Science.gov

Sample records for long-term cellular responses

  1. 3D printed cellular solid outperforms traditional stochastic foam in long-term mechanical response.

    PubMed

    Maiti, A; Small, W; Lewicki, J P; Weisgraber, T H; Duoss, E B; Chinn, S C; Pearson, M A; Spadaccini, C M; Maxwell, R S; Wilson, T S

    2016-01-01

    3D printing of polymeric foams by direct-ink-write is a recent technological breakthrough that enables the creation of versatile compressible solids with programmable microstructure, customizable shapes, and tunable mechanical response including negative elastic modulus. However, in many applications the success of these 3D printed materials as a viable replacement for traditional stochastic foams critically depends on their mechanical performance and micro-architectural stability while deployed under long-term mechanical strain. To predict the long-term performance of the two types of foams we employed multi-year-long accelerated aging studies under compressive strain followed by a time-temperature-superposition analysis using a minimum-arc-length-based algorithm. The resulting master curves predict superior long-term performance of the 3D printed foam in terms of two different metrics, i.e., compression set and load retention. To gain deeper understanding, we imaged the microstructure of both foams using X-ray computed tomography, and performed finite-element analysis of the mechanical response within these microstructures. This indicates a wider stress variation in the stochastic foam with points of more extreme local stress as compared to the 3D printed material, which might explain the latter's improved long-term stability and mechanical performance.

  2. 3D printed cellular solid outperforms traditional stochastic foam in long-term mechanical response

    PubMed Central

    Maiti, A.; Small, W.; Lewicki, J. P.; Weisgraber, T. H.; Duoss, E. B.; Chinn, S. C.; Pearson, M. A.; Spadaccini, C. M.; Maxwell, R. S.; Wilson, T. S.

    2016-01-01

    3D printing of polymeric foams by direct-ink-write is a recent technological breakthrough that enables the creation of versatile compressible solids with programmable microstructure, customizable shapes, and tunable mechanical response including negative elastic modulus. However, in many applications the success of these 3D printed materials as a viable replacement for traditional stochastic foams critically depends on their mechanical performance and micro-architectural stability while deployed under long-term mechanical strain. To predict the long-term performance of the two types of foams we employed multi-year-long accelerated aging studies under compressive strain followed by a time-temperature-superposition analysis using a minimum-arc-length-based algorithm. The resulting master curves predict superior long-term performance of the 3D printed foam in terms of two different metrics, i.e., compression set and load retention. To gain deeper understanding, we imaged the microstructure of both foams using X-ray computed tomography, and performed finite-element analysis of the mechanical response within these microstructures. This indicates a wider stress variation in the stochastic foam with points of more extreme local stress as compared to the 3D printed material, which might explain the latter’s improved long-term stability and mechanical performance. PMID:27117858

  3. 3D printed cellular solid outperforms traditional stochastic foam in long-term mechanical response

    DOE PAGESBeta

    Maiti, A.; Small, W.; Lewicki, J.; Weisgraber, T. H.; Duoss, E. B.; Chinn, S. C.; Pearson, M. A.; Spadaccini, C. M.; Maxwell, R. S.; Wilson, T. S.

    2016-04-27

    3D printing of polymeric foams by direct-ink-write is a recent technological breakthrough that enables the creation of versatile compressible solids with programmable microstructure, customizable shapes, and tunable mechanical response including negative elastic modulus. However, in many applications the success of these 3D printed materials as a viable replacement for traditional stochastic foams critically depends on their mechanical performance and micro-architectural stability while deployed under long-term mechanical strain. To predict the long-term performance of the two types of foams we employed multi-year-long accelerated aging studies under compressive strain followed by a time-temperature-superposition analysis using a minimum-arc-length-based algorithm. The resulting master curvesmore » predict superior long-term performance of the 3D printed foam in terms of two different metrics, i.e., compression set and load retention. To gain deeper understanding, we imaged the microstructure of both foams using X-ray computed tomography, and performed finite-element analysis of the mechanical response within these microstructures. As a result, this indicates a wider stress variation in the stochastic foam with points of more extreme local stress as compared to the 3D printed material, which might explain the latter’s improved long-term stability and mechanical performance.« less

  4. 3D printed cellular solid outperforms traditional stochastic foam in long-term mechanical response

    NASA Astrophysics Data System (ADS)

    Maiti, A.; Small, W.; Lewicki, J. P.; Weisgraber, T. H.; Duoss, E. B.; Chinn, S. C.; Pearson, M. A.; Spadaccini, C. M.; Maxwell, R. S.; Wilson, T. S.

    2016-04-01

    3D printing of polymeric foams by direct-ink-write is a recent technological breakthrough that enables the creation of versatile compressible solids with programmable microstructure, customizable shapes, and tunable mechanical response including negative elastic modulus. However, in many applications the success of these 3D printed materials as a viable replacement for traditional stochastic foams critically depends on their mechanical performance and micro-architectural stability while deployed under long-term mechanical strain. To predict the long-term performance of the two types of foams we employed multi-year-long accelerated aging studies under compressive strain followed by a time-temperature-superposition analysis using a minimum-arc-length-based algorithm. The resulting master curves predict superior long-term performance of the 3D printed foam in terms of two different metrics, i.e., compression set and load retention. To gain deeper understanding, we imaged the microstructure of both foams using X-ray computed tomography, and performed finite-element analysis of the mechanical response within these microstructures. This indicates a wider stress variation in the stochastic foam with points of more extreme local stress as compared to the 3D printed material, which might explain the latter’s improved long-term stability and mechanical performance.

  5. Biosynthetic hydrogels--studies on chemical and physical characteristics on long-term cellular response for tissue engineering.

    PubMed

    Thankam, Finosh Gnanaprakasam; Muthu, Jayabalan

    2014-07-01

    Biosynthetic hydrogels can meet the drawbacks caused by natural and synthetic ones for biomedical applications. In the current article we present a novel biosynthetic alginate-poly(propylene fumarate) copolymer based chemically crosslinked hydrogel scaffolds for cardiac tissue engineering applications. Partially crosslinked PA hydrogel and fully cross linked PA-A hydrogel scaffolds were prepared. The influence of chemical and physical (morphology and architecture of hydrogel) characteristics on the long term cellular response was studied. Both these hydrogels were cytocompatible and showed no genotoxicity upon contact with fibroblast cells. Both PA and PA-A were able to resist deleterious effects of reactive oxygen species and sustain the viability of L929 cells. The hydrogel incubated oxidative stress induced cells were capable of maintaining the intra cellular reduced glutathione (GSH) expression to the normal level confirmed their protective effect. Relatively the PA hydrogel was found to be unstable in the cell culture medium. The PA-A hydrogel was able to withstand appreciable cyclic stretching. The cyclic stretching introduced complex macro and microarchitectural features with interconnected pores and more structured bound water which would provide long-term viability of around 250% after the 24th day of culture. All these qualities make PA-A hydrogel form a potent candidate for cardiac tissue engineering.

  6. Prediction of long-term aging of cellular plastics

    SciTech Connect

    Fan, Y.; Kokko, E.

    1995-09-01

    Chlorofluorocarbon(CFC)-based cellular plastics are facing the challenge of environmental protection. The cellular plastic industry has been looking for new blowing agents as alternatives for CFCs since the Montreal Protocol was signed in 1987. The prediction of long-term thermal performance of newly developed cellular plastics thus becomes apparent. In this paper, the model ACP aging of cellular plastic is introduced. This model was originally developed for evaluating the thermal performance of carbon dioxide, CFC-11, CFC-12, CFC-22, n-Pentane, neo-Pentane and cyclo-Pentane. In comparison with short-term measurements, the ACP program now is able to predict the aging performance of cellular plastics is to combine the short-term measurements and model simulation. 21 refs., 5 figs., 4 tabs.

  7. Fluorescent PEGulated Oligourethane Nanoparticles for Long-Term Cellular Tracing.

    PubMed

    Mondal, Tathagata; Sarkar, Jayita; Ghosh, Suhrit

    2016-07-25

    We have introduced a new ABA-type amphiphilic block copolymer consisting of functional oligourethane hydrophobic blocks and two polyethylene glycol (PEG) hydrophilic blocks. The polymer was synthesized in a single step by step-growth polymerization between two monomers, namely tetraphenylethylene (TPE)-diol and hexamehylene di-isocyanate in the presence of a monofunctional impurity PEG-2000. The polymer exhibits facile self-assembly in water by synergistic effects of H-bonding and π-π interaction among the oligourethane core, leading to the formation of robust nanoparticles with remarkable aggregation-induced emission (AIE). These nanoparticles show very low critical aggregation concentration, stability over a large pH window, and excellent biocompatibility as revealed by an MTT assay. Cellular imaging with cancer cells showed facile cellular uptake and, more importantly, retention of AIE in cellular milieu for long times, which was successfully utilized for long-term cancer cell tracking. PMID:27359123

  8. Strong effect of long-term Sparicotyle chrysophrii infection on the cellular and innate immune responses of gilthead sea bream, Sparus aurata.

    PubMed

    Henry, M A; Nikoloudaki, C; Tsigenopoulos, C; Rigos, G

    2015-07-01

    One thousand healthy recipient gilthead sea bream, Sparus aurata, cohabited with 250 donor fish parasitized by Sparicotyle chrysophrii (Van Beneden and Hesse, 1963) (Monogenea: Polyopisthocotylea), a common parasite of the gills of this fish species. Controls consisted of 1000 healthy fish kept in a separate tank. After 10 weeks, fish were weighed and parasite load, hemoglobin concentration and immunological parameters were assessed. Rather than the absence of parasite, hemoglobin concentration was a better marker of the health status of the fish, because S.chrysophrii had detached from the strongly anemic gills of some animals leaving fish with affected immune system but without parasites. The parasite infection seemed to trigger a cellular response of the fish immune system but to inhibit its humoral components. Thus, parasitized fish may control the parasite infection through the action of reactive oxygen species but they may become more sensitive to potential secondary bacterial or parasitical infections. This phenomenon was demonstrated not only through significant differences between recipient and control fish but also through strong correlations between those parameters and parasite load, fish weight and/or hemoglobin concentration.

  9. The neuronal response at extended timescales: long-term correlations without long-term memory

    PubMed Central

    Soudry, Daniel; Meir, Ron

    2014-01-01

    Long term temporal correlations frequently appear at many levels of neural activity. We show that when such correlations appear in isolated neurons, they indicate the existence of slow underlying processes and lead to explicit conditions on the dynamics of these processes. Moreover, although these slow processes can potentially store information for long times, we demonstrate that this does not imply that the neuron possesses a long memory of its input, even if these processes are bidirectionally coupled with neuronal response. We derive these results for a broad class of biophysical neuron models, and then fit a specific model to recent experiments. The model reproduces the experimental results, exhibiting long term (days-long) correlations due to the interaction between slow variables and internal fluctuations. However, its memory of the input decays on a timescale of minutes. We suggest experiments to test these predictions directly. PMID:24744724

  10. A Limited Antigen-Specific Cellular Response Is Sufficient for the Early Control of Mycobacterium tuberculosis in the Lung but Is Insufficient for Long-Term Survival

    PubMed Central

    Turner, Joanne; Dobos, Karen M.; Keen, Marc A; Frank, Anthony A.; Ehlers, Stefan; Orme, Ian M.; Belisle, John T.; Cooper, Andrea M.

    2004-01-01

    Mice that were transgenic for a T-cell receptor (TCR) specific for ovalbumin peptide323-339 (DO11.10) were able to survive an infection with Mycobacterium tuberculosis for approximately 80 days. This limited early control of infection was associated with gamma interferon production, inducible nitric oxide synthase expression within the lung, and an influx of clonotypic lymphocytes. The control of M. tuberculosis was lost in DO11.10 mice bred in a rag mutant background, demonstrating that the immune responsiveness was recombinase dependent and likely to be associated with the expression of an alternative α TCR by DO11.10 mice. A characterization of the antigen specificity in DO11.10 TCR transgenic mice demonstrated that the specificity was limited and dominated by the 26-kDa (Rv1411c) lipoprotein of M. tuberculosis. This study identifies this lipoprotein as an important and potent inducer of protective T cells within the lungs of mice infected with M. tuberculosis and therefore as a possible target for vaccination. PMID:15213116

  11. Long-term habituation of the C-start escape response in zebrafish larvae.

    PubMed

    Roberts, Adam C; Pearce, Kaycey C; Choe, Ronny C; Alzagatiti, Joseph B; Yeung, Anthony K; Bill, Brent R; Glanzman, David L

    2016-10-01

    The cellular and molecular basis of long-term memory in vertebrates remains poorly understood. Knowledge regarding long-term memory has been impeded by the enormous complexity of the vertebrate brain, particularly the mammalian brain, as well as by the relative complexity of the behavioral alterations examined in most studies of long-term memory in vertebrates. Here, we demonstrate a long-term form of nonassociative learning-specifically, long-term habituation (LTH)-of a simple reflexive escape response, the C-start, in zebrafish larvae. The C-start is triggered by the activation of one of a pair of giant neurons in the zebrafish's hindbrain, the Mauthner cells. We show that LTH of the C-start requires the activity of NMDA receptors and involves macromolecular synthesis. We further show that the long-term habituated reflex can by rapidly dishabituated by a brief tactile stimulus. Our results set the stage for rigorous, mechanistic investigations of the long-term memory for habituation of a reflexive behavioral response, one that is mediated by a relatively simple, neurobiologically tractable, neural circuit. Moreover, the demonstration of NMDAR and transcriptionally dependent LTH in a translucent vertebrate organism should facilitate the use of optical recording, and optogenetic manipulation, of neuronal activity to elucidate the cellular basis of a long-term vertebrate memory. PMID:27555232

  12. Long-term habituation of the C-start escape response in zebrafish larvae.

    PubMed

    Roberts, Adam C; Pearce, Kaycey C; Choe, Ronny C; Alzagatiti, Joseph B; Yeung, Anthony K; Bill, Brent R; Glanzman, David L

    2016-10-01

    The cellular and molecular basis of long-term memory in vertebrates remains poorly understood. Knowledge regarding long-term memory has been impeded by the enormous complexity of the vertebrate brain, particularly the mammalian brain, as well as by the relative complexity of the behavioral alterations examined in most studies of long-term memory in vertebrates. Here, we demonstrate a long-term form of nonassociative learning-specifically, long-term habituation (LTH)-of a simple reflexive escape response, the C-start, in zebrafish larvae. The C-start is triggered by the activation of one of a pair of giant neurons in the zebrafish's hindbrain, the Mauthner cells. We show that LTH of the C-start requires the activity of NMDA receptors and involves macromolecular synthesis. We further show that the long-term habituated reflex can by rapidly dishabituated by a brief tactile stimulus. Our results set the stage for rigorous, mechanistic investigations of the long-term memory for habituation of a reflexive behavioral response, one that is mediated by a relatively simple, neurobiologically tractable, neural circuit. Moreover, the demonstration of NMDAR and transcriptionally dependent LTH in a translucent vertebrate organism should facilitate the use of optical recording, and optogenetic manipulation, of neuronal activity to elucidate the cellular basis of a long-term vertebrate memory.

  13. Increasing long term response by selecting for favorable minor alleles

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Long-term response of genomic selection can be improved by considering allele frequencies of selected markers or quantitative trait loci (QTLs). A previous formula to weight allele frequency of favorable minor alleles was tested, and 2 new formulas were developed. The previous formula used nonlinear...

  14. Network, cellular, and molecular mechanisms underlying long-term memory formation.

    PubMed

    Carasatorre, Mariana; Ramírez-Amaya, Víctor

    2013-01-01

    The neural network stores information through activity-dependent synaptic plasticity that occurs in populations of neurons. Persistent forms of synaptic plasticity may account for long-term memory storage, and the most salient forms are the changes in the structure of synapses. The theory proposes that encoding should use a sparse code and evidence suggests that this can be achieved through offline reactivation or by sparse initial recruitment of the network units. This idea implies that in some cases the neurons that underwent structural synaptic plasticity might be a subpopulation of those originally recruited; However, it is not yet clear whether all the neurons recruited during acquisition are the ones that underwent persistent forms of synaptic plasticity and responsible for memory retrieval. To determine which neural units underlie long-term memory storage, we need to characterize which are the persistent forms of synaptic plasticity occurring in these neural ensembles and the best hints so far are the molecular signals underlying structural modifications of the synapses. Structural synaptic plasticity can be achieved by the activity of various signal transduction pathways, including the NMDA-CaMKII and ACh-MAPK. These pathways converge with the Rho family of GTPases and the consequent ERK 1/2 activation, which regulates multiple cellular functions such as protein translation, protein trafficking, and gene transcription. The most detailed explanation may come from models that allow us to determine the contribution of each piece of this fascinating puzzle that is the neuron and the neural network.

  15. Network, cellular, and molecular mechanisms underlying long-term memory formation.

    PubMed

    Carasatorre, Mariana; Ramírez-Amaya, Víctor

    2013-01-01

    The neural network stores information through activity-dependent synaptic plasticity that occurs in populations of neurons. Persistent forms of synaptic plasticity may account for long-term memory storage, and the most salient forms are the changes in the structure of synapses. The theory proposes that encoding should use a sparse code and evidence suggests that this can be achieved through offline reactivation or by sparse initial recruitment of the network units. This idea implies that in some cases the neurons that underwent structural synaptic plasticity might be a subpopulation of those originally recruited; However, it is not yet clear whether all the neurons recruited during acquisition are the ones that underwent persistent forms of synaptic plasticity and responsible for memory retrieval. To determine which neural units underlie long-term memory storage, we need to characterize which are the persistent forms of synaptic plasticity occurring in these neural ensembles and the best hints so far are the molecular signals underlying structural modifications of the synapses. Structural synaptic plasticity can be achieved by the activity of various signal transduction pathways, including the NMDA-CaMKII and ACh-MAPK. These pathways converge with the Rho family of GTPases and the consequent ERK 1/2 activation, which regulates multiple cellular functions such as protein translation, protein trafficking, and gene transcription. The most detailed explanation may come from models that allow us to determine the contribution of each piece of this fascinating puzzle that is the neuron and the neural network. PMID:22976275

  16. Long-term potentiation and evoked spike responses in the cingulate cortex of freely mobile rats.

    PubMed

    Gorkin, A G; Reymann, K G; Aleksandrov, Yu I

    2003-10-01

    Long-term potentiation of synaptic efficiency is regarded as a major candidate for the role of the physiological mechanism of long-term memory. However, the limited development of concepts of the cellular and subcellular characteristics of the induction of long-term potentiation in animals in conditions of free behavior does not correspond to the importance of this question. The present study was undertaken to determine whether the characteristics of potentiation in the cingulate cortex in response to stimulation of fibers of the subiculo-cingulate tract are truly long-term, i.e., develop through all known phases and last at least 24 h, in freely moving animals. In addition, the study aims included identification of the effects of application of blockers of different types of glutamate receptors on the development of long-term potentiation and identification of the characteristics of spike responses of single cingulate cortex neurons to stimulation of the subiculo-cingulate tract. Long-term potentiation, lasting more than 24 h, was obtained in freely moving adult rats not treated with GABA blockers. Injection of glutamate NMDA synapse blockers led to significant decreases in evoked cingulate cortex potentials in response to test stimulation. Activatory short-latency spike responses were characterized by a low probability of spike generation, and this increased with increases in the stimulation current. These data demonstrated that it is methodologically possible to compare, in freely moving rats, the involvement of individual neurons in the mechanisms involved in learning one or another type of adaptive behavior and the dynamics of their evoked spike activity during the formation of long-term potentiation. PMID:14635990

  17. Redesigning the AIDS response for long-term impact.

    PubMed

    Larson, Heidi J; Bertozzi, Stefano; Piot, Peter

    2011-11-01

    Three decades since the human immunodeficiency virus (HIV) was identified, the pandemic of acquired immunodeficiency syndrome (AIDS) has developed into diverse epidemics around the world. In many populations, HIV infection has become endemic. While there is good progress on expanding access to treatment, with an estimated 6.6 million people on antiretroviral therapy at the end of 2010, prevention efforts are still highly inadequate with 2.6 million new infections occurring in 2009. Demand for treatment is increasing while funding is becoming more scarce and activism is waning. In 2007, the Joint United Nations Programme on HIV/AIDS (UNAIDS) established an independent forum called aids2031 to take a critical look at the global HIV/AIDS response. This paper outlines four key areas for a re-designed AIDS response based on the deliberations of this initiative and on the learning and experience of the first three decades of the epidemic: (i) a new culture of knowledge generation and utilization; (ii) transformed prevention and treatment to increase effectiveness; (iii) increased efficiency through better management and maximizing synergies with other programmes; and (iv) investment for the long term. Across all these areas is a strong emphasis on local capacity building, leadership, programme priorities and budgets.

  18. Environmental and Genetic Preconditioning for Long-Term Anoxia Responses Requires AMPK in Caenorhabditis elegans

    PubMed Central

    LaRue, Bobby L.; Padilla, Pamela A.

    2011-01-01

    Background Preconditioning environments or therapeutics, to suppress the cellular damage associated with severe oxygen deprivation, is of interest to our understanding of diseases associated with oxygen deprivation. Wildtype C. elegans exposed to anoxia enter into a state of suspended animation in which energy-requiring processes reversibly arrest. C. elegans at all developmental stages survive 24-hours of anoxia exposure however, the ability of adult hermaphrodites to survive three days of anoxia significantly decreases. Mutations in the insulin-like signaling receptor (daf-2) and LIN-12/Notch (glp-1) lead to an enhanced long-term anoxia survival phenotype. Methodology/Principal Findings In this study we show that the combined growth environment of 25°C and a diet of HT115 E. coli will precondition adult hermaphrodites to survive long-term anoxia; many of these survivors have normal movement after anoxia treatment. Animals fed the drug metformin, which induces a dietary-restriction like state in animals and activates AMPK in mammalian cell culture, have a higher survival rate when exposed to long-term anoxia. Mutations in genes encoding components of AMPK (aak-2, aakb-1, aakb-2, aakg-2) suppress the environmentally and genetically induced long-term anoxia survival phenotype. We further determine that there is a correlation between the animals that survive long-term anoxia and increased levels of carminic acid staining, which is a fluorescent dye that incorporates in with carbohydrates such as glycogen. Conclusions/Significance We conclude that small changes in growth conditions such as increased temperature and food source can influence the physiology of the animal thus affecting the responses to stress such as anoxia. Furthermore, this supports the idea that metformin should be further investigated as a therapeutic tool for treatment of oxygen-deprived tissues. Finally, the capacity for an animal to survive long bouts of severe oxygen deprivation is likely

  19. A Three-Dose Intramuscular Injection Schedule of Anthrax Vaccine Adsorbed Generates Sustained Humoral and Cellular Immune Responses to Protective Antigen and Provides Long-Term Protection against Inhalation Anthrax in Rhesus Macaques

    PubMed Central

    Sabourin, Carol L.; Niemuth, Nancy A.; Li, Han; Semenova, Vera A.; Rudge, Thomas L.; Mayfield, Heather J.; Schiffer, Jarad; Mittler, Robert S.; Ibegbu, Chris C.; Wrammert, Jens; Ahmed, Rafi; Brys, April M.; Hunt, Robert E.; Levesque, Denyse; Estep, James E.; Barnewall, Roy E.; Robinson, David M.; Plikaytis, Brian D.; Marano, Nina

    2012-01-01

    A 3-dose (0, 1, and 6 months) intramuscular (3-IM) priming series of a human dose (HuAVA) and dilutions of up to 1:10 of anthrax vaccine adsorbed (AVA) provided statistically significant levels of protection (60 to 100%) against inhalation anthrax for up to 4 years in rhesus macaques. Serum anti-protective antigen (anti-PA) IgG and lethal toxin neutralization activity (TNA) were detectable following a single injection of HuAVA or 1:5 AVA or following two injections of diluted vaccine (1:10, 1:20, or 1:40 AVA). Anti-PA and TNA were highly correlated (overall r2 = 0.89 for log10-transformed data). Peak responses were seen at 6.5 months. In general, with the exception of animals receiving 1:40 AVA, serum anti-PA and TNA responses remained significantly above control levels at 28.5 months (the last time point measured for 1:20 AVA), and through 50.5 months for the HuAVA and 1:5 and 1:10 AVA groups (P < 0.05). PA-specific gamma interferon (IFN-γ) and interleukin-4 (IL-4) CD4+ cell frequencies and T cell stimulation indices were sustained through 50.5 months (the last time point measured). PA-specific memory B cell frequencies were highly variable but, in general, were detectable in peripheral blood mononuclear cells (PBMC) by 2 months, were significantly above control levels by 7 months, and remained detectable in the HuAVA and 1:5 and 1:20 AVA groups through 42 months (the last time point measured). HuAVA and diluted AVA elicited a combined Th1/Th2 response and robust immunological priming, with sustained production of high-avidity PA-specific functional antibody, long-term immune cell competence, and immunological memory (30 months for 1:20 AVA and 52 months for 1:10 AVA). Vaccinated animals surviving inhalation anthrax developed high-magnitude anamnestic anti-PA IgG and TNA responses. PMID:22933399

  20. The Long Term Effects of Cellular-Telephone-Delivered Telephone Intervention Problem Solving (TIPS) For Schizophrenia Spectrum Disorders (SSDs).

    PubMed

    Beebe, Lora Humphrey; Smith, Kathlene; Phillips, Chad; Velligan, Dawn; Tavakoli, Abbas

    2014-11-01

    Introduction. Although an extensive body of literature suggests that face-to-face problem-solving interventions are an effective means of fostering psychiatric medication adherence for persons with SSDs, the majority of outpatients with SSDs lack access to this proven intervention. There is a need for exploration of alternate delivery methods for problem solving. Design. This randomized controlled trial will examine the effectiveness of cellular telephone delivered Telephone Intervention - Problem Solving (TIPS) upon medication adherence, medication self efficacy and symptom management in outpatients with SSDs over 9 monthsMethods. To ensure consistent telephone access, all one hundred twenty eight participants will be provided a basic cellular telephone with unlimited local calling for 9 months. Participants will be randomly assigned to treatment as usual plus weekly TIPS or treatment as usual only (TAU). Assessment of serum medication levels, pill count medication adherence, medication attitudes and psychiatric symptoms will be conducted at baseline and every 3 months on all participants. Summary.In addition to testing the long term effect of TIPS, this study will provide information on the responses to our cellular telephone delivery method. We believe this information will be critical as we continue to explore a variety of cellular telephone technologies to provide needed interventions to persons with SSDs in a feasible, economical way.

  1. [Long-term potentiation and unit evoked responses in the cingulate cortex of freely moving rats].

    PubMed

    Gorkin, A G; Reymann, K G; Aleksandrov, Iu I

    2002-01-01

    Long-term potentiation (LTP) of synaptic efficacy is considered to be the most probable physiological mechanism of long-term memory. However, lack of understanding of cellular and subcellular mechanisms of LTP induction in freely behaving animals does not correspond to the importance of the problem. It was tested whether the characteristics of potentiation in the cingulate cortex after tetanization of the subiculocingulate tract (SCT) meet the criteria of true LTP (that passes all known stages in its development and lasts for more than a day in freely-behaving animals). Additionally, characteristics of spike responses to SCT stimulation and the effects of application of different glutamate receptor blockers were studied. Without application of GABA receptor blockers, the LTP lasted for more than 24 hours. Application of NMDA glutamate receptor blockers significantly inhibited field potentials evoke by testing stimulation. Short-latency spike responses to SCT stimulation were recorded with low probability that increased with stimulation intensity. The obtained data reveal the possibility to compare the involvement of cingulate neurons in acquisition of adaptive behavior and changes in their spike responses during the LTP development in freely-moving rats. PMID:12528373

  2. Long-term depression of synaptic transmission in the cerebellum: cellular and molecular mechanisms revisited.

    PubMed

    Levenes, C; Daniel, H; Crépel, F

    1998-05-01

    Long-term depression (LTD) of synaptic transmission at parallel fiber (PF)-Purkinje cell (PC) synapses in the cerebellum has been the first established example of enduring decrease of synaptic efficacy in the central nervous system. This review focuses on the underlying cellular and molecular mechanisms. Thus, at the level of the postsynaptic membranes of PCs, induction of LTD requires concommitent activation of voltage-gated calcium channels (VGCCs) and of ionotropic and metabotopic glutamate receptors, of the alpha-amino-3 hydroxy-5-methyl-isoxalone-4-propionate (AMPA) and mGluR1 alpha types respectively. Subsequent intracellular cascades involve production of nitric oxide from arginine and of cGMP, activation of phospholipase A2 and of several protein kinases including protein kinase C and tyrosine kinases. Activation of protein kinase G and of phosphatases are also likely to be involved in LTD induction. In contrast, there are still uncertainties concerning a major role of release of calcium from internal stores in LTD induction. Finally protein synthesis is required for a late phase of LTD to occur. All available experimental evidence points towards a postsynaptic site for LTD expression. In particular, electrophysiological data demonstrate a genuine modification of the functional properties of AMPA receptors of PCs during LTD, and immunocytochemical evidence suggests that this might result from a phosphorylation of these receptors.

  3. Long term country-wide rainfall monitoring employing cellular communication networks

    NASA Astrophysics Data System (ADS)

    Overeem, Aart; Leijnse, Hidde; Uijlenhoet, Remko

    2013-04-01

    Accurate rainfall observations with high spatial and temporal resolutions are needed for hydrological applications, agriculture, meteorology, and climate monitoring. However, the majority of the land surface of the earth lacks accurate rainfall information and the number of rain gauges is even severely declining in Europe, South-America, and Africa. This calls for alternative sources of rainfall information. Various studies have shown that microwave links from operational cellular telecommunication networks may be employed for rainfall monitoring. Such networks cover 20% of the land surface of the earth and have a high density, especially in urban areas. The basic principle of rainfall monitoring using microwave links is as follows. Rainfall attenuates the electromagnetic signals transmitted from one telephone tower to another. By measuring the received power at one end of a microwave link as a function of time, the path-integrated attenuation due to rainfall can be calculated. Previous studies have shown that average rainfall intensities over the length of a link can be derived from the path-integrated attenuation. This is particularly interesting for those countries where few surface rainfall observations are available. Here we present preliminary results of long term country-wide rainfall monitoring employing cellular communication networks. A dataset from a commercial microwave link network over the Netherlands is analyzed, containing data from an unprecedented number of links (~ 2000) covering the land surface of the Netherlands (35500 square kilometres). This dataset spans from January 2011 through October 2012. Daily rainfall maps (1 km spatial resolution) are derived from the microwave link data and compared to maps from a gauge-adjusted radar dataset. The performance of the rainfall retrieval algorithm will be investigated, particularly a possible seasonal dependence.

  4. How Do Observer's Responses Affect Visual Long-Term Memory?

    ERIC Educational Resources Information Center

    Makovski, Tal; Jiang, Yuhong V.; Swallow, Khena M.

    2013-01-01

    How does responding to an object affect explicit memory for visual information? The close theoretical relationship between action and perception suggests that items that require a response should be better remembered than items that require no response. However, conclusive evidence for this claim is lacking, as semantic coherence, category size,…

  5. Radiation-induced cellular senescence results from a slippage of long-term G2 arrested cells into G1 phase.

    PubMed

    Ye, Caiyong; Zhang, Xurui; Wan, Jianghua; Chang, Lei; Hu, Wentao; Bing, Zhitong; Zhang, Sheng; Li, Junhong; He, Jinpeng; Wang, Jufang; Zhou, Guangming

    2013-05-01

    Diploid cells undergoing senescence and mitotic slippage have been reported in the literature. However, the mechanisms triggering senescence in long-term G2-arrested cells are currently unclear. Previously, we reported that the cell cycle of the human uveal melanoma cell line, 92-1, is suspended for up to 6 d upon exposure to 10 Gy ionizing radiation (IR), followed by senescence. In the current study, we initially distinguished senescence in long-term blocked 92-1 cells from mitotic slippage by confirming the blockage of cells in the G2 phase. We subsequently showed that the genes essential for G2-M transition are prematurely downregulated at both the transcriptional and translational levels. Furthermore, levels of the G1-specific markers, Cyclin D1 and Caveolin-1, were distinctly increased, while S/G2-specific markers, Cyclin B1 and Aurora A, were significantly downregulated. These findings collectively imply that long-term G2-arrested cells undergo senescence via G2 slippage. To our knowledge, this is the first study to report that the cellular process of G2 slippage is the mechanism responsible for senescence of cells under long-term G2 arrest. PMID:23574719

  6. Radiation-induced cellular senescence results from a slippage of long-term G2 arrested cells into G1 phase

    PubMed Central

    Ye, Caiyong; Zhang, Xurui; Wan, Jianghua; Chang, Lei; Hu, Wentao; Bing, Zhitong; Zhang, Sheng; Li, Junhong; He, Jinpeng; Wang, Jufang; Zhou, Guangming

    2013-01-01

    Diploid cells undergoing senescence and mitotic slippage have been reported in the literature. However, the mechanisms triggering senescence in long-term G2-arrested cells are currently unclear. Previously, we reported that the cell cycle of the human uveal melanoma cell line, 92-1, is suspended for up to 6 d upon exposure to 10 Gy ionizing radiation (IR), followed by senescence. In the current study, we initially distinguished senescence in long-term blocked 92-1 cells from mitotic slippage by confirming the blockage of cells in the G2 phase. We subsequently showed that the genes essential for G2-M transition are prematurely downregulated at both the transcriptional and translational levels. Furthermore, levels of the G1-specific markers, Cyclin D1 and Caveolin-1, were distinctly increased, while S/G2-specific markers, Cyclin B1 and Aurora A, were significantly downregulated. These findings collectively imply that long-term G2-arrested cells undergo senescence via G2 slippage. To our knowledge, this is the first study to report that the cellular process of G2 slippage is the mechanism responsible for senescence of cells under long-term G2 arrest. PMID:23574719

  7. Long-Term Effectiveness of the Response Restriction Method for Establishing Diurnal Bladder Control

    ERIC Educational Resources Information Center

    van Oorsouw, Wietske M. W. J.; Duker, P. C.; Melein, L.; Averink, M.

    2009-01-01

    The long-term effectiveness of the response restriction method for establishing diurnal bladder control was assessed with 48 participants with intellectual disabilities. Intervals of assessment ranged from 28 to 66 months across the individuals following initial baseline. Difference scores in terms of the mean number of toileting accidents per…

  8. Physician Responses to an Educational Intervention on Improving Their Long-Term Prescribing of Sedatives.

    ERIC Educational Resources Information Center

    Sleath, Betsy; Collins, Ted

    1997-01-01

    A Medicaid retrospective therapeutic intervention was designed to notify physicians about their patients' long-term use of sedatives and suggest to them that they reevaluate the patient's need for sedative hypnotic medication. Physicians' responses and follow-up actions are reported. Practice implications and the need for physician education are…

  9. Increasing long-term response by selecting for favorable minor alleles

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Long-term response of genomic selection can be improved by considering allele frequencies of selected markers or quantitative trait loci (QTLs). A previous formula to weight allele frequency of favorable minor alleles was tested, and 2 new formulas were developed. The previous formula used nonlinear...

  10. Coordinated Approaches to Quantify Long-Term Ecosystem dynamics in Response to Global Change

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Climate change and its impact on ecosystems are usually assessed at decadal and century time scales. Ecological responses to climate change at those scales are strongly regulated by long-term processes, such as changes in species composition, carbon dynamics in soil and by big trees, and nutrient r...

  11. [Specific long-term cellular changes under effects of low doses of radiation].

    PubMed

    Bychkovskaia, I B; Stepanov, R P; Fedortseva, R F

    2002-01-01

    We examined the peculiar form of a tissue postirradiative reaction characterizing by massive, dose-independent transition of cell populations to the steady state modification with the essential raise of cell damage and cell loss probability as compared with the probability level of the same alterations in controls. We described some other signs of such type of cellular transformation. It was found that the indicated cellular condition occurred both in active and slowly proliferating tissues. The reaction occurred at relatively low doses of irradiation. Some nonmutagenic factors also may evoke such effects. Our experimental data allow us to suppose the epigenetic mechanizms taking part in the induction and preservation of such alterations. The discovered form of cellular reaction manifestating in different biological objects may be considered as some general biological tendency. The importance of the studied reaction in the pathogenesis of late consequences of low dose irradiation is discussed. PMID:11898627

  12. The impact of nonlinear functional responses on the long-term evolution of food web structure.

    PubMed

    Drossel, Barbara; McKane, Alan J; Quince, Christopher

    2004-08-21

    We investigate the long-term web structure emerging in evolutionary food web models when different types of functional responses are used. We find that large and complex webs with several trophic layers arise only if the population dynamics is such that it allows predators to focus on their best prey species. This can be achieved using modified Lotka-Volterra or Holling/Beddington functional responses with effective couplings that depend on the predator's efficiency at exploiting the prey, or a ratio-dependent functional response with adaptive foraging. In contrast, if standard Lotka-Volterra or Holling/Beddington functional responses are used, long-term evolution generates webs with almost all species being basal, and with additionally many links between these species. Interestingly, in all cases studied, a large proportion of weak links result naturally from the evolution of the food webs.

  13. Plant community feedbacks and long-term ecosystem responses to multi-factored global change

    PubMed Central

    Langley, J. Adam; Hungate, Bruce A.

    2014-01-01

    While short-term plant responses to global change are driven by physiological mechanisms, which are represented relatively well by models, long-term ecosystem responses to global change may be determined by shifts in plant community structure resulting from other ecological phenomena such as interspecific interactions, which are represented poorly by models. In single-factor scenarios, plant communities often adjust to increase ecosystem response to that factor. For instance, some early global change experiments showed that elevated CO2 favours plants that respond strongly to elevated CO2, generally amplifying the response of ecosystem productivity to elevated CO2, a positive community feedback. However, most ecosystems are subject to multiple drivers of change, which can complicate the community feedback effect in ways that are more difficult to generalize. Recent studies have shown that (i) shifts in plant community structure cannot be reliably predicted from short-term plant physiological response to global change and (ii) that the ecosystem response to multi-factored change is commonly less than the sum of its parts. Here, we survey results from long-term field manipulations to examine the role community shifts may play in explaining these common findings. We use a simple model to examine the potential importance of community shifts in governing ecosystem response. Empirical evidence and the model demonstrate that with multi-factored change, the ecosystem response depends on community feedbacks, and that the magnitude of ecosystem response will depend on the relationship between plant response to one factor and plant response to another factor. Tradeoffs in the ability of plants to respond positively to, or to tolerate, different global change drivers may underlie generalizable patterns of covariance in responses to different drivers of change across plant taxa. Mechanistic understanding of these patterns will help predict the community feedbacks that determine

  14. The effect of gene interactions on the long-term response to selection

    PubMed Central

    Paixão, Tiago; Barton, Nicholas H.

    2016-01-01

    The role of gene interactions in the evolutionary process has long been controversial. Although some argue that they are not of importance, because most variation is additive, others claim that their effect in the long term can be substantial. Here, we focus on the long-term effects of genetic interactions under directional selection assuming no mutation or dominance, and that epistasis is symmetrical overall. We ask by how much the mean of a complex trait can be increased by selection and analyze two extreme regimes, in which either drift or selection dominate the dynamics of allele frequencies. In both scenarios, epistatic interactions affect the long-term response to selection by modulating the additive genetic variance. When drift dominates, we extend Robertson’s [Robertson A (1960) Proc R Soc Lond B Biol Sci 153(951):234−249] argument to show that, for any form of epistasis, the total response of a haploid population is proportional to the initial total genotypic variance. In contrast, the total response of a diploid population is increased by epistasis, for a given initial genotypic variance. When selection dominates, we show that the total selection response can only be increased by epistasis when some initially deleterious alleles become favored as the genetic background changes. We find a simple approximation for this effect and show that, in this regime, it is the structure of the genotype−phenotype map that matters and not the variance components of the population. PMID:27044080

  15. Long-term moderate exercise accelerates the recovery of stress-evoked cardiovascular responses.

    PubMed

    Hsu, Yuan-Chang; Tsai, Sheng-Feng; Yu, Lung; Chuang, Jih-Ing; Wu, Fong-Sen; Jen, Chauying J; Kuo, Yu-Min

    2016-01-01

    Psychological stress is an important global health problem. It is well documented that stress increases the incidences of various cardiovascular disorders. Regular exercise is known to reduce resting blood pressure (BP) and heart rate (HR). This study was designed to clarify the effects of long-term exercise on stress-evoked cardiovascular responses and to emphasize post-stress recovery effects. Male Wistar rats underwent 8 weeks of moderate treadmill training, with cardiovascular responses, autonomic nervous system activities and local Fos reactivity changes in the cardiovascular regulation center were monitored before, during and after immobilization stress. A spectral analysis of cardiovascular parameters was used to examine autonomic nervous activities. We found that long-term exercise (i) lowered resting BP, HR and sympathetic activity, but increased resting parasympathetic activity and baroreflex sensitivity (BRS); (ii) accelerated post-stress recovery of stress-evoked cardiovascular and sympathetic responses along with increased BRS and (iii) accelerated post-stress recovery of stress-evoked neuron activations in the paraventricular nucleus, but delayed it in the nucleus of the tractus solitarius. We conclude that, in rats, long-term exercise accelerated recovery of stress-evoked cardiovascular responses differentially altering hypothalamic and medullar neuron activities.

  16. Long-Term Calorie Restriction Enhances Cellular Quality-Control Processes in Human Skeletal Muscle.

    PubMed

    Yang, Ling; Licastro, Danilo; Cava, Edda; Veronese, Nicola; Spelta, Francesco; Rizza, Wanda; Bertozzi, Beatrice; Villareal, Dennis T; Hotamisligil, Gökhan S; Holloszy, John O; Fontana, Luigi

    2016-01-26

    Calorie restriction (CR) retards aging, acts as a hormetic intervention, and increases serum corticosterone and HSP70 expression in rodents. However, less is known regarding the effects of CR on these factors in humans. Serum cortisol and molecular chaperones and autophagic proteins were measured in the skeletal muscle of subjects on CR diets for 3-15 years and in control volunteers. Serum cortisol was higher in the CR group than in age-matched sedentary and endurance athlete groups (15.6 ± 4.6 ng/dl versus 12.3 ± 3.9 ng/dl and 11.2 ± 2.7 ng/dl, respectively; p ≤ 0.001). HSP70, Grp78, beclin-1, and LC3 mRNA and/or protein levels were higher in the skeletal muscle of the CR group compared to controls. Our data indicate that CR in humans is associated with sustained rises in serum cortisol, reduced inflammation, and increases in key molecular chaperones and autophagic mediators involved in cellular protein quality control and removal of dysfunctional proteins and organelles. PMID:26774472

  17. Long-Term Calorie Restriction Enhances Cellular Quality-Control Processes in Human Skeletal Muscle.

    PubMed

    Yang, Ling; Licastro, Danilo; Cava, Edda; Veronese, Nicola; Spelta, Francesco; Rizza, Wanda; Bertozzi, Beatrice; Villareal, Dennis T; Hotamisligil, Gökhan S; Holloszy, John O; Fontana, Luigi

    2016-01-26

    Calorie restriction (CR) retards aging, acts as a hormetic intervention, and increases serum corticosterone and HSP70 expression in rodents. However, less is known regarding the effects of CR on these factors in humans. Serum cortisol and molecular chaperones and autophagic proteins were measured in the skeletal muscle of subjects on CR diets for 3-15 years and in control volunteers. Serum cortisol was higher in the CR group than in age-matched sedentary and endurance athlete groups (15.6 ± 4.6 ng/dl versus 12.3 ± 3.9 ng/dl and 11.2 ± 2.7 ng/dl, respectively; p ≤ 0.001). HSP70, Grp78, beclin-1, and LC3 mRNA and/or protein levels were higher in the skeletal muscle of the CR group compared to controls. Our data indicate that CR in humans is associated with sustained rises in serum cortisol, reduced inflammation, and increases in key molecular chaperones and autophagic mediators involved in cellular protein quality control and removal of dysfunctional proteins and organelles.

  18. Adaptive response studies may help choose astronauts for long-term space travel

    NASA Astrophysics Data System (ADS)

    Mortazavi, S.

    Long-term manned exploratory missions are planned for the next decades. Exposure to high-energy neutrons, protons and high charge and energy particles during a deep space mission, requires proper radiation protection planning against the detrimental effects of space radiation. It has been estimated that exposure to unpredictable extremely large solar particle events would kill the astronauts without massive shielding in interplanetary space. Recent findings concerning the induction of adaptive response by neutrons or high levels of external and internal exposures including radon in human cells have opened a new horizon for possible implications of adaptive response in radiation protection and especially in protection against detrimental effects of high levels of radiation during a long-term space journey. Significant adaptive response has been demonstrated in humans after exposure to high levels of natural radiation. It has been shown that in some individuals who fail to show an adaptive response, extraordinary synergism was observed. Interestingly, it was observed that even when the frequency of chromosome aberrations in cells exposed to adapting dose alone or challenge dose alone, were not different than those of other study participants, a severe synergism observed in the cells exposed to challenge dose after an adapting dose. Based on the results obtained in this experiment, due to possible interactions between a chronic low dose and an acute high dose, a common G2 radiosensitivity assay cannot predict radiation risk during a long-term space mission. It can be suggested that the magnitude of adaptive response in lymphocyte samples of potential crew for a deep space mission should be assessed in ground based laboratory studies. Selected space crew who show a high magnitude of adaptive response in ground experiments, will be exposed to adapting higher than normal background radiation doses during mission and they will be considerably more resistant to high doses

  19. Evidence of bacterioplankton community adaptation in response to long-term mariculture disturbance

    PubMed Central

    Xiong, Jinbo; Chen, Heping; Hu, Changju; Ye, Xiansen; Kong, Dingjiang; Zhang, Demin

    2015-01-01

    Understanding the underlying mechanisms that shape the temporal dynamics of a microbial community has important implications for predicting the trajectory of an ecosystem’s response to anthropogenic disturbances. Here, we evaluated the seasonal dynamics of bacterioplankton community composition (BCC) following more than three decades of mariculture disturbance in Xiangshan Bay. Clear seasonal succession and site (fish farm and control site) separation of the BCC were observed, which were primarily shaped by temperature, dissolved oxygen and sampling time. However, the sensitive bacterial families consistently changed in relative abundance in response to mariculture disturbance, regardless of the season. Temporal changes in the BCC followed the time-decay for similarity relationship at both sites. Notably, mariculture disturbance significantly (P < 0.001) flattened the temporal turnover but intensified bacterial species-to-species interactions. The decrease in bacterial temporal turnover under long-term mariculture disturbance was coupled with a consistent increase in the percentage of deterministic processes that constrained bacterial assembly based on a null model analysis. The results demonstrate that the BCC is sensitive to mariculture disturbance; however, a bacterioplankton community could adapt to a long-term disturbance via attenuating temporal turnover and intensifying species-species interactions. These findings expand our current understanding of microbial assembly in response to long-term anthropogenic disturbances. PMID:26471739

  20. Nurses' responses to initial moral distress in long-term care.

    PubMed

    Edwards, Marie P; McClement, Susan E; Read, Laurie R

    2013-10-01

    While researchers have examined the types of ethical issues that arise in long-term care, few studies have explored long-term care nurses' experiences of moral distress and fewer still have examined responses to initial moral distress. Using an interpretive description approach, 15 nurses working in long-term care settings within one city in Canada were interviewed about their responses to experiences of initial moral distress, resources or supports they identified as helpful or potentially helpful in dealing with these situations, and factors that hindered nurses in their responses. Using a thematic analysis process, three major themes were identified from the nurses' experiences: (i) the context of the situation matters; (ii) the value of coming together as a team; and (iii) looking for outside direction. The work of responding to initial moral distress was more fruitful if opportunities existed to discuss conflicts with other team members and if managers supported nurses in moving their concerns forward through meetings or conversations with the team, physician, or family. Access to objective others and opportunities for education about ethics were also identified as important for dealing with value conflicts.

  1. Bacterial bioluminescence response to long-term exposure to reverse osmosis treated effluents from dye industries.

    PubMed

    Ravindran, J; Manikandan, B; Shirodkar, P V; Francis, K X; Mani Murali, R; Vethamony, P

    2014-10-01

    The bacterial bioluminescence assay is one of the novel means for toxicity detection. The bioluminescence response of 2 marine bioluminescent bacteria was tested upon their long-term exposure to 9 different reverse osmosis (RO) rejects with varying chemical composition sampled from various dye industries. Bioluminescent bacteria were cultured in the RO reject samples, at different concentrations, and their growth rate and luminescence was measured for 24 h. The RO reject samples caused sublethal effects upon exposure and retarded the growth of bacteria, confirming their toxic nature. Further, continuation of the exposure showed that the initial luminescence, though reduced, recovered and increased beyond the control cultures irrespective of cell density, and finally decreased once again. The present study emphasizes the need of evolving a long-term exposure assay and shows that the method followed in this study is suitable to evaluate the toxicants that exert delayed toxicity, using lower concentrations of toxicants as well as coloured samples.

  2. Long-Term Viscoelastic Response of E-glass/Bismaleimide Composite in Seawater Environment

    NASA Astrophysics Data System (ADS)

    Yian, Zhao; Zhiying, Wang; Keey, Seah Leong; Boay, Chai Gin

    2015-12-01

    The effect of seawater absorption on the long-term viscoelastic response of E-glass/BMI composite is presented in this paper. The diffusion of seawater into the composite shows a two-stage behavior, dominated by Fickian diffusion initially and followed by polymeric relaxation. The Glass transition temperature (Tg) of the composite with seawater absorption is considerably lowered due to the plasticization effect. However the effect of water absorption at 50 °C is found to be reversible after drying process. The time-temperature superposition (TTS) was performed based on the results of Dynamic Mechanical Analysis to construct the master curve of storage modulus. The shift factors exhibit Arrhenius behavior when temperature is well below Tg and Vogel-Fulcher-Tammann (VFT) like behavior when temperature gets close to glass transition region. As a result, a semi-empirical formulation is proposed to account for the seawater absorption effect in predicting long-term viscoelastic response of BMI composites based on temperature dependent storage modulus and TTS. The predicted master curves show that the degradation of storage modulus accelerates with both seawater exposure and increasing temperature. The proposed formulation can be applied to predict the long-term durability of any thermorheologically simple composite materials in seawater environment.

  3. The Role of Hippocampal NMDA Receptors in Long-Term Emotional Responses following Muscarinic Receptor Activation.

    PubMed

    Hoeller, Alexandre A; Costa, Ana Paula R; Bicca, Maíra A; Matheus, Filipe C; Lach, Gilliard; Spiga, Francesca; Lightman, Stafford L; Walz, Roger; Collingridge, Graham L; Bortolotto, Zuner A; de Lima, Thereza C M

    2016-01-01

    Extensive evidence indicates the influence of the cholinergic system on emotional processing. Previous findings provided new insights into the underlying mechanisms of long-term anxiety, showing that rats injected with a single systemic dose of pilocarpine--a muscarinic receptor (mAChR) agonist--displayed persistent anxiogenic-like responses when evaluated in different behavioral tests and time-points (24 h up to 3 months later). Herein, we investigated whether the pilocarpine-induced long-term anxiogenesis modulates the HPA axis function and the putative involvement of NMDA receptors (NMDARs) following mAChRs activation. Accordingly, adult male Wistar rats presented anxiogenic-like behavior in the elevated plus-maze (EPM) after 24 h or 1 month of pilocarpine injection (150 mg/kg, i.p.). In these animals, mAChR activation disrupted HPA axis function inducing a long-term increase of corticosterone release associated with a reduced expression of hippocampal GRs, as well as consistently decreased NMDAR subunits expression. Furthermore, in another group of rats injected with memantine--an NMDARs antagonist (4 mg/kg, i.p.)--prior to pilocarpine, we found inhibition of anxiogenic-like behaviors in the EPM but no further alterations in the pilocarpine-induced NMDARs downregulation. Our data provide evidence that behavioral anxiogenesis induced by mAChR activation effectively yields short- and long-term alterations in hippocampal NMDARs expression associated with impairment of hippocampal inhibitory regulation of HPA axis activity. This is a novel mechanism associated with anxiety-like responses in rats, which comprise a putative target to future translational studies. PMID:26795565

  4. The Role of Hippocampal NMDA Receptors in Long-Term Emotional Responses following Muscarinic Receptor Activation.

    PubMed

    Hoeller, Alexandre A; Costa, Ana Paula R; Bicca, Maíra A; Matheus, Filipe C; Lach, Gilliard; Spiga, Francesca; Lightman, Stafford L; Walz, Roger; Collingridge, Graham L; Bortolotto, Zuner A; de Lima, Thereza C M

    2016-01-01

    Extensive evidence indicates the influence of the cholinergic system on emotional processing. Previous findings provided new insights into the underlying mechanisms of long-term anxiety, showing that rats injected with a single systemic dose of pilocarpine--a muscarinic receptor (mAChR) agonist--displayed persistent anxiogenic-like responses when evaluated in different behavioral tests and time-points (24 h up to 3 months later). Herein, we investigated whether the pilocarpine-induced long-term anxiogenesis modulates the HPA axis function and the putative involvement of NMDA receptors (NMDARs) following mAChRs activation. Accordingly, adult male Wistar rats presented anxiogenic-like behavior in the elevated plus-maze (EPM) after 24 h or 1 month of pilocarpine injection (150 mg/kg, i.p.). In these animals, mAChR activation disrupted HPA axis function inducing a long-term increase of corticosterone release associated with a reduced expression of hippocampal GRs, as well as consistently decreased NMDAR subunits expression. Furthermore, in another group of rats injected with memantine--an NMDARs antagonist (4 mg/kg, i.p.)--prior to pilocarpine, we found inhibition of anxiogenic-like behaviors in the EPM but no further alterations in the pilocarpine-induced NMDARs downregulation. Our data provide evidence that behavioral anxiogenesis induced by mAChR activation effectively yields short- and long-term alterations in hippocampal NMDARs expression associated with impairment of hippocampal inhibitory regulation of HPA axis activity. This is a novel mechanism associated with anxiety-like responses in rats, which comprise a putative target to future translational studies.

  5. Investigation into the impact of audience response devices on short- and long-term content retention.

    PubMed

    Rush, Bonnie R; White, Brad J; Allbaugh, Rachel A; Jones, Meredyth L; Klocke, Emily E; Miesner, Matt; Towle-Millard, Heather A; Roush, James K

    2013-01-01

    Audience Response Systems (ARSs) may enhance short-term knowledge retention. Long-term knowledge retention is more difficult to demonstrate. According to previous studies, ARS questions requiring application of knowledge or peer interaction are more effective in maintaining student attention. The purpose of this study was to determine if peer discussion or individual-knowledge questions enhance short- and/or long-term knowledge retention. Third-year veterinary students responded to ARS questions posed in individual knowledge (n=3 questions) and peer discussion (n=3 questions) format from six different instructors. To test short-term memory, the same questions were delivered during the course examination (within 21 days). To test long-term retention, these questions were posed during a retention exercise (four months later). On the course examination, students had a higher (p<.01) probability (±SE) of correctly answering ARS individual-knowledge questions (93.8 ± 1.8%) compared to novel (previously unseen, non-ARS control) course examination questions (87.5 ± 3.1%), but the probability of correctly answering examination questions previously posed using ARS peer discussion format (89.5 ± 3.0%) did not differ from individual knowledge or novel examination questions. The positive impact of ARS-knowledge questions was not maintained through the retention exercise. Neither individual knowledge (70.5 ± 6.4%) nor peer-discussion questions (67.5 ± 6.9%) performed better on the retention exercise than the questions that appeared only on the course examination (68.6 ± 6.1%). Curricular strategies that emphasize content review may be more powerful than strategies that strengthen initial learning for long-term content retention.

  6. Neurophysiological predictors of long term response to AChE inhibitors in AD patients

    PubMed Central

    Di, L; Oliviero, A; Pilato, F; Saturno, E; Dileone, M; Marra, C; Ghirlanda, S; Ranieri, F; Gainotti, G; Tonali, P

    2005-01-01

    Background: In vivo evaluation of cholinergic circuits of the human brain has recently been introduced using a transcranial magnetic stimulation (TMS) protocol based on coupling peripheral nerve stimulation with motor cortex TMS (short latency afferent inhibition, SAI). SAI is reduced in Alzheimer's disease (AD) and drugs enhancing cholinergic transmission increase SAI. Methods: We evaluated whether SAI testing, together with SAI test-retest, after a single dose of the acetylcholinesterase (AChE) inhibitor rivastigmine, might be useful in predicting the response after 1 year treatment with rivastigmine in 16 AD patients. Results: Fourteen AD patients had pathologically reduced SAI. SAI was increased after administration of a single oral dose of rivastigmine in AD patients with abnormal baseline SAI, but individual responses to rivastigmine varied widely, with SAI change ranging from an increase in inhibition of ∼50% of test size to no change. Baseline SAI and the increase in SAI after a single dose of rivastigmine were correlated with response to long term treatment. A normal SAI in baseline conditions, or an abnormal SAI in baseline conditions that was not greatly increased by a single oral dose of rivastigmine, were invariably associated with poor response to long term treatment, while an abnormal SAI in baseline conditions in conjunction with a large increase in SAI after a single dose of rivastigmine was associated with good response to long term treatment in most of the patients. Conclusions: Evaluation of SAI may be useful for identifying AD patients likely to respond to treatment with AChE inhibitors. PMID:16024879

  7. Long-term prediction test procedure for most ICs, based on linear response theory

    NASA Technical Reports Server (NTRS)

    Litovchenko, V.; Ivakhnenko, I.

    1991-01-01

    Experimentally, thermal annealing is known to be a factor which enables a number of different integrated circuits (IC's) to recover their operating characteristics after suffering radiation damage in the space radiation environment; thus, decreasing and limiting long term cumulative total-dose effects. This annealing is also known to be accelerated at elevated temperatures both during and after irradiation. Linear response theory (LRT) was applied, and a linear response function (LRF) to predict the radiation/annealing response of sensitive parameters of IC's for long term (several months or years) exposure to the space radiation environment were constructed. Compressing the annealing process from several years in orbit to just a few hours or days in the laboratory is achieved by subjecting the IC to elevated temperatures or by increasing the typical spaceflight dose rate by several orders of magnitude for simultaneous radiation/annealing only. The accomplishments are as follows: (1) the test procedure to make predictions of the radiation response was developed; (2) the calculation of the shift in the threshold potential due to the charge distribution in the oxide was written; (3) electron tunneling processes from the bulk Si to the oxide region in an MOS IC were estimated; (4) in order to connect the experimental annealing data to the theoretical model, constants of the model of the basic annealing process were established; (5) experimental data obtained at elevated temperatures were analyzed; (6) time compression and reliability of predictions for the long term region were shown; (7) a method to compress test time and to make predictions of response for the nonlinear region was proposed; and (8) nonlinearity of the LRF with respect to log(t) was calculated theoretically from a model.

  8. Long-Term Non-Progression and Broad HIV-1-Specific Proliferative T-Cell Responses

    PubMed Central

    Imami, Nesrina; Westrop, Samantha J.; Grageda, Nathali; Herasimtschuk, Anna A.

    2013-01-01

    Complex mechanisms underlying the maintenance of fully functional, proliferative, HIV-1-specific T-cell responses involve processes from early T-cell development through to the final stages of T-cell differentiation and antigen recognition. Virus-specific proliferative CD4 and CD8 T-cell responses, important for the control of infection, are observed in some HIV-1+ patients during early stages of disease, and are maintained in long-term non-progressing subjects. In the vast majority of HIV-1+ patients, full immune functionality is lost when proliferative HIV-1-specific T-cell responses undergo a variable progressive decline throughout the course of chronic infection. This appears irreparable despite administration of potent combination antiretroviral therapy, which to date is non-curative, necessitating life-long administration and the development of effective, novel, therapeutic interventions. While a sterilizing cure, involving clearance of virus from the host, remains a primary aim, a “functional cure” may be a more feasible goal with considerable impact on worldwide HIV-1 infection. Such an approach would enable long-term co-existence of host and virus in the absence of toxic and costly drugs. Effective immune homeostasis coupled with a balanced response appropriately targeting conserved viral antigens, in a manner that avoids hyperactivation and exhaustion, may prove to be the strongest correlate of durable viral control. This review describes novel concepts underlying full immune functionality in the context of HIV-1 infection, which may be utilized in future strategies designed to improve upon existing therapy. The aim will be to induce long-term non-progressor or elite controller status in every infected host, through immune-mediated control of viremia and reduction of viral reservoirs, leading to lower HIV-1 transmission rates. PMID:23459797

  9. Forest herb layer response to long-term light deficit along a forest developmental series

    NASA Astrophysics Data System (ADS)

    Plue, J.; Van Gils, B.; De Schrijver, A.; Peppler-Lisbach, C.; Verheyen, K.; Hermy, M.

    2013-11-01

    Temperate deciduous forest communities are slow-changing systems, with herbaceous understorey communities displaying a delayed response to overstorey canopy and light dynamics. While light availability constrains herbaceous understorey diversity and composition in space and time, its response in the long-term absence of light has seldom been quantified, particularly as it is often confounded by covariation in soil conditions. We studied a developmental high-forest series in two widespread NW-European temperate deciduous forest communities with different dominant canopy tree species: Stellario-Carpinetum (Oak-hornbeam canopy) and Milio-Fagetum (Beech canopy). All plots had soil conditions which were not significantly different, enabling investigation into the direct effects of the long-term absence of light on the herbaceous understorey, disentangled from the confounding effects of soil variation. Plant species richness measures declined with canopy cover continuity in the herb layer of the oak-hornbeam stands, whereas richness in the herb layer of the beech stands displayed a unimodal response. Nonetheless, in both plant communities, species richness and closed-forest species richness were negatively affected by the extended absence of light in stands with the longest period of continuous canopy cover. The long-term limitation or decline in quantitative and qualitative light availability as a result of extended periods of canopy cover was shown to be the primary driver behind losses in alpha-diversity, community composition turn-over and individual species dynamics. Heliophilous species were lost from both communities, while closed-forest species also declined, as a direct consequence of the prolonged period without ample light on the forest floor. This study demonstrates how the herb layer is affected by the absence of light on the forest floor mediated by long periods of continuous canopy cover. Despite different temporal responses in herb layer richness and

  10. Selective CD28 Antagonist Blunts Memory Immune Responses and Promotes Long-Term Control of Skin Inflammation in Nonhuman Primates.

    PubMed

    Poirier, Nicolas; Chevalier, Melanie; Mary, Caroline; Hervouet, Jeremy; Minault, David; Baker, Paul; Ville, Simon; Le Bas-Bernardet, Stephanie; Dilek, Nahzli; Belarif, Lyssia; Cassagnau, Elisabeth; Scobie, Linda; Blancho, Gilles; Vanhove, Bernard

    2016-01-01

    Novel therapies that specifically target activation and expansion of pathogenic immune cell subsets responsible for autoimmune attacks are needed to confer long-term remission. Pathogenic cells in autoimmunity include memory T lymphocytes that are long-lived and present rapid recall effector functions with reduced activation requirements. Whereas the CD28 costimulation pathway predominantly controls priming of naive T cells and hence generation of adaptive memory cells, the roles of CD28 costimulation on established memory T lymphocytes and the recall of memory responses remain controversial. In contrast to CD80/86 antagonists (CTLA4-Ig), selective CD28 antagonists blunt T cell costimulation while sparing CTLA-4 and PD-L1-dependent coinhibitory signals. Using a new selective CD28 antagonist, we showed that Ag-specific reactivation of human memory T lymphocytes was prevented. Selective CD28 blockade controlled both cellular and humoral memory recall in nonhuman primates and induced long-term Ag-specific unresponsiveness in a memory T cell-mediated inflammatory skin model. No modification of memory T lymphocytes subsets or numbers was observed in the periphery, and importantly no significant reactivation of quiescent viruses was noticed. These findings indicate that pathogenic memory T cell responses are controlled by both CD28 and CTLA-4/PD-L1 cosignals in vivo and that selectively targeting CD28 would help to promote remission of autoimmune diseases and control chronic inflammation.

  11. Selective CD28 Antagonist Blunts Memory Immune Responses and Promotes Long-Term Control of Skin Inflammation in Nonhuman Primates.

    PubMed

    Poirier, Nicolas; Chevalier, Melanie; Mary, Caroline; Hervouet, Jeremy; Minault, David; Baker, Paul; Ville, Simon; Le Bas-Bernardet, Stephanie; Dilek, Nahzli; Belarif, Lyssia; Cassagnau, Elisabeth; Scobie, Linda; Blancho, Gilles; Vanhove, Bernard

    2016-01-01

    Novel therapies that specifically target activation and expansion of pathogenic immune cell subsets responsible for autoimmune attacks are needed to confer long-term remission. Pathogenic cells in autoimmunity include memory T lymphocytes that are long-lived and present rapid recall effector functions with reduced activation requirements. Whereas the CD28 costimulation pathway predominantly controls priming of naive T cells and hence generation of adaptive memory cells, the roles of CD28 costimulation on established memory T lymphocytes and the recall of memory responses remain controversial. In contrast to CD80/86 antagonists (CTLA4-Ig), selective CD28 antagonists blunt T cell costimulation while sparing CTLA-4 and PD-L1-dependent coinhibitory signals. Using a new selective CD28 antagonist, we showed that Ag-specific reactivation of human memory T lymphocytes was prevented. Selective CD28 blockade controlled both cellular and humoral memory recall in nonhuman primates and induced long-term Ag-specific unresponsiveness in a memory T cell-mediated inflammatory skin model. No modification of memory T lymphocytes subsets or numbers was observed in the periphery, and importantly no significant reactivation of quiescent viruses was noticed. These findings indicate that pathogenic memory T cell responses are controlled by both CD28 and CTLA-4/PD-L1 cosignals in vivo and that selectively targeting CD28 would help to promote remission of autoimmune diseases and control chronic inflammation. PMID:26597009

  12. Nitromusk and Polycyclic Musk Compounds as Long-Term Inhibitors of Cellular Xenobiotic Defense Systems Mediated by Multidrug Transporters

    PubMed Central

    Luckenbach, Till; Epel, David

    2005-01-01

    Synthetic musk compounds, widely used as fragrances in consumer products, have been detected in human tissue and, surprisingly, in aquatic organisms such as fish and mollusks. Although their persistence and potential to bioaccumulate are of concern, the toxicity and environmental risks of these chemicals are generally regarded as low. Here, however, we show that nitromusks and polycyclic musks inhibit the activity of multidrug efflux transporters responsible for multixenobiotic resistance (MXR) in gills of the marine mussel Mytilus californianus. The IC10 (concentration that inhibits 10%) values for the different classes of musks were in the range of 0.09–0.39 μM, and IC50 values were 0.74–2.56 μM. The immediate consequence of inhibition of efflux transporters is that normally excluded xenobiotics will now be able to enter the cell. Remarkably, the inhibitory effects of a brief 2-hr exposure to musks were only partially reversed after a 24- to 48-hr recovery period in clean seawater. This unexpected consequence of synthetic musks—a long-term loss of efflux transport activity—will result in continued accumulation of normally excluded toxicants even after direct exposure to the musk has ended. These findings also point to the need to determine whether other environmental chemicals have similar long-term effects on these transporters. The results are relevant to human health because they raise the possibility that exposure to common xenobiotics and pharmaceuticals could cause similar long-term inhibition of these transporters and lead to increased exposure to normally excluded toxicants. PMID:15626642

  13. Sex-related long-term behavioral and hippocampal cellular alterations after nociceptive stimulation throughout postnatal development in rats.

    PubMed

    Lima, Márcia; Malheiros, Jackeline; Negrigo, Aline; Tescarollo, Fabio; Medeiros, Magda; Suchecki, Deborah; Tannús, Alberto; Guinsburg, Ruth; Covolan, Luciene

    2014-02-01

    Early noxious stimuli may alter the neurogenesis rate in the dentate gyrus and the behavioral repertoire of adult rats. This study evaluated the long-term effects of noxious stimulation, imposed in different phases of development, on nociceptive and anxiety-like behaviors, hippocampal activation, cell proliferation, hippocampal BDNF and plasma corticosterone levels in 40 day-old male and female adolescents. Noxious stimulation was induced by intra-plantar injection of Complete Freund's adjuvant (CFA), on postnatal days (P) 1 (group P1), 8 (P8) or 21 (P21). Control animals were not stimulated in any way. On P21 a subset of animals from each group received BrdU and was perfused on P40 for identification of proliferating cells in the granule cell layer of the dentate gyrus. Another subset of rats was subjected to behavioral testing on P40 and one week later, to magnetic resonance imaging (MRI) acquisition. Noxious stimulation evoked hypoalgesia in adolescents, mainly in females (P < 0.02), reflected by greater latency to withdraw the paw and less paw lickings in the hot plate test than controls (P < 0.001). It also resulted in more time spent in the open arms, e.g., less anxiety-like behavior than controls (P < 0.01), especially in females (P < 0.01, compared with males). Proliferative cell rate in the dentate gyrus was the highest in P8 males and females (P < 0.001), with males exhibiting more proliferation than females on P1 and P8, which was directly related to the hippocampal levels of BDNF and inversely related to plasma corticosterone. Sex differences were also detected in manganese-enhanced MRI signal, which was more prominent in P1 females than males (P < 0.01). This study represents the first step of investigation on the cellular basis of the sex-dependent long-term consequences of nociceptive stimuli in newborns. PMID:24148811

  14. An empirical response function for the long-term fate of excess atmospheric CO2

    NASA Astrophysics Data System (ADS)

    Lord, Natalie S.; Ridgwell, Andy; Thorne, Mike. C.; Lunt, Dan. J.

    2015-04-01

    The long-term fate of fossil fuel CO2 emitted to the atmosphere is neutralization by a number of sedimentological and geological processes operating on timescales ranging from thousands to hundreds of thousands of years. However, the response of these carbon cycle processes to increasing total emissions is not known, such as whether saturation of the long-term CO2 sinks might occur or a weakening of the associated feedbacks. This could have important implications for components of the Earth system that are slow to respond to changes in temperature, such as ice sheets and methane hydrates. Here we use a 3D ocean-based Earth system model to assess the relative importance and timescales of these processes for different total emissions. A multi-exponential analysis is performed on an ensemble of 1 Myr duration CO2 decay curves spanning cumulative emissions of up to 20,000 PgC, generating an empirical response function characterizing the long-term (> 1 kyr) fate of CO2. For a realistic time-dependent carbon release, a simple pulse-response description results in large predictive errors early on in the simulation. As a result, we develop a convolution-based description of atmospheric CO2 decay which significantly decreases these initial residuals. Our response function represents a simple and practical tool for rapidly projecting the atmospheric lifetime of a wide range of CO2 emission sizes, and in convolution form, can be used across a large range of rates of release, allowing it to be used in place of more complex models for assessing the long-term atmospheric CO2 perturbation following future anthropogenic emissions. Our analysis also reveals that, as the marine CO2 sinks become saturated, both the fraction of total emissions that are removed from the atmosphere via carbonate weathering and burial and the timescale of removal progressively increase. However, we find that the ultimate CO2 sink - silicate weathering feedback - is approximately invariant with respect to

  15. Long-term ecosystem response to the Exxon Valdez oil spill.

    PubMed

    Peterson, Charles H; Rice, Stanley D; Short, Jeffrey W; Esler, Daniel; Bodkin, James L; Ballachey, Brenda E; Irons, David B

    2003-12-19

    The ecosystem response to the 1989 spill of oil from the Exxon Valdez into Prince William Sound, Alaska, shows that current practices for assessing ecological risks of oil in the oceans and, by extension, other toxic sources should be changed. Previously, it was assumed that impacts to populations derive almost exclusively from acute mortality. However, in the Alaskan coastal ecosystem, unexpected persistence of toxic subsurface oil and chronic exposures, even at sublethal levels, have continued to affect wildlife. Delayed population reductions and cascades of indirect effects postponed recovery. Development of ecosystem-based toxicology is required to understand and ultimately predict chronic, delayed, and indirect long-term risks and impacts. PMID:14684812

  16. Long-term ecosystem response to the Exxon Valdez oil spill.

    PubMed

    Peterson, Charles H; Rice, Stanley D; Short, Jeffrey W; Esler, Daniel; Bodkin, James L; Ballachey, Brenda E; Irons, David B

    2003-12-19

    The ecosystem response to the 1989 spill of oil from the Exxon Valdez into Prince William Sound, Alaska, shows that current practices for assessing ecological risks of oil in the oceans and, by extension, other toxic sources should be changed. Previously, it was assumed that impacts to populations derive almost exclusively from acute mortality. However, in the Alaskan coastal ecosystem, unexpected persistence of toxic subsurface oil and chronic exposures, even at sublethal levels, have continued to affect wildlife. Delayed population reductions and cascades of indirect effects postponed recovery. Development of ecosystem-based toxicology is required to understand and ultimately predict chronic, delayed, and indirect long-term risks and impacts.

  17. Intranasal immunization with protective antigen of Bacillus anthracis induces a long-term immunological memory response.

    PubMed

    Woo, Sun-Je; Kang, Seok-Seong; Park, Sung-Moo; Yang, Jae Seung; Song, Man Ki; Yun, Cheol-Heui; Han, Seung Hyun

    2015-10-01

    Although intranasal vaccination has been shown to be effective for the protection against inhalational anthrax, establishment of long-term immunity has yet to be achieved. Here, we investigated whether intranasal immunization with recombinant protective antigen (rPA) of Bacillus anthracis induces immunological memory responses in the mucosal and systemic compartments. Intranasal immunization with rPA plus cholera toxin (CT) sustained PA-specific antibody responses for 6 months in lung, nasal washes, and vaginal washes as well as serum. A significant induction of PA-specific memory B cells was observed in spleen, cervical lymph nodes (CLNs) and lung after booster immunization. Furthermore, intranasal immunization with rPA plus CT remarkably generated effector memory CD4(+) T cells in the lung. PA-specific CD4(+) T cells preferentially increased the expression of Th1- and Th17-type cytokines in lung, but not in spleen or CLNs. Collectively, the intranasal immunization with rPA plus CT promoted immunologic memory responses in the mucosal and systemic compartments, providing long-term immunity.

  18. Understanding groundwater systems and system responses to external stimulations through the long-term monitoring

    NASA Astrophysics Data System (ADS)

    Lee, J.; Park, D.; Piao, J.; Woo, N. C.

    2013-12-01

    A total of 335 monitoring stations (497 of monitoring wells), organized the National Groundwater Monitoring Network (NGMN), has been established at 117 watersheds in Korea since 1995, and water-level, temperature and electrical conductivity (EC) have been recorded by every hour to every six hours. Basically the monitoring stations are implemented with two wells for alluvium and bedrock aquifer at depths of 6.1 m and 71.6 m, respectively. Using these long-term monitoring data, we have tried to understand the groundwater systems in Korea and the system responses to external stimulations such as precipitation events, earthquakes, and groundwater over-exploitation. In this study, water-level, temperature and EC data were analyzed for the Han-river, Geum-river, Yeongsan-Seomjin-river and Nakdong-river basins, Korea, for the three years from 2010 to 2012. Precipitation data were obtained from the automatic weather systems of Korea Meteorological Administration (KMA) at the same period of time. These data will be used to assess the relationship between groundwater and precipitation using the Genetic Mapping Tools (GMT) and Fast Fourier Transform analysis, and to calculate the recharge rate each rainfall event. At each monitoring stations, groundwater system will be defined based on the water-level responses to precipitation events, and their response rate will be calculated for specific amount of precipitation. Later, these data will be used for the calculation of sustainability of the watershed for long-term water resource management.

  19. Long-term trends in ecological systems: A basis for understanding responses to global change

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This book presents long-term data and cross-site comparisons from 50 sites in the US, including 26 sites in the Long Term Ecological Research Program, 14 in the USFS, and 7 in the USDA Agricultural Research Service. The intent of this book is twofold: (1) to illustrate the importance of long-term da...

  20. Response contingency directs long-term cocaine-induced neuroplasticity in prefrontal and striatal dopamine terminals.

    PubMed

    Wiskerke, Joost; Schoffelmeer, Anton N M; De Vries, Taco J

    2016-10-01

    Exposure to addictive substances such as cocaine is well-known to alter brain organisation. Cocaine-induced neuroadaptations depend on several factors, including drug administration paradigm. To date, studies addressing the consequences of cocaine exposure on dopamine transmission have either not been designed to investigate the role of response contingency or focused only on short-term neuroplasticity. We demonstrate a key role of response contingency in directing long-term cocaine-induced neuroplasticity throughout projection areas of the mesocorticolimbic dopamine system. We found enhanced electrically-evoked [(3)H]dopamine release from superfused brain slices of nucleus accumbens shell and core, dorsal striatum and medial prefrontal cortex three weeks after cessation of cocaine self-administration. In yoked cocaine rats receiving the same amount of cocaine passively, sensitised dopamine terminal reactivity was only observed in the nucleus accumbens core. Control sucrose self-administration experiments demonstrated that the observed neuroadaptations were not the result of instrumental learning per se. Thus, long-term withdrawal from cocaine self-administration is associated with widespread sensitisation of dopamine terminals throughout frontostriatal circuitries. PMID:27593624

  1. Rangeland monitoring reveals long-term plant responses to precipitation and grazing at the landscape scale

    USGS Publications Warehouse

    Munson, Seth M.; Duniway, Michael C.; Johanson, Jamin K.

    2015-01-01

    Managers of rangeland ecosystems require methods to track the condition of natural resources over large areas and long periods of time as they confront climate change and land use intensification. We demonstrate how rangeland monitoring results can be synthesized using ecological site concepts to understand how climate, site factors, and management actions affect long-term vegetation dynamics at the landscape-scale. Forty-six years of rangeland monitoring conducted by the Bureau of Land Management (BLM) on the Colorado Plateau reveals variable responses of plant species cover to cool-season precipitation, land type (ecological site groups), and grazing intensity. Dominant C3 perennial grasses (Achnatherum hymenoides, Hesperostipa comata), which are essential to support wildlife and livestock on the Colorado Plateau, had responses to cool-season precipitation that were at least twice as large as the dominant C4 perennial grass (Pleuraphis jamesii) and woody vegetation. However, these C3 perennial grass responses to precipitation were reduced by nearly one-third on grassland ecological sites with fine- rather than coarse-textured soils, and there were no detectable C3 perennial grass responses to precipitation on ecological sites dominated by a dense-growing shrub, Coleogyne ramosissima. Heavy grazing intensity further reduced the responses of C3 perennial grasses to cool-season precipitation on ecological sites with coarse-textured soils and surprisingly reduced the responses of shrubs as well. By using ecological site groups to assess rangeland condition, we were able to improve our understanding of the long-term relationships between vegetation change and climate, land use, and site characteristics, which has important implications for developing landscape-scale monitoring strategies.

  2. Long-Term Prognostic Significance of Extent of Rectal Cancer Response to Preoperative Radiation and Chemotherapy

    PubMed Central

    Ruo, Leyo; Tickoo, Satish; Klimstra, David S.; Minsky, Bruce D.; Saltz, Leonard; Mazumdar, Madhu; Paty, Philip B.; Wong, W. Douglas; Larson, Steven M.; Cohen, Alfred M.; Guillem, Jose G.

    2002-01-01

    Objective To determine whether selected clinicopathologic factors, including the extent of pathologic response to preoperative radiation and chemotherapy (RT ± chemo), have an impact on long-term recurrence-free survival (RFS) in patients with locally advanced primary rectal cancer after optimal multimodality therapy. Summary Background Data Although complete pathologic response to preoperative RT ± chemo has been detected in up to 30% of rectal cancers, its significance on long-term outcome has not been widely reported. Previous retrospective studies evaluating clinical outcome in patients with complete or near-complete pathologic response documented good prognosis in this population but were limited by median follow-up in the range of 2 to 3 years. Methods Sixty-nine patients with locally advanced (T3–4 and/or N1) primary rectal cancer were prospectively identified. All were treated at one institution with preoperative RT to the pelvis (at least 4,500 cGy). Forty patients received concurrent preoperative 5-fluorouracil-based chemotherapy and 27 received both pre- and postoperative chemotherapy. Patients underwent resection 4 to 7 weeks after completion of RT. TNM stage, angiolymphatic or perineural invasion, and extent of response to preoperative RT ± chemo were determined by pathologic evaluation. Adverse pathologic features were defined as the presence of angiolymphatic and/or perineural invasion. RFS at 5 years was determined by the Kaplan-Meier method. Results With a median follow-up of 69 months, 5-year RFS was 79%. RFS was significantly worse for patients with aggressive pathologic features and positive nodal status identified in the postirradiated surgical specimen. Risk ratios for RFS were 3.68 for the presence of aggressive pathologic features and 4.64 for node-positive rectal cancers. In patients with greater than 95% rectal cancer response to preoperative RT ± chemo, only one patient has died as a consequence of cancer, another has died of an

  3. Transcriptomic response of Listeria monocytogenes during the transition to the long-term-survival phase.

    PubMed

    Wen, Jia; Deng, Xiangyu; Li, Zengxin; Dudley, Edward G; Anantheswaran, Ramaswamy C; Knabel, Stephen J; Zhang, Wei

    2011-09-01

    Listeria monocytogenes can change its cellular morphology from bacilli to cocci during the transition to the long-term-survival (LTS) phase. The LTS cells demonstrated increased baro- and thermotolerance compared to their vegetative counterparts. So far, the underlying mechanisms that trigger this morphological and physiological transition remain largely unknown. In this study, we compared the transcriptomic profiles of L. monocytogenes serotype 4b strain F2365 at different growth stages in tryptic soy broth with yeast extract (TSBYE) using a whole-genome DNA chip approach. We identified a total of 225 differentially expressed genes (≥4-fold; P < 0.05) during the transition to the LTS phase in TSBYE. Genes related to cell envelope structure, energy metabolism, and transport were most significantly upregulated in the LTS phase. The upregulation of compatible solute transporters may lead to the accumulation of cellular solutes, lowering intracellular water activity and thus increasing bacterial stress resistance during the transition to the LTS phase. The downregulation of genes associated with protein synthesis may indicate a status of metabolic dormancy of the LTS cells. The transcriptomic profiles of resuscitated LTS cells in fresh TSBYE resembled those of log-phase cells (r=0.94), as the LTS cells rapidly resume metabolic activities and transit back to log phase with decreased baro- and thermotolerance. PMID:21764970

  4. Growth, microcystin-production and proteomic responses of Microcystis aeruginosa under long-term exposure to amoxicillin.

    PubMed

    Liu, Ying; Chen, Shi; Zhang, Jian; Gao, Baoyu

    2016-04-15

    Ecological risk of antibiotics due to the induction of antibiotic-resistant bacteria has been widely investigated, while studies on the hazard of antibiotic contaminants via the regulation of cyanobacteria were still limited. This study focused on the long-term action effect and mechanism of amoxicillin (a broadly used antibiotic) in Microcystis aeruginosa at environmentally relevant concentrations through 30 days of semi-continuous culture. Amoxicillin stimulated the photosynthesis activity and the production of microcystins, and interaction of differential proteins under amoxicillin exposure further manifested the close correlation between the two processes. D1 protein, ATP synthase subunits alpha and beta, enolase, triosephosphate isomerase and phosphoglycerate kinase were candidate target positions of amoxicillin in M. aeruginosa under long-term exposure. Amoxicillin affected the cellular biosynthesis process and the metabolism of carbohydrate and nucleoside phosphate according to the proteomic responses. Under exposure to amoxicillin, stimulated growth rate at the beginning phase and increased production and release of microcystins during the whole exposure period would lead to a higher contamination of M. aeruginosa cells and microcystins, indicating that amoxicillin was harmful to aquatic environments through the promotion of cyanobacterial bloom. PMID:26900975

  5. Highly Stable Near-Infrared Fluorescent Organic Nanoparticles with a Large Stokes Shift for Noninvasive Long-Term Cellular Imaging.

    PubMed

    Zhang, Jinfeng; Chen, Rui; Zhu, Zelin; Adachi, Chihaya; Zhang, Xiaohong; Lee, Chun-Sing

    2015-12-01

    Fluorescent organic nanoparticles based on small molecules have been regarded as promising candidates for bioimaging in recent years. In this study, we report a highly stable near-infrared (NIR) fluorescent organic nanoprobes based on nanoparticles of an anthraquinone derivate with strong aggregation-induced emission (AIE) characteristics and a large Stokes shift (>175 nm). These endow the nanoprobe with high fluorescent brightness and high signal-to-noise ratio. On the other hand, the nanoprobe also shows low cytotoxicity, good stability over a wide pH range, superior resistance against photodegradation and photobleaching comparing to typical commercial fluorescent organic dyes such as fluorescein sodium. Endowed with such merits in term of optical performance, biocompatibility, and stability, the nanoprobe is demonstrated to be an ideal fluorescent probe for noninvasive long-term cellular tracing and imaging applications. As an example, it is shown that strong red fluorescence from the nanoprobe can still be clearly observed in A549 human lung cancer cells after incubation for six generations over 15 days.

  6. Factors Affecting Antioxidant Response in Fish from a Long-term Mercury-Contaminated Reservoir.

    PubMed

    Sevcikova, M; Modra, H; Blahova, J; Dobsikova, R; Kalina, J; Zitka, O; Kizek, R; Svobodova, Z

    2015-11-01

    The objective of this work was to evaluate antioxidant defence and oxidative damage in organs (liver, gills, kidney, and brain) of five fish species (Aspius aspius, Esox lucius, Sander lucioperca, Abramis brama, Rutilus rutilus) from the long-term mercury-contaminated Skalka Reservoir in the Czech Republic. Special emphasis was placed on a comprehensive assessment of the factors that may affect the antioxidant response to mercury in fish. Antioxidant enzymes (glutathione reductase, glutathione peroxidase, and glutathione-S-transferase) did not significantly respond to mercury contamination. Levels of the analysed enzymes and oxidative damage to lipids were predominantly determined by a separate organ factor or species factor, or by the combination of both (p < 0.001). Levels of total glutathione and the reduced/oxidized glutathione ratio were influenced by mercury contamination in combination with their specific organ distribution (p < 0.001). Our results suggest that species and type of organ alone or in combination are more important factors than chronic exposure to mercury contamination with respect to effects on antioxidant defence in fish under field conditions. Our findings suggest that the main antioxidant defensive mechanism in fish from the studied long-term mercury contaminated site was the inter-tissue distribution of glutathione.

  7. Factors Affecting Antioxidant Response in Fish from a Long-term Mercury-Contaminated Reservoir.

    PubMed

    Sevcikova, M; Modra, H; Blahova, J; Dobsikova, R; Kalina, J; Zitka, O; Kizek, R; Svobodova, Z

    2015-11-01

    The objective of this work was to evaluate antioxidant defence and oxidative damage in organs (liver, gills, kidney, and brain) of five fish species (Aspius aspius, Esox lucius, Sander lucioperca, Abramis brama, Rutilus rutilus) from the long-term mercury-contaminated Skalka Reservoir in the Czech Republic. Special emphasis was placed on a comprehensive assessment of the factors that may affect the antioxidant response to mercury in fish. Antioxidant enzymes (glutathione reductase, glutathione peroxidase, and glutathione-S-transferase) did not significantly respond to mercury contamination. Levels of the analysed enzymes and oxidative damage to lipids were predominantly determined by a separate organ factor or species factor, or by the combination of both (p < 0.001). Levels of total glutathione and the reduced/oxidized glutathione ratio were influenced by mercury contamination in combination with their specific organ distribution (p < 0.001). Our results suggest that species and type of organ alone or in combination are more important factors than chronic exposure to mercury contamination with respect to effects on antioxidant defence in fish under field conditions. Our findings suggest that the main antioxidant defensive mechanism in fish from the studied long-term mercury contaminated site was the inter-tissue distribution of glutathione. PMID:26276034

  8. Hippocampal BDNF content in response to short- and long-term exercise.

    PubMed

    Sheikhzadeh, Farzam; Etemad, Asieh; Khoshghadam, Sahar; Asl, Naser Ahmadi; Zare, Peyman

    2015-07-01

    The hippocampus is a region in the brain that is crucial for learning and memory. Previous researches proved that brain-derived neurotrophic factor (BDNF) is a probable responsible protein in the learning and memory formation process. BDNF content is thought to be affected by environmental enrichment and physical activity. The purpose of this research was to identify the effect of short- and long-term forced exercise on hippocampal BDNF levels. A total of 30 Wistar rats were randomly divided into three groups (control, short-term exercise and long-term exercise) and treated by treadmill running based on their group. As the treadmill running period finished, the animals were anesthetized. The hippocampus was dissected out immediately and BDNF content of the samples was assessed by ELISA. None of the exercise paradigms did make any significant change on hippocampal BDNF levels. Although exercise was proposed to up-regulate BDNF levels, these results show that the intensity or the duration of running paradigm used in forced exercise protocols here was not enough to affect BDNF levels in the hippocampus significantly.

  9. Hippocampal BDNF content in response to short- and long-term exercise.

    PubMed

    Sheikhzadeh, Farzam; Etemad, Asieh; Khoshghadam, Sahar; Asl, Naser Ahmadi; Zare, Peyman

    2015-07-01

    The hippocampus is a region in the brain that is crucial for learning and memory. Previous researches proved that brain-derived neurotrophic factor (BDNF) is a probable responsible protein in the learning and memory formation process. BDNF content is thought to be affected by environmental enrichment and physical activity. The purpose of this research was to identify the effect of short- and long-term forced exercise on hippocampal BDNF levels. A total of 30 Wistar rats were randomly divided into three groups (control, short-term exercise and long-term exercise) and treated by treadmill running based on their group. As the treadmill running period finished, the animals were anesthetized. The hippocampus was dissected out immediately and BDNF content of the samples was assessed by ELISA. None of the exercise paradigms did make any significant change on hippocampal BDNF levels. Although exercise was proposed to up-regulate BDNF levels, these results show that the intensity or the duration of running paradigm used in forced exercise protocols here was not enough to affect BDNF levels in the hippocampus significantly. PMID:25860428

  10. Long-term treatment with responsive brain stimulation in adults with refractory partial seizures

    PubMed Central

    Bergey, Gregory K.; Mizrahi, Eli M.; Goldman, Alica; King-Stephens, David; Nair, Dileep; Srinivasan, Shraddha; Jobst, Barbara; Gross, Robert E.; Shields, Donald C.; Barkley, Gregory; Salanova, Vicenta; Olejniczak, Piotr; Cole, Andrew; Cash, Sydney S.; Noe, Katherine; Wharen, Robert; Worrell, Gregory; Murro, Anthony M.; Edwards, Jonathan; Duchowny, Michael; Spencer, David; Smith, Michael; Geller, Eric; Gwinn, Ryder; Skidmore, Christopher; Eisenschenk, Stephan; Berg, Michel; Heck, Christianne; Van Ness, Paul; Fountain, Nathan; Rutecki, Paul; Massey, Andrew; O'Donovan, Cormac; Labar, Douglas; Duckrow, Robert B.; Hirsch, Lawrence J.; Courtney, Tracy; Sun, Felice T.; Seale, Cairn G.

    2015-01-01

    Objective: The long-term efficacy and safety of responsive direct neurostimulation was assessed in adults with medically refractory partial onset seizures. Methods: All participants were treated with a cranially implanted responsive neurostimulator that delivers stimulation to 1 or 2 seizure foci via chronically implanted electrodes when specific electrocorticographic patterns are detected (RNS System). Participants had completed a 2-year primarily open-label safety study (n = 65) or a 2-year randomized blinded controlled safety and efficacy study (n = 191); 230 participants transitioned into an ongoing 7-year study to assess safety and efficacy. Results: The average participant was 34 (±11.4) years old with epilepsy for 19.6 (±11.4) years. The median preimplant frequency of disabling partial or generalized tonic-clonic seizures was 10.2 seizures a month. The median percent seizure reduction in the randomized blinded controlled trial was 44% at 1 year and 53% at 2 years (p < 0.0001, generalized estimating equation) and ranged from 48% to 66% over postimplant years 3 through 6 in the long-term study. Improvements in quality of life were maintained (p < 0.05). The most common serious device-related adverse events over the mean 5.4 years of follow-up were implant site infection (9.0%) involving soft tissue and neurostimulator explantation (4.7%). Conclusions: The RNS System is the first direct brain responsive neurostimulator. Acute and sustained efficacy and safety were demonstrated in adults with medically refractory partial onset seizures arising from 1 or 2 foci over a mean follow-up of 5.4 years. This experience supports the RNS System as a treatment option for refractory partial seizures. Classification of evidence: This study provides Class IV evidence that for adults with medically refractory partial onset seizures, responsive direct cortical stimulation reduces seizures and improves quality of life over a mean follow-up of 5.4 years. PMID:25616485

  11. Long-term successional forest dynamics: species and community responses to climatic variability

    SciTech Connect

    Kardol, Paul; Todd Jr, Donald E; Hanson, Paul J; Mulholland, Patrick J

    2010-01-01

    Question: Are tree dynamics sensitive to climatic variability, and do tree species differ in their responses to climatic variability? Hence, is vulnerability of forest communities to climatic variability depending on stand composition? Location: Mixed young forest at Walker Branch Watershed near Oak Ridge, East-Tennessee, USA. Methods: Using a long-term data set (1967-2006), we analyzed temporal forest dynamics at the tree and species level, and we analyzed community dynamics for forest stands that different in their initial species composition (i.e., Chestnut Oak, Oak-Hickory, Pine, and Yellow poplar stands). Using summer drought and growing season temperature as defined climate drivers, we evaluated relationships between forest dynamics and climate across levels of organization. Results: Over the 4-decade studied period, forest communities underwent successional change and substantially increased their biomass. Variation in summer drought and growing season temperature contributed to temporal biomass dynamics for some tree species, but not for others. Stand-level responses to climatic variability were shown to be related to responses of specific component species; however, not for Pine stands. Pinus echinata, the dominant species in stands initially identified as Pine stands, decreased over time due to periodical outbreaks of the pine bark beetle (Dendroctonus frontalis). The outbreaks on Walker Branch could not be directly related to climatic conditions. Conclusions: Our results imply that vulnerability of developing forests to predicted climate conditions is stand-type dependent, and hence, is a function of species composition. Autogenic successional processes (or insect outbreaks) were found to prevail over climatic variability in determining long-term forest dynamics for stands dominated by sensitive species, emphasizing the importance of studying interactions between forest succession and climate change.

  12. Long-term effectiveness of the response restriction method for establishing diurnal bladder control.

    PubMed

    van Oorsouw, Wietske M W J; Duker, P C; Melein, L; Averink, M

    2009-01-01

    The long-term effectiveness of the response restriction method for establishing diurnal bladder control was assessed with 48 participants with intellectual disabilities. Intervals of assessment ranged from 28 to 66 months across the individuals following initial baseline. Difference scores in terms of the mean number of toileting accidents per hour were related to participants' stereotypic behaviour and their housing conditions, as these were hypothesized to differentially influence the maintenance of diurnal bladder control. It was found that (a) across all participants there was a statistically significant decrease of the mean number of toileting accidents during follow-up as compared to initial baseline (b) stereotypic behaviour failed to be related to maintenance of bladder control, and (c) housing condition was significantly related to the above dependent variable, in that those living in a residential facility were more likely to wear a diaper again as compared to those living with their family. Implications for the clinical practice are discussed. PMID:19643573

  13. Long-term total ozone response caused by extra-terrestrial factors

    NASA Astrophysics Data System (ADS)

    Krivolutsky, A.; Knyazeva, N.; Perejaslova, G.; Bazilevskaya, G.; Nazarova, M.

    The observations of solar proton fluxes from boards of "Meteor", GOES satellites, galactic cosmic ray fluxes measured in the stratosphere by balloons, solar radio irradiance and total ozone records (ground based and TOMS data) for 1960-2000 period, has been used to investigate spatial and temporal structure of total ozone response to cosmic influence. Linear simple and multiply regression analysis has been used in our study. Yearly averaged data were used for analysis to e timates long-t erm effects in ozone response. Ozone data were grouped in different latitudinal belts of 100 width for Northern Hemisphere from equator to 800 N. Simple linear regression analysis for individual cosmic factors revealed negative total ozone response (in accordance to the conception of ozone destruction by additional amount of NOx produced by solar protons in the atmosphere of the Earth)0 for the years of strong solar proton events for latitudes which were higher than 45 N However, positive response for lower latitudes was found, when the same regression method was used. In the case of GCR influence on ozone the decadal response of ozone was revealed at high latitudes, which was in phase with galactic cosmic ray flux and in contract to the mentioned conception of ozone destruction by the NOx . Multiply regression analysis gave the long-term ozone variation of cosmic nature similar to real variations of total ozone.

  14. Metabolic Syndrome and Inflammatory Responses to Long-Term Particulate Air Pollutants

    PubMed Central

    Chen, Jiu-Chiuan; Schwartz, Joel

    2008-01-01

    Background Human data linking inflammation with long-term particulate matter (PM) exposure are still lacking. Emerging evidence suggests that people with metabolic syndrome (MS) may be a more susceptible population. Objectives Our goal was to examine potential inflammatory responses associated with long-term PM exposure and MS-dependent susceptibility. Methods We conducted secondary analyses of white blood cell (WBC) count and MS data from The Third National Health and Nutrition Examination Survey and PM10 (PM with aerodynamic diameter < 10 μm) data from the U.S. Environmental Protection Agency Aerometric Information Retrieval System. Estimated 1-year PM10 exposures were aggregated at the centroid of each residential census-block group, using distance-weighted averages from all monitors in the residing and adjoining counties. We restricted our analyses to adults (20–89 years of age) with normal WBC (4,000–11,000 × 106/L), no existing cardiovascular disease, complete PM10 and MS data, and living in current residences > 1 year (n = 2,978; age 48.5 ± 17.8 years). Mixed-effects models were constructed to account for autocorrelation and potential confounders. Results After adjustment for demographics, socioeconomic factors, lifestyles, residential characteristics, and MS, we observed a statistically significant association between WBC count and estimated local PM10 levels (p = 0.035). Participants from the least polluted areas (1-year PM10 < 1st quartile cutoff: 27.8 μg/m3) had lower WBC counts than the others (difference = 145 × 106/L; 95% confidence interval, 10–281). We also noted a graded association between PM10 and WBC across subpopulations with increasing MS components, with 91 × 106/L difference in WBC for those with no MS versus 214, 338, and 461 × 106/L for those with 3, 4, and 5 metabolic abnormalities (trend-test p = 0.15). Conclusions Our study revealed a positive association between long-term PM exposure and hematological markers of

  15. Long-term measurement of impedance in chronically implanted depth and subdural electrodes during responsive neurostimulation in humans.

    PubMed

    Sillay, Karl A; Rutecki, Paul; Cicora, Kathy; Worrell, Greg; Drazkowski, Joseph; Shih, Jerry J; Sharan, Ashwini D; Morrell, Martha J; Williams, Justin; Wingeier, Brett

    2013-09-01

    Long-term stability of the electrode-tissue interface may be required to maintain optimal neural recording with subdural and deep brain implants and to permit appropriate delivery of neuromodulation therapy. Although short-term changes in impedance at the electrode-tissue interface are known to occur, long-term changes in impedance have not previously been examined in detail in humans. To provide further information about short- and long-term impedance changes in chronically implanted electrodes, a dataset from 191 persons with medically intractable epilepsy participating in a trial of an investigational responsive neurostimulation device (the RNS(®) System, NeuroPace, Inc.) was reviewed. Monopolar impedance measurements were available for 391 depth and subdural leads containing a total of 1564 electrodes; measurements were available for median 802 days post-implant (range 28-1634). Although there were statistically significant short-term impedance changes, long-term impedance was stable after one year. Impedances for depth electrodes transiently increased during the third week after lead implantation and impedances for subdural electrodes increased over 12 weeks post-implant, then were stable over the subsequent long-term follow-up. Both depth and subdural electrode impedances demonstrated long-term stability, suggesting that the quality of long-term electrographic recordings (the data used to control responsive brain stimulation) can be maintained over time. PMID:23538208

  16. The long-term influence of repetitive cellular cardiac rejections on left ventricular longitudinal myocardial deformation in heart transplant recipients.

    PubMed

    Clemmensen, Tor Skibsted; Løgstrup, Brian Bridal; Eiskjaer, Hans; Høyer, Søren; Poulsen, Steen Hvitfeldt

    2015-04-01

    The aim of the study was to evaluate the long-term influence of repeated acute cellular rejections on left ventricular longitudinal deformation in heart transplantation (HTX) patients. One hundred and seventy-eight HTX patients were included in the study. Rejections were classified according to the International Society of Heart and Lung Transplantation (ISHLT) classification (0R-3R). Patients were divided into three groups according to rejection scores (RSs). Group 1: <50% of biopsies with 1R rejection and no ≥2R rejections; Group 2: ≥50% of biopsies with 1R rejection or one biopsy with ≥2R rejection; Group 3: ≥Two biopsies with ≥2R rejections. All patients had a comprehensive echocardiographic examination and coronary angiography. We found significantly decreasing global longitudinal strain (GLS) comparing to rejection groups (GLS group 1: -16.8 ± 2.4 (%); GLS group 2: -15.9 ± 3.3 (%); GLS group 3: -14.5 ± 2.9 (%), P = 0.0003). After excluding patients with LVEF < 50% or vasculopathy, GLS was still significantly reduced according to RS groups (P = 0.0096). Total number of 1R and 2R rejections correlated significant to GLS in a linear regression model. In contrast, we found fractional shortening and LVEF to be unaffected by repeated rejections. In conclusion, repeated cardiac rejections lead to impaired graft function as detected by decreasing magnitude of GLS. In contrast, traditional systolic graft function surveillance by LVEF did not correlate to rejection burden.

  17. Functional Responses of Salt Marsh Microbial Communities to Long-Term Nutrient Enrichment

    PubMed Central

    Graves, Christopher J.; Makrides, Elizabeth J.; Schmidt, Victor T.; Giblin, Anne E.; Cardon, Zoe G.

    2016-01-01

    ABSTRACT Environmental nutrient enrichment from human agricultural and waste runoff could cause changes to microbial communities that allow them to capitalize on newly available resources. Currently, the response of microbial communities to nutrient enrichment remains poorly understood, and, while some studies have shown no clear changes in community composition in response to heavy nutrient loading, others targeting specific genes have demonstrated clear impacts. In this study, we compared functional metagenomic profiles from sediment samples taken along two salt marsh creeks, one of which was exposed for more than 40 years to treated sewage effluent at its head. We identified strong and consistent increases in the relative abundance of microbial genes related to each of the biochemical steps in the denitrification pathway at enriched sites. Despite fine-scale local increases in the abundance of denitrification-related genes, the overall community structures based on broadly defined functional groups and taxonomic annotations were similar and varied with other environmental factors, such as salinity, which were common to both creeks. Homology-based taxonomic assignments of nitrous oxide reductase sequences in our data show that increases are spread over a broad taxonomic range, thus limiting detection from taxonomic data alone. Together, these results illustrate a functionally targeted yet taxonomically broad response of microbial communities to anthropogenic nutrient loading, indicating some resolution to the apparently conflicting results of existing studies on the impacts of nutrient loading in sediment communities. IMPORTANCE In this study, we used environmental metagenomics to assess the response of microbial communities in estuarine sediments to long-term, nutrient-rich sewage effluent exposure. Unlike previous studies, which have mainly characterized communities based on taxonomic data or primer-based amplification of specific target genes, our whole

  18. Response of Simulated Drinking Water Biofilm Mechanical and Structural Properties to Long-Term Disinfectant Exposure.

    PubMed

    Shen, Yun; Huang, Conghui; Monroy, Guillermo L; Janjaroen, Dao; Derlon, Nicolas; Lin, Jie; Espinosa-Marzal, Rosa; Morgenroth, Eberhard; Boppart, Stephen A; Ashbolt, Nicholas J; Liu, Wen-Tso; Nguyen, Thanh H

    2016-02-16

    Mechanical and structural properties of biofilms influence the accumulation and release of pathogens in drinking water distribution systems (DWDS). Thus, understanding how long-term residual disinfectants exposure affects biofilm mechanical and structural properties is a necessary aspect for pathogen risk assessment and control. In this study, elastic modulus and structure of groundwater biofilms was monitored by atomic force microscopy (AFM) and optical coherence tomography (OCT) during three months of exposure to monochloramine or free chlorine. After the first month of disinfectant exposure, the mean stiffness of monochloramine- or free-chlorine-treated biofilms was 4 to 9 times higher than those before treatment. Meanwhile, the biofilm thickness decreased from 120 ± 8 μm to 93 ± 6-107 ± 11 μm. The increased surface stiffness and decreased biofilm thickness within the first month of disinfectant exposure was presumably due to the consumption of biomass. However, by the second to third month during disinfectant exposure, the biofilm mean stiffness showed a 2- to 4-fold decrease, and the biofilm thickness increased to 110 ± 7-129 ± 8 μm, suggesting that the biofilms adapted to disinfectant exposure. After three months of the disinfectant exposure process, the disinfected biofilms showed 2-5 times higher mean stiffness (as determined by AFM) and 6-13-fold higher ratios of protein over polysaccharide, as determined by differential staining and confocal laser scanning microscopy (CLSM), than the nondisinfected groundwater biofilms. However, the disinfected biofilms and nondisinfected biofilms showed statistically similar thicknesses (t test, p > 0.05), suggesting that long-term disinfection may not significantly remove net biomass. This study showed how biofilm mechanical and structural properties vary in response to a complex DWDS environment, which will contribute to further research on the risk assessment and control of biofilm-associated-pathogens in DWDS.

  19. Adaptive response studies may help choose astronauts for long-term space travel

    NASA Astrophysics Data System (ADS)

    Mortazavi, S. M. Javad; Cameron, J. R.; Niroomand-rad, A.

    Long-term manned exploratory missions are planned for the future. Exposure to high-energy neutrons, protons and high charge and energy particles during a deep space mission, needs protection against the detrimental effects of space radiation. It has been suggested that exposure to unpredictable extremely large solar particle events would kill the astronauts without massive shielding. To reduce this risk to astronauts and to minimize the need for shielding, astronauts with highest significant adaptive responses should be chosen. It has been demonstrated that some humans living in very high natural radiation areas have acquired high adaptive responses to external radiation. Therefore, we suggest that for a deep space mission the adaptive response of all potential crew members be measured and only those with high adaptive response be chosen. We also proclaim that chronic exposure to elevated levels of radiation can considerably decrease radiation susceptibility and better protect astronauts against the unpredictable exposure to sudden and dramatic increase in flux due to solar flares and coronal mass ejections.

  20. Adaptive response studies may help choose astronauts for long-term space travel.

    PubMed

    Mortazavi, S M; Cameron, J R; Niroomand-rad, A

    2003-01-01

    Long-term manned exploratory missions are planned for the future. Exposure to high-energy neutrons, protons and high charge and energy particles during a deep space mission, needs protection against the detrimental effects of space radiation. It has been suggested that exposure to unpredictable extremely large solar particle events would kill the astronauts without massive shielding. To reduce this risk to astronauts and to minimize the need for shielding, astronauts with highest significant adaptive responses should be chosen. It has been demonstrated that some humans living in very high natural radiation areas have acquired high adaptive responses to external radiation. Therefore, we suggest that for a deep space mission the adaptive response of all potential crew members be measured and only those with high adaptive response be chosen. We also proclaim that chronic exposure to elevated levels of radiation can considerably decrease radiation susceptibility and better protect astronauts against the unpredictable exposure to sudden and dramatic increase in flux due to solar flares and coronal mass ejections.

  1. Adaptive response studies may help choose astronauts for long-term space travel.

    PubMed

    Mortazavi, S M; Cameron, J R; Niroomand-rad, A

    2003-01-01

    Long-term manned exploratory missions are planned for the future. Exposure to high-energy neutrons, protons and high charge and energy particles during a deep space mission, needs protection against the detrimental effects of space radiation. It has been suggested that exposure to unpredictable extremely large solar particle events would kill the astronauts without massive shielding. To reduce this risk to astronauts and to minimize the need for shielding, astronauts with highest significant adaptive responses should be chosen. It has been demonstrated that some humans living in very high natural radiation areas have acquired high adaptive responses to external radiation. Therefore, we suggest that for a deep space mission the adaptive response of all potential crew members be measured and only those with high adaptive response be chosen. We also proclaim that chronic exposure to elevated levels of radiation can considerably decrease radiation susceptibility and better protect astronauts against the unpredictable exposure to sudden and dramatic increase in flux due to solar flares and coronal mass ejections. PMID:12971409

  2. Identification of long-term survivors in primary breast cancer by dynamic modelling of tumour response

    PubMed Central

    Cameron, D A; Gregory, W M; Bowman, A; Anderson, E D C; Levack, P; Forouhi, P; Leonard, R C F

    2000-01-01

    Although clinical response to primary chemotherapy in stage II and III breast cancer is associated with a survival advantage, it is the degree of pathological response in the breast and ipsilateral axilla that best identifies patients with a good long-term outcome. A mathematical model of the initial response of 39 locally advanced tumours to anthracycline-based primary chemotherapy has been previously shown to predict subsequent clinical tumour size. This model allows for the possibility of primary resistant disease, the presence of which should therefore be associated with a worse outcome. This study reports the application of this model to an additional five patients with locally advanced breast cancer, as well as to 63 patients with operable breast cancer, and confirms the biological reality of the model parameters for these 100 breast cancers treated with primary anthracycline-based chemotherapy. The tumours that responded to chemotherapy had higher cell-kill (P< 0.0005), lower resistance (P< 0.0001) and slower tumour regrowth (P< 0.002). Furthermore, ER-negative tumours had higher cell-kill (P< 0.05), as compared with ER-positive tumours. All patients with a pathological complete response had zero resistance according to the model. Furthermore, the long-term implication of chemo-resistant disease was demonstrated by survival analysis of these two groups of patients. At a median follow-up of 3.7 years, there was a statistically significantly worse survival for the 37 patients with locally advanced breast cancer identified by the model to have more than 8% primary resistant tumour (P< 0.003). The specificity of this putative prognostic indicator was confirmed in the 63 patients presenting with operable disease where, at a median follow-up of 7.7 years, those women with a resistant fraction of greater than 8% had a significantly worse survival (P< 0.05). Application of this model to patients treated with neoadjuvant chemotherapy may allow earlier identification

  3. Long-term human response to uncertain environmental conditions in the Andes

    PubMed Central

    Dillehay, Tom D.; Kolata, Alan L.

    2004-01-01

    Human interaction with the physical environment has increasingly transformed Earth-system processes. Reciprocally, climate anomalies and other processes of environmental change of natural and anthropogenic origin have been affecting, and often disrupting, societies throughout history. Transient impact events, despite their brevity, can have significant long-term impact on society, particularly if they occur in the context of ongoing, protracted environmental change. Major climate events can affect human activities in critical conjunctures that shape particular trajectories of social development. Here we report variable human responses to major environmental events in the Andes with a particular emphasis on the period from anno Domini 500–1500 on the desert north coast of Perú. We show that preindustrial agrarian societies implemented distinct forms of anticipatory response to environmental change and uncertainty. We conclude that innovations in production strategies and agricultural infrastructures in these indigenous societies reflect differential social response to both transient (El Niño–Southern Oscillation events) and protracted (desertification) environmental change. PMID:15024122

  4. Comment and response document for the long-term surveillance plan for the Falls City disposal site, Falls City, Texas

    SciTech Connect

    1996-11-01

    This is the Comment and Response Document dated November 1996 for the Long-Term Surveillance Plan for the Falls City Disposal Site in Falls City, Texas. The site is part of the U.S. DOE`s Uranium Mill Tailings Remedial Action Project (UMTRA). Several comments regarding the hydrology and surface erosion described in the Long-Term Surveillance Plan are addressed in this document.

  5. Long-term effects of maternal separation on chronic stress response suppressed by amitriptyline treatment.

    PubMed

    Cotella, E M; Mestres Lascano, I; Franchioni, L; Levin, G M; Suárez, M M

    2013-07-01

    Abstract The early-life environment has many long-term effects on mammals. Maternal interaction and early stressful events may affect regulation of the HPA axis during adulthood, leading to differential glucocorticoid secretion in response to stressful situations. These adverse experiences during postnatal development may even sensitize specific neurocircuits to subsequent stressors. Later in life, the overreaction of the HPA axis to stress can constitute a risk factor for metabolic and mental diseases. As tricyclic antidepressants are known to correct glucocorticoid hypersecretion during depression, we treated maternally separated animals with amitriptyline, at a lower dose than habitually used in depression models, to prevent the response to chronic stress during adulthood. Male Wistar rats were separated from the mother for 4.5 h every day for the first 3 weeks of life. From postnatal day 50, animals were subjected to chronic variable stress during 24 d (five types of stressors at different times of day). During the stress, protocol rats were orally administered amitriptyline (5 mg/kg) daily. We observed that maternal separation caused a reduction in plasma ACTH levels (p < 0.05), but evoked hypersecretion of corticosterone (p < 0.05) when it was combined with stress in adulthood. This rise was completely prevented by antidepressant treatment with amitriptyline.

  6. Long-Term Mineral Soil Carbon Response to Forest Harvesting in New England

    NASA Astrophysics Data System (ADS)

    Neurath, R. A.; Zummo, L. M.; Friedland, A. J.

    2010-12-01

    Soils are the largest global terrestrial carbon reservoir. In temperate systems, mineral soil horizons contain the largest fraction of the soil carbon pool. Disturbance of mineral soil due to land-use change results in the mineralization and release of carbon as carbon dioxide to the atmosphere. The dynamics of this response are poorly understood. We examined a chronosequence of forested plots harvested 5, 25, 55, 75, and 120 years ago, as well as an old growth plot, from the Bartlett Experimental Forest in New Hampshire to determine the magnitude and timing of carbon loss following forest biomass harvest. Our results show a significant, long-term depletion in mineral soil carbon following harvest. Total carbon concentrations declined 29% from the 5-year (79.8 Mg C ha-1) to the 55-year (56.4 Mg C ha-1) plots, and had still not reached full recovery in the 120-year (85.2 Mg C ha-1) plot, which contained 5.4 Mg C ha-1 less than at the 5-year plot. Carbon isotope (δ13C) results suggest microbial processes, stimulated by the physical disturbance of the soil, are responsible for the significant depletion of mineral soil carbon following harvest. Our study reveals the need to consider mineral soil carbon in forest management practices.

  7. Man's physiologic response to long-term work during thermal and pollutant stress.

    PubMed

    Gliner, J A; Raven, P B; Horvath, S M; Drinkwater, B L; Sutton, J C

    1975-10-01

    Metabolic, temperature, and cardiorespiratory responses of 19 healthy males, age range 18-30 yr for one group and 40-55 yr for another, were studied during 210 minutes submaximal work at 35% Vo2 max. The subjects were exposed to four different pollutant gas mixtures at two different temperatures, 25 degrees C and 35 degrees C (relative humidity 30%). The four gas mixtures were filtered air (FA), 50 ppm carbon monoxide in filtered air (CO), 0.24 ppm peroxyacetyl nitrate in filtered air (PAN), and a combination of all three mixtures (PANCO). In the CO exposure, the heart rate was significantly greater than that observed during FA conditions (P less than 0.05). Metabolic and thermoregulatory responses to long-term work were not different in the various pollutant environments. Significant decreases in stroke volume and increases in heart rate were observed during the course of the 25 degrees C exposures with no alteration in cardiac output. Heart rates were higher during 35 degrees C exposures while cardiac output remained at the same level with a consequent further reduction in stroke output.

  8. Long-term functional plasticity in plant hydraulic architecture in response to supplemental moisture

    PubMed Central

    von Arx, Georg; Archer, Steven R.; Hughes, Malcolm K.

    2012-01-01

    Background and Aims Plasticity in structural and functional traits related to water balance may determine plant performance and survival in ecosystems characterized by water limitation or high levels of rainfall variability, particularly in perennial herbaceous species with long generation cycles. This paper addresses whether and the extent to which several such seasonal to long-term traits respond to changes in moisture availability. Methods Using a novel approach that integrates ecology, physiology and anatomy, a comparison was made of lifetime functional traits in the root xylem of a long-lived perennial herb (Potentilla diversifolia, Rosaceae) growing in dry habitats with those of nearby individuals growing where soil moisture had been supplemented for 14 years. Traditional parameters such as specific leaf area (SLA) and above-ground growth were also assessed. Key Results Individuals from the site receiving supplemental moisture consistently showed significant responses in all considered traits related to water balance: SLA was greater by 24 %; roots developed 19 % less starch storing tissue, an indicator for drought-stress tolerance; and vessel size distributions shifted towards wider elements that collectively conducted water 54 % more efficiently – but only during the years for which moisture was supplemented. In contrast, above-ground growth parameters showed insignificant or inconsistent responses. Conclusions The phenotypic changes documented represent consistent, dynamic responses to increased moisture availability that should increase plant competitive ability. The functional plasticity of xylem anatomy quantified in this study constitutes a mechanistic basis for anticipating the differential success of plant species in response to climate variability and change, particularly where water limitation occurs. PMID:22396436

  9. Survival Response and Rearrangement of Plasmid DNA of Lactococcus lactis during Long-Term Starvation

    PubMed Central

    Kim, Woojin S.; Park, Ji Hyeon; Ren, Jun; Su, Ping; Dunn, Noel W.

    2001-01-01

    The survival response of Lactococcus lactis during long-term starvation was investigated. The cells were cultured with different levels of glucose (the sole energy source) and either were kept in the resultant spent medium or transferred to fresh medium (without glucose) for up to 2 years. The survival of the cells during starvation was not dependent on the nature of transition phase, as expected, but on the nature of medium in which the cells were kept. The proliferation of cells, despite the apparent lack of glucose, could have been due to some cells being able to utilize the small amounts of peptides still present in the spent medium or to use energy sources provided by the breakup of dead cells. The 1- and 2-year-old cultures contained cells with vastly changed morphotypes. When these isolates were examined, it was revealed that the original plasmids present in the parent were rearranged in a certain way, and an entirely new plasmid was generated. Changes were also evident in the chromosomal DNA and in gene expression. Furthermore, all of the isolates exhibited a growth advantage relative to the parent cells when grown in energy-limiting media. When they were tested against different types of stresses, they exhibited a higher resistance against the bile salt and hydrogen peroxide stresses compared to the parent. Because of the similar changes observed in the 2-year-old isolates, a similar survival strategy may be operational in those cells that survive for that length of time. PMID:11571161

  10. Cerebral artery alpha-1 AR subtypes: high altitude long-term acclimatization responses.

    PubMed

    Goyal, Ravi; Goyal, Dipali; Chu, Nina; Van Wickle, Jonathan; Longo, Lawrence D

    2014-01-01

    In response to hypoxia and other stress, the sympathetic (adrenergic) nervous system regulates arterial contractility and blood flow, partly through differential activities of the alpha1 (α1) - adrenergic receptor (AR) subtypes (α1A-, α1B-, and α1D-AR). Thus, we tested the hypothesis that with acclimatization to long-term hypoxia (LTH), contractility of middle cerebral arteries (MCA) is regulated by changes in expression and activation of the specific α1-AR subtypes. We conducted experiments in MCA from adult normoxic sheep maintained near sea level (300 m) and those exposed to LTH (110 days at 3801 m). Following acclimatization to LTH, ovine MCA showed a 20% reduction (n = 5; P<0.05) in the maximum tension achieved by 10-5 M phenylephrine (PHE). LTH-acclimatized cerebral arteries also demonstrated a statistically significant (P<0.05) inhibition of PHE-induced contractility in the presence of specific α1-AR subtype antagonists. Importantly, compared to normoxic vessels, there was significantly greater (P<0.05) α1B-AR subtype mRNA and protein levels in LTH acclimatized MCA. Also, our results demonstrate that extracellular regulated kinase 1 and 2 (ERK1/2)-mediated negative feedback regulation of PHE-induced contractility is modulated by α1B-AR subtype. Overall, in ovine MCA, LTH produces profound effects on α1-AR subtype expression and function.

  11. Dynamic response of Permian brachiopod communities to long-term environmental change.

    PubMed

    Olszewski, Thomas D; Erwin, Douglas H

    2004-04-15

    The fossil record preserves numerous natural experiments that can shed light on the response of ecological communities to environmental change. However, directly observing the community dynamics of extinct organisms is not possible. As an alternative, neutral ecological models suggest that species abundance distributions reflect dynamical processes like migration, competition, recruitment, and extinction. Live-dead comparisons suggest that such distributions can be faithfully preserved in the rock record. Here we use a maximum-likelihood approach to show that brachiopod (lamp shell) abundance distributions from four temporally distinct ecological landscapes from the Glass Mountains, Texas (of the Permian period), exhibit significant differences. Further, all four are better fitted by zero-sum multinomial distributions, characteristic of Hubbell's neutral model, than by log-normal distributions, as predicted by the traditional ecological null hypothesis. Using the neutral model as a guide, we suggest that sea level fluctuations spanning about 10 Myr altered the degrees of isolation and exchange among local communities within these ecological landscapes. Neither these long-term environmental changes nor higher-frequency sea level fluctuations resulted in wholesale extinction or major innovation within evolutionary lineages.

  12. Dynamic response of Permian brachiopod communities to long-term environmental change.

    PubMed

    Olszewski, Thomas D; Erwin, Douglas H

    2004-04-15

    The fossil record preserves numerous natural experiments that can shed light on the response of ecological communities to environmental change. However, directly observing the community dynamics of extinct organisms is not possible. As an alternative, neutral ecological models suggest that species abundance distributions reflect dynamical processes like migration, competition, recruitment, and extinction. Live-dead comparisons suggest that such distributions can be faithfully preserved in the rock record. Here we use a maximum-likelihood approach to show that brachiopod (lamp shell) abundance distributions from four temporally distinct ecological landscapes from the Glass Mountains, Texas (of the Permian period), exhibit significant differences. Further, all four are better fitted by zero-sum multinomial distributions, characteristic of Hubbell's neutral model, than by log-normal distributions, as predicted by the traditional ecological null hypothesis. Using the neutral model as a guide, we suggest that sea level fluctuations spanning about 10 Myr altered the degrees of isolation and exchange among local communities within these ecological landscapes. Neither these long-term environmental changes nor higher-frequency sea level fluctuations resulted in wholesale extinction or major innovation within evolutionary lineages. PMID:15085129

  13. Long-term stability of the cortisol awakening response over adolescence.

    PubMed

    Platje, Evelien; Vermeiren, Robert R J M; Branje, Susan J T; Doreleijers, Theo A H; Meeus, Wim H J; Koot, Hans M; Frijns, Tom; van Lier, Pol A C; Jansen, Lucres M C

    2013-02-01

    The cortisol awakening response (CAR) has been widely assessed as a measure of hypothalamic-pituitary-adrenal (HPA) axis activity. Short-term stability is high; however, little is known about the long-term stability of the CAR. Because there are indications that development in adolescence influences HPA axis activity, this study investigated the stability of the CAR over adolescence. Participants were 229 boys and 181 girls from an adolescent general population sample who were assessed in three consecutive years, at mean ages of 15.0 (SD=0.4), 16.0 (SD=0.4) and 17.0 (SD=0.4) years. Cortisol was analyzed in saliva sampled at awakening, and 30 and 60min later. Stability was investigated both as rank-order and as mean-level stability. Effects of physical development during adolescence on stability were investigated as well. Rank-order stability was moderate to low, with tracking coefficients (interpretable as stability coefficients over time) of .15 (p<.001) for cortisol at awakening and .24 (p<.001) for cortisol 30 and 60min after awakening. Mean-levels of cortisol at awakening did not change, while the response to awakening increased over the years (linear slopes for cortisol 30 and 60min after awakening all p<.01). The increase may reflect the physical development of the adolescents. This is the first study, in a large population based sample, indicating that the rank-order of the CAR is stable over the course of several years. Interestingly, mean-levels of the cortisol response to awakening increased over the years, suggesting a maturation of HPA axis reactivity in relation to physical development over adolescence. Physical development should therefore be taken into account when investigating the CAR as a measure of HPA axis activity in adolescence. PMID:22776421

  14. Early and delayed long-term transcriptional changes and short-term transient responses during cold acclimation in olive leaves

    PubMed Central

    Leyva-Pérez, María de la O; Valverde-Corredor, Antonio; Valderrama, Raquel; Jiménez-Ruiz, Jaime; Muñoz-Merida, Antonio; Trelles, Oswaldo; Barroso, Juan Bautista; Mercado-Blanco, Jesús; Luque, Francisco

    2015-01-01

    Low temperature severely affects plant growth and development. To overcome this constraint, several plant species from regions having a cool season have evolved an adaptive response, called cold acclimation. We have studied this response in olive tree (Olea europaea L.) cv. Picual. Biochemical stress markers and cold-stress symptoms were detected after the first 24 h as sagging leaves. After 5 days, the plants were found to have completely recovered. Control and cold-stressed plants were sequenced by Illumina HiSeq 1000 paired-end technique. We also assembled a new olive transcriptome comprising 157,799 unigenes and found 6,309 unigenes differentially expressed in response to cold. Three types of response that led to cold acclimation were found: short-term transient response, early long-term response, and late long-term response. These subsets of unigenes were related to different biological processes. Early responses involved many cold-stress-responsive genes coding for, among many other things, C-repeat binding factor transcription factors, fatty acid desaturases, wax synthesis, and oligosaccharide metabolism. After long-term exposure to cold, a large proportion of gene down-regulation was found, including photosynthesis and plant growth genes. Up-regulated genes after long-term cold exposure were related to organelle fusion, nucleus organization, and DNA integration, including retrotransposons. PMID:25324298

  15. Early and delayed long-term transcriptional changes and short-term transient responses during cold acclimation in olive leaves.

    PubMed

    Leyva-Pérez, María de la O; Valverde-Corredor, Antonio; Valderrama, Raquel; Jiménez-Ruiz, Jaime; Muñoz-Merida, Antonio; Trelles, Oswaldo; Barroso, Juan Bautista; Mercado-Blanco, Jesús; Luque, Francisco

    2015-02-01

    Low temperature severely affects plant growth and development. To overcome this constraint, several plant species from regions having a cool season have evolved an adaptive response, called cold acclimation. We have studied this response in olive tree (Olea europaea L.) cv. Picual. Biochemical stress markers and cold-stress symptoms were detected after the first 24 h as sagging leaves. After 5 days, the plants were found to have completely recovered. Control and cold-stressed plants were sequenced by Illumina HiSeq 1000 paired-end technique. We also assembled a new olive transcriptome comprising 157,799 unigenes and found 6,309 unigenes differentially expressed in response to cold. Three types of response that led to cold acclimation were found: short-term transient response, early long-term response, and late long-term response. These subsets of unigenes were related to different biological processes. Early responses involved many cold-stress-responsive genes coding for, among many other things, C-repeat binding factor transcription factors, fatty acid desaturases, wax synthesis, and oligosaccharide metabolism. After long-term exposure to cold, a large proportion of gene down-regulation was found, including photosynthesis and plant growth genes. Up-regulated genes after long-term cold exposure were related to organelle fusion, nucleus organization, and DNA integration, including retrotransposons.

  16. Early and delayed long-term transcriptional changes and short-term transient responses during cold acclimation in olive leaves.

    PubMed

    Leyva-Pérez, María de la O; Valverde-Corredor, Antonio; Valderrama, Raquel; Jiménez-Ruiz, Jaime; Muñoz-Merida, Antonio; Trelles, Oswaldo; Barroso, Juan Bautista; Mercado-Blanco, Jesús; Luque, Francisco

    2015-02-01

    Low temperature severely affects plant growth and development. To overcome this constraint, several plant species from regions having a cool season have evolved an adaptive response, called cold acclimation. We have studied this response in olive tree (Olea europaea L.) cv. Picual. Biochemical stress markers and cold-stress symptoms were detected after the first 24 h as sagging leaves. After 5 days, the plants were found to have completely recovered. Control and cold-stressed plants were sequenced by Illumina HiSeq 1000 paired-end technique. We also assembled a new olive transcriptome comprising 157,799 unigenes and found 6,309 unigenes differentially expressed in response to cold. Three types of response that led to cold acclimation were found: short-term transient response, early long-term response, and late long-term response. These subsets of unigenes were related to different biological processes. Early responses involved many cold-stress-responsive genes coding for, among many other things, C-repeat binding factor transcription factors, fatty acid desaturases, wax synthesis, and oligosaccharide metabolism. After long-term exposure to cold, a large proportion of gene down-regulation was found, including photosynthesis and plant growth genes. Up-regulated genes after long-term cold exposure were related to organelle fusion, nucleus organization, and DNA integration, including retrotransposons. PMID:25324298

  17. Investigating the long-term geodetic response to magmatic intrusions at volcanoes in northern California

    NASA Astrophysics Data System (ADS)

    Parker, A. L.; Biggs, J.; Annen, C.; Houseman, G. A.; Yamasaki, T.; Wright, T. J.; Walters, R. J.; Lu, Z.

    2014-12-01

    Ratios of intrusive to extrusive activity at volcanic arcs are thought to be high, with estimates ranging between 5:1 and 30:1. Understanding the geodetic response to magmatic intrusion is therefore fundamental to large-scale studies of volcano deformation, providing insight into the dynamics of the inter-eruptive period of the volcano cycle and the building of continental crust. In northern California, we identify two volcanoes - Medicine Lake Volcano (MLV) and Lassen Volcanic Center (LaVC) - that exhibit long-term (multi-decadal) subsidence. We test the hypothesis that deformation at these volcanoes results from processes associated with magmatic intrusions. We first constrain the spatial and temporal characteristics of the deformation fields, establishing the first time-series of deformation at LaVC using InSAR data, multi-temporal analysis techniques and global weather models. Although the rates of deformation at the two volcanoes are similar (~1 cm/yr), our results show that the ratio of vertical to horizontal displacements is significantly different, suggesting contrasting source geometries. To test the origin of deformation, we develop modeling strategies to investigate thermal and viscoelastic processes associated with magmatic intrusions. The first model we develop couples analytical geodetic models to a numerical model of volume loss due to cooling and crystallization based upon temperature-melt fraction relationships from petrological experiments. This model provides evidence that magmatic intrusion at MLV has occurred more recently than the last eruption ~1 ka. The second model we test uses a finite element approach to simulate the time-dependent viscoelastic response of the crust to magmatic intrusion. We assess the magnitude and timescales of ground deformation that may result from these processes, exploring the model parameter space before applying the models to our InSAR observations of subsidence in northern California.

  18. Collagen Type III and VI Turnover in Response to Long-Term Immobilization

    PubMed Central

    Sun, Shu; Henriksen, Kim; Karsdal, Morten A.; Byrjalsen, Inger; Rittweger, Jörn; Armbrecht, Gabriele; Belavy, Daniel L.; Felsenberg, Dieter; Nedergaard, Anders F.

    2015-01-01

    Background Muscle mass and function are perturbed by immobilization and remobilization. When muscle mass changes, the quality and quantity of the extracellular matrix protein, particularly the collagens, change with it. In this study, we investigated the temporal profile of three peptide biomarkers derived from turnover of collagen type III and type VI in a long-term immobilization and remobilization study. We also compared individual biomarker levels with Lean body Mass (LBM) and changes therein, hypothesizing that these biomarkers would be biomarkers of the remodeling processes associated with immobilization and/or remobilization. Methods In the Berlin bed rest study, 20 young men were recruited and randomly assigned to 8-week’s strict bed rest with or without resistive vibration exercise countermeasure. We measured three neo-epitope ELISA kits in the serum samples of this study: Pro-C3, measured the synthesis of collagen type III; Pro-C6, measured the synthesis of collagen type VI; and C6M measured the degradation of collagen type VI induced by MMP-2 and MMP-9 cleavage. Results Pro-C3 and Pro-C6 biomarkers are up-regulated with both immobilization and remobilization, whereas C6M is hardly affected at all. We found that Pro-C3 and C6M levels are related to LBM at baseline and that high levels of Pro-C6 are associated with smaller changes in muscle mass during both immobilization and remobilization. Conclusion The Pro-C3 and–C6 biomarkers change likely reflect remodeling changes in response to unloading or reloading, whereas C6M does not appear to respond to unloading. Pro-C3 and C6M levels correlate with LBM at baseline, while Pro-C6 is related to the anabolic and catabolic responses to unloading and reloading. PMID:26641456

  19. Proliferation rate but not mismatch repair affects the long-term response of colon carcinoma cells to 5FU treatment.

    PubMed

    Choudhary, B; Hanski, M L; Zeitz, M; Hanski, C

    2012-07-01

    The role of mismatch repair (MMR) in the response of colon carcinoma cells to 5-fluorouracil (5FU) is not well understood. In most of the in vitro studies only short-term response was investigated. We focussed here on the influence of MMR status on the mechanism of the short- and long-term response to clinically relevant 5FU concentrations by using isogenic or semiisogenic cell line pairs expressing/nonexpressing the hMLH1 protein, an important component of the MMR system. We show that the lower survival of MMR-proficient than of MMR-deficient cells in the clonogenic survival assay is due to a more frequent early cell arrest and to subsequent senescence. By contrast, the long-term cell growth after treatment, which is also affected by long-term arrest and senescence, is independent from the MMR status. The overall effect on the long-term cell growth is a cumulative result of cell proliferation rate-dependent growth inhibition, apoptosis and necrotic cell death. The main long-term cytotoxic effect of 5FU is the inhibition of growth while apoptosis and the necrotic cell death are minor contributions.

  20. Physiological responses to fertilization recorded in tree rings: isotopic lessons from a long-term fertilization trial - 2008

    EPA Science Inventory

    Nitrogen fertilizer applications are common land-use management tools, but details on physiological responses to these applications are often lacking, particularly for long-term responses over decades of forest management. We used tree-ring growth patterns and stable isotopes to...

  1. Physiological responses to fertilization recorded in tree rings: Isotopic lessons from a long-term fertilization trial

    EPA Science Inventory

    Nitrogen fertilizer applications are common land use management tools, but details on physiological responses to these applications are often lacking, particularly for long-term responses over decades of forest management. We used tree ring growth patterns and stable isotopes to ...

  2. Active Traction Force Response to Long-Term Cyclic Stretch Is Dependent on Cell Pre-stress.

    PubMed

    Cirka, Heather; Monterosso, Melissa; Diamantides, Nicole; Favreau, John; Wen, Qi; Billiar, Kristen

    2016-04-26

    Mechanical stimulation is recognized as a potent modulator of cellular behaviors such as proliferation, differentiation, and extracellular matrix assembly. However, the study of how cell-generated traction force changes in response to stretch is generally limited to short-term stimulation. The goal of this work is to determine how cells actively alter their traction force in response to long-term physiological cyclic stretch as a function of cell pre-stress. We have developed, to our knowledge, a novel method to assess traction force after long-term (24 h) uniaxial or biaxial cyclic stretch under conditions of high cell pre-stress with culture on stiff (7.5 kPa) polyacrylamide gels (with or without transforming growth factor β1 (TGF-β1)) and low pre-stress by treating with blebbistatin or culture on soft gels (0.6 kPa). In response to equibiaxial stretch, valvular interstitial cells on stiff substrates decreased their traction force (from 300 nN to 100 nN) and spread area (from 3000 to 2100 μm(2)). With uniaxial stretch, the cells had similar decreases in traction force and area and reoriented perpendicular to the stretch. TGF-β1-treated valvular interstitial cells had higher pre-stress (1100 nN) and exhibited a larger drop in traction force with uniaxial stretch, but the percentage changes in force and area with stretch were similar to the non-TGF-β1-treated group. Cells with inhibited myosin II motors increased traction force (from 41 nN to 63 nN) and slightly reoriented toward the stretch direction. In contrast, cells cultured on soft gels increased their traction force significantly, from 15 nN to 45 nN, doubled their spread area, elongated from an initially rounded morphology, and reoriented perpendicular to the uniaxial stretch. Contractile-moment measurements provided results consistent with total traction force measurements. The combined results indicate that the change in traction force in response to external cyclic stretch is dependent upon the

  3. Emergency Response and Long Term Planning: Two sides of the Coin for Managing Water Resources

    NASA Astrophysics Data System (ADS)

    Metchis, K.; Beller-Simms, N.

    2014-12-01

    As projected by the US National Climate Assessment and the IPCC, extreme climate and weather events are occurring more frequently and with more intensity across the nation. Communities - and the water resource managers that serve them - are facing difficult choices to increase emergency preparedness, recover from costly impacts, and increase long term resilience. The presentation is based on a recent set of case studies about what happened in six communities that experienced one or more extreme events, focusing on water resource management. Two of the case studies will be presented, revealing that building climate resilience is not just about long term planning - it is also about taking the steps to be prepared for - and to be able to recover from - emergency events. The results of this study have implications for educating local officials on ways to think about resilience to balance both long-term and short-term preparedness.

  4. Long-term mountain tundra composition's responses to grazing pressure in the context of environmental changes

    NASA Astrophysics Data System (ADS)

    Saccone, Patrick; Pyykkonen, Tuija; Eskelinen, Anu; Virtanen, Risto

    2013-04-01

    Strong changes in northern tundra in response to climate changes are expected and in particular an increasing shrubiness. However, global changes contain not only warming or shifts in snow-cover but also changes in land-use, e.g. for arctic low productive ecosystems changes in grazing pressure. Grazing could also represent an important driver of future Arctic tundra communities. However, the relative importance of biotic and abiotic drivers of plant communities' composition remains largely unknown, in particular because short-term experiments provided to conflicting evidences. Here, we present the results from a long-term (23 years) experiment set up in 1989 at Kilpisjärvi in the north-western Finnish Lapland. The experiment consisted in the transplantation of twenty 40x50 cm blocks of Vaccinium myrtillus heath including 5-10 cm thick soil layer from a 660 m.a.s.l. dry slope to a snowbed 150m higher in elevation containing dry and wet sites. We considered the transplantation at higher altitude in snowbed conditions an increase in harsher conditions (shorter growing season, lower productivity). Half of the transplanted blocks were protected from herbivores and the percentage cover of each plant species was estimated in mid-august 2012 from a central 12.5 x12.5 cm area in each block. Our results showed that the dominance of the shrub V. myrtillus was strongly reduced as response to transplantation to snowbed. Consequently the competitive pressure also decreased and allowed an increase of the species richness. Soil moisture differences between installation locations induced divergence in plant communities' composition allowing the increase in abundance of subordinate species as bryophytes and graminoids in wet and dry sites respectively. Excluding herbivory, some species assumed high dominance reducing the community diversity. In the wet exclosures, quarter of the surface was covered by a moss and V. myrtillus co-dominated. The strongest changes occurred in dry

  5. A Long Term View of Forest Response to Environmental Change: 25 Years of Studying Harvard Forest

    NASA Astrophysics Data System (ADS)

    Munger, J. W.; Wofsy, S. C.; Lindaas, J.; David, F.; David, O.

    2014-12-01

    Forests influence the budgets of greenhouse gases, and understanding how they will respond to environmental change is critical to accurately predicting future GHG trends. The time scale for climate change is long and forest growth is slow, thus very long measurement periods are required to observe meaningful forest response. We established an eddy flux tower within a mixed forest stand dominated by red oak and red maple at the Harvard Forest LTER site in 1989 where CO2, H2O and energy fluxes together with meteorological observations have been measured continuously. An array of plots for biometric measurements was established in 1993. Flux measurement at an adjacent hemlock stand began in 2000. Records of land use and disturbance and vegetation plot data extend back to 1907. The combined suite of measurements merges observations of instantaneous ecosystem responses to environmental forcing with details of vegetation dynamics and forest growth that represent the emergent properties relevant to long-term ecosystem change. Both the deciduous stand and hemlock stand are accumulating biomass. Each has added over 20 Mg-C ha-1 as woody biomass in trees >10cm dbh since 1990, even though the hemlock stand is older. Net carbon exchange shows enhanced uptake in early spring and late fall months in response to warmer temperatures and likely an increase in evergreen foliage at the deciduous site. Net carbon uptake efficiency at the deciduous stand has increased over time as well as indicated by peak NEE under optimum light conditions. The trend is only partly explained by variation in mean leaf area index and cannot be directly attributed to climate response. The combination of longer growing season and increased uptake efficiency yields a general trend of increasing annual NEE (Fig. 1). However, significant excursions in the trend highlight the sensitivity of forest carbon stocks. The pulse of high annual carbon uptake (peak 6 Mg-C ha-1y-1 in 2008) from 2000-2008 is only

  6. Seagrass ecosystem response to long-term high CO2 in a Mediterranean volcanic vent.

    PubMed

    Apostolaki, Eugenia T; Vizzini, Salvatrice; Hendriks, Iris E; Olsen, Ylva S

    2014-08-01

    We examined the long-term effect of naturally acidified water on a Cymodocea nodosa meadow growing at a shallow volcanic CO2 vent in Vulcano Island (Italy). Seagrass and adjacent unvegetated habitats growing at a low pH station (pH = 7.65 ± 0.02) were compared with corresponding habitats at a control station (pH = 8.01 ± 0.01). Density and biomass showed a clear decreasing trend at the low pH station and the below- to above-ground biomass ratio was more than 10 times lower compared to the control. C content and δ(13)C of leaves and epiphytes were significantly lower at the low pH station. Photosynthetic activity of C. nodosa was stimulated by low pH as seen by the significant increase in Chla content of leaves, maximum electron transport rate and compensation irradiance. Seagrass community metabolism was intense at the low pH station, with significantly higher net community production, respiration and gross primary production than the control community, whereas metabolism of the unvegetated community did not differ between stations. Productivity was promoted by the low pH, but this was not translated into biomass, probably due to nutrient limitation, grazing or poor environmental conditions. The results indicate that seagrass response in naturally acidified conditions is dependable upon species and geochemical characteristics of the site and highlight the need for a better understanding of complex interactions in these environments. PMID:25081848

  7. A long-term copper exposure on freshwater ecosystem using lotic mesocosms: Primary producer community responses.

    PubMed

    Roussel, Hélène; Ten-Hage, Loïc; Joachim, Sandrine; Le Cohu, René; Gauthier, Laury; Bonzom, Jean-Marc

    2007-02-28

    Copper is commonly used as an algicide and plant herbicide in the aquatic environment. Despite of its frequent application in rivers, ponds and lakes, few studies have been performed at the ecosystem level on primary producers' communities. A long-term lotic mesocosms study was carried on, in 20m long channels, under environmentally realistic concentrations of copper (0, 5, 25 and 75 microgL(-1)) delivered continuously for 18 months. Results showed significant effects at the 25 and 75 microgL(-1) copper treatment levels on the phytoplankton, periphyton and macrophyte community structure. Effects on biomass and abundance were dissimilar depending on the studied community. Phytoplankton showed no abundance variation with treatment, whereas periphyton had higher biomass and macrophytes had lower coverage at 25 and 75 microgL(-1). Taxa richness was significantly affected for all primary producers communities at 25 and 75 microgL(-1). Some taxa seemed to be sensitive to copper, i.e. Cocconeis spp., Epithemia sp., Gomphonema spp., Lemna minor, Nasturtium officinale and filamentous macroalgae. Other taxa appeared to be tolerant or facilitated by indirect effects, i.e. Leptolyngbya sp., Mougeotia sp., Nitzschia palea, Pseudanabaena sp. and Ulothrix sp. and therefore increased in the 25 and 75 microgL(-1) treatments. Important indirect factors influenced the community responses, such as trophic interactions like decrease of grazing pressure, competition for light and nutrients and temperature favouring blue-green algae development. After 18 months of copper exposure, the no observed effect concentration at community level (NOEC(community)) for primary producers was set up at 5 or 4mugL(-1), if we consider the average effective concentration, with a lowest observed effect concentration (LOEC(community)) at 25 or 20 microgL(-1) (AEC). PMID:17239970

  8. Compensatory responses of the insulin signaling pathway restore muscle glucose uptake following long-term denervation

    PubMed Central

    Callahan, Zachary J; Oxendine, Michael; Wheatley, Joshua L; Menke, Chelsea; Cassell, Emily A; Bartos, Amanda; Geiger, Paige C; Schaeffer, Paul J

    2015-01-01

    We investigated the role of muscle activity in maintaining normal glucose homeostasis via transection of the sciatic nerve, an extreme model of disuse atrophy. Mice were killed 3, 10, 28, or 56 days after transection or sham surgery. There was no difference in muscle weight between sham and transected limbs at 3 days post surgery, but it was significantly lower following transection at the other three time points. Transected muscle weight stabilized by 28 days post surgery with no further loss. Myocellular cross-sectional area was significantly smaller at 10, 28, and 56 days post transection surgery. Additionally, muscle fibrosis area was significantly greater at 56 days post transection. In transected muscle there was reduced expression of genes encoding transcriptional regulators of metabolism (PPARα, PGC-1α, PGC-1β, PPARδ), a glycolytic enzyme (PFK), a fatty acid transporter (M-CPT 1), and an enzyme of mitochondrial oxidation (CS) with transection. In denervated muscle, glucose uptake was significantly lower at 3 days but was greater at 56 days under basal and insulin-stimulated conditions. Although GLUT 4 mRNA was significantly lower at all time points in transected muscle, Western blot analysis showed greater expression of GLUT4 at 28 and 56 days post surgery. GLUT1 mRNA was unchanged; however, GLUT1 protein expression was also greater in transected muscles. Surgery led to significantly higher protein expression for Akt2 as well as higher phosphorylation of Akt. While denervation may initially lead to reduced glucose sensitivity, compensatory responses of insulin signaling appeared to restore and improve glucose uptake in long-term-transected muscle. PMID:25896980

  9. An individual-based model simulating goat response variability and long-term herd performance.

    PubMed

    Puillet, L; Martin, O; Sauvant, D; Tichit, M

    2010-12-01

    Finding ways of increasing the efficiency of production systems is a key issue of sustainability. System efficiency is based on long-term individual efficiency, which is highly variable and management driven. To study the effects of management on herd and individual efficiency, we developed the model simulation of goat herd management (SIGHMA). This dynamic model is individual-based and represents the interactions between technical operations (relative to replacement, reproduction and feeding) and individual biological processes (performance dynamics based on energy partitioning and production potential). It simulates outputs at both herd and goat levels over 20 years. A farmer's production project (i.e. a targeted milk production pattern) is represented by configuring the herd into female groups reflecting the organisation of kidding periods. Each group is managed by discrete events applying decision rules to simulate the carrying out of technical operations. The animal level is represented by a set of individual goat models. Each model simulates a goat's biological dynamics through its productive life. It integrates the variability of biological responses driven by genetic scaling parameters (milk production potential and mature body weight), by the regulations of energy partitioning among physiological functions and by responses to diet energy defined by the feeding strategy. A sensitivity analysis shows that herd efficiency was mainly affected by feeding management and to a lesser extent by the herd production potential. The same effects were observed on herd milk feed costs with an even lower difference between production potential and feeding management. SIGHMA was used in a virtual experiment to observe the effects of feeding strategies on herd and individual performances. We found that overfeeding led to a herd production increase and a feed cost decrease. However, this apparent increase in efficiency at the herd level (as feed cost decreased) was related

  10. Threshold responses of songbirds to long-term timber management on an active industrial forest

    USGS Publications Warehouse

    Becker, D.A.; Wood, P.B.; Keyser, P.D.; Wigley, T.B.; Dellinger, R.; Weakland, C.A.

    2011-01-01

    Forest managers often seek to balance economic benefits from timber harvesting with maintenance of habitat for wildlife, ecosystem function, and human uses. Most research on the relationship between avian abundance and active timber management has been short-term, lasting one to two years, creating the need to investigate long-term avian responses and to identify harvest thresholds when a small change in habitat results in a disproportionate response in relative abundance and nest success. Our objectives were to identify trends in relative abundance and nest success and to identify landscape-scale disturbance thresholds for avian species and habitat guilds in response to a variety of harvest treatments (clear-cuts, heavy and light partial harvests) over 14 years. We conducted point counts and monitored nests at an industrial forest in the central Appalachians of West Virginia during 1996-1998, 2001-2003, and 2007-2009. Early successional species increased in relative abundance across all three time periods, whereas interior-edge and forest-interior guilds peaked in relative abundance mid-study after which the forest-interior guild declined. Of 41 species with >10 detections, four (10%) declined significantly, 13 (32%) increased significantly (only three species among all periods), and 9 (22%) peaked in abundance mid-study (over the entire study period, four species had no significant change in abundance, four declined, and one increased). Based on piecewise linear models, forest-interior and interior-edge guilds' relative abundance harvest thresholds were 28% total harvests (all harvests combined), 10% clear-cut harvests, and 18% light partial harvests, after which abundances declined. Harvest thresholds for the early successional guild were 42% total harvests, 11% clear-cut harvest, and 10% light partial harvests, and relative abundances increased after surpassing thresholds albeit at a reduced rate of increase after the clear-cut threshold. Threshold confidence

  11. Emergency planning and long-term care: least paid, least powerful, most responsible.

    PubMed

    Covan, Eleanor Krassen; Fugate-Whitlock, Elizabeth

    2010-11-01

    As disasters can occur anywhere, planning to avoid emergencies is an international concern. Our research specifically addresses planning for the needs and safety of a vulnerable population, long-term care residents. Our initial purposes in this evaluation research were to assess the utility of a template to gather emergency management information for individual long-term care communities, to report on how prepared they are to cope with emergencies that have occurred elsewhere in areas like ours, and to assess the effectiveness of employing gerontology students in the planning process. As we began analyzing our data, we realized that it is imperative to consider whether it is possible for long-term care communities to respond effectively to disasters. In our findings we focus on the impact of gender in the planning process, the importance of size with regard to template utility, the positive and negative consequences of student aid, and the fact that gathering plans for individual long-term care communities may have detracted from collaborative community planning. PMID:20924876

  12. Corn response to long-term applications of cattle manure, swine effluent, and inorganic nitrogen fertilizer

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Cattle (Bos taurus) manure and swine (Sus scrofa) effluent are applied to cropland to recycle nutrients, build soil quality, and increase crop productivity. The objective of this study was to determine the long-term effects of land application of cattle manure and swine effluent using the Kansas Nut...

  13. LONG TERM RESPONSE OF RATS TO SINGLE INTRATRACHEAL EXPOSURE OF LIBBY AMPHIBOLE (LA) OR AMOSITE

    EPA Science Inventory

    In former mine workers of Libby, Montana, exposure to amphibole-contaminated vermiculite has been associated with increased incidences of asbestosis and mesothelioma. In this study, we investigated long term effects of Libby amphibole (LA) exposure in a rat model. Rat respirable ...

  14. Long term response of rats to single intratracheal exposure of Libby amphibole or amosite

    EPA Science Inventory

    In former mine workers and residents of Libby, Montana, exposure to amphibolecontaminated vermiculite has been associated with increased incidences of asbestosis and mesothelioma. In this study, we investigated long-term effects of Libby amphibole (LA) exposure relative to the w...

  15. Comment and response document for the long-term surveillance plan for the Falls City Disposal Site, Falls City, Texas

    SciTech Connect

    1996-10-01

    This document contains the comments made by the US Nuclear Regulatory Commission on the Department of Energy`s (DOE) Long-Term Surveillance Plan for the Falls City Disposal Site, Falls City, Texas. DOE`s responses to the comments are also included.

  16. Measurement and Analysis of Individualized Care Inventory Responses Comparing Long-Term Care Nurses and Care Aides

    ERIC Educational Resources Information Center

    O'Rourke, Norm; Chappell, Neena L.; Caspar, Sienna

    2009-01-01

    Purpose: Motivating and enabling formal caregivers to provide individualized resident care has become an increasingly important objective in long-term care (LTC) facilities. The current study set out to examine the structure of responses to the individualized care inventory (ICI). Design and Methods: Samples of 242 registered nurses (RNs)/licensed…

  17. Long-Term Results of a Problem-Solving Approach to Response to Intervention: Discussion and Implications

    ERIC Educational Resources Information Center

    Carney, Karen J.; Stiefel, Gilbert S.

    2008-01-01

    Two general models exist for implementing Response to Intervention (RtI) for struggling students, the standard protocol model and the problem-solving model. This study examined the long-term outcomes of one example of the problem-solving method, the Instructional Support Team (IST), in a field setting. Academic records of 32 students were reviewed…

  18. Comment and response document for the long-term surveillance plan for the Collins Ranch Disposal Site, Lakeview, Oregon

    SciTech Connect

    Not Available

    1994-08-01

    This document contains comments made by the U.S. Nuclear Regulatory Commission addressing their concerns over the long-term monitoring program for the Collins Ranch Disposal Site, UMTRA project. Responses are included as well as plans for implementation of changes, if any are deemed necessary.

  19. Temporary treatment during primary HIV infection does not affect virologic response to subsequent long-term treatment.

    PubMed

    Grijsen, Marlous L; Wit, Ferdinand W N M; Jurriaans, Suzanne; Kroon, Frank P; Schippers, Emile F; Koopmans, Peter; Gras, Luuk; Lange, Joep M A; Prins, Jan M

    2014-01-01

    Temporary cART during primary HIV-infection (PHI) did not select for drug resistance mutations after treatment interruption and did not affect the subsequent virological response to long-term cART. Our data demonstrate that fear of drug resistance development is not a valid argument to refrain from temporary early treatment during PHI.

  20. Comment and response document for the final long-term surveillance plan for the Green River, Utah, disposal site

    SciTech Connect

    Not Available

    1994-08-01

    This document contains comments made by the U.S. Nuclear Regulatory Commission addressing their concerns over the long-term monitoring program for the Green River Disposal Site, UMTRA project. Responses are included as well as plans for implementation of changes, if any are deemed necessary.

  1. Environmental response to sewage treatment strategies: Hong Kong's experience in long term water quality monitoring.

    PubMed

    Xu, Jie; Lee, Joseph H W; Yin, Kedong; Liu, Hongbin; Harrison, Paul J

    2011-11-01

    In many coastal cities around the world, marine outfalls are used for disposal of partially treated wastewater effluent. The combined use of land-based treatment and marine discharge can be a cost-effective and environmentally acceptable sewage strategy. Before 2001, screened sewage was discharged into Victoria Harbour through many small outfalls. After 2001, the Hong Kong Harbour Area Treatment Scheme (HATS) was implemented to improve the water quality in Victoria Harbour and surrounding waters. Stage I of HATS involved the construction of a 24 km long deep tunnel sewerage system to collect sewage from the densely populated urban areas of Hong Kong to a centralized sewage treatment plant at Stonecutters Island. A sewage flow of 1.4 million m3 d(-1) receives Chemically Enhanced Primary Treatment (CEPT) followed by discharge via a 1.2 km long outfall 2 km west of the harbor. The ecosystem recovery in Victoria Harbour and the environmental response to sewage abatement after the implementation of HATS was studied using a 21-year data set from long term monthly water quality monitoring. Overall, the pollution control scheme has achieved the intended objectives. The sewage abatement has resulted in improved water quality in terms of a significant reduction in nutrients and an increase in bottom DO levels. Furthermore, due to the efficient tidal mixing and flushing, the impact of the HATS discharge on water quality in the vicinity of the outfall location is relatively limited. However, Chl a concentrations have not been reduced in Victoria Harbour where algal growth is limited by hydrodynamic mixing and water clarity rather than nutrient concentrations. Phosphorus removal in the summer is suggested to reduce the risk of algal blooms in the more weakly-flushed and stratified southern waters, while nutrient removal is less important in other seasons due to the pronounced role played by hydrodynamic mixing. The need for disinfection of the effluent to reduce bacterial (E

  2. Long-term care and health information technology: opportunities and responsibilities for long-term and post-acute care providers.

    PubMed

    MacTaggart, Patricia; Thorpe, Jane Hyatt

    2013-01-01

    Long-term and post-acute care providers (LTPAC) need to understand the multiple aspects of health information technology (HIT) in the context of health systems transformation in order to be a viable participant. The issues with moving to HIT are not just technical and funding, but include legal and policy, technical and business operations, and very significantly, governance. There are many unanswered questions. However, changes in payment methodologies, service delivery models, consumer expectations, and regulatory requirements necessitate that LTPAC providers begin their journey. PMID:24159273

  3. Plant phenological responses to extreme events - A long term perspective from the Chihuahuan Desert

    NASA Astrophysics Data System (ADS)

    Browning, D. M.; Peters, D. P.; Anderson, J.; Yao, J.

    2011-12-01

    Arid and semi-arid regions of the southwestern USA are especially sensitive to changes in temperature as well as drought frequency and intensity. Timing of periodic life cycle events (i.e., phenology) is an integrated and salient indicator of plant responses to climate change. We examine an 18-year dataset of monthly observations of plant phenology for two species of perennial grasses and a deciduous shrub (honey mesquite) distributed across three upland grassland sites and three mesquite-dominated sites on the Jornada Basin USDA-LTER in southern New Mexico, USA. Precipitation is highly variable between years and across space. Long-term phenology data collection spanned a multi-year drought (1994-2003) followed by a sequence of years with average to very high rainfall (2004 - 2008). Our objective was to compare and contrast responses to extreme dry and wet cycles in the timing and duration of first leaf and fruit production for two grasses (Bouteloua eriopoda [black grama], Sporobolus flexuosus [mesa dropseed]) with one co-existing shrub that has displaced grasses in this system (Prosopis glandulosa [honey mesquite]). Monthly field observations yield estimates of phenological status and abundance for 18 growing seasons from 1993 to 2010. All three species most commonly initiated new growth prior to onset of the monsoon rains (March or April). Timing of first growth for mesquite was less variable (standard deviation = 0.47) than for black grama (SD = 1.42) and mesa dropseed (SD = 1.22) grasses. Initial growth for grasses was delayed to September in 2006 following twelve months of deficit values for PDSI. The appearance of first fruit for grasses occurred consistently in August or September, although the number of plants producing fruit was highly variable from year to year. The largest numbers of fruit-bearing grasses were observed in late fall 2008 in response to heavy monsoon rains in 2006 and 2008. Mesquite demonstrated remarkable synchrony in the production of

  4. Are long-term trends in lake carbon dioxide flux responsive to climaticvariability and change?

    NASA Astrophysics Data System (ADS)

    Golub, M.; Desai, A. R.

    2012-12-01

    Inland water bodies are major but understudied conduits of carbon in within the global land-ocean-atmosphere carbon cycle. While many researchers have shown significant 20th century trends in physical and biological lake processes driven by climatic change, there is less research on how these influence lake-atmosphere carbon dioxide flux. We investigated the effects of climatic drivers on physical features and CO2 flux in lakes. We estimated the long-term trends in ice phenology, thermal structure, and amount of carbon exchanged, using 15-25-year time series of measurements of temperature, alkalinity, pH for eleven lakes monitored by the North Temperate Lakes Long-Term Ecological Research (NTL-LTER) program. Lakes coherently responded to regional climatic warming, showing declining ice cover duration, prolonged growing season, and increasingly warmer waters. Long-term trends of CO2 trends varied among lakes, however, with the majority of lakes showing a weakening source of CO2 to atmosphere. We further compared the sensitivity of CO2 flux to climate forcing in lakes as a function of trophic states, dissolved organic carbon concentrations, and morphometric features. These results provide new insights into our understanding about the role of lakes in regional and global carbon balances, on the sensitivity of CO2 flux to climatic variability, and in improving prediction of future carbon-climate change feedbacks.

  5. Short- and long-term behavioural, physiological and stoichiometric responses to predation risk indicate chronic stress and compensatory mechanisms.

    PubMed

    Van Dievel, Marie; Janssens, Lizanne; Stoks, Robby

    2016-06-01

    Prey organisms are expected to use different short- and long-term responses to predation risk to avoid excessive costs. Contrasting both types of responses is important to identify chronic stress responses and possible compensatory mechanisms in order to better understand the full impact of predators on prey life history and population dynamics. Using larvae of the damselfly Enallagma cyathigerum, we contrasted the effects of short- and long-term predation risk, with special focus on consequences for body stoichiometry. Under short-term predation risk, larvae reduced growth rate, which was associated with a reduced food intake, increased metabolic rate and reduced glucose content. Under long-term predation risk, larvae showed chronic predator stress as indicated by persistent increases in metabolic rate and reduced food intake. Despite this, larvae were able to compensate for the short-term growth reduction under long-term predation risk by relying on physiological compensatory mechanisms, including reduced energy storage. Only under long-term predation risk did we observe an increase in body C:N ratio, as predicted under the general stress paradigm (GSP). Although this was caused by a predator-induced decrease in N content, there was no associated increase in C content. These stoichiometric changes could not be explained by GSP responses because, under chronic predation risk, there was no decrease in N-rich proteins or increase in C-rich fat and sugars; instead glycogen decreased. Our results highlight the importance of compensatory mechanisms and the value of explicitly integrating physiological mechanisms to obtain insights into the temporal dynamics of non-consumptive effects, including effects on body stoichiometry.

  6. Functional-morphological parallels of the hypothalamo-pituitary-adrenal system response reaction to long-term hypokinesia

    NASA Technical Reports Server (NTRS)

    Tsvetov, Y. P.; Razin, S. I.; Rychko, A. V.

    1980-01-01

    The effect of 2 and 4 week hypokinesia regimens on the hypothalamo-pituitary-adrenal system (HPAS) was investigated in 110 inbred mice. Progressive exhaustion and pathological reorganization of the HPAS morphofunctional structures was revealed. On the basis of established facts of interlineary and interspecies differences in the HPAS response, it is suggested that the animal body response reaction to the long term effects of hypokinesia depends largely on its HPAS resistance and the values of this system's defensive adaptation potential.

  7. Long-term macroinvertebrate response to flow abstraction at Alpine water intakes

    NASA Astrophysics Data System (ADS)

    Gabbud, Chrystelle; Savioz, Amélie; Lane, Stuart

    2016-04-01

    The natural flow hydrological characteristics of Alpine streams, dominated by snowmelt and glacier melt, have been established for many years. More recently, the ecosystems that they sustain have been described and explained, following the hydrological, biochemical, morphodynamic, and biotic elements specific to Alpine streams. However, natural Alpine flow regimes may be strongly modified by hydroelectric power production, which impacts upon both river discharge and sediment transfer, and hence on downstream flora and fauna. These kinds of impacts are well studied where river are regulated by dams, with sediments retained behind walls, but they are much less focus on water intakes, whose storage capacity is very smaller and thus have to flush flow and sediment regularly. Here we focus on the impacts of flow abstraction on macroinvertebrates, the most widely ecological group used in freshwater biomonitoring as they act typically as indicators of environmental health. Some key generalizations can be made. For instance, in European glacially fed river systems, Plecoptera, Chironomidae, Ephemeroptera, Simuliidae, and Diptera are the main taxa found in spring as they are better adapted to cold conditions. Petts and Bickerton (1994) published macroinvertebrate samples from the upper part of the glacial stream system the Borgne d'Arolla (Valais, Switzerland), highlighting that: (1) taxa variability and productivity decline in the river because of flow abstraction, (2) 60 % of the communities were provided by tributaries, (3) there is migration upstream of the species in response to the passage from a dominant ice-melt to a snow-melt regime, (4) the colonisation is difficult because of a significant modification of the habitat in the river by sediment transport, until it becomes warmer, clearer and more stable further downstream. In order to establish the long-term impacts of flow abstraction upon instream ecology where sediment delivery is maintained but transport

  8. Short- and long-term responses to molybdenum-99 shortages in nuclear medicine.

    PubMed

    Ballinger, J R

    2010-11-01

    Most nuclear medicine studies use (99)Tc(m), which is the decay product of (99)Mo. The world supply of (99)Mo comes from only five nuclear research reactors and availability has been much reduced in recent times owing to problems at the largest reactors. In the short-term there are limited actions that can be taken owing to capacity issues on alternative imaging modalities. In the long-term, stability of (99)Mo supply will rely on a combination of replacing conventional reactors and developing new technologies.

  9. Short- and long-term responses to molybdenum-99 shortages in nuclear medicine

    PubMed Central

    Ballinger, J R

    2010-01-01

    Most nuclear medicine studies use 99Tcm, which is the decay product of 99Mo. The world supply of 99Mo comes from only five nuclear research reactors and availability has been much reduced in recent times owing to problems at the largest reactors. In the short-term there are limited actions that can be taken owing to capacity issues on alternative imaging modalities. In the long-term, stability of 99Mo supply will rely on a combination of replacing conventional reactors and developing new technologies. PMID:20965898

  10. Behavioural and physiological responses of shelter dogs to long-term confinement.

    PubMed

    Dalla Villa, Paolo; Barnard, Shanis; Di Fede, Elisa; Podaliri, Michele; Candeloro, Luca; Di Nardo, Antonio; Siracusa, Carlo; Serpell, James A

    2013-01-01

    In Italy, National Law (281/1991) prohibits euthanasia of shelter dogs if they are not dangerous or suffering seriously. Adoption rates in rescue shelters are often lower than entrance rates, leading inevitably to overcrowded facilities where animals are likely to spend the rest of their lives in kennels. In this situation, housing conditions (i.e. space provided, environmental, and social stimulation) may have an impact on canine welfare. In this research project, the effects of two different forms of housing (group- and pair housing) on long-term shelter dogs were compared using behavioural and physiological parameters. Observational data and saliva samples were collected from dogs exposed to both experimental settings; behaviour and cortisol concentration levels were used as welfare indicators. Pair housing offered fewer social and environmental stimuli and behavioural analysis showed a significant decrease in locomotor, exploratory, and social behaviour. Cortisol levels show that this parameter varied independently of housing conditions. Although this study found no evidence suggesting that one form of confinement reduced animal welfare more than the other (e.g. in terms of abnormal behaviour, or higher cortisol concentrations), the type of confinement did affect the expression of a variety of behaviours and these variations should not be ignored with respect to housing decisions for long-term shelter dogs. PMID:23888421

  11. Long-term response of oceans to CO2 removal from the atmosphere

    NASA Astrophysics Data System (ADS)

    Mathesius, Sabine; Hofmann, Matthias; Caldeira, Ken; Schellnhuber, Hans Joachim

    2015-12-01

    Carbon dioxide removal (CDR) from the atmosphere has been proposed as a measure for mitigating global warming and ocean acidification. To assess the extent to which CDR might eliminate the long-term consequences of anthropogenic CO2 emissions in the marine environment, we simulate the effect of two massive CDR interventions with CO2 extraction rates of 5 GtC yr-1 and 25 GtC yr-1, respectively, while CO2 emissions follow the extended RCP8.5 pathway. We falsify two hypotheses: the first being that CDR can restore pre-industrial conditions in the ocean by reducing the atmospheric CO2 concentration back to its pre-industrial level, and the second being that high CO2 emissions rates (RCP8.5) followed by CDR have long-term oceanic consequences that are similar to those of low emissions rates (RCP2.6). Focusing on pH, temperature and dissolved oxygen, we find that even after several centuries of CDR deployment, past CO2 emissions would leave a substantial legacy in the marine environment.

  12. Ectopic AP4 expression induces cellular senescence via activation of p53 in long-term confluent retinal pigment epithelial cells.

    PubMed

    Wang, Yiping; Wong, Matthew Man-Kin; Zhang, Xiaojian; Chiu, Sung-Kay

    2015-11-15

    When cells are grown to confluence, cell-cell contact inhibition occurs and drives the cells to enter reversible quiescence rather than senescence. Confluent retinal pigment epithelial (RPE) cells exhibiting contact inhibition was used as a model in this study to examine the role of overexpression of transcription factor AP4, a highly expressed transcription factor in many types of cancer, in these cells during long-term culture. We generated stable inducible RPE cell clones expressing AP4 or AP4 without the DNA binding domain (DN-AP4) and observed that, when cultured for 24 days, RPE cells with a high level of AP4 exhibit a large, flattened morphology and even cease proliferating; these changes were not observed in DN-AP4-expressing cells or non-induced cells. In addition, AP4-expressing cells exhibited senescence-associated β-galactosidase activity and the senescence-associated secretory phenotype. We demonstrated that the induced cellular senescence was mediated by enhanced p53 expression and that AP4 regulates the p53 gene by binding directly to two of the three E-boxes present on the promoter of the p53 gene. Moreover, we showed that serum is essential for AP4 in inducing p53-associated cellular senescence. Collectively, we showed that overexpression of AP4 mediates cellular senescence involving in activation of p53 in long-term post-confluent RPE cells.

  13. Long-term morphological response to dredging including cut-across-shoal in a tidal channel-shoal system

    NASA Astrophysics Data System (ADS)

    Wang, Yu-Hai; Wang, Chong-Hao; Tang, Li-Qun; Liu, Da-Bin; Guo, Chuan-Sheng; Liu, Chun-Jing; Zhao, Hui-Ming

    2014-12-01

    This study examines long-term channel-shoal stability in the Tieshan Bay, which is located on the southwest coast of China. A large-scale channel-shoal system has historically existed in the outer Tieshan Bay. A navigation waterway is initiated by cutting and dredging a mid-channel shoal to supply coal to a power plant on the middle coast of the Tieshan Bay. Dredging of the access channel to the Tieshan Port was conducted in two stages followed by land reclamation. It is thus of practical meaning to explore how the channel-shoal system will evolve in long term afterwards. This study uses the process-based finite-volume coastal ocean model (FVCOM) to investigate long-term (centennial) morphological evolution of the channel-shoal system. After well calibration of hydrodynamics and sediment transport, the model forecasts morphodynamic evolution in hundred years. The simulations show that continuous erosion in tidal channels and accretion over shoals and intertidal flats occur. However, the cutting and access channels will be subjected to long-term siltation. A secondary channel indicating the reorientation of the access channel will emerge, and a localized channel-ridge system at the junction of the major channels will be formed. The overall erosion/accretion pattern demonstrates the combined effect of bottom friction and advective sediment transport processes to be responsible for the channel-shoal formation. Dredging of the tidal channels will stimulate the stability of the channel-shoal pattern. It suggests that the navigation waterway should be set up following the long-term morphological evolution of the channel-shoal system at a design stage and maintenance dredging volume might thus be minimized.

  14. Long-term attenuated electrophysiological response to errors following multiple sports concussions.

    PubMed

    De Beaumont, Louis; Beauchemin, Maude; Beaulieu, Christelle; Jolicoeur, Pierre

    2013-01-01

    This study extracted the error-related negativity (ERN) waveform component recorded from a visual-spatial attention and a visual short-term memory task to assess rigorously the long-term and cumulative effects of concussions on evaluative processes of cognitive control related to performance monitoring. This study demonstrates that, relative to control athletes, multiply concussed athletes show significant ERN amplitude reduction elicited by error generation. These cumulative effects of concussions on ERN amplitude were found in two distinct experimental paradigms designed to solicit concussion-sensitive cognitive abilities such as attention and short-term memory. This suggests that the mechanisms that contribute to the evaluation of cognitive performance may be significantly affected following multiple concussions even in low-conflict situations.

  15. Ecosystem responses to long-term nutrient management in an urban estuary: Tampa Bay, Florida, USA

    NASA Astrophysics Data System (ADS)

    Greening, H.; Janicki, A.; Sherwood, E. T.; Pribble, R.; Johansson, J. O. R.

    2014-12-01

    In subtropical Tampa Bay, Florida, USA, we evaluated restoration trajectories before and after nutrient management strategies were implemented using long-term trends in nutrient loading, water quality, primary production, and seagrass extent. Following citizen demands for action, reduction in wastewater nutrient loading of approximately 90% in the late 1970s lowered external total nitrogen (TN) loading by more than 50% within three years. Continuing nutrient management actions from public and private sectors were associated with a steadily declining TN load rate and with concomitant reduction in chlorophyll-a concentrations and ambient nutrient concentrations since the mid-1980s, despite an increase of more than 1 M people living within the Tampa Bay metropolitan area. Water quality (chlorophyll-a concentration, water clarity as indicated by Secchi disk depth, total nitrogen concentration and dissolved oxygen) and seagrass coverage are approaching conditions observed in the 1950s, before the large increases in human population in the watershed. Following recovery from an extreme weather event in 1997-1998, water clarity increased significantly and seagrass is expanding at a rate significantly different than before the event, suggesting a feedback mechanism as observed in other systems. Key elements supporting the nutrient management strategy and concomitant ecosystem recovery in Tampa Bay include: 1) active community involvement, including agreement about quantifiable restoration goals; 2) regulatory and voluntary reduction in nutrient loadings from point, atmospheric, and nonpoint sources; 3) long-term water quality and seagrass extent monitoring; and 4) a commitment from public and private sectors to work together to attain restoration goals. A shift from a turbid, phytoplankton-based system to a clear water, seagrass-based system that began in the 1980s following comprehensive nutrient loading reductions has resulted in a present-day Tampa Bay which looks and

  16. Memantine alters striatal plasticity inducing a shift of synaptic responses toward long-term depression.

    PubMed

    Mancini, Maria; Ghiglieri, Veronica; Bagetta, Vincenza; Pendolino, Valentina; Vannelli, Anna; Cacace, Fabrizio; Mineo, Desireé; Calabresi, Paolo; Picconi, Barbara

    2016-02-01

    Memantine is an open channel blocker that antagonizes NMDA receptors reducing the inappropriate calcium (Ca(2+)) influx occurring in presence of moderately increased glutamate levels. At the same time, memantine has the ability to preserve the transient physiological activation of NMDA receptor, essential for learning and memory formation at synaptic level. In the present study we investigated the effects exerted by memantine on striatal synaptic plasticity in rat striatal spiny projection neurons (SPNs). In vitro application of memantine in striatal slices elicited a disruption of long-term potentiation (LTP) induction and maintenance, and revealed, in the majority of the recorded neurons, a long-term depression (LTD), whose amplitude was concentration-dependent (0.3-10 μM). Interestingly, preincubation with the dopamine (DA) D2 receptor antagonist sulpiride (10 μM) prevented memantine-induced LTD and restored LTP. Moreover, the DA D2 agonist quinpirole (10 μM), similarly to memantine, induced LTD in a subgroup of SPNs. In addition, memantine-induced LTD was also prevented by the CB1 endocannabinoid receptor antagonist AM 251 (1 μM). These results suggest that the actions exerted by memantine on striatal synaptic plasticity, and in particular the induction of LTD observed in SPNs, could be attributed to its ability to activate DA D2 receptors. By contrast, blockade of NMDA receptor is not involved in memantine-induced LTD since APV (30 μM) and MK801 (10 μM), two NMDA receptor antagonists, failed to induce this form of synaptic plasticity. Our data indicate that memantine could be used as treatment of neurological disorders in which DA D2 receptor represents a possible therapeutic target.

  17. Global environmental change and the nature of aboveground net primary productivity responses: insights from long-term experiments.

    PubMed

    Smith, Melinda D; La Pierre, Kimberly J; Collins, Scott L; Knapp, Alan K; Gross, Katherine L; Barrett, John E; Frey, Serita D; Gough, Laura; Miller, Robert J; Morris, James T; Rustad, Lindsey E; Yarie, John

    2015-04-01

    Many global change drivers chronically alter resource availability in terrestrial ecosystems. Such resource alterations are known to affect aboveground net primary production (ANPP) in the short term; however, it is unknown if patterns of response change through time. We examined the magnitude, direction, and pattern of ANPP responses to a wide range of global change drivers by compiling 73 datasets from long-term (>5 years) experiments that varied by ecosystem type, length of manipulation, and the type of manipulation. Chronic resource alterations resulted in a significant change in ANPP irrespective of ecosystem type, the length of the experiment, and the resource manipulated. However, the pattern of ecosystem response over time varied with ecosystem type and manipulation length. Continuous directional responses were the most common pattern observed in herbaceous-dominated ecosystems. Continuous directional responses also were frequently observed in longer-term experiments (>11 years) and were, in some cases, accompanied by large shifts in community composition. In contrast, stepped responses were common in forests and other ecosystems (salt marshes and dry valleys) and with nutrient manipulations. Our results suggest that the response of ANPP to chronic resource manipulations can be quite variable; however, responses persist once they occur, as few transient responses were observed. Shifts in plant community composition over time could be important determinants of patterns of terrestrial ecosystem sensitivity, but comparative, long-term studies are required to understand how and why ecosystems differ in their sensitivity to chronic resource alterations.

  18. Long-term heat stress induces the inflammatory response in dairy cows revealed by plasma proteome analysis.

    PubMed

    Min, Li; Zheng, Nan; Zhao, Shengguo; Cheng, Jianbo; Yang, Yongxin; Zhang, Yangdong; Yang, Hongjian; Wang, Jiaqi

    2016-03-01

    In this work we employed a comparative proteomic approach to evaluate seasonal heat stress and investigate proteomic alterations in plasma of dairy cows. Twelve lactating Holstein dairy cows were used and the treatments were: heat stress (n = 6) in hot summer (at the beginning of the moderate heat stress) and no heat stress (n = 6) in spring natural ambient environment, respectively. Subsequently, heat stress treatment lasted 23 days (at the end of the moderate heat stress) to investigate the alterations of plasma proteins, which might be employed as long-term moderate heat stress response in dairy cows. Changes in plasma proteins were analyzed by two-dimensional electrophoresis (2-DE) combined with mass spectrometry. Analysis of the properties of the identified proteins revealed that the alterations of plasma proteins were related to inflammation in long-term moderate heat stress. Furthermore, the increase in plasma tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) directly demonstrated that long-term moderate heat stress caused an inflammatory response in dairy cows. PMID:26851364

  19. Presynaptic long-term plasticity

    PubMed Central

    Yang, Ying; Calakos, Nicole

    2013-01-01

    Long-term synaptic plasticity is a major cellular substrate for learning, memory, and behavioral adaptation. Although early examples of long-term synaptic plasticity described a mechanism by which postsynaptic signal transduction was potentiated, it is now apparent that there is a vast array of mechanisms for long-term synaptic plasticity that involve modifications to either or both the presynaptic terminal and postsynaptic site. In this article, we discuss current and evolving approaches to identify presynaptic mechanisms as well as discuss their limitations. We next provide examples of the diverse circuits in which presynaptic forms of long-term synaptic plasticity have been described and discuss the potential contribution this form of plasticity might add to circuit function. Finally, we examine the present evidence for the molecular pathways and cellular events underlying presynaptic long-term synaptic plasticity. PMID:24146648

  20. Assessing Forest Carbon Response to Climate Change and Disturbances Using Long-term Hydro-climatic Observations and Simulations

    NASA Astrophysics Data System (ADS)

    Trettin, C.; Dai, Z.; Amatya, D. M.

    2014-12-01

    Long-term climatic and hydrologic observations on the Santee Experimental Forest in the lower coastal plain of South Carolina were used to estimate long-term changes in hydrology and forest carbon dynamics for a pair of first-order watersheds. Over 70 years of climate data indicated that warming in this forest area in the last decades was faster than the global mean; 35+ years of hydrologic records showed that forest ecosystem succession three years following Hurricane Hugo caused a substantial change in the ratio of runoff to precipitation. The change in this relationship between the paired watersheds was attributed to altered evapotranspiration processes caused by greater abundance of pine in the treatment watershed and regeneration of the mixed hardwood-pine forest on the reference watershed. The long-term records and anomalous observations are highly valuable for reliable calibration and validation of hydrological and biogeochemical models capturing the effects of climate variability. We applied the hydrological model MIKESHE that showed that runoff and water table level are sensitive to global warming, and that the sustained warming trends can be expected to decrease stream discharge and lower the mean water table depth. The spatially-explicit biogeochemical model Forest-DNDC, validated using biomass measurements from the watersheds, was used to assess carbon dynamics in response to high resolution hydrologic observation data and simulation results. The simulations showed that the long-term spatiotemporal carbon dynamics, including biomass and fluxes of soil carbon dioxide and methane were highly regulated by disturbance regimes, climatic conditions and water table depth. The utility of linked-modeling framework demonstrated here to assess biogeochemical responses at the watershed scale suggests applications for assessing the consequences of climate change within an urbanizing forested landscape. The approach may also be applicable for validating large

  1. Response feedback triggers long-term consolidation of perceptual learning independently of performance gains

    PubMed Central

    Dobres, Jonathan; Watanabe, Takeo

    2012-01-01

    Visual perceptual learning (VPL) is defined as a long-term performance enhancement on a visual task, and is typically thought of as a manifestation of plasticity in visual processing. It is thought that neural representations relevant to a recently learned task are consolidated over the course of hours or days and made robust against the effects of deterioration and interference. However, recent work has shown that when these representations are reactivated by further task exposure, they become plastic again and are vulnerable to deterioration effects. Here we used a perceptual learning paradigm in combination with performance feedback (knowledge of task accuracy provided to the observer in real-time) to investigate behavioral factors that influence consolidation. Subjects were trained to detect two coherent motion directions embedded in noise over several days. It was found that without feedback, performance improvements accrued during training rapidly deteriorated upon exposure to novel, neighboring motion directions. However, when one of the two directions was consistently paired with feedback during training, the paired direction was resilient against the effects of deterioration. This benefit coincides with a gradual inhibition of learning for the unpaired stimuli. Furthermore, this stabilizing effect operates independently of the magnitude of performance gains during training and suggests a useful behavioral marker for the study of consolidation processes. PMID:22904354

  2. Change of exposure response over time and long-term risk of silicosis among a cohort of Chinese pottery workers.

    PubMed

    Sun, Yi; Bochmann, Frank; Morfeld, Peter; Ulm, Kurt; Liu, Yuewei; Wang, Heijiao; Yang, Lei; Chen, Weihong

    2011-07-01

    An analysis was conducted on a cohort of Chinese pottery workers to estimate the exposure-response relationship between respirable crystalline silica dust exposure and the incidence of radiographically diagnosed silicosis, and to estimate the long-term risk of developing silicosis until the age of 65. The cohort comprised 3,250 employees with a median follow-up duration of around 37 years. Incident cases of silicosis were identified via silicosis registries (Chinese X-ray stage I, similar to International Labor Organisation classification scheme profusion category 1/1). Individual exposure to respirable crystalline silica dust was estimated based on over 100,000 historical dust measurements. The association between dust exposure, incidence and long-time risk of silicosis was quantified by Poisson regression analysis adjusted for age and smoking. The risk of silicosis depended not only on the cumulative respirable crystalline silica dust exposures, but also on the time-dependent respirable crystalline silica dust exposure pattern (long-term average concentration, highest annual concentration ever experienced and time since first exposure). A long-term "excess" risk of silicosis of approximately 1.5/1,000 was estimated among workers with all annual respirable crystalline silica dust concentration estimates less than 0.1 mg/m(3), using the German measurement strategy. This study indicates the importance of proper consideration of exposure information in risk quantification in epidemiological studies.

  3. Opportunistic Visitors: Long-Term Behavioural Response of Bull Sharks to Food Provisioning in Fiji

    PubMed Central

    Brunnschweiler, Juerg M.; Barnett, Adam

    2013-01-01

    Shark-based tourism that uses bait to reliably attract certain species to specific sites so that divers can view them is a growing industry globally, but remains a controversial issue. We evaluate multi-year (2004–2011) underwater visual (n = 48 individuals) and acoustic tracking data (n = 82 transmitters; array of up to 16 receivers) of bull sharks Carcharhinus leucas from a long-term shark feeding site at the Shark Reef Marine Reserve and reefs along the Beqa Channel on the southern coast of Viti Levu, Fiji. Individual C. leucas showed varying degrees of site fidelity. Determined from acoustic tagging, the majority of C. leucas had site fidelity indexes >0.5 for the marine reserve (including the feeding site) and neighbouring reefs. However, during the time of the day (09:00–12:00) when feeding takes place, sharks mainly had site fidelity indexes <0.5 for the feeding site, regardless of feeding or non-feeding days. Site fidelity indexes determined by direct diver observation of sharks at the feeding site were lower compared to such values determined by acoustic tagging. The overall pattern for C. leucas is that, if present in the area, they are attracted to the feeding site regardless of whether feeding or non-feeding days, but they remain for longer periods of time (consecutive hours) on feeding days. The overall diel patterns in movement are for C. leucas to use the area around the feeding site in the morning before spreading out over Shark Reef throughout the day and dispersing over the entire array at night. Both focal observation and acoustic monitoring show that C. leucas intermittently leave the area for a few consecutive days throughout the year, and for longer time periods (weeks to months) at the end of the calendar year before returning to the feeding site. PMID:23516496

  4. Opportunistic visitors: long-term behavioural response of bull sharks to food provisioning in Fiji.

    PubMed

    Brunnschweiler, Juerg M; Barnett, Adam

    2013-01-01

    Shark-based tourism that uses bait to reliably attract certain species to specific sites so that divers can view them is a growing industry globally, but remains a controversial issue. We evaluate multi-year (2004-2011) underwater visual (n = 48 individuals) and acoustic tracking data (n = 82 transmitters; array of up to 16 receivers) of bull sharks Carcharhinus leucas from a long-term shark feeding site at the Shark Reef Marine Reserve and reefs along the Beqa Channel on the southern coast of Viti Levu, Fiji. Individual C. leucas showed varying degrees of site fidelity. Determined from acoustic tagging, the majority of C. leucas had site fidelity indexes >0.5 for the marine reserve (including the feeding site) and neighbouring reefs. However, during the time of the day (09:00-12:00) when feeding takes place, sharks mainly had site fidelity indexes <0.5 for the feeding site, regardless of feeding or non-feeding days. Site fidelity indexes determined by direct diver observation of sharks at the feeding site were lower compared to such values determined by acoustic tagging. The overall pattern for C. leucas is that, if present in the area, they are attracted to the feeding site regardless of whether feeding or non-feeding days, but they remain for longer periods of time (consecutive hours) on feeding days. The overall diel patterns in movement are for C. leucas to use the area around the feeding site in the morning before spreading out over Shark Reef throughout the day and dispersing over the entire array at night. Both focal observation and acoustic monitoring show that C. leucas intermittently leave the area for a few consecutive days throughout the year, and for longer time periods (weeks to months) at the end of the calendar year before returning to the feeding site. PMID:23516496

  5. Foliage responses of spruce trees to long-term low-grade sulfur dioxide deposition.

    PubMed

    Meng, F R; Bourque, C P; Belczewski, R F; Whitney, N J; Arp, P A

    1995-01-01

    Foliage on spruce trees (Picea rubens Sarg.) growing on dry SO(2) deposition zones (dry SO(2) deposition ranging from 0.5 and 8.5 S kg ha(-1) year(-1)) downwind from a SO(2) emission source was analyzed to assess chronic effects of long-term low-grade SO(2) deposition on net photosynthesis, stomatal conductance, dark respiration, stomatal antechamber wax structures, elemental concentrations in and on foliage (bulk and surficial concentrations), and types of epiphytic fungi that reside in the phylloplane. Elemental distributions on stomatal antechambers, on fungal colonies, and on smooth surfaces between stomates and fungus colonies were determined with a scanning electronic microscope (SEM) by way of X-ray scanning. It was found that net photosynthesis of newly developed spruce foliage (current-year, and 1-year-old) was not significantly affected by the local SO(2) deposition rates. Sulfur dioxide deposition, however, may have contributed to the gradual decrease in net photosynthesis with increasing needle age. Dark respiration rates were significantly higher on foliage taken from high SO(2) deposition zones. Stomatal rod-web structures deteriorated to flakes with increasing needle age and increasing SO(2) deposition. Further inspection of the needle surfaces revealed an increasing abundance of fungal colonies with increasing needle age. Many fungal taxa were isolated and identified. It was found that black yeasts responded positively, and Xylohypha pinicola responded negatively to high rates of SO(2) deposition. Surficial concentrations of elements such as P, S, K, Cl, Ca were about 10 times higher on fungal colonies than on smooth needle surfaces. Surficial Ca contents on 4 or 5-year-old needles decreased with increasing SO(2) deposition, but surficial S concentrations remained the same. In contrast, bulk foliar Ca and S concentrations increased with increasing SO(2) deposition.

  6. Foliage responses of spruce trees to long-term low-grade sulfur dioxide deposition.

    PubMed

    Meng, F R; Bourque, C P; Belczewski, R F; Whitney, N J; Arp, P A

    1995-01-01

    Foliage on spruce trees (Picea rubens Sarg.) growing on dry SO(2) deposition zones (dry SO(2) deposition ranging from 0.5 and 8.5 S kg ha(-1) year(-1)) downwind from a SO(2) emission source was analyzed to assess chronic effects of long-term low-grade SO(2) deposition on net photosynthesis, stomatal conductance, dark respiration, stomatal antechamber wax structures, elemental concentrations in and on foliage (bulk and surficial concentrations), and types of epiphytic fungi that reside in the phylloplane. Elemental distributions on stomatal antechambers, on fungal colonies, and on smooth surfaces between stomates and fungus colonies were determined with a scanning electronic microscope (SEM) by way of X-ray scanning. It was found that net photosynthesis of newly developed spruce foliage (current-year, and 1-year-old) was not significantly affected by the local SO(2) deposition rates. Sulfur dioxide deposition, however, may have contributed to the gradual decrease in net photosynthesis with increasing needle age. Dark respiration rates were significantly higher on foliage taken from high SO(2) deposition zones. Stomatal rod-web structures deteriorated to flakes with increasing needle age and increasing SO(2) deposition. Further inspection of the needle surfaces revealed an increasing abundance of fungal colonies with increasing needle age. Many fungal taxa were isolated and identified. It was found that black yeasts responded positively, and Xylohypha pinicola responded negatively to high rates of SO(2) deposition. Surficial concentrations of elements such as P, S, K, Cl, Ca were about 10 times higher on fungal colonies than on smooth needle surfaces. Surficial Ca contents on 4 or 5-year-old needles decreased with increasing SO(2) deposition, but surficial S concentrations remained the same. In contrast, bulk foliar Ca and S concentrations increased with increasing SO(2) deposition. PMID:15091479

  7. Long-term niacin treatment induces insulin resistance and adrenergic responsiveness in adipocytes by adaptive downregulation of phosphodiesterase 3B.

    PubMed

    Heemskerk, Mattijs M; van den Berg, Sjoerd A A; Pronk, Amanda C M; van Klinken, Jan-Bert; Boon, Mariëtte R; Havekes, Louis M; Rensen, Patrick C N; van Dijk, Ko Willems; van Harmelen, Vanessa

    2014-04-01

    The lipid-lowering effect of niacin has been attributed to the inhibition of cAMP production in adipocytes, thereby inhibiting intracellular lipolysis and release of nonesterified fatty acids (NEFA) to the circulation. However, long-term niacin treatment leads to a normalization of plasma NEFA levels and induces insulin resistance, for which the underlying mechanisms are poorly understood. The current study addressed the effects of long-term niacin treatment on insulin-mediated inhibition of adipocyte lipolysis and focused on the regulation of cAMP levels. APOE*3-Leiden.CETP transgenic mice treated with niacin for 15 wk were subjected to an insulin tolerance test and showed whole body insulin resistance. Similarly, adipocytes isolated from niacin-treated mice were insulin resistant and, interestingly, exhibited an increased response to cAMP stimulation by 8Br-cAMP, β1- and β2-adrenergic stimulation. Gene expression analysis of the insulin and β-adrenergic pathways in adipose tissue indicated that all genes were downregulated, including the gene encoding the cAMP-degrading enzyme phosphodiesterase 3B (PDE3B). In line with this, we showed that insulin induced a lower PDE3B response in adipocytes isolated from niacin-treated mice. Inhibiting PDE3B with cilostazol increased lipolytic responsiveness to cAMP stimulation in adipocytes. These data show that long-term niacin treatment leads to a downregulation of PDE3B in adipocytes, which could explain part of the observed insulin resistance and the increased responsiveness to cAMP stimulation.

  8. Long-term lesser prairie-chicken nest ecology in response to grassland management

    USGS Publications Warehouse

    Fritts, Sarah R.; Grisham, Blake A.; Haukos, David A.; Boal, Clint W.; Patten, Michael; Wolfe, Don H.; Dixon, Charles; Cox, Robert D.; Heck, Willard R.

    2016-01-01

    Long-term population and range declines from habitat loss and fragmentation caused the lesser prairie-chicken (Tympanuchus pallidicinctus) to be a species of concern throughout its range. Current lesser prairie-chicken range in New Mexico and Texas is partially restricted to sand shinnery oak (Quercus havardii; hereafter shinnery oak) prairies, on which cattle grazing is the main socioeconomic driver for private landowners. Cattle producers within shinnery oak prairies often focus land management on shrub eradication using the herbicide tebuthiuron to promote grass production for forage; however, herbicide application alone, and in combination with grazing, may affect nest site selection and nest survival of lesser prairie-chickens through the reduction of shinnery oak and native grasses. We used a controlled, paired, completely randomized design study to assess the influence of grazing and tebuthiuron application and their combined use on nest site selection and nest survival from 2001 to 2010 in Roosevelt County, New Mexico, USA at 2 spatial scales (i.e., treatment and microhabitat) in 4 treatments: tebuthiuron with grazing, tebuthiuron without grazing, no tebuthiuron with grazing, and a control of no tebuthiuron and no grazing. Grazing treatment was a short-duration system in which plots were grazed once during the dormant season and once during the growing season. Stocking rate was calculated each season based on measured forage production and applied to remove ≤25% of available herbaceous material per season. At the treatment scale, we compared nest site selection among treatments using 1-way χ2 tests and nest survival among treatments using a priori candidate nest survival models in Program MARK. At the microhabitat scale, we identified important habitat predictors of nest site selection and nest survival using logistic regression and a priori candidate nest survival models in Program MARK, respectively. Females typically used treatments as expected and

  9. Experimentally simulating paternity uncertainty: immediate and long-term responses of male and female reed warblers Acrocephalus scirpaceus.

    PubMed

    Hoi, Herbert; Krištofík, Ján; Darolová, Alžbeta

    2013-01-01

    In many socially monogamous species, both sexes seek copulation outside the pair bond in order to increase their reproductive success. In response, males adopt counter-strategies to combat the risk of losing paternity. However, no study so far has tried to experimentally prove the function of behaviour for paternity assurance. Introducing a potential extra-pair partner during the female fertile period provides a standardised method to examine how pair members respond immediately (e.g. increase mate guarding or copulation frequency) or long term (e.g. later parental investment and paternity uncertainty). In this study on a socially monogamous passerine species, we experimentally confronted pairs of reed warblers with a conspecific male (caged male simulating an intruder) during egg-laying. Our results revealed that occurrence of an intruder during that period triggered aggression against the intruder, depending on the presence of the female. The male territory owner also attacked the female partner to drive her away from the intruder. Thus territory defence in reed warblers also serves to protect paternity. The increase in paternity uncertainty did not affect later paternal investment. Paternal investment was also independent of the actual paternity losses. In females, the experiment elicited both, immediate and long-term responses. E.g. female copulation solicitations during the intruder experiment were only observed for females which later turned out to have extra-pair chicks in their nest. In relation to long term response females faced with an intruder invested later less in offspring feeding, and had less extra-pair chicks in their nests. Extra-pair paternity also seems to be affected by female quality (body size). In conclusion female reed warblers seem to seek extra-pair fertilizations but we could demonstrate that males adopt paternity assurance tactics which seems to efficiently help them to reduce paternity uncertainty. PMID:23658637

  10. Polyamine Accumulation and Near Loss of Morphogenesis in Long-Term Callus Cultures of Rice (Restoration of Plant Regeneration by Manipulation of Cellular Polyamine Levels).

    PubMed Central

    Bajaj, S.; Rajam, M. V.

    1996-01-01

    We have shown (S. Bajaj and M.V. Rajam [1995] Plant Cell Rep 14: 717-720) that a significant reduction in morphogenetic potential occurs in callus cultures of rice (Oryza sativa L. cv TN-1) (up to 1 year old), and that plant regeneration could be improved in such cultures with spermidine treatment. We now show a near loss in plant regeneration capacity, concomitant with massive polyamine accumulation (primarily the diamine putrescine), due to the increase in arginine decarboxylase activity and an altered putrescine-to-spermidine ratio in 20- and 36-month-old rice callus cultures. The blockage of polyamine accumulation due to the reduction in arginine decarboxylase activity by a putrescine synthesis inhibitor, [alpha]-difluoromethylarginine, completely restored plant regeneration capacity in these long-term cultures. Additionally, spermidine treatment of long-term cultures caused an increase in cellular spermidine content and a reduction in putrescine content and arginine decarboxylase activity, leading to an adjustment in putrescine-to-spermidine ratio and the restoration of plant regeneration ability. PMID:12226449

  11. Quantitative and compositional responses of ammonia-oxidizing archaea and bacteria to long-term field fertilization.

    PubMed

    Xue, Chao; Zhang, Xu; Zhu, Chen; Zhao, Jun; Zhu, Ping; Peng, Chang; Ling, Ning; Shen, Qirong

    2016-01-01

    Archaeal (AOA) and bacterial (AOB) ammonia-oxidizer responses to long-term field fertilization in a Mollisol soil were assessed through pyrosequencing of amoA genes. Long-term fertilization treatments including chemical fertilizer (NPK), NPK plus manure (NPKM), and no fertilization over 23 years altered soil properties resulting in significant shifts in AOA and AOB community composition and abundance. NPK exhibited a strong influence on AOA and AOB composition while the addition of manure neutralized the community change induced by NPK. NPK also led to significant soil acidification and enrichment of Nitrosotalea. Nitrosospira cluster 9 and 3c were the most abundant AOB populations with opposing responses to fertilization treatments. NPKM had the largest abundance of ammonia-oxidizers and highest potential nitrification activity (PNA), suggesting high N loss potential due to a doubling of nutrient input compared to NPK. PNA was strongly correlated to AOA and AOB community composition indicating that both were important in ammonium oxidization in this Mollisol soil. Total N and organic C were the most important factors driving shifts in AOA and AOB community composition. The AOA community was strongly correlated to the activities of all sugar hydrolysis associated soil enzymes and was more responsive to C and N input than AOB. PMID:27356769

  12. Quantitative and compositional responses of ammonia-oxidizing archaea and bacteria to long-term field fertilization

    PubMed Central

    Xue, Chao; Zhang, Xu; Zhu, Chen; Zhao, Jun; Zhu, Ping; Peng, Chang; Ling, Ning; Shen, Qirong

    2016-01-01

    Archaeal (AOA) and bacterial (AOB) ammonia-oxidizer responses to long-term field fertilization in a Mollisol soil were assessed through pyrosequencing of amoA genes. Long-term fertilization treatments including chemical fertilizer (NPK), NPK plus manure (NPKM), and no fertilization over 23 years altered soil properties resulting in significant shifts in AOA and AOB community composition and abundance. NPK exhibited a strong influence on AOA and AOB composition while the addition of manure neutralized the community change induced by NPK. NPK also led to significant soil acidification and enrichment of Nitrosotalea. Nitrosospira cluster 9 and 3c were the most abundant AOB populations with opposing responses to fertilization treatments. NPKM had the largest abundance of ammonia-oxidizers and highest potential nitrification activity (PNA), suggesting high N loss potential due to a doubling of nutrient input compared to NPK. PNA was strongly correlated to AOA and AOB community composition indicating that both were important in ammonium oxidization in this Mollisol soil. Total N and organic C were the most important factors driving shifts in AOA and AOB community composition. The AOA community was strongly correlated to the activities of all sugar hydrolysis associated soil enzymes and was more responsive to C and N input than AOB. PMID:27356769

  13. Structural and functional responses of extremity veins to long-term gravitational loading or unloading—lessons from animal systems

    NASA Astrophysics Data System (ADS)

    Monos, Emil; Raffai, Gábor; Dörnyei, Gabriella; Nádasy, György L.; Fehér, Erzsébet

    2007-02-01

    Long, transparent tubular tilt-cages were developed to maintain experimental rats either in 45∘ head-up (orthostasis model), or in 45∘ head-down body position (antiorthostasis model) for several weeks. In order to study the functional and structural changes in extremity blood vessels, also novel pressure angiograph systems, as well as special quantitative electron microscopic methods were applied. It was found that several adaptive mechanisms are activated in the lower limb superficial veins and microvessels of muscles when an organism is exposed to long-term (1-2 weeks) orthostatic-type gravitational load including a reversible amplification of the pressure-dependent myogenic response, tuning of the myogenic tone by Ca++- and voltage-sensitive K+ channels in humans, augmentation of the intramural sympathetic innervation involving an increased nerve terminal density and synaptic vesicle count with functional remodeling, reorganization of vascular network properties (microvascular rarefaction in muscles, decreased branching angles in superficial veins), and responses of an endothelin and platelet-derived growth factor (PDGF) containing vesicle system in the endothelium. On the other hand, when applying long-term head-down tilting, the effects are dichotomous, e.g. it suppresses significantly the pressure-induced myogenic response, however does not diminish the adventitial sympathetic innervation density.

  14. Quantitative and compositional responses of ammonia-oxidizing archaea and bacteria to long-term field fertilization

    NASA Astrophysics Data System (ADS)

    Xue, Chao; Zhang, Xu; Zhu, Chen; Zhao, Jun; Zhu, Ping; Peng, Chang; Ling, Ning; Shen, Qirong

    2016-06-01

    Archaeal (AOA) and bacterial (AOB) ammonia-oxidizer responses to long-term field fertilization in a Mollisol soil were assessed through pyrosequencing of amoA genes. Long-term fertilization treatments including chemical fertilizer (NPK), NPK plus manure (NPKM), and no fertilization over 23 years altered soil properties resulting in significant shifts in AOA and AOB community composition and abundance. NPK exhibited a strong influence on AOA and AOB composition while the addition of manure neutralized the community change induced by NPK. NPK also led to significant soil acidification and enrichment of Nitrosotalea. Nitrosospira cluster 9 and 3c were the most abundant AOB populations with opposing responses to fertilization treatments. NPKM had the largest abundance of ammonia-oxidizers and highest potential nitrification activity (PNA), suggesting high N loss potential due to a doubling of nutrient input compared to NPK. PNA was strongly correlated to AOA and AOB community composition indicating that both were important in ammonium oxidization in this Mollisol soil. Total N and organic C were the most important factors driving shifts in AOA and AOB community composition. The AOA community was strongly correlated to the activities of all sugar hydrolysis associated soil enzymes and was more responsive to C and N input than AOB.

  15. Plant community and soil chemistry responses to long-term nitrogen inputs drive changes in alpine bacterial communities.

    PubMed

    Yuan, Xia; Knelman, Joseph E; Gasarch, Eve; Wang, Deli; Nemergut, Diana R; Seastedt, Timothy R

    2016-06-01

    Bacterial community composition and diversity was studied in alpine tundra soils across a plant species and moisture gradient in 20 y-old experimental plots with four nutrient addition regimes (control, nitrogen (N), phosphorus (P) or both nutrients). Different bacterial communities inhabited different alpine meadows, reflecting differences in moisture, nutrients and plant species. Bacterial community alpha-diversity metrics were strongly correlated with plant richness and the production of forbs. After meadow type, N addition proved the strongest determinant of bacterial community structure. Structural Equation Modeling demonstrated that tundra bacterial community responses to N addition occur via changes in plant community composition and soil pH resulting from N inputs, thus disentangling the influence of direct (resource availability) vs. indirect (changes in plant community structure and soil pH) N effects that have remained unexplored in past work examining bacterial responses to long-term N inputs in these vulnerable environments. Across meadow types, the relative influence of these indirect N effects on bacterial community structure varied. In explicitly evaluating the relative importance of direct and indirect effects of long-term N addition on bacterial communities, this study provides new mechanistic understandings of the interaction between plant and microbial community responses to N inputs amidst environmental change. PMID:27459784

  16. Drastic changes in aquatic bacterial populations from the Cuatro Cienegas Basin (Mexico) in response to long-term environmental stress.

    PubMed

    Pajares, Silvia; Eguiarte, Luis E; Bonilla-Rosso, German; Souza, Valeria

    2013-12-01

    Understanding the changes of aquatic microbial community composition in response to changes in temperature and ultraviolet irradiation is relevant for predicting biogeochemical modifications in the functioning of natural microbial communities under global climate change scenarios. Herein we investigate shifts in the bacterioplankton composition in response to long-term changes in temperature and UV radiation. For this purpose, 15 mesocosms were seeded with composite aquatic microbial communities from natural pools within the Cuatro Cienegas Basin (Mexican Chihuahuan desert) and were subject to different temperatures and UV conditions. 16S rRNA gene clone libraries were obtained from water samples at the mid-point (4 months) and the end of the experiment (8 months). An increase in bacterial diversity over time was found in the treatment of constant temperature and UV protection, which suggests that stable environments promote the establishment of complex and diverse bacterial community. Drastic changes in the phylogenetic bacterioplankton composition and structure were observed in response to fluctuating temperature and increasing UV radiation and temperature. Fluctuating temperature induced the largest decrease of bacterial richness during the experiment, indicating that frequent temperature changes drive the reduction in abundance of several species, most notably autotrophs. The long-term impact of these environmental stresses reduced diversity and selected for generalist aquatic bacterial populations, such as Porphyrobacter. These changes at the community level occur at an ecological time scale, suggesting that under global warming scenarios cascade effects on the food web are possible if the microbial diversity is modified.

  17. Quantitative and compositional responses of ammonia-oxidizing archaea and bacteria to long-term field fertilization.

    PubMed

    Xue, Chao; Zhang, Xu; Zhu, Chen; Zhao, Jun; Zhu, Ping; Peng, Chang; Ling, Ning; Shen, Qirong

    2016-01-01

    Archaeal (AOA) and bacterial (AOB) ammonia-oxidizer responses to long-term field fertilization in a Mollisol soil were assessed through pyrosequencing of amoA genes. Long-term fertilization treatments including chemical fertilizer (NPK), NPK plus manure (NPKM), and no fertilization over 23 years altered soil properties resulting in significant shifts in AOA and AOB community composition and abundance. NPK exhibited a strong influence on AOA and AOB composition while the addition of manure neutralized the community change induced by NPK. NPK also led to significant soil acidification and enrichment of Nitrosotalea. Nitrosospira cluster 9 and 3c were the most abundant AOB populations with opposing responses to fertilization treatments. NPKM had the largest abundance of ammonia-oxidizers and highest potential nitrification activity (PNA), suggesting high N loss potential due to a doubling of nutrient input compared to NPK. PNA was strongly correlated to AOA and AOB community composition indicating that both were important in ammonium oxidization in this Mollisol soil. Total N and organic C were the most important factors driving shifts in AOA and AOB community composition. The AOA community was strongly correlated to the activities of all sugar hydrolysis associated soil enzymes and was more responsive to C and N input than AOB.

  18. Long-term complete responses after 131I-tositumomab therapy for relapsed or refractory indolent non-Hodgkin's lymphoma

    PubMed Central

    Buchegger, F; Antonescu, C; Delaloye, A Bischof; Helg, C; Kovacsovics, T; Kosinski, M; Mach, J-P; Ketterer, N

    2006-01-01

    We present the long-term results of 18 chemotherapy relapsed indolent (N=12) or transformed (N=6) NHL patients of a phase II anti-CD20 131I-tositumomab (Bexxar®) therapy study. The biphasic therapy included two injections of 450 mg unlabelled antibody combined with 131I-tositumomab once as dosimetric and once as therapeutic activity delivering 75 or 65 cGy whole-body radiation dose to patients with normal or reduced platelet counts, respectively. Two patients were not treated due to disease progression during dosimetry. The overall response rate was 81% in the 16 patients treated, including 50% CR/CRu and 31% PR. Median progression free survival of the 16 patients was 22.5 months. Median overall survival has not been reached after a median observation of 48 months. Median PFS of complete responders (CR/CRu) has not been reached and will be greater than 51 months. Short-term side effects were mainly haematological and transient. Among the relevant long-term side effects, one patient previously treated with CHOP chemotherapy died from secondary myelodysplasia. Four patients developed HAMA. In conclusion, 131I-tositumomab RIT demonstrated durable responses especially in those patients who achieved a complete response. Six of eight CR/CRu are ongoing after 46–70 months. PMID:16685263

  19. Plant community and soil chemistry responses to long-term nitrogen inputs drive changes in alpine bacterial communities.

    PubMed

    Yuan, Xia; Knelman, Joseph E; Gasarch, Eve; Wang, Deli; Nemergut, Diana R; Seastedt, Timothy R

    2016-06-01

    Bacterial community composition and diversity was studied in alpine tundra soils across a plant species and moisture gradient in 20 y-old experimental plots with four nutrient addition regimes (control, nitrogen (N), phosphorus (P) or both nutrients). Different bacterial communities inhabited different alpine meadows, reflecting differences in moisture, nutrients and plant species. Bacterial community alpha-diversity metrics were strongly correlated with plant richness and the production of forbs. After meadow type, N addition proved the strongest determinant of bacterial community structure. Structural Equation Modeling demonstrated that tundra bacterial community responses to N addition occur via changes in plant community composition and soil pH resulting from N inputs, thus disentangling the influence of direct (resource availability) vs. indirect (changes in plant community structure and soil pH) N effects that have remained unexplored in past work examining bacterial responses to long-term N inputs in these vulnerable environments. Across meadow types, the relative influence of these indirect N effects on bacterial community structure varied. In explicitly evaluating the relative importance of direct and indirect effects of long-term N addition on bacterial communities, this study provides new mechanistic understandings of the interaction between plant and microbial community responses to N inputs amidst environmental change.

  20. Using Long-Term Experimental Warming To Distinguish Vegetation Responses To Warming From Other Environmental Drivers Related To Climate Change

    NASA Astrophysics Data System (ADS)

    Gould, W. A.; Welker, J. M.; Mercado-Díaz, J. A.; Anderson, A.; Menken, M.

    2010-12-01

    Long term studies of vegetation change throughout the tundra biome show increases in the height, canopy extent and dominance of vascular vegetation versus bryophytes and lichens, with mixed responses of the dominant shrub and graminoid growth forms. Increases in vascular vegetation are recorded for sites with and without measurable climatic warming over recent decades, but with other potential drivers, i.e., increased summer precipitation. Experimental warming of tundra vegetation at Toolik Lake, Alaska shows a clear increase in shrub abundance relative to graminoids, with correlated higher NDVI values, increasing canopy heights, and thaw depths. Responses were similar between moist and dry tundra vegetation, with greater responses in moist vegetation. NDVI, with its ability to distinguish shrub from graminoid vegetation, may be a tool to distinguish fine scale differences in the response of tundra vegetation to climatic change, i.e., shifting balances of shrub and graminoid relative abundances that may be related to distinct climatic change drivers.

  1. Long term ex vivo culturing of Drosophila brain as a method to live image pupal brains: insights into the cellular mechanisms of neuronal remodeling

    PubMed Central

    Rabinovich, Dana; Mayseless, Oded; Schuldiner, Oren

    2015-01-01

    Holometabolous insects, including Drosophila melanogaster, undergo complete metamorphosis that includes a pupal stage. During metamorphosis, the Drosophila nervous system undergoes massive remodeling and growth, that include cell death and large-scale axon and synapse elimination as well as neurogenesis, developmental axon regrowth, and formation of new connections. Neuronal remodeling is an essential step in the development of vertebrate and invertebrate nervous systems. Research on the stereotypic remodeling of Drosophila mushroom body (MB) γ neurons has contributed to our knowledge of the molecular mechanisms of remodeling but our knowledge of the cellular mechanisms remain poorly understood. A major hurdle in understanding various dynamic processes that occur during metamorphosis is the lack of time-lapse resolution. The pupal case and opaque fat bodies that enwrap the central nervous system (CNS) make live-imaging of the central brain in-vivo impossible. We have established an ex vivo long-term brain culture system that supports the development and neuronal remodeling of pupal brains. By optimizing culture conditions and dissection protocols, we have observed development in culture at kinetics similar to what occurs in vivo. Using this new method, we have obtained the first time-lapse sequence of MB γ neurons undergoing remodeling in up to a single cell resolution. We found that axon pruning is initiated by blebbing, followed by one-two nicks that seem to initiate a more widely spread axon fragmentation. As such, we have set up some of the tools and methodologies needed for further exploration of the cellular mechanisms of neuronal remodeling, not limited to the MB. The long-term ex vivo brain culture system that we report here could be used to study dynamic aspects of neurodevelopment of any Drosophila neuron. PMID:26379498

  2. Cyclophilin A as a potential genetic adjuvant to improve HIV-1 Gag DNA vaccine immunogenicity by eliciting broad and long-term Gag-specific cellular immunity in mice

    PubMed Central

    Hou, Jue; Zhang, Qicheng; Liu, Zheng; Wang, Shuhui; Li, Dan; Liu, Chang; Liu, Ying; Shao, Yiming

    2016-01-01

    Previous research has shown that host Cyclophilin A (CyPA) can promote dendritic cell maturation and the subsequent innate immune response when incorporated into an HIV-1 Gag protein to circumvent the resistance of dendritic cells to HIV-1 infection. This led us to hypothesize that CyPA may improve HIV-1 Gag-specific vaccine immunogenicity via binding with Gag antigen. The adjuvant effect of CyPA was evaluated using a DNA vaccine with single or dual expression cassettes. Mouse studies indicated that CyPA specifically and markedly promoted HIV-1 Gag-specific cellular immunity but not an HIV-1 Env-specific cellular response. The Gag/CyPA dual expression cassettes stimulated a greater Gag-specific cellular immune response, than Gag immunization alone. Furthermore, CyPA induced a broad Gag-specific T cell response and strong cellular immunity that lasted up to 5 months. In addition, CyPA skewed to cellular rather than humoral immunity. To investigate the mechanisms of the adjuvant effect, site-directed mutagenesis in CyPA, including active site residues H54Q and F60A resulted in mutants that were co-expressed with Gag in dual cassettes. The immune response to this vaccine was analyzed in vivo. Interestingly, the wild type CyPA markedly increased Gag cellular immunity, but the H54Q and F60A mutants drastically reduced CyPA adjuvant activation. Therefore, we suggest that the adjuvant effect of CyPA was based on Gag-CyPA-specific interactions. Herein, we report that Cyclophilin A can augment HIV-1 Gag-specific cellular immunity as a genetic adjuvant in multiplex DNA immunization strategies, and that activity of this adjuvant is specific, broad, long-term, and based on Gag-CyPA interaction. PMID:26305669

  3. In situ stomatal responses to long-term CO 2 enrichment in calcareous grassland plants

    NASA Astrophysics Data System (ADS)

    Lauber, Wolfgang; Körner, Christian

    A calcareous grassland community growing under full season CO 2 enrichment at low altitude in the Swiss Jura mountains was investigated for diurnal and seasonal variations of leaf diffusive conductance. A new CO 2 enrichment method (Screen aided CO 2 control, SACC) permitted in situ leaf porometry under natural climatic conditions without disturbance of plants. At 600 ppm CO 2, leaf conductance in the dominant species, Bromus erectus (a species so far not showing a growth response to elevated CO 2) was reduced to half the values measured in controls. In contrast, leaf conductance in Carex flacca, a species of low cover (the only species so far exhibiting a dramatic growth stimulation by CO 2 fertilization) remained almost unaffected by elevated CO 2. Sanguisorba minor, Plantago media, and Cirsium acaule showed intermediate responses. Trifolium montanum, studied only on a single day, showed a reduction like Bromus. Differences between treatments were largest under humid conditions and disappeared during dry periods. In none of the species studied did stomatal density or stomatal index differ between treatments. A parallel investigation of whole ecosystem evapotranspiration indicated only small (<10%) and non significant CO 2 responses, suggesting that both aerodynamic effects at the canopy level and a great interspecific variation of leaf level responses overshadow the clear CO 2 response of Bromus stomata. The different stomatal responses to CO 2 enrichment are likely to alter species specific water consumption, and may thus affect community structure in the long run.

  4. Plant hydraulic responses to long-term dry season nitrogen deposition alter drought tolerance in a Mediterranean-type ecosystem.

    PubMed

    Pivovaroff, Alexandria L; Santiago, Louis S; Vourlitis, George L; Grantz, David A; Allen, Michael F

    2016-07-01

    Anthropogenic nitrogen (N) deposition represents a significant N input for many terrestrial ecosystems. N deposition can affect plants on scales ranging from photosynthesis to community composition, yet few studies have investigated how changes in N availability affect plant water relations. We tested the effects of N addition on plant water relations, hydraulic traits, functional traits, gas exchange, and leaf chemistry in a semi-arid ecosystem in Southern California using long-term experimental plots fertilized with N for over a decade. The dominant species were Artemisia california and Salvia mellifera at Santa Margarita Ecological Reserve and Adenostoma fasciculatum and Ceanothus greggii at Sky Oaks Field Station. All species, except Ceanothus, showed increased leaf N concentration, decreased foliar carbon to N ratio, and increased foliar N isotopic composition with fertilization, indicating that added N was taken up by study species, yet each species had a differing physiological response to long-term N addition. Dry season predawn water potentials were less negative with N addition for all species except Adenostoma, but there were no differences in midday water potentials, or wet season water potentials. Artemisia was particularly responsive, as N addition increased stem hydraulic conductivity, stomatal conductance, and leaf carbon isotopic composition, and decreased wood density. The alteration of water relations and drought resistance parameters with N addition in Artemisia, as well as Adenostoma, Ceanothus, and Salvia, indicate that N deposition can affect the ability of native Southern California shrubs to respond to drought.

  5. Vaccination against H5 avian influenza virus induces long-term humoral immune responses in flamingoes (Phoenicopterus spp.).

    PubMed

    Fernández-Bellon, Hugo; Vergara-Alert, Júlia; Almagro, Vanessa; Rivas, Raquel; Sánchez, Azucena; Martínez, María Carmen; Majó, Natàlia; Busquets, Núria; Ramis, Antonio

    2016-06-01

    Avian influenza (AI) can represent a threat to endangered wild birds, as demonstrated with the H5N1 highly pathogenic AI (HPAI) outbreaks. Vaccination against AI using inactivated H5-vaccines has been shown to induce humoral immune response in zoo bird species. In this study, the long-term efficacy of H5-vaccination was evaluated in flamingoes from Barcelona Zoo. Specific H5-antibody titres were maintained at high levels (geometric mean titres ≥32) for over 7 years after vaccination, both against the H5N9 and H5N3 vaccine strains, as well as H5N3 and H5N1 reference strains. In addition the breadth of the immune response was also studied by testing antibody production against H1-, H3-, H4-, H7-, and H10-subtypes. It was observed that most flamingoes presented specific antibodies against H1 virus subtypes, but titres to the other HA-subtypes were rarely detected. We show that AI-vaccines can induce immunity lasting seven years in flamingoes, which suggests that vaccination can provide long term protection from HPAI outbreaks in zoo birds.

  6. Plant hydraulic responses to long-term dry season nitrogen deposition alter drought tolerance in a Mediterranean-type ecosystem.

    PubMed

    Pivovaroff, Alexandria L; Santiago, Louis S; Vourlitis, George L; Grantz, David A; Allen, Michael F

    2016-07-01

    Anthropogenic nitrogen (N) deposition represents a significant N input for many terrestrial ecosystems. N deposition can affect plants on scales ranging from photosynthesis to community composition, yet few studies have investigated how changes in N availability affect plant water relations. We tested the effects of N addition on plant water relations, hydraulic traits, functional traits, gas exchange, and leaf chemistry in a semi-arid ecosystem in Southern California using long-term experimental plots fertilized with N for over a decade. The dominant species were Artemisia california and Salvia mellifera at Santa Margarita Ecological Reserve and Adenostoma fasciculatum and Ceanothus greggii at Sky Oaks Field Station. All species, except Ceanothus, showed increased leaf N concentration, decreased foliar carbon to N ratio, and increased foliar N isotopic composition with fertilization, indicating that added N was taken up by study species, yet each species had a differing physiological response to long-term N addition. Dry season predawn water potentials were less negative with N addition for all species except Adenostoma, but there were no differences in midday water potentials, or wet season water potentials. Artemisia was particularly responsive, as N addition increased stem hydraulic conductivity, stomatal conductance, and leaf carbon isotopic composition, and decreased wood density. The alteration of water relations and drought resistance parameters with N addition in Artemisia, as well as Adenostoma, Ceanothus, and Salvia, indicate that N deposition can affect the ability of native Southern California shrubs to respond to drought. PMID:27017604

  7. Vaccination against H5 avian influenza virus induces long-term humoral immune responses in flamingoes (Phoenicopterus spp.).

    PubMed

    Fernández-Bellon, Hugo; Vergara-Alert, Júlia; Almagro, Vanessa; Rivas, Raquel; Sánchez, Azucena; Martínez, María Carmen; Majó, Natàlia; Busquets, Núria; Ramis, Antonio

    2016-06-01

    Avian influenza (AI) can represent a threat to endangered wild birds, as demonstrated with the H5N1 highly pathogenic AI (HPAI) outbreaks. Vaccination against AI using inactivated H5-vaccines has been shown to induce humoral immune response in zoo bird species. In this study, the long-term efficacy of H5-vaccination was evaluated in flamingoes from Barcelona Zoo. Specific H5-antibody titres were maintained at high levels (geometric mean titres ≥32) for over 7 years after vaccination, both against the H5N9 and H5N3 vaccine strains, as well as H5N3 and H5N1 reference strains. In addition the breadth of the immune response was also studied by testing antibody production against H1-, H3-, H4-, H7-, and H10-subtypes. It was observed that most flamingoes presented specific antibodies against H1 virus subtypes, but titres to the other HA-subtypes were rarely detected. We show that AI-vaccines can induce immunity lasting seven years in flamingoes, which suggests that vaccination can provide long term protection from HPAI outbreaks in zoo birds. PMID:27151883

  8. AAV-based Neonatal Gene Therapy for Hemophilia A: Long-Term Correction and Avoidance of Immune Responses in Mice

    PubMed Central

    Hu, Chuhong; Lipshutz, Gerald S.

    2012-01-01

    Hemophilia A gene therapy has been hampered by immune responses to vector-associated antigens and by neutralizing antibodies or inhibitors to the factor VIII (FVIII) protein; these ‘inhibitors’ more commonly effect hemophilia A patients than those with hemophilia B. A gene replacement strategy beginning in the neonatal period may avoid the development of these immune responses and lead to prolonged expression with correction of phenotype thereby avoiding long-term consequences. Serotype rh10 AAV was developed splitting the FVIII coding sequence into heavy and light chains with the chicken β-actin promoter/CMV enhancer for dual recombinant AAV vector delivery. Coinjection of virions of each FVIII chain intravenously to mice on the second day of life was performed. Mice express sustained FVIII antigen levels of ≥5% to 22 months of life without the development of antibodies to FVIII. Phenotypic correction was manifest in all AAV-FVIII-treated mice as demonstrated by functional assay and reduction in bleeding time. This study demonstrates the use of AAV in a gene replacement strategy in neonatal mice that establishes both long-term phenotypic correction of hemophilia A and lack of antibody development to FVIII in this disease model where AAV is administered shortly after birth. These studies support consideration of gene replacement therapy for diseases that are diagnosed in utero or in the early neonatal period. PMID:22241178

  9. Response to Long-Term NaHCO3-Derived Alkalinity in Model Lotus japonicus Ecotypes Gifu B-129 and Miyakojima MG-20: Transcriptomic Profiling and Physiological Characterization

    PubMed Central

    Rocco, Rubén; Bordenave, Cesar D.; Escaray, Francisco J.; Antonelli, Cristian; Calzadilla, Pablo; Gárriz, Andrés; Serna, Eva; Carrasco, Pedro; Menendez, Ana B.

    2014-01-01

    The current knowledge regarding transcriptomic changes induced by alkalinity on plants is scarce and limited to studies where plants were subjected to the alkaline salt for periods not longer than 48 h, so there is no information available regarding the regulation of genes involved in the generation of a new homeostatic cellular condition after long-term alkaline stress. Lotus japonicus is a model legume broadly used to study many important physiological processes including biotic interactions and biotic and abiotic stresses. In the present study, we characterized phenotipically the response to alkaline stress of the most widely used L. japonicus ecotypes, Gifu B-129 and MG-20, and analyzed global transcriptome of plants subjected to 10 mM NaHCO3 during 21 days, by using the Affymetrix Lotus japonicus GeneChip®. Plant growth assessment, gas exchange parameters, chlorophyll a fluorescence transient (OJIP) analysis and metal accumulation supported the notion that MG-20 plants displayed a higher tolerance level to alkaline stress than Gifu B-129. Overall, 407 and 459 probe sets were regulated in MG-20 and Gifu B-129, respectively. The number of probe sets differentially expressed in roots was higher than that of shoots, regardless the ecotype. Gifu B-129 and MG-20 also differed in their regulation of genes that could play important roles in the generation of a new Fe/Zn homeostatic cellular condition, synthesis of plant compounds involved in stress response, protein-degradation, damage repair and root senescence, as well as in glycolysis, gluconeogenesis and TCA. In addition, there were differences between both ecotypes in the expression patterns of putative transcription factors that could determine distinct arrangements of flavonoid and isoflavonoid compounds. Our results provided a set of selected, differentially expressed genes deserving further investigation and suggested that the L. japonicus ecotypes could constitute a useful model to search for common and

  10. Response to long-term NaHCO3-derived alkalinity in model Lotus japonicus Ecotypes Gifu B-129 and Miyakojima MG-20: transcriptomic profiling and physiological characterization.

    PubMed

    Babuin, María Florencia; Campestre, María Paula; Rocco, Rubén; Bordenave, Cesar D; Escaray, Francisco J; Antonelli, Cristian; Calzadilla, Pablo; Gárriz, Andrés; Serna, Eva; Carrasco, Pedro; Ruiz, Oscar A; Menendez, Ana B

    2014-01-01

    The current knowledge regarding transcriptomic changes induced by alkalinity on plants is scarce and limited to studies where plants were subjected to the alkaline salt for periods not longer than 48 h, so there is no information available regarding the regulation of genes involved in the generation of a new homeostatic cellular condition after long-term alkaline stress. Lotus japonicus is a model legume broadly used to study many important physiological processes including biotic interactions and biotic and abiotic stresses. In the present study, we characterized phenotipically the response to alkaline stress of the most widely used L. japonicus ecotypes, Gifu B-129 and MG-20, and analyzed global transcriptome of plants subjected to 10 mM NaHCO3 during 21 days, by using the Affymetrix Lotus japonicus GeneChip®. Plant growth assessment, gas exchange parameters, chlorophyll a fluorescence transient (OJIP) analysis and metal accumulation supported the notion that MG-20 plants displayed a higher tolerance level to alkaline stress than Gifu B-129. Overall, 407 and 459 probe sets were regulated in MG-20 and Gifu B-129, respectively. The number of probe sets differentially expressed in roots was higher than that of shoots, regardless the ecotype. Gifu B-129 and MG-20 also differed in their regulation of genes that could play important roles in the generation of a new Fe/Zn homeostatic cellular condition, synthesis of plant compounds involved in stress response, protein-degradation, damage repair and root senescence, as well as in glycolysis, gluconeogenesis and TCA. In addition, there were differences between both ecotypes in the expression patterns of putative transcription factors that could determine distinct arrangements of flavonoid and isoflavonoid compounds. Our results provided a set of selected, differentially expressed genes deserving further investigation and suggested that the L. japonicus ecotypes could constitute a useful model to search for common and

  11. Long term response of acid-sensitive Vermont Lakes to sulfate deposition

    EPA Science Inventory

    Atmospheric deposition of sulfur can negatively affect the health of lakes and streams, particularly in poorly buffered catchments. In response to the Clean Air Act Amendments, wet deposition of sulfate decreased more than 35% in Vermont between 1990 and 2008. However, most of ...

  12. Size-dependent long-term tissue response to biostable nanowires in the brain.

    PubMed

    Gällentoft, Lina; Pettersson, Lina M E; Danielsen, Nils; Schouenborg, Jens; Prinz, Christelle N; Linsmeier, Cecilia Eriksson

    2015-02-01

    Nanostructured neural interfaces, comprising nanotubes or nanowires, have the potential to overcome the present hurdles of achieving stable communication with neuronal networks for long periods of time. This would have a strong impact on brain research. However, little information is available on the brain response to implanted high-aspect-ratio nanoparticles, which share morphological similarities with asbestos fibres. Here, we investigated the glial response and neuronal loss in the rat brain after implantation of biostable and structurally controlled nanowires of different lengths for a period up to one year post-surgery. Our results show that, as for lung and abdominal tissue, the brain is subject to a sustained, local inflammation when biostable and high-aspect-ratio nanoparticles of 5 μm or longer are present in the brain tissue. In addition, a significant loss of neurons was observed adjacent to the 10 μm nanowires after one year. Notably, the inflammatory response was restricted to a narrow zone around the nanowires and did not escalate between 12 weeks and one year. Furthermore, 2 μm nanowires did not cause significant inflammatory response nor significant loss of neurons nearby. The present results provide key information for the design of future neural implants based on nanomaterials.

  13. Therapeutic Responses of Psychopathic Sexual Offenders: Treatment Attrition, Therapeutic Change, and Long-Term Recidivism

    ERIC Educational Resources Information Center

    Olver, Mark E.; Wong, Stephen C. P.

    2009-01-01

    The authors examined the therapeutic responses of psychopathic sex offenders (greater than or equal to 25 Psychopathy Checklist-Revised; PCL-R) in terms of treatment dropout and therapeutic change, as well as sexual and violent recidivism over a 10-year follow-up among 156 federally incarcerated sex offenders treated in a high-intensity inpatient…

  14. The Long-Term Sustainability of Different Item Response Theory Scaling Methods

    ERIC Educational Resources Information Center

    Keller, Lisa A.; Keller, Robert R.

    2011-01-01

    This article investigates the accuracy of examinee classification into performance categories and the estimation of the theta parameter for several item response theory (IRT) scaling techniques when applied to six administrations of a test. Previous research has investigated only two administrations; however, many testing programs equate tests…

  15. Long-term modulation of the exercise ventilatory response in goats.

    PubMed Central

    Martin, P A; Mitchell, G S

    1993-01-01

    1. To test the hypothesis that repeated associations of exercise and increased respiratory dead space elicit mechanisms that augment future ventilatory responses to exercise alone, experiments were conducted on normal adult goats familiarized with experimental procedures. 2. Measurements of ventilation, arterial blood gases and CO2 production were made at rest, during mild steady-state exercise (4 km h-1; 5% grade) and with increased dead space at rest in seven goats before and after training. In Series I experiments, training consisted of fourteen to twenty exercise trials explicitly paired with increased dead space (0.8 l) over 2 days. Increased dead space predominantly represents a CO2 chemoreceptor stimulus with only mild hypoxic stimulation. Post-training measurements were made 1-6 h and 1 week after training was completed. 3. The same goats repeated a slightly modified protocol several months later (Series II; 6 trials per day for 4 days) to determine if responses were both repeatable and reversible, and to investigate training effects on dynamic ventilatory responses at the onset of exercise. 4. In Series I experiments, resting minute ventilation and breathing frequency were elevated 1-6 h post-training compared to baseline (44 and 74% respectively), whereas resting tidal volume decreased (14%). One week post-training, resting values had returned to baseline. Series II training had no significant effects on resting measurements. 5. Relative to baseline, arterial partial pressure of CO2 (Pa,CO2) values decreased significantly more from rest to exercise 1-6 h post-training in both Series I (2.7 +/- 0.2 vs. 1.8 +/- 0.9 mmHg) and Series II (3.4 +/- 0.6 vs. 2.0 +/- 0.6 mmHg). The exercise ventilatory response increased 25-28% 1-6 h post-training (both series), largely due to a greater exercise frequency response, but returned to baseline 1 week post-training. Training had no effect on ventilatory responses to CO2 at rest, suggesting that decreases in CO2

  16. Long-Term Response of Terrestrial Productivity to Elevated CO2 Remains a Grand Challenge in Terrestrial Biogeochemistry (Invited)

    NASA Astrophysics Data System (ADS)

    Finzi, A.

    2013-12-01

    There is large variability in the long-term response of terrestrial net primary production (NPP) to elevated concentrations of atmospheric CO2 (eCO2). In some ecosystems productivity remains higher under eCO2 compared to aCO2 at the decadal time scale. In other ecosystem productivity under eCO2 increases transiently, returning to levels observed at aCO2 in a few years or less. The diversity of ecosystem responses is as fascinating as it is difficult to understand. A number of scientists, including this one, have postulated that soil water and nutrient supply constrain productivity responses and that in the absence of increases in soil resource uptake productivity must decline because there is little evidence for increases in resource use efficiency, with perhaps the exception of grassland water-use efficiency in some instances. This contention is challenged by the data as they are currently understood. As such there is no unifying explanation for the diversity of these responses and hence models cannot be reasonably expected to accurately predict the timing and magnitude of terrestrial-C sequestration over the next century. Research on the impacts of elevated CO2 has not yet answered a fundamentally important, policy-relevant question in global change science. In this talk I present an analysis of the NPP literature from long-term experiments at eCO2 published to date (>5 years duration) in an effort to stimulate a discussion of why productivity responses to eCO2 vary from ecosystem to ecosystem. Explaining variations in productivity response to eCO2 is a grand challenge in terrestrial biogeochemistry.

  17. Long-Term Persistance of the Pathophysiologic Response to Severe Burn Injury

    PubMed Central

    Finnerty, Celeste C.; Williams, Felicia N.; Kraft, Robert; Suman, Oscar E.; Mlcak, Ronald P.; Herndon, David N.

    2011-01-01

    Background Main contributors to adverse outcomes in severely burned pediatric patients are profound and complex metabolic changes in response to the initial injury. It is currently unknown how long these conditions persist beyond the acute phase post-injury. The aim of the present study was to examine the persistence of abnormalities of various clinical parameters commonly utilized to assess the degree hypermetabolic and inflammatory alterations in severely burned children for up to three years post-burn to identify patient specific therapeutic needs and interventions. Methodology/Principal Findings Patients: Nine-hundred seventy-seven severely burned pediatric patients with burns over 30% of the total body surface admitted to our institution between 1998 and 2008 were enrolled in this study and compared to a cohort non-burned, non-injured children. Demographics and clinical outcomes, hypermetabolism, body composition, organ function, inflammatory and acute phase responses were determined at admission and subsequent regular intervals for up to 36 months post-burn. Statistical analysis was performed using One-way ANOVA, Student's t-test with Bonferroni correction where appropriate with significance accepted at p<0.05. Resting energy expenditure, body composition, metabolic markers, cardiac and organ function clearly demonstrated that burn caused profound alterations for up to three years post-burn demonstrating marked and prolonged hypermetabolism, p<0.05. Along with increased hypermetabolism, significant elevation of cortisol, catecholamines, cytokines, and acute phase proteins indicate that burn patients are in a hyperinflammatory state for up to three years post-burn p<0.05. Conclusions Severe burn injury leads to a much more profound and prolonged hypermetabolic and hyperinflammatory response than previously shown. Given the tremendous adverse events associated with the hypermetabolic and hyperinflamamtory responses, we now identified treatment needs for

  18. Long-Term Exposure to High Altitude Affects Response Inhibition in the Conflict-monitoring Stage.

    PubMed

    Ma, Hailin; Wang, Yan; Wu, Jianhui; Luo, Ping; Han, Buxin

    2015-09-01

    To investigate the effects of high-altitude exposure on response inhibition, event-related potential (ERP) components N2 and P3 were measured in Go/NoGo task. The participants included an 'immigrant' high-altitude group (who had lived at high altitude for three years but born at low altitude) and a low-altitude group (living in low altitude only). Although the behavioural data showed no significant differences between the two groups, a delayed latency of NoGo-N2 was found in the high-altitude group compared to the low-altitude group. Moreover, larger N2 and smaller P3 amplitudes were found in the high-altitude group compared to the low-altitude group, for both the Go and NoGo conditions. These findings suggest that high-altitude exposure affects response inhibition with regard to processing speed during the conflict monitoring stage. In addition, high altitude generally increases the neural activity in the matching step of information processing and attentional resources. These results may provide some insights into the neurocognitive basis of the effects on high-altitude exposure on response inhibition.

  19. System responses to long-term drought and re-watering of two contrasting alfalfa varieties.

    PubMed

    Kang, Yun; Han, Yuanhong; Torres-Jerez, Ivone; Wang, Mingyi; Tang, Yuhong; Monteros, Maria; Udvardi, Michael

    2011-12-01

    Systems analysis of two alfalfa varieties, Wisfal (Medicago sativa ssp. falcata var. Wisfal) and Chilean (M. sativa ssp. sativa var. Chilean), with contrasting tolerance/sensitivity to drought revealed common and divergent responses to drought stress. At a qualitative level, molecular, biochemical, and physiological responses to drought stress were similar in the two varieties, indicating that they employ the same strategies to cope with drought. However, quantitative differences in responses at all levels were revealed that may contribute to greater drought tolerance in Wisfal. These included lower stomatal density and conductance in Wisfal; delayed leaf senescence compared with Chilean; greater root growth following a drought episode, and greater accumulation of osmolytes, including raffinose and galactinol, and flavonoid antioxidants in roots and/or shoots of Wisfal. Genes encoding transcription factors and other regulatory proteins, and genes involved in the biosynthesis of osmolytes and (iso)flavonoids were differentially regulated between the two varieties and represent potential targets for improving drought tolerance in alfalfa in the future.

  20. Long-Term Exposure to High Altitude Affects Response Inhibition in the Conflict-monitoring Stage.

    PubMed

    Ma, Hailin; Wang, Yan; Wu, Jianhui; Luo, Ping; Han, Buxin

    2015-01-01

    To investigate the effects of high-altitude exposure on response inhibition, event-related potential (ERP) components N2 and P3 were measured in Go/NoGo task. The participants included an 'immigrant' high-altitude group (who had lived at high altitude for three years but born at low altitude) and a low-altitude group (living in low altitude only). Although the behavioural data showed no significant differences between the two groups, a delayed latency of NoGo-N2 was found in the high-altitude group compared to the low-altitude group. Moreover, larger N2 and smaller P3 amplitudes were found in the high-altitude group compared to the low-altitude group, for both the Go and NoGo conditions. These findings suggest that high-altitude exposure affects response inhibition with regard to processing speed during the conflict monitoring stage. In addition, high altitude generally increases the neural activity in the matching step of information processing and attentional resources. These results may provide some insights into the neurocognitive basis of the effects on high-altitude exposure on response inhibition. PMID:26324166

  1. Long-Term Care

    MedlinePlus

    ... this page please turn Javascript on. Long-Term Care What Is Long-Term Care? Long-term care involves a variety of services ... the Escape (Esc) button on your keyboard.) Most Care Provided at Home Long-term care is provided ...

  2. Water Relations, Gas Exchange, and Nutrient Response to a Long Term Constant Water Deficit

    NASA Technical Reports Server (NTRS)

    Berry, Wade L.; Goldstein, Guillermo; Dreschel, Thomas W.; Wheeler, Raymond M.; Sager, John C.; Knott, William M.

    1992-01-01

    Wheat plants (Triticum aestivum) were grown for 43 days in a micro-porous tube nutrient delivery system. Roots were unable to penetrate the microporous tube, but grew on the surface and maintained capillary contact with the nutrient solution on the inside of the tube through the 5-microns pores of the porous tube. Water potential in the system was controlled at -0.4, -0.8, and -3.0 kPa by adjusting the applied pressure (hydrostatic head) to the nutrient solution flowing through the microporous tubes. A relatively small decrease in applied water potential from -0.4 to -3.0 kPa resulted in a 34% reduction of shoot growth but only a moderate reduction in the mid-day leaf water potential from - 1.3 to - 1.7 MPa. Carbon dioxide assimilation decreased and water use efficiency increased with the more negative applied water Potentials, while intercellular C02 concentration remained constant. The physiological responses observed in this study in response to small constant differences in applied water potentials were much greater than expected from either the applied water potential or the observed plant water potential. Even though the micro-porous tube may not represent natural conditions and could possibly introduce morphological and physiological artifacts , it enables a high degree of control of water potential that facilitates the investigation of many aspects of water relations not practical with other experimental systems.

  3. Brain ischemia changes the long term response to antidepressant drugs in mice.

    PubMed

    Deplanque, Dominique; Venna, Venugopal Reddy; Bordet, Régis

    2011-06-01

    Depression is a frequent but often unrecognized and under treated complication of stroke that has scarcely been investigated in animal models particularly regarding treatment issues. Using the Forced Swim Test (FST) and testing spontaneous motor activity, we studied whether a transient focal cerebral ischemia modifies mice behaviours and antidepressant drug effects. We first evaluated whether FST realized 2 days or 1 week after brain reperfusion may be routinely used in male Swiss mice previously submitted to a 15, 30 or 60-min transient occlusion of the right middle cerebral artery. We then evaluated behavioural changes up to 5 weeks in mice previously submitted to a 15-min ischemia. Behaviours according to the administration of imipramine or fluvoxamine at 1 and 5 weeks after a 15-min ischemia were finally evaluated. Transient ischemia was associated with a decrease in immobility in the FST performed 2 days after reperfusion while no changes were observed in 1 and 5 weeks post-ischemia groups. Changes were related neither to brain ischemia duration nor to infarct volume. At both 1 and 5 weeks after brain ischemia, a dramatic decrease in the antidepressant response to imipramine related to a decrease in climbing behaviour was observed while the effects of fluvoxamine were improved through an increase in both climbing and swimming. Behaviours in the FST were unrelated to any spontaneous motor activity changes. Responses to anti-depressant drugs are strongly modified in mice previously submitted to brain ischemia. Present results underline that not all antidepressant drugs are appropriate after ischemic stroke.

  4. Effects of approach and services under differential response on long term child safety and welfare.

    PubMed

    Loman, L Anthony; Siegel, Gary L

    2015-01-01

    An outcome analysis was conducted based on an extended follow-up of the implementation of differential response program reforms in Child Protective Services offices in 10 counties in a Midwestern U.S. State. Random assignment was conducted of families that were first determined to be appropriate for family assessments. Experimental families (n=2,382) were each assigned to a non-forensic family assessment, and control families (n=2,247) each received a forensic investigation. Families were assigned continuously over a 15-month period and then tracked from 45 to 60 months from the date of assignment. Detailed information on services provided and family responses was obtained via two subsamples of experimental and control families. Measures of family engagement and service reception and utilization were utilized to determine instrumental outcomes introduced through family assessments. Improved family engagement and increased and broadened services were found to have occurred, and it was theorized that these changes mediated extended outcomes. Extended outcomes included reductions of rates of subsequent screened-in reports of child maltreatment, proportions of families that experienced child removals, and instances of new safety threats and problems in parenting. Differences in outcomes were found among the participating counties with 4 counties accounting for most outcome differences. The relationships between instrumental and extended outcomes were discussed with suggestions for further research. PMID:24957562

  5. Long-Term Response of High-Elevation Lakes to Changes in Atmospheric Deposition and Air Temperature

    NASA Astrophysics Data System (ADS)

    Mast, M.; Turk, J. T.; Campbell, D. H.; Clow, D. W.; Ingersoll, G. P.

    2008-12-01

    High-elevation lakes are often sensitive indicators of environmental and climate change. Here we evaluate over two decades of water-quality data from a long-term monitoring network of remote high-mountain lakes in three Colorado wilderness areas. In two of the areas, lake sulfate concentrations have decreased by a factor of 2-3 times since the mid-1980s, which is consistent with declines in precipitation sulfate measured at 11 high-elevation NADP stations in Colorado. The downward trends in lake and precipitation chemistry are likely the result of regional declines in sulfate emissions from power plants and nonferrous metal smelters. By contrast, lake sulfate concentrations increased dramatically in the third wilderness area despite declines in atmospherically deposited sulfate. In lakes in these areas, sulfate is derived primarily from pyrite oxidation in contrast to the other wilderness areas where sulfate is dominated by atmospheric sources. It is hypothesized that the upward trend in sulfate reflects enhanced pyrite weathering caused by an increase in annual air temperature of about 2-degrees Celsius since the mid-1980's. These results indicate the water-quality response of remote lakes to improvements in air quality may be complicated by long-term changes in climate.

  6. Treatment Response and Long-Term Outcome of Peginterferon α and Ribavirin Therapy in Korean Patients with Chronic Hepatitis C

    PubMed Central

    Jung, Chang Ho; Um, Soon Ho; Kim, Tae Hyung; Yim, Sun Young; Suh, Sang Jun; Yim, Hyung Joon; Seo, Yeon Seok; Choi, Hyuk Soon; Chun, Hoon Jai

    2016-01-01

    Background/Aims Peginterferon plus ribavirin remains a standard therapy for patients with chronic hepatitis C (CHC) in Korea. We investigated the efficacy and long-term outcome of peginterferon and ribavirin therapy in Korean patients with CHC, particularly in relation to the stage of liver fibrosis. Methods The incidence of sustained virological response (SVR), hepatic decompensation, hepatocellular carcinoma, and liver-related death was analyzed in 304 patients with CHC; the patients were followed up for a median of 54 months. Results Among patients with HCV genotype 1, the SVR rate was 36.7% (18/49) and 67% (69/103) for patients with and without cirrhosis, respectively (p<0.001). For patients with non-1 HCV genotypes, the SVR rates were 86.0% (37/43) in cirrhotic patients and 86.2% (94/109) in noncirrhotic patients. SVR significantly reduced the risk of liver-related death, hepatic decompensation, and hepatocellular carcinoma, which had hazard ratios of 0.27, 0.16, and 0.22, respectively (all p<0.05). However, despite the SVR rate, patients with advanced fibrosis were still at risk of developing liver-related complications. Conclusions A relatively high SVR rate was achieved by peginterferon plus ribavirin therapy in Korean patients with CHC, which improved their long-term outcomes. However, all CHC patients with advanced hepatic fibrosis should receive close follow-up observations, even after successful antiviral treatment. PMID:27114417

  7. Long term response of a Concanavalin-A based fluorescence glucose sensing assay

    NASA Astrophysics Data System (ADS)

    Locke, Andrea K.; Cummins, Brian M.; Abraham, Alexander A.; Coté, Gerard L.

    2015-03-01

    Competitive binding assays comprised of the protein Concanavalin A (ConA) have shown potential for use in continuous glucose monitoring devices. However, its time-dependent, thermal instability can impact the lifetime of these ConA based assays. In an attempt to design sensors with longer in vivo lifetimes, different groups have immobilized the protein to various surfaces. For example, Ballerstadt et al. have shown that immobilizing ConA onto the interior of a micro-dialysis membrane and allowing dextran to be freely suspended within solution allowed for successful in vivo glucose sensing up to 16 days. This work explores the glucose response of an assay comprised of modified ConA and a single fluorescently labeled competing ligand in free solution to increase the in vivo sensing lifetime without immobilization,. The behavior of this assay in the presence of varying glucose concentrations is monitored via fluorescence anisotropy over a 30 day period.

  8. Mechanical Flexibility Reduces the Foreign Body Response to Long-Term Implanted Microelectrodes in Rabbit Cortex

    PubMed Central

    Sohal, Harbaljit S.; Clowry, Gavin J.

    2016-01-01

    Micromotion between the brain and implanted electrodes is a major contributor to the failure of invasive microelectrodes. Movements of the electrode tip cause recording instabilities while spike amplitudes decline over the weeks/months post-implantation due to glial cell activation caused by sustained mechanical trauma. We compared the glial response over a 26–96 week period following implantation in the rabbit cortex of microwires and a novel flexible electrode. Horizontal sections were used to obtain a depth profile of the radial distribution of microglia, astrocytes and neurofilament. We found that the flexible electrode was associated with decreased gliosis compared to the microwires over these long indwelling periods. This was in part due to a decrease in overall microgliosis and enhanced neuronal density around the flexible probe, especially at longer periods of implantation. PMID:27788240

  9. Spectral response of solvent-cast polyvinyl chloride (PVC) thin film used as a long-term UV dosimeter.

    PubMed

    Amar, Abdurazaq; Parisi, Alfio V

    2013-08-01

    The spectral response of solvent-cast polyvinyl chloride (PVC) thin film suitable for use as a long-term UV dosimeter has been determined by measuring the UV induced change in the 1064 cm(-1) peak intensity of the PVC's infrared (IR) spectra as a function of the wavelength of the incident radiation. Measurements using cut-off filters, narrow band-pass filters and monochromatic radiation showed that the 16 μm PVC film responds mainly to the UVB band. The maximum response was at 290 nm and decreasing exponentially with wavelength up to about 340 nm independent of temperature and exposure dose. The most suitable concentration (W/V%) of PVC/Tetrahydrofuran solution was found to be 10% and the best thickness for the dosimeter was determined as 16 μm.

  10. Effects of sildenafil on long-term retention of an inhibitory avoidance response in mice.

    PubMed

    Baratti, C M; Boccia, M M

    1999-12-01

    Sildenafil (1, 3, 10, and 30mg/kg, intraperitoneally (i.p.)), a cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5) inhibitor, facilitated retention performance of a one-trial step-through inhibitor avoidance task, when administered to male Swiss mice immediately after training, as indicated by performance on a retention test 48 h later. The dose-response curve was an inverted U in this dose range, although only the dose of 3 mg/kg of sildenafil produced significant effects. Sildenafil did not affect response latencies in mice not given the footshock on the training trial, indicating that the actions of sildenafil on retention were not due to non-specific proactive effects on retention performance. The effects of sildenafil (3 mg/kg, i.p.) were time-dependent, and the administration of sildenafil (3 mg/kg, i.p.) 30 min prior to the retention test did not affect retention in mice given post-training injections of vehicle or sildenafil (3 mg/kg, i.p.). However, the administration of sildenafil (3mg/kg, i.p.) 30 min before training also enhanced retention performace. Further, when mice were trained and received immediate post-training sildenafil (3 mg/kg) and were tested for retention either 1 week or 1 month later, at each retention interval the performance was comparable to that found with a 48-h retention interval. Finally, an enhancement of retention was also observed in female Swiss mice that received sildenafil (3 mg/kg, i.p.) immediately, but not 180min, after training. These findings could indicate that the actions of sildenafil on retention are not sex-dependent. The results suggest that sildenafil influences retention by modulating time-dependent mechanisms involved in memory storage and that the effects are long lasting. A possible participation of the nitric oxide (NO)-guanylyl cyclase-cGMP system also is suggested. PMID:10780288

  11. Evaluation of long-term antibody responses to two inactivated bovine viral diarrhoea virus (BVDV) vaccines.

    PubMed

    González, Ana M; Arnaiz, Ignacio; Yus, Eduardo; Eiras, Carmen; Sanjuán, María; Diéguez, Francisco J

    2014-03-01

    The aim of the present study was to determine the serological response of heifers after vaccination with two inactivated bovine viral diarrhoea virus (BVDV) vaccines by means of various ELISA tests. Three dairy farms were selected from the Galicia region of Spain. In each herd, a batch of heifers to be vaccinated for the first time was selected and followed for 15 months. Heifers from farm 1 (n=25) were vaccinated with Vaccine A, whereas heifers from farm 2 (n=16) were vaccinated with Vaccine B. Heifers from farm 3 (n=17), where no BVDV vaccines were used, acted as controls. Blood samples were analyzed periodically for BVDV antibodies, using five commercial ELISAs, based on BVDV p80 antigen or whole virus. At the end of the study, none of the animals vaccinated with Vaccine A seroconverted according to p80 antibody status, whereas up to 80% tested positive by ELISA against whole virus antigen. For the animals vaccinated with Vaccine B, 2/16 animals seroconverted according to p80 antibody ELISAs, whereas all had seroconverted according to the ELISA against whole virus antigen. In most cases, based on the use of ELISAs to detect specific antibodies against the p80 protein, at 15 months post-vaccination with inactivated BVDV vaccines the responses did not seem to interfere with detection of antibody to BVDV infection. However, the finding of a small proportion of vaccinated animals seropositive against BVDV p80 antigen suggests that antibodies that interfere with diagnosis of BVDV infection within the herd could exist, even when using p80 ELISAs.

  12. Effects of sildenafil on long-term retention of an inhibitory avoidance response in mice.

    PubMed

    Baratti, C M; Boccia, M M

    1999-12-01

    Sildenafil (1, 3, 10, and 30mg/kg, intraperitoneally (i.p.)), a cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5) inhibitor, facilitated retention performance of a one-trial step-through inhibitor avoidance task, when administered to male Swiss mice immediately after training, as indicated by performance on a retention test 48 h later. The dose-response curve was an inverted U in this dose range, although only the dose of 3 mg/kg of sildenafil produced significant effects. Sildenafil did not affect response latencies in mice not given the footshock on the training trial, indicating that the actions of sildenafil on retention were not due to non-specific proactive effects on retention performance. The effects of sildenafil (3 mg/kg, i.p.) were time-dependent, and the administration of sildenafil (3 mg/kg, i.p.) 30 min prior to the retention test did not affect retention in mice given post-training injections of vehicle or sildenafil (3 mg/kg, i.p.). However, the administration of sildenafil (3mg/kg, i.p.) 30 min before training also enhanced retention performace. Further, when mice were trained and received immediate post-training sildenafil (3 mg/kg) and were tested for retention either 1 week or 1 month later, at each retention interval the performance was comparable to that found with a 48-h retention interval. Finally, an enhancement of retention was also observed in female Swiss mice that received sildenafil (3 mg/kg, i.p.) immediately, but not 180min, after training. These findings could indicate that the actions of sildenafil on retention are not sex-dependent. The results suggest that sildenafil influences retention by modulating time-dependent mechanisms involved in memory storage and that the effects are long lasting. A possible participation of the nitric oxide (NO)-guanylyl cyclase-cGMP system also is suggested.

  13. Sympathoinhibitory and depressor responses to long-term infusion of nifedipine in spontaneously hypertensive rats on high-salt diet.

    PubMed

    Huang, B S; Murzenok, P P; Leenen, F H

    2000-12-01

    Short-term (by hour) intracerebroventricular (i.c.v.) or i.v. infusion of nifedipine at low rates evokes parallel decreases in renal sympathetic nerve activity (RSNA) and blood pressure (BP) in spontaneously hypertensive rats (SHR). In the present study, effects of long-term administration of nifedipine on BP and control of sympathetic tone were examined in SHR on a high-salt (8%) diet. From 6 to 8 weeks of age, for 2 weeks concomitant with taking a high-salt diet, rats were also treated with subcutaneous infusion of nifedipine at 10, 50, or 100 microg/kg/h or vehicle solvent as control using osmotic minipumps. At the end of the 2-week treatment period, mean arterial pressure (MAP), heart rate (HR), and RSNA at rest and in response to air-jet stress, i.c.v. injection of the alpha-adrenoceptor agonist guanabenz (25 microg), and i.v. injection of the ganglionic blocker hexamethonium were recorded in conscious rats. In rats on nifedipine 50 or 100 microg/kg/h, resting MAP was significantly lower (136+/-4 or 130+/-4 vs. 145+/-2 mm Hg in control rats, p < 0.05 for both), the sympathoinhibitory and depressor responses to i.c.v. guanabenz were significantly decreased, and the absolute decreases in MAP in response to i.v. injection of hexamethonium were significantly smaller. Sympathoexcitatory and pressor responses to air-jet stress, however, were not affected by nifedipine. Infusion of nifedipine at the three rates for 2 weeks caused concentrations of plasma nifedipine in a dose-related manner. Nifedipine was not detected in tissues of rats treated with 10 microg/kg/h nifedipine but was present in brain and other tissues of rats treated with nifedipine at the two higher rates. Thus in SHR on high-salt intake long-term treatment with nifedipine at 50 or 100 microg/kg/h decreased resting BP and the sympathetic component in BP control. In addition to possible peripheral effects, long-term administration of nifedipine may also act centrally to decrease sympathetic activity

  14. Climate change reduces offspring fitness in littoral spawners: a study integrating organismic response and long-term time-series.

    PubMed

    Bartolini, Fabrizio; Barausse, Alberto; Pörtner, Hans-Otto; Giomi, Folco

    2013-02-01

    Integrating long-term ecological observations with experimental findings on species response and tolerance to environmental stress supports an understanding of climate effects on population dynamics. Here, we combine the two approaches, laboratory experiments and analysis of multi-decadal time-series, to understand the consequences of climate anomalies and ongoing change for the population dynamics of a eurythermal littoral species, Carcinus aestuarii. For the generation of cause and effect hypotheses we investigated the thermal response of crab embryos at four developmental stages. We first measured metabolic rate variations in embryos following acute warming (16-24 °C) and after incubation at 20 and 24 °C for limited periods. All experiments consistently revealed differential thermal responses depending on the developmental stage. Temperature-induced changes in metabolic activity of early embryonic stages of blastula and gastrula suggested the onset of abnormal development. In contrast, later developmental stages, characterized by tissue and organ differentiation, were marginally affected by temperature anomalies, indicating enhanced resilience to thermal stress. Then, we extended these findings to a larger, population scale, by analyzing a time-series of C. aestuarii landings in the Venice lagoon from 1945 to 2010 (ripe crabs were recorded separately) in relation to temperature. Landings and extreme climatic events showed marked long-term and short-term variations. We found negative relationships between landings and thermal stress indices on both timescales, with time lags consistent with an impact on crab early life stages. When quantitatively evaluating the influence of thermal stress on population dynamics, we found that it has a comparable effect to that of the biomass of spawners. This work provides strong evidence that physiological responses to climatic anomalies translate into population-level changes and that apparently tolerant species may be

  15. From Gaged to Ungaged- Predicting Long-term Environmental Flows, and Ecosystems Responses.

    NASA Astrophysics Data System (ADS)

    Sengupta, A.; Adams, S. K.; Stein, E. D.; Mazor, R.; Bledsoe, B. P.

    2015-12-01

    Modern management needs, such as water supply, quality, and ecosystem protection place numerous demands on instream flows. Many regions are interested in developing numeric flow criteria as a way of ensuring maintenance of flow patterns that protect biological resources while meeting other demands. Developing flow criteria requires the capacity to generate reliable time series of the daily flow at any stream reach of interest and to relate flow patterns to biological indicators of stream health. Most stream reaches are not gaged, and it is impractical to develop detailed models for all reaches where flow alteration needs to be evaluated. We present a novel mechanistic approach to efficiently predict flows and flow alteration at all ungaged stream locations within a region of interest. We used an "ensemble approach" whereby a series of regionally representative models were developed and calibrated. New sites of interest are assigned to one of the ensemble models based on similarity of catchment properties. For southern California, we selected 43 gaged sites representing the range of geomorphology, and watershed characteristics of streams in the region. For each gaged site, we developed a hydrologic model (HEC-HMS) to predict daily flows for a period representing dry, wet and normal precipitation. The final goal is to relate flow alterations to ecological responses, the models were calibrated to three separate performance metrics that reflect conditions important for instream biological communities- proportion of low flow days, flashiness and Nash Sutcliffe efficiency for overall model performance. We cross-validated the models using a "jack-knife" approach. Models were assigned to novel 840 bioassessment sites based on the results of a Random Forest model that identified catchment properties that most affected the runoff patterns. Daily flow data for existing and "reference conditions" was simulated for a 23-year period for current and reference (undeveloped

  16. Water Relations, Gas Exchange, and Nutrient Response to a Long Term Constant Water Deficit

    NASA Technical Reports Server (NTRS)

    Berry, Wade L.; Goldstein, Guillermo; Dreschel, Thomas W.; Wheeler, Raymond M.; Sager, John C.; Knott, William M.

    1992-01-01

    Wheat plants (Triticum aestivum) were grown for 43 days in a micro-porous tube nutrient delivery system. Roots were unable to penetrate the microporous tube, but grew on the surface and maintained capillary contact with the nutrient solution on the inside of the tube through the 5-micron pores of the porous tube. Water potential in the system was controlled at -0.4, -0.8, and -3.0 kPa by adjusting the applied pressure (hydrostatic head) to the nutrient solution flowing through the microporous tubes. A relatively small decrease in applied water potential from -0.4 to -3.0 kPa resulted in a 34% reduction of shoot growth but only a moderate reduction in the midday leaf water potential from -1.3 to -1.7 MPa. Carbon dioxide assimilation decreased and water use efficiency increased with the more negative applied water potentials, while intercellular CO2 concentration remained constant. This was associated with a decrease in stomatal conductance to water vapor from 1.90 to 0.98 mol/(sq m sec) and a decrease in total apparent hydraulic conductance from 47 to 12 (micro)mol/(sec MPa). Although the applied water potentials were in the -0.4 to -3.0 kPa range, the actual water potential perceived by the plant roots appeared to be in the range of -0.26 to -0.38 MPa as estimated by the leaf water potential of bagged plants. The amount of K, Ca, Mg, Zn, Cu, and B accumulated with each unit of transpired water increased as the applied water potential became less negative. The increase in accumulation ranged from 1.4-fold for K to 2.2-fold for B. The physiological responses observed in this study in response to small constant differences in applied water potentials were much greater than expected from either the applied water potential or the observed plant water potential. Even though the micro-porous tube may not represent natural conditions and could possibly introduce morphological and physiological artifacts, it enables a high degree of control of water potential that

  17. Soil Microbial Community Responses to Long-Term Global Change Factors in a California Grassland

    NASA Astrophysics Data System (ADS)

    Qin, K.; Peay, K.

    2015-12-01

    Soil fungal and bacterial communities act as mediators of terrestrial carbon and nutrient cycling, and interact with the aboveground plant community as both pathogens and mutualists. However, these soil microbial communities are sensitive to changes in their environment. A better understanding of the response of soil microbial communities to global change may help to predict future soil microbial diversity, and assist in creating more comprehensive models of terrestrial carbon and nutrient cycles. This study examines the effects of four global change factors (increased temperature, increased variability in precipitation, nitrogen deposition, and CO2 enrichment) on soil microbial communities at the Jasper Ridge Global Change Experiment (JRGCE), a full-factorial global change manipulative experiment on three hectares of California grassland. While similar studies have examined the effects of global change on soil microbial communities, few have manipulated more factors or been longer in duration than the JRGCE, which began field treatments in 1998. We find that nitrogen deposition, CO2 enrichment, and increased variability in precipitation significantly affect the structure of both fungal and bacterial communities, and explain more of the variation in the community structures than do local soil chemistry or aboveground plant community. Fungal richness is correlated positively with soil nitrogen content and negatively with soil water content. Arbuscular mycorrhizal fungi (AMF), which associate closely with herbaceous plants' roots and assist in nutrient uptake, decrease in both richness and relative abundance in elevated CO2 treatments.

  18. Physiological responses of Tillandsia albida (Bromeliaceae) to long-term foliar metal application.

    PubMed

    Kováčik, Jozef; Klejdus, Bořivoj; Stork, František; Hedbavny, Josef

    2012-11-15

    The impact of 2-month foliar application of cadmium, nickel and their combination (10 μM) on Tillandsia albida was studied. Cadmium caused damage of tissue but assimilation pigments were depressed in Cd+Ni variant only. Stress-related parameters (ROS and peroxidase activities) were elevated by Cd and Cd+Ni while MDA content remained unaffected. Free amino acids accumulated the most in Ni alone but soluble proteins were not influenced. Among phenolic acids, mainly vanillin contributed to increase of their sum in all variants while soluble phenols even decreased in Cd+Ni and flavonols slightly increased in Cd variants. Phenolic enzymes showed negligible responses to almost all treatments. Mineral nutrients (K, Ca, Na, Mg, Fe, and Zn) were not affected by metal application but N content increased. Total Cd or Ni amounts reached over 400 μg g(-1) DW and were not affected if metal alone and combined treatment is compared while absorbed content differed (ca. 50% of total Cd was absorbed while almost all Ni was absorbed). These data indicate tolerance of T. albida to foliar metal application and together with strong xerophytic morphology, use for environmental studies is recommended. PMID:22989857

  19. Using historic aerial photography and paleohydrologic techniques to assess long-term ecological response to two Montana dam removals.

    PubMed

    Schmitz, Denine; Blank, Matt; Ammondt, Selita; Patten, Duncan T

    2009-07-01

    The restorative potential of dam removal on ecosystem function depends on the reversibility of dam effects and its operations. While dam removal is an established engineering practice, the need for an understanding of the ecological response remains. We used paleoflood hydrology, hydrologic modeling, and aerial photo interpretation to investigate the long-term ecologic responses to dam failure and breach. We investigated downstream geomorphic and vegetation responses to a dam failure (Pattengail Dam in 1927) and a controlled dam breach, which used natural sediment removal (Mystic Lake Dam in 1985). Our data showed vegetation responses indicative of channel and floodplain evolution at Pattengail. The size of the flood following the Pattengail dam failure initiated a series of channel adjustments and reworked over 19ha of floodplain downstream of the dam. In Mystic, we observed few flood stage indicators and a slight response in floodplain vegetation. We made several findings. (1) Dam removal effects on channel evolution and floodplain development depend on reach types and their responsiveness to flow regime change. (2) Ecologic response to dam removal depends on the sizes and timing of high flow events during and following removal. (3) Paleohydrology can be used to assess historic floods (>20 years). We see the utility of assessing the ecological responsiveness of a system to previous fluvial events or changes in flow regime. Informed about the character of a system based on its history, dam removal scientists can use these tools to set realistic restoration goals for removing a dam. PMID:19042079

  20. Using historic aerial photography and paleohydrologic techniques to assess long-term ecological response to two Montana dam removals.

    PubMed

    Schmitz, Denine; Blank, Matt; Ammondt, Selita; Patten, Duncan T

    2009-07-01

    The restorative potential of dam removal on ecosystem function depends on the reversibility of dam effects and its operations. While dam removal is an established engineering practice, the need for an understanding of the ecological response remains. We used paleoflood hydrology, hydrologic modeling, and aerial photo interpretation to investigate the long-term ecologic responses to dam failure and breach. We investigated downstream geomorphic and vegetation responses to a dam failure (Pattengail Dam in 1927) and a controlled dam breach, which used natural sediment removal (Mystic Lake Dam in 1985). Our data showed vegetation responses indicative of channel and floodplain evolution at Pattengail. The size of the flood following the Pattengail dam failure initiated a series of channel adjustments and reworked over 19ha of floodplain downstream of the dam. In Mystic, we observed few flood stage indicators and a slight response in floodplain vegetation. We made several findings. (1) Dam removal effects on channel evolution and floodplain development depend on reach types and their responsiveness to flow regime change. (2) Ecologic response to dam removal depends on the sizes and timing of high flow events during and following removal. (3) Paleohydrology can be used to assess historic floods (>20 years). We see the utility of assessing the ecological responsiveness of a system to previous fluvial events or changes in flow regime. Informed about the character of a system based on its history, dam removal scientists can use these tools to set realistic restoration goals for removing a dam.

  1. Historical land-use influences the long-term stream turbidity response to a wildfire.

    PubMed

    Harrison, Evan T; Dyer, Fiona; Wright, Daniel W; Levings, Chris

    2014-02-01

    Wildfires commonly result in an increase in stream turbidity. However, the influence of pre-fire land-use practices on post-fire stream turbidity is not well understood. The Lower Cotter Catchment (LCC) in south-eastern Australia is part of the main water supply catchment for Canberra with land in the catchment historically managed for a mix of conservation (native eucalypt forest) and pine (Pinus radiata) plantation. In January 2003, wildfires burned almost all of the native and pine forests in the LCC. A study was established in 2005 to determine stream post-fire turbidity recovery within the native and pine forest areas of the catchment. Turbidity data loggers were deployed in two creeks within burned native forest and burned pine forest areas to determine turbidity response to fire in these areas. As a part of the study, we also determined changes in bare soil in the native and pine forest areas since the fire. The results suggest that the time, it takes turbidity levels to decrease following wildfire, is dependent upon the preceding land-use. In the LCC, turbidity levels decreased more rapidly in areas previously with native vegetation compared to areas which were previously used for pine forestry. This is likely because of a higher percentage of bare soil areas for a longer period of time in the ex-pine forest estate and instream stores of fine sediment from catchment erosion during post-fire storm events. The results of our study show that the previous land-use may exert considerable control over on-going turbidity levels following a wildfire.

  2. Circulating hormones and pituitary responsiveness in young epileptic men receiving long-term antiepileptic medication.

    PubMed

    Macphee, G J; Larkin, J G; Butler, E; Beastall, G H; Brodie, M J

    1988-01-01

    Impairment of libido and sexual potency are commonly reported by male epileptic patients. This may be partly a consequence of medication. Circulating hormones were measured in 53 postpubertal male epileptic patients less than 45 years of age and in an age-matched control group (n = 40), consisting of 14 untreated epileptic patients and 26 unmedicated healthy subjects. A subgroup also underwent a combined gonadotrophin- and thyrotrophin-releasing hormone (LH-RH/TRH) pituitary stimulation test. Untreated patients did not differ from healthy subjects for any parameter, and their data were combined for comparison with the treated epileptic patients. Total testosterone (T), androstenedione, and basal follicle-stimulating hormone concentrations were similar in all patient groups. Patients receiving more than one drug had higher sex hormone binding globulin (SHBG) (p less than 0.01) and lower free T and dehydroepiandrosterone sulphate (DHAS) levels (both p less than 0.001) than controls. Carbamazepine (CBZ) monotherapy also reduced free T (p less than 0.05) and DHAS (p less than 0.001) and increased basal prolactin (p less than 0.01). In these two groups of patients, basal luteinising hormone (LH) was elevated (p less than 0.01), presumably as a pituitary response to increased T catabolism. There was a negative correlation between free T and circulating CBZ (r = -0.54, p less than 0.05) in the monotherapy patients. Phenytoin (PHT) was associated with a rise in SHBG (p less than 0.01) and a fall in DHAS (p less than 0.001). Basal LH was also elevated, but this just failed to reach statistical significance (p less than 0.1).(ABSTRACT TRUNCATED AT 250 WORDS)

  3. Historical Land-Use Influences the Long-Term Stream Turbidity Response to a Wildfire

    NASA Astrophysics Data System (ADS)

    Harrison, Evan T.; Dyer, Fiona; Wright, Daniel W.; Levings, Chris

    2014-02-01

    Wildfires commonly result in an increase in stream turbidity. However, the influence of pre-fire land-use practices on post-fire stream turbidity is not well understood. The Lower Cotter Catchment (LCC) in south-eastern Australia is part of the main water supply catchment for Canberra with land in the catchment historically managed for a mix of conservation (native eucalypt forest) and pine ( Pinus radiata) plantation. In January 2003, wildfires burned almost all of the native and pine forests in the LCC. A study was established in 2005 to determine stream post-fire turbidity recovery within the native and pine forest areas of the catchment. Turbidity data loggers were deployed in two creeks within burned native forest and burned pine forest areas to determine turbidity response to fire in these areas. As a part of the study, we also determined changes in bare soil in the native and pine forest areas since the fire. The results suggest that the time, it takes turbidity levels to decrease following wildfire, is dependent upon the preceding land-use. In the LCC, turbidity levels decreased more rapidly in areas previously with native vegetation compared to areas which were previously used for pine forestry. This is likely because of a higher percentage of bare soil areas for a longer period of time in the ex-pine forest estate and instream stores of fine sediment from catchment erosion during post-fire storm events. The results of our study show that the previous land-use may exert considerable control over on-going turbidity levels following a wildfire.

  4. Responses of Emergent Behaviour in Headwater Catchments to Long-term and Short-term Environmental Change

    NASA Astrophysics Data System (ADS)

    Tetzlaff, D.; Soulsby, C.; Malcolm, I. A.; Brewer, M. J.

    2007-12-01

    Emergent behaviour of hydrological processes at the catchment scale often results in relatively simple and predictable functional characteristics which are underpinned by heterogeneous, complex processes at the small scale. It is unclear how such small-scale processes are affected by long- and short-term perturbations in forcing factors affected by various environmental changes. This leads to uncertainty in how emergent behaviour will change and how hydrology and hydrochemistry will respond at the catchment scale. A powerful resource in improving predictions of such responses is applying advanced statistical analysis to long-term data sets of conservative tracers, particularly in gauged catchments that are subject to marked environmental change. Changes in tracer behaviour can provide an integrated insight into the emergent response of system functioning and its non-linear characteristics. In this paper, we present the analysis of long-term tracer data collected since 1982 in 2 small (ca. 1km2) experimental catchments in the Scottish highlands. These have been affected by marked change and variability in driving variables of climate, land cover and rainfall chemistry: Annual rainfall ranged between 1490 and 2500mm and an average 1°C increase in air temperatures was observed over the monitoring period. In addition, forestry operations resulted in 70% of each catchment being clear felled. Finally, air pollution legislation targeting acid emissions has improved the quality of precipitation, resulting in a marked reduction in acid deposition. Long-term (20 year, weekly) time-series analyses of two tracers are used to assess changes in emergent catchment behaviour. Chloride input-output time series are analysed using a range of residence time models which highlighted non-stationarity in the catchment mean residence times (which ranged between 2-11 months for individual years) and corresponding residence time distributions. At the catchments scale these were driven

  5. Exploring the long-term response of undisturbed Mediterranean catchments to changes in atmospheric inputs through time series analysis.

    PubMed

    Bernal, S; Belillas, C; Ibáñez, J J; Àvila, A

    2013-08-01

    The aim of this study was to gain insights on the potential hydrological and biogeochemical mechanisms controlling the response of two nested Mediterranean catchments to long-term changes in atmospheric inorganic nitrogen and sulphate deposition. One catchment was steep and fully forested (TM9, 5.9 ha) and the other one had gentler slopes and heathlands in the upper part while side slopes were steep and forested (TM0, 205 ha). Both catchments were highly responsive to the 45% decline in sulphate concentration measured in atmospheric deposition during the 1980s and 1990s, with stream concentrations decreasing by 1.4 to 3.4 μeq L(-1) y(-1). Long-term changes in inorganic nitrogen in both, atmospheric deposition and stream water were small compared to sulphate. The quick response to changes in atmospheric inputs could be explained by the small residence time of water (4-5 months) in these catchments (inferred from chloride time series variance analysis), which was attributed to steep slopes and the role of macropore flow bypassing the soil matrix during wet periods. The estimated residence time for sulphate (1.5-3 months) was substantially lower than for chloride suggesting unaccounted sources of sulphate (i.e., dry deposition, or depletion of soil adsorbed sulphate). In both catchments, inorganic nitrogen concentration in stream water was strongly damped compared to precipitation and its residence time was of the order of decades, indicating that this essential nutrient was strongly retained in these catchments. Inorganic nitrogen concentration tended to be higher at TM0 than at TM9 which was attributed to the presence of nitrogen fixing species in the heathlands. Our results indicate that these Mediterranean catchments react rapidly to environmental changes, which make them especially vulnerable to changes in atmospheric deposition.

  6. Early Response to Psychotherapy and Long-term Change in Worry Symptoms in Older Adults with Generalized Anxiety Disorder

    PubMed Central

    Bradford, Andrea; Cully, Jeffrey; Rhoades, Howard; Kunik, Mark; Kraus-Schuman, Cynthia; Wilson, Nancy; Stanley, Melinda

    2010-01-01

    Objectives To determine the association of early and long-term reductions in worry symptoms after cognitive behavioral therapy for generalized anxiety disorder (GAD) in older adults. Design Substudy of larger randomized controlled trial Setting Family medicine clinic and large multi-specialty health organization in Houston, TX, between March 2004 and August 2006 Participants Patients (N=76) 60 years or older with a principal or coprincipal diagnosis of GAD, excluding those with significant cognitive impairment, bipolar disorder, psychosis or active substance abuse. Intervention Cognitive behavioral therapy, up to 10 sessions over 12 weeks, or enhanced usual care (regular, brief telephone calls and referrals to primary care provider as needed) Measurements Penn State Worry Questionnaire (PSWQ) administered by telephone at baseline, 1 month (mid-treatment), 3 months (post-treatment), and at 3-month intervals through 15 months (1-year follow-up). We used binary logistic regression analysis to determine the association between early (1-month) response and treatment responder status (reduction of more than 8.5 points on the PSWQ) at 3 and 15 months. We also used hierarchical linear modeling to determine the relationship of early response to the trajectory of score change after post-treatment. Results Reduction in PSWQ scores after the first month predicted treatment response at post-treatment and follow-up, controlling for treatment arm and baseline PSWQ score. The magnitude of early reduction also predicted the slope of score change from post-treatment through the 15-month assessment. Conclusions Early symptom reduction is associated with long-term outcomes after psychotherapy in older adults with GAD. PMID:21427643

  7. Cross-regional prediction of long-term trajectory of stream water DOC response to climate change

    NASA Astrophysics Data System (ADS)

    Laudon, Hjalmar; Buttle, Jim; Carey, Sean K.; McDonnell, Jeff; McGuire, Kevin; Seibert, Jan; Shanley, Jamie; Soulsby, Chris; Tetzlaff, Doerthe

    2012-09-01

    There is no scientific consensus about how dissolved organic carbon (DOC) in surface waters is regulated. Here we combine recent literature data from 49 catchments with detailed stream and catchment process information from nine well established research catchments at mid- to high latitudes to examine the question of how climate controls stream water DOC. We show for the first time that mean annual temperature (MAT) in the range from -3° to +10° C has a strong control over the regional stream water DOC concentration in catchments, with highest concentrations in areas ranging between 0° and +3° C MAT. Although relatively large deviations from this model occur for individual streams, catchment topography appears to explain much of this divergence. These findings suggest that the long-term trajectory of stream water DOC response to climate change may be more predictable than previously thought.

  8. Differential responses of ammonia-oxidizing archaea and bacteria to long-term fertilization in a New England salt marsh

    PubMed Central

    Peng, Xuefeng; Yando, Erik; Hildebrand, Erica; Dwyer, Courtney; Kearney, Anne; Waciega, Alex; Valiela, Ivan; Bernhard, Anne E.

    2013-01-01

    Since the discovery of ammonia-oxidizing archaea (AOA), new questions have arisen about population and community dynamics and potential interactions between AOA and ammonia-oxidizing bacteria (AOB). We investigated the effects of long-term fertilization on AOA and AOB in the Great Sippewissett Marsh, Falmouth, MA, USA to address some of these questions. Sediment samples were collected from low and high marsh habitats in July 2009 from replicate plots that received low (LF), high (HF), and extra high (XF) levels of a mixed NPK fertilizer biweekly during the growing season since 1974. Additional untreated plots were included as controls (C). Terminal restriction fragment length polymorphism analysis of the amoA genes revealed distinct shifts in AOB communities related to fertilization treatment, but the response patterns of AOA were less consistent. Four AOB operational taxonomic units (OTUs) predictably and significantly responded to fertilization, but only one AOA OTU showed a significant pattern. Betaproteobacterial amoA gene sequences within the Nitrosospira-like cluster dominated at C and LF sites, while sequences related to Nitrosomonas spp. dominated at HF and XF sites. We identified some clusters of AOA sequences recovered primarily from high fertilization regimes, but other clusters consisted of sequences recovered from all fertilization treatments, suggesting greater physiological diversity. Surprisingly, fertilization appeared to have little impact on abundance of AOA or AOB. In summary, our data reveal striking patterns for AOA and AOB in response to long-term fertilization, and also suggest a missing link between community composition and abundance and nitrogen processing in the marsh. PMID:23346081

  9. Long-term caffeine consumption reverses tumor-induced suppression of the innate immune response in adult mice.

    PubMed

    Mandal, Anup; Poddar, Mrinal K

    2008-12-01

    Caffeine (1,3,7-trimethylxanthine), the active principle alkaloid of coffee ( Coffea arabica) and tea ( Camellia sinensis) possesses a restraining effect on tumor-induced suppression of the specific immune response in adult mice. The present study deals with the effect of long-term consumption of caffeine in the development of Ehrlich ascites carcinoma (EAC) cells in adult Swiss female mice, in relation to the innate immune response and tumor growth. Although the consumption of caffeine alone for more than 12 consecutive days did not affect the innate immune response parameters, continuation of its treatment following intraperitoneal EAC cell inoculation not only reduced the IN VIVO tumor growth but also reduced/restored the EAC cell-induced suppression of the innate immune response. These results suggest that caffeine may inhibit IN VIVO tumor growth through reduction of the cancer cell-induced suppression of the innate immune response. CNS:central nervous system EAC:Ehrlich ascites carcinoma ESR:erythrocyte sedimentation rate GABA:gamma-aminobutyric acid Hb:hemoglobin HPA:hypothalamic-pituitary-adrenal HPG:hypothalamic-pituitary-gonadal PCV:packed cell volume RBC:red blood cell WBC:white blood cell.

  10. DNA microarray analyses of the long-term adaptive response of Escherichia coli to acetate and propionate.

    PubMed

    Polen, T; Rittmann, D; Wendisch, V F; Sahm, H

    2003-03-01

    In its natural environment, Escherichia coli is exposed to short-chain fatty acids, such as acetic acid or propionic acid, which can be utilized as carbon sources but which inhibit growth at higher concentrations. DNA microarray experiments revealed expression changes during exponential growth on complex medium due to the presence of sodium acetate or sodium propionate at a neutral external pH. The adaptive responses to acetate and propionate were similar and involved genes in three categories. First, the RNA levels for chemotaxis and flagellum genes increased. Accordingly, the expression of chromosomal fliC'-'lacZ and flhDC'-'lacZ fusions and swimming motility increased after adaptation to acetate or propionate. Second, the expression of many genes that are involved in the uptake and utilization of carbon sources decreased, indicating some kind of catabolite repression by acetate and propionate. Third, the expression of some genes of the general stress response increased, but the increases were more pronounced after short-term exposure for this response than for the adaptive response. Adaptation to propionate but not to acetate involved increased expression of threonine and isoleucine biosynthetic genes. The gene expression changes after adaptation to acetate or propionate were not caused solely by uncoupling or osmotic effects but represented specific characteristics of the long-term response of E. coli to either compound. PMID:12620868

  11. Plant responses to short- and long-term exposures to high carbon dioxide levels in closed environments

    NASA Astrophysics Data System (ADS)

    Grodzinski, B.; Woodrow, L.; Leonardos, E. D.; Dixon, M.; Tsujita, M. J.

    1996-01-01

    When higher plants are exposed to elevated levels of CO_2 for both short- and long-term periods photosynthetic C-gain and photoassimilate export from leaves are generally increased. Water use efficiency is increased on a leaf area basis. During long-term exposures, photosynthesis rates on leaf and whole plant bases are altered in a species specific manner. The most common pattern in C_3 plants is an enhanced rate of whole plant photosynthesis in a well irradiated canopy. Nevertheless, in some herbaceous species prolonged exposure to high CO_2 results in remobilization of nitrogenous reserves (i.e., leaf protein degradation) and reduced rates of mature leaf photosynthesis when assayed at ambient CO_2 and O_2 levels. Both short- and long-term exposures to those CO_2 levels (i.e., 100 to 2,000 mul.l^-1) which modify photosynthesis and export, also modify both endogenous ethylene gas (C_2H_4) release, and substrate, 1-aminocyclopropane-1-carboxylic acid (ACC), saturated C_2H_4 release rates from irradiated leaves. Photosynthetically active canopy leaves contribute most of the C_2H_4 released from the canopy. Prolonged growth at high CO_2 results in a persistent increase in the rate of endogenous C_2H_4 release from leaves which can, only in part, be attributed to the increase of the endogenous pools of C_2H_4 pathway intermediates (e.g., methionine, M-ACC, and ACC). The capacity for increasing the rate of C_2H_4 release in response to short-term exposures to varying CO_2 levels does not decline after prolonged growth at high CO_2. When leaves, whole plants, and model canopies of tomato plants are exposed to exogenous C_2H_4 a reduction in the rate of photosynthesis can, in each case, be attributed to the classical effects of C_2H_4 on plant development and morphology. The effect of C_2H_4 on CO_2 gas exchange of plant canopies is shown to be dependent on the canopy leaf area index.

  12. The American bullfrog (Rana catesbeiana) exhibits differential cardiovascular responses to LTC4 after short- and long-term cold exposure.

    PubMed

    Sun, J; Herman, C A

    1995-02-01

    Mean arterial pressure (MAP) and heart rate (HR) responses to leukotriene (LT)C4 have been studied in warm (W-A) and cold-acclimated (C-A) America bullfrogs, Rana catesbeiana, but nothing is known about how the length of cold treatment affects the response to LTC4 or how responses are affected by return to room temperature following cold exposure. In this study, two groups of frogs were placed at 5 degrees either for 30 days (C-A) or for 1 day (W-C) and LTC4 dose-response curves obtained at 5 degrees. After the frogs were removed from cold, the baseline MAP and HR were monitored for 120 min, and dose-response curves were repeated at 2, 24, and 48 hr. The LTC4 dose-response curves were also obtained during the three experimental days on frogs which had never been placed at cold temperature (W-A). C-A frogs showed greater MAP response than W-C frogs at 5 degrees, and also showed the greatest MAP response of the three groups 48 hr after the animals were removed from cold temperature. These data suggest that up regulation of LTC4 receptors may have occurred in C-A frogs. Cold exposure alone eliminated reflex HR response to LTC4 in both C-A and W-C groups. Longer duration of action was also observed in these groups. The results demonstrate that short-term cold exposure can affect the response to LTC4 in frogs, but that physiological adjustments occur in frogs undergoing long-term exposure.

  13. Targeted demersal fish species exhibit variable responses to long-term protection from fishing at the Houtman Abrolhos Islands

    NASA Astrophysics Data System (ADS)

    Bornt, Katrina R.; McLean, Dianne L.; Langlois, Tim J.; Harvey, Euan S.; Bellchambers, Lynda M.; Evans, Scott N.; Newman, Stephen J.

    2015-12-01

    Natural fluctuations in the abundance and length of targeted fish are often disrupted by acute environmental changes and anthropogenic impacts, particularly fishing pressure. Long-term assessments of targeted fish populations inside and outside areas closed to fishing are often necessary to elucidate these effects, yet few of these studies extend over long time periods. We assessed trends in the abundance and length of six targeted fish species in areas open and closed to fishing on seven occasions spanning a 9-year period (2005-2010 and 2013) at the Houtman Abrolhos Islands, Western Australia. Shallow (8-12 m) and deep (22-26 m) coral-dominated reef sites were sampled across four geographically separated island groups using baited remote underwater stereo-video (stereo-BRUV). Between 2005 and 2010, populations of Lethrinus miniatus, Lethrinus nebulosus, Plectropomus leopardus, and Chrysophrys auratus became increasingly dominated by larger individuals, potentially indicative of an ageing population. Between 2010 and 2013, however, there was a significant increase in the proportion of smaller L. miniatus, L. nebulosus, and P. leopardus in both open and closed areas, reflecting increased recruitment perhaps due to changing environmental conditions associated with a marine heat wave anomaly. This recruitment pulse was not observed for the other species in this study ( Chr. auratus, Choerodon rubescens, and Glaucosoma hebraicum). Lethrinus miniatus, L. nebulosus, Chr. auratus, and P. leopardus were larger in closed areas relative to open areas; however, they were not more abundant. These complex responses to protection also varied across sampling years for certain species (e.g., P. leopardus). Monitoring changes over the long-term in areas open and closed to fishing provides a sound basis for separating environmental variability from that associated with fishing mortality, which is crucial for optimising fisheries management.

  14. Reduced responses to heroin-cue-induced craving in the dorsal striatum: effects of long-term methadone maintenance treatment.

    PubMed

    Wang, Yarong; Wang, Hanyue; Li, Wei; Zhu, Jia; Gold, Mark S; Zhang, Dongsheng; Wang, Lina; Li, Yongbin; Yan, Xuejiao; Cheng, Jiajie; Li, Qiang; Wang, Wei

    2014-10-01

    Methadone maintenance treatment (MMT) is safe and effective for heroin addiction, but the neural basis of the length effects of long-term MMT on brain activity during craving in former heroin addicts is unclear. This study explored it by comparing the brain activations of heroin addicts with different length of MMT during pictorial presentation of heroin-related cue. Fifteen male former heroin addicts successfully treated by MMT less than 1 year (Group A), 15 matched patients with 2-3 year MMT (Group B) and 17 healthy controls underwent functional magnetic resonance imaging while heroin-related and neutral stimuli were present to them. Subjective cue-elicited craving was measured with visual analog scale before and after imaging. Then, partial correlation analysis to reveal the relationship between drug-related blood oxygen level dependent (BOLD) signal intensity and heroin or methadone use history. Finally, self-reported craving was not different between Group A and B before and after scanning. Compared with Group A, Group B had a significant reduced brain activity to heroin-related minus neural cues in the bilateral caudate. After controlling for the variable heroin use history, the drug-related BOLD signal intensity in the bilateral caudate was negatively correlated with MMT duration and total methadone consumption. When MMT history was controlled, the drug-related activity intensity in right caudate had a positive correlation with heroin daily dosage. Long-term MMT may improve heroin-craving response by modulating the impaired function in the bilateral dorsal striatum caused by former heroin use.

  15. Long-term adaptive response to high-frequency light signals in the unicellular photosynthetic eukaryote Dunaliella salina.

    PubMed

    Combe, Charlotte; Hartmann, Philipp; Rabouille, Sophie; Talec, Amelie; Bernard, Olivier; Sciandra, Antoine

    2015-06-01

    Productivity of microalgal cultivation processes is tightly related to photosynthetic efficiency, and therefore to light availability at the cell scale. In an agitated, highly turbid suspension,the light signal received by a single phytoplankton cell moving in a dense culture is a succession of flashes. The growth characteristics of microalgae under such dynamic light conditions are thus fundamental information to understand nonlinear properties of the photosynthetic process and to improve cultivation process design and operation. Studies of the long term consequences of dynamic illumination regime on photosynthesis require a very specific experimental set-up where fast varying signals are applied on the long term. In order to investigate the growth response of the unicellular photosynthetic eukaryote Dunaliella salina (Chlorophyceae) to intermittent light exposure, different light regimes using LEDs with the same average total light dose were applied in continuous cultures. Flashing light with different durations of light flashes (△t of 30 s, 15 s, 2 s and 0.1 s) followed by dark periods of variable length (0.67 ≤ L:D ≤ 2) yielding flash frequencies in the range 0.017-5 Hz, were compared to continuous illumination. Specific growth rate, photosynthetic pigments, lipid productivity and elemental composition were measured on two duplicates for each irradiance condition. The different treatments of intermittent light led to specific growth rates ranging from 0.25 to 0.93 day(-1) . While photosynthetic efficiency was enhanced with increased flash frequency, no significant differences were observed in the particular carbon and chlorophyll content. Pigment analysis showed that within this range of flash frequency, cells progressively photoacclimated to the average light intensity.

  16. Renal responses to long-term carotid baroreflex activation therapy in patients with drug-resistant hypertension.

    PubMed

    Alnima, Teba; de Leeuw, Peter W; Tan, Frans E S; Kroon, Abraham A

    2013-06-01

    Carotid baroreflex activation has been demonstrated to provide enduring reductions in arterial blood pressure. The aim of this study was to investigate the effect of long-term therapy on renal function. A total of 322 patients were enrolled in the Rheos Pivotal Trial. Group 1 consisted of 236 patients who started baroreflex activation therapy 1 month after device implantation, whereas in the 86 patients from group 2 the device was activated 6 months later. Serum creatinine and urine albumin/creatinine ratio were collected at screening (before device activation), and at months 6 and 12. Multilevel statistical analyses were adjusted for various covariables. Serum creatinine increased from 78 to 84 μmol/L, and glomerular filtration rate decreased from 92 to 87 mL/min per 1.73 m(2) in group 1 at month 6 (P<0.05). These values did not change any further after 12 months of therapy. Patients with highest glomerular filtration rate showed the greatest decrease in glomerular filtration. Group 2 showed the same trends as group 1 even before device activation at month 6. Systolic blood pressure reduction seemed to be significantly related to the change in glomerular filtration rate in both groups. Albumin/creatinine ratio did not change in both groups during follow-up. In conclusion, baroreflex activation therapy in hypertensive patients is associated with an initial mild decrease in glomerular filtration rate, which may be considered as a normal hemodynamic response to the drop in blood pressure. Long-term treatment does not result in further decrease in renal function, indicating baroreflex activation as a safe and effective therapy.

  17. Long term response stability of a well-type ionization chamber used in calibration of high dose rate brachytherapy sources

    PubMed Central

    Vandana, S.; Sharma, S. D.

    2010-01-01

    Well-type ionization chamber is often used to measure strength of brachytherapy sources. This study aims to check long term response stability of High Dose Rate (HDR)-1000 Plus well-type ionization chamber in terms of reference air kerma rate (RAKR) of a reference 137Cs brachytherapy source and recommend an optimum frequency of recalibration. An HDR-1000 Plus well-type ionization chamber, a reference 137Cs brachytherapy source (CDCSJ5), and a MAX-4000 electrometer were used in this study. The HDR-1000 Plus well-type chamber was calibrated in terms of reference air kerma rate by the Standards Laboratory of the International Atomic Energy Agency (IAEA), Vienna. The response of the chamber was verified at regular intervals over a period of eight years using the reference 137Cs source. All required correction factors were applied in the calculation of the RAKR of the 137Cs source. This study reveals that the response of the HDR-1000 Plus well-type chamber was well within ±0.5% for about three years after calibration/recalibration. However, it shows deviations larger than ±0.5% after three years of calibration/recalibration and the maximum variation in response of the chamber during an eight year period was 1.71%. The optimum frequency of recalibration of a high dose rate well-type chamber should be three years. PMID:20589119

  18. Long term response stability of a well-type ionization chamber used in calibration of high dose rate brachytherapy sources.

    PubMed

    Vandana, S; Sharma, S D

    2010-04-01

    Well-type ionization chamber is often used to measure strength of brachytherapy sources. This study aims to check long term response stability of High Dose Rate (HDR)-1000 Plus well-type ionization chamber in terms of reference air kerma rate (RAKR) of a reference (137)Cs brachytherapy source and recommend an optimum frequency of recalibration. An HDR-1000 Plus well-type ionization chamber, a reference (137)Cs brachytherapy source (CDCSJ5), and a MAX-4000 electrometer were used in this study. The HDR-1000 Plus well-type chamber was calibrated in terms of reference air kerma rate by the Standards Laboratory of the International Atomic Energy Agency (IAEA), Vienna. The response of the chamber was verified at regular intervals over a period of eight years using the reference (137)Cs source. All required correction factors were applied in the calculation of the RAKR of the (137)Cs source. This study reveals that the response of the HDR-1000 Plus well-type chamber was well within +/-0.5% for about three years after calibration/recalibration. However, it shows deviations larger than +/-0.5% after three years of calibration/recalibration and the maximum variation in response of the chamber during an eight year period was 1.71%. The optimum frequency of recalibration of a high dose rate well-type chamber should be three years.

  19. Physics-Based Continuous Simulation of Long-Term Near-Surface Hydrologic Response for the Coos Bay Experimental Catchment

    NASA Astrophysics Data System (ADS)

    Ebel, B. A.; Loague, K.; Montgomery, D. R.; Dietrich, W. E.

    2007-12-01

    The study reported here employed the physics-based InHM to simulate continuous hydrologic response from 1990 through 1996 for the Coos Bay (CB1) experimental catchment. InHM dynamically simulates 3D variably- saturated subsurface flow using Richards equation and 2D surface and open channel flow using the diffusion- wave approximation to the depth-integrated shallow-water equations. The uniqueness of the boundary-value problem (BVP) used in a previous study to successfully simulate three sprinkling experiments was assessed, via model performance evaluation against piezometric and discharge data, for 33 events extracted from the seven- year continuous record. The simulations conducted in this effort suggest the potential for interaction between the deeper water table and near-surface hydrologic response, which is in agreement with the detailed field observations made during the CB1 sprinkling experiments. The InHM simulations could not adequately reproduce the observed pore-water pressures, suggesting that detailed characterization of the locations and connectivities of bedrock fractures would be necessary to simulate distributed hydrologic response at locations where bedrock fracture flow is important. The results from this study suggest that uniqueness is a problem for physics-based models when employing a BVP used successfully for smaller magnitude storms to simulate larger storms. The long-term simulations conducted here, combined with previous event-based hydrologic- response simulations and field-based observations, highlight the challenges in characterizing / simulating fractured bedrock flow at small catchments like CB1.

  20. Classification of childhood asthma phenotypes and long-term clinical responses to inhaled anti-inflammatory medications

    PubMed Central

    Howrylak, Judie A.; Fuhlbrigge, Anne L.; Strunk, Robert C.; Zeiger, Robert S.; Weiss, Scott T.; Raby, Benjamin A.

    2014-01-01

    Background Although recent studies have identified the presence of phenotypic clusters in asthmatic patients, the clinical significance and temporal stability of these clusters have not been explored. Objective Our aim was to examine the clinical relevance and temporal stability of phenotypic clusters in children with asthma. Methods We applied spectral clustering to clinical data from 1041 children with asthma participating in the Childhood Asthma Management Program. Posttreatment randomization follow-up data collected over 48 months were used to determine the effect of these clusters on pulmonary function and treatment response to inhaled anti-inflammatory medication. Results We found 5 reproducible patient clusters that could be differentiated on the basis of 3 groups of features: atopic burden, degree of airway obstruction, and history of exacerbation. Cluster grouping predicted long-term asthma control, as measured by the need for oral prednisone (P < .0001) or additional controller medications (P = .001), as well as longitudinal differences in pulmonary function (P < .0001). We also found that the 2 clusters with the highest rates of exacerbation had different responses to inhaled corticosteroids when compared with the other clusters. One cluster demonstrated a positive response to both budesonide (P = .02) and nedocromil (P = .01) compared with placebo, whereas the other cluster demonstrated minimal responses to both budesonide (P = .12) and nedocromil (P = .56) compared with placebo. Conclusion Phenotypic clustering can be used to identify longitudinally consistent and clinically relevant patient subgroups, with implications for targeted therapeutic strategies and clinical trials design. PMID:24892144

  1. On the importance of spectral responsivity of Robertson-Berger-type ultraviolet radiometers for long-term observations.

    PubMed

    di Sarra, Alcide; Disterhoft, Patrick; DeLuisi, John J

    2002-07-01

    A system to determine the spectral responsivity of ultraviolet (UV) radiometers has been developed and is routinely operated at the Central Ultraviolet Calibration Facility, at the National Oceanic and Atmospheric Administration. The instrument and the measurement methodologies are described. Results of measurements from thermally controlled broadband UV radiometers of the Robertson-Berger (R-B)-type are described. Systematic differences in the spectral response curves for these instruments have been detected. The effect of these differences on the field operation of UV-B radiometers has been studied by calculating the instrumental response from modeled UV spectra. The differences of the weighted spectral UV irradiances, measured by two radiometers with different spectral response functions, caused by the daily variation in the position of the sun were estimated for fixed values of total ozone, altitude and albedo, and for cloud-free conditions. These differences increase with the solar zenith angle and are as large as 8%. Larger differences in the instrumental response may be produced by ozone variations. Thus, care must be taken when analyzing data from R-B radiometers and comparing results from different instruments. Routine cycling of UV-B radiometers in operative networks without a careful determination of the spectral responsivity, or small drifts of the spectral responsivity, may strongly affect the accuracy of UV radiation measurements and produce an erroneous trend. Because of the possible differences among radiometers, it would not be practical to derive the long-term behavior of UV radiation without routine and thorough characterization of the spectral responsivities of the instruments. PMID:12126309

  2. Physiological responses to fertilization recorded in tree rings: isotopic lessons from a long-term fertilization trial.

    PubMed

    Brooks, J Renée; Coulombe, Rob

    2009-06-01

    Nitrogen fertilizer applications are common land use management tools, but details on physiological responses to these applications are often lacking, particularly for long-term responses over decades of forest management. We used tree ring growth patterns and stable isotopes to understand long-term physiological responses to fertilization using a controlled fertilization experiment begun in 1964 in Washington State (USA), in which three levels of nitrogen fertilizer were applied: 157, 314; and 471 kg/ha. Basal area increment (BAI) increased more than fourfold in the highest treatment to twofold in the lowest, and a significant increase in BAI was observed for 20 years. Latewood delta 13C sharply decreased by 1.4 per thousand after fertilization and was significantly lower than controls for four years, but no differences existed between fertilization levels, and the effect disappeared after four years, indicating that intrinsic water use efficiency (A/gs) increased in response to fertilization. Earlywood delta 13C showed similar trends but was more variable. Latewood delta 18O increased significantly above controls by approximately 2 per thousand in all treatments, but the duration differed with treatment level, with the effect being longer for higher levels of fertilization and lasting as long as nine years after fertilization. Because source water and relative humidity were the same between experimental plots, we interpreted the delta 18O increase with treatment as a decrease in leaf-level transpiration. Earlywood delta 18O did not show any treatment effects. Because the Pacific Northwest has a mediterranean climate with dry summers, we speculated that fertilization caused a substantial increase in leaf area, causing the trees to transpire themselves into drought stress during the late summer. We estimate from the delta 18O data that stomatal conductance (gs) was reduced by approximately 30%. Using the delta 13C data to estimate assimilation rates (A), A during

  3. Silica Vesicle Nanovaccine Formulations Stimulate Long-Term Immune Responses to the Bovine Viral Diarrhoea Virus E2 Protein

    PubMed Central

    Mody, Karishma T.; Mahony, Donna; Cavallaro, Antonino S.; Zhang, Jun; Zhang, Bing; Mahony, Timothy J.; Yu, Chengzhong; Mitter, Neena

    2015-01-01

    Bovine Viral Diarrhoea Virus (BVDV) is one of the most serious pathogen, which causes tremendous economic loss to the cattle industry worldwide, meriting the development of improved subunit vaccines. Structural glycoprotein E2 is reported to be a major immunogenic determinant of BVDV virion. We have developed a novel hollow silica vesicles (SV) based platform to administer BVDV-1 Escherichia coli-expressed optimised E2 (oE2) antigen as a nanovaccine formulation. The SV-140 vesicles (diameter 50 nm, wall thickness 6 nm, perforated by pores of entrance size 16 nm and total pore volume of 0.934 cm3g-1) have proven to be ideal candidates to load oE2 antigen and generate immune response. The current study for the first time demonstrates the ability of freeze-dried (FD) as well as non-FD oE2/SV140 nanovaccine formulation to induce long-term balanced antibody and cell mediated memory responses for at least 6 months with a shortened dosing regimen of two doses in small animal model. The in vivo ability of oE2 (100 μg)/SV-140 (500 μg) and FD oE2 (100 μg)/SV-140 (500 μg) to induce long-term immunity was compared to immunisation with oE2 (100 μg) together with the conventional adjuvant Quil-A from the Quillaja saponira (10 μg) in mice. The oE2/SV-140 as well as the FD oE2/SV-140 nanovaccine generated oE2-specific antibody and cell mediated responses for up to six months post the final second immunisation. Significantly, the cell-mediated responses were consistently high in mice immunised with oE2/SV-140 (1,500 SFU/million cells) at the six-month time point. Histopathology studies showed no morphological changes at the site of injection or in the different organs harvested from the mice immunised with 500 μg SV-140 nanovaccine compared to the unimmunised control. The platform has the potential for developing single dose vaccines without the requirement of cold chain storage for veterinary and human applications. PMID:26630001

  4. Silica Vesicle Nanovaccine Formulations Stimulate Long-Term Immune Responses to the Bovine Viral Diarrhoea Virus E2 Protein.

    PubMed

    Mody, Karishma T; Mahony, Donna; Cavallaro, Antonino S; Zhang, Jun; Zhang, Bing; Mahony, Timothy J; Yu, Chengzhong; Mitter, Neena

    2015-01-01

    Bovine Viral Diarrhoea Virus (BVDV) is one of the most serious pathogen, which causes tremendous economic loss to the cattle industry worldwide, meriting the development of improved subunit vaccines. Structural glycoprotein E2 is reported to be a major immunogenic determinant of BVDV virion. We have developed a novel hollow silica vesicles (SV) based platform to administer BVDV-1 Escherichia coli-expressed optimised E2 (oE2) antigen as a nanovaccine formulation. The SV-140 vesicles (diameter 50 nm, wall thickness 6 nm, perforated by pores of entrance size 16 nm and total pore volume of 0.934 cm3 g(-1)) have proven to be ideal candidates to load oE2 antigen and generate immune response. The current study for the first time demonstrates the ability of freeze-dried (FD) as well as non-FD oE2/SV140 nanovaccine formulation to induce long-term balanced antibody and cell mediated memory responses for at least 6 months with a shortened dosing regimen of two doses in small animal model. The in vivo ability of oE2 (100 μg)/SV-140 (500 μg) and FD oE2 (100 μg)/SV-140 (500 μg) to induce long-term immunity was compared to immunisation with oE2 (100 μg) together with the conventional adjuvant Quil-A from the Quillaja saponira (10 μg) in mice. The oE2/SV-140 as well as the FD oE2/SV-140 nanovaccine generated oE2-specific antibody and cell mediated responses for up to six months post the final second immunisation. Significantly, the cell-mediated responses were consistently high in mice immunised with oE2/SV-140 (1,500 SFU/million cells) at the six-month time point. Histopathology studies showed no morphological changes at the site of injection or in the different organs harvested from the mice immunised with 500 μg SV-140 nanovaccine compared to the unimmunised control. The platform has the potential for developing single dose vaccines without the requirement of cold chain storage for veterinary and human applications. PMID:26630001

  5. Caffeine alters the behavioural and body temperature responses to mephedrone without causing long-term neurotoxicity in rats.

    PubMed

    Shortall, Sinead E; Green, A Richard; Fone, Kevin Cf; King, Madeleine V

    2016-07-01

    Administration of caffeine with 3,4-methylenedioxymethamphetamine (MDMA) alters the pharmacological properties of MDMA in rats. The current study examined whether caffeine alters the behavioural and neurochemical effects of mephedrone, which has similar psychoactive effects to MDMA. Rats received either saline, mephedrone (10 mg/kg), caffeine (10 mg/kg) or combined caffeine and mephedrone intraperitoneally twice weekly on consecutive days for three weeks. Locomotor activity (days 1 and 16), novel object discrimination (NOD, day 2), elevated plus maze (EPM) exploration (day 8), rectal temperature changes (day 9) and pre-pulse inhibition (PPI) of acoustic startle response (day 15) were assessed. Seven days after the final injection, brain regions were collected for the measurement of 5-hydroxytryptamine (5-HT), dopamine and their metabolites. Combined caffeine and mephedrone further enhanced the locomotor response observed following either drug administered alone, and converted mephedrone-induced hypothermia to hyperthermia. Co-administration also abolished mephedrone-induced anxiogenic response on the EPM, but