan M.

    2017-01-01

    Background DFN-02 is a novel intranasal spray formulation composed of sumatriptan 10?mg and a permeation-enhancing excipient comprised of 0.2% 1-O-n-Dodecyl-?-D-Maltopyranoside (DDM). This composition of DFN-02 allows sumatriptan to be rapidly absorbed into the systemic circulation and exhibit pharmacokinetics comparable to subcutaneously administered sumatriptan. Rapid rate of absorption is suggested to be important for optimal efficacy. The objective of this study was to evaluate the safety...

  2. Effect of long term selenium yeast intervention on activity and gene expression of antioxidant and xenbiotic metabolising enzymes in healthy elderly volunteers from the Danish Prevention of Cancer by Intervention by Selenium (PRECISE) Pilot Study

    DEFF Research Database (Denmark)

    Ravn-Haren, Gitte; Krath, Britta; Overvad, Kim

    2008-01-01

    Numerous mechanisms have been proposed to explain the anti-carcinogenic effects of Se, among them altered carcinogen metabolism. We investigated the effect of Se supplementation on activities of glutathione peroxidase (GPX), glutathione reductase (GR) and glutathione S-transferase (GST) in differ...... genes could increase the risk of cancer. However, further studies are needed to establish whether the observed effect in leucocytes reflects a similar expression pattern in target tissues....

  3. Relationship of Extreme Chromosomal Instability with Long-term Survival in a Retrospective Analysis of Primary Breast Cancer

    DEFF Research Database (Denmark)

    Roylance, Rebecca; Endesfelder, David; Gorman, Patricia

    2011-01-01

    Background: Chromosomal instability (CIN) is thought to be associated with poor prognosis in solid tumors; however, evidence from preclinical and mouse tumor models suggest that CIN may paradoxically enhance or impair cancer cell fitness. Breast cancer prognostic expression signature sets, which...... with survival outcome. Results: There was increased CIN and clonal eterogeneity in ER-negative compared with ER-positive breast cancer. Consistent with a negative impact of CIN on cellular fitness, extreme CIN in ER-negative breast cancer was an independent variable associated with improved long-term survival...

  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. 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

  6. Fearful expressions enhance recognition memory: electrophysiological evidence.

    Science.gov (United States)

    Righi, S; Marzi, T; Toscani, M; Baldassi, S; Ottonello, S; Viggiano, M P

    2012-01-01

    Facial expressions play a key role in affective and social behavior. However, the temporal dynamics of the brain responses to emotional faces remain still unclear, in particular an open question is at what stage of face processing expressions might influence encoding and recognition memory. To try and answer this question we recorded the event-related potentials (ERPs) elicited in an old/new recognition task. A novel aspect of the present design was that whereas faces were presented during the study phase with either a happy, fearful or neutral expression, they were always neutral during the memory retrieval task. The ERP results showed three main findings: An enhanced early fronto-central positivity for faces encoded as fearful, both during the study and the retrieval phase. During encoding subsequent memory (Dm effect) was influenced by emotion. At retrieval the early components P100 and N170 were modulated by the emotional expression of the face at the encoding phase. Finally, the later ERP components related to recognition memory were modulated by the previously encoded facial expressions. Overall, these results suggest that face recognition is modulated by top-down influences from brain areas associated with emotional memory, enhancing encoding and retrieval in particular for fearful emotional expressions. Copyright © 2011 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

    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.

  8. Concerning long-term geomagnetic variations and space climatology

    Directory of Open Access Journals (Sweden)

    K.-H. Glassmeier

    2004-11-01

    Full Text Available During geomagnetic polarity transitions the surface magnetic field of the Earth decays to about 25% and less of its present value. This implies a shrinking of the terrestrial magnetosphere and posses the question of whether magnetospheric magnetic field variations scale in the same manner. Furthermore, the geomagnetic main field also controls the magnetospheric magnetic field and space weather conditions. Long-term geomagnetic variations are thus intimately related to space climate. We critically assess existing scaling relations and derive new ones for various magnetospheric parameters. For example, we find that ring current perturbations do not increase with decreasing dipole moment. And we derive a scaling relation for the polar electrojet contribution, indicating a weak increase with increasing internal field. From this we infer that the ratio between external and internal field contributions may be weakly enhanced during polarity transitions. Our scaling relations also provide more insight on the importance of the internal geomagnetic field contribution for space climate.

  9. Long-Term Visual Functioning After Eclampsia

    NARCIS (Netherlands)

    Wiegman, Marjon J.; de Groot, Jan C.; Jansonius, Nomdo M.; Aarnoudse, Jan G.; Groen, Henk; Faas, Marijke M.; Zeeman, Gerda G.

    OBJECTIVE: Complete neurocognitive recovery after eclampsia has been questioned with the expression of neurocognitive deficits by affected women and demonstration of cerebral white matter lesions on magnetic resonance imaging years after eclampsia. We hypothesized that formerly eclamptic women may

  10. Enhanced gene expression from retroviral vectors

    Directory of Open Access Journals (Sweden)

    Micklem David R

    2008-02-01

    Full Text Available Abstract Background Retroviruses are widely used to transfer genes to mammalian cells efficiently and stably. However, genetic elements required for high-level gene expression are incompatible with standard systems. The retroviral RNA genome is produced by cellular transcription and post-transcriptional processing within packaging cells: Introns present in the retroviral genomic transcript are removed by splicing, while polyadenylation signals lead to the production of ineffective truncated genomes. Furthermore strong enhancer/promoters within the retroviral payload lead to detrimental competition with the retroviral enhancer/promoter. Results By exploiting a new method of producing the retroviral genome in vitro it is possible to produce infectious retroviral particles carrying a high-level expression cassette that completely prohibits production of infectious retroviral particles by conventional methods. We produced an expression cassette comprising a strong enhancer/promoter, an optimised intron, the GFP open reading frame and a strong polyadenylation signal. This cassette was cloned into both a conventional MMLV retroviral vector and a vector designed to allow in vitro transcription of the retroviral genome by T7 RNA polymerase. When the conventional retroviral vector was transfected into packaging cells, the expression cassette drove strong GFP expression, but no infectious retrovirus was produced. Introduction of the in vitro produced uncapped retroviral genomic transcript into the packaging cells did not lead to any detectable GFP expression. However, infectious retrovirus was easily recovered, and when used to infect target primary human cells led to very high GFP expression – up to 3.5 times greater than conventional retroviral LTR-driven expression. Conclusion Retroviral vectors carrying an optimized high-level expression cassette do not produce infectious virions when introduced into packaging cells by transfection of DNA

  11. AAV2-mediated CLN2 gene transfer to rodent and non-human primate brain results in long-term TPP-I expression compatible with therapy for LINCL.

    Science.gov (United States)

    Sondhi, D; Peterson, D A; Giannaris, E L; Sanders, C T; Mendez, B S; De, B; Rostkowski, A B; Blanchard, B; Bjugstad, K; Sladek, J R; Redmond, D E; Leopold, P L; Kaminsky, S M; Hackett, N R; Crystal, R G

    2005-11-01

    Late infantile neuronal ceroid lipofuscinosis (LINCL) is a fatal, autosomal recessive disease resulting from mutations in the CLN2 gene with consequent deficiency in its product tripeptidyl peptidase I (TPP-I). In the central nervous system (CNS), the deficiency of TPP-I results in the accumulation of proteins in lysosomes leading to a loss of neurons causing progressive neurological decline, and death by ages 10-12 years. To establish the feasibility of treating the CNS manifestations of LINCL by gene transfer, an adeno-associated virus 2 (AAV2) vector encoding the human CLN2 cDNA (AAV2CUhCLN2) was assessed for its ability to establish therapeutic levels of TPP-I in the brain. In vitro studies demonstrated that AAV2CUhCLN2 expressed CLN2 and produced biologically active TPP-I protein of which a fraction was secreted as the pro-TPP-I precursor and was taken up by nontransduced cells (ie, cross-correction). Following AAV2-mediated CLN2 delivery to the rat striatum, enzymatically active TPP-I protein was detected. By immunohistochemistry TPP-I protein was detected in striatal neurons (encompassing nearly half of the target structure) for up to 18 months. At the longer time points following striatal administration, TPP-I-positive cell bodies were also observed in the substantia nigra, frontal cerebral cortex and thalamus of the injected hemisphere, and the frontal cerebral cortex of the noninjected hemisphere. These areas of the brain contain neurons that extend axons into the striatum, suggesting that CNS circuitry may aid the distribution of the gene product. To assess the feasibility of human CNS delivery, a total of 3.6 x 10(11) particle units of AAV2CUhCLN2 was administered to the CNS of African green monkeys in 12 distributed doses. Assessment at 5 and 13 weeks demonstrated widespread detection of TPP-I in neurons, but not glial cells, at all regions of injection. The distribution of TPP-I-positive cells was similar between the two time points at all injection

  12. Blood folate status and expression of proteins involved in immune function, inflammation, and coagulation: biochemical and proteomic changes in the plasma of humans in response to long-term synthetic folic acid supplementation.

    Science.gov (United States)

    Duthie, Susan J; Horgan, Graham; de Roos, Baukje; Rucklidge, Garry; Reid, Martin; Duncan, Gary; Pirie, Lynn; Basten, Graham P; Powers, Hilary J

    2010-04-05

    We used plasma proteomics to identify human proteins responsive to folate status. Plasma was collected from subjects treated with placebo or 1.2 mg of folic acid daily for 12 weeks in a randomized controlled trial. Homocysteine and folate were measured by immunoassay and uracil misincorporation by electrophoresis. The plasma proteome was assessed by 2-D gel electrophoresis, and proteins were identified by LC MS/MS. 5-methylTHF increased 5-fold (P = 0.000003) in response to intervention. Red cell folate doubled (P = 0.013), and lymphocyte folate increased 44% (P = 0.0001). Hcy and uracil dropped 22% (P = 0.0005) and 25% (P = 0.05), respectively. ApoE A-1, alpha-1-antichymotrypsin, antithrombin, and serum amyloid P were downregulated, while albumin, IgM C, and complement C3 were upregulated (P metabolic pathways related to complement fixation (e.g., C1, C3, C4, Factor H, Factor 1, Factor B, clusterin), coagulation (e.g., antithrombin, alpha-1-antitrypsin, kininogen) and mineral transport (e.g., transthyretin, haptoglobin, ceruloplasmin). Low folate status pre- and post-treatment were associated with lower levels of proteins involved in activation and regulation of immune function and coagulation. Supplementation with synthetic folic acid increased expression of these proteins but did not substantially disrupt the balance of these pathways.

  13. Reforming long-term care financing through insurance

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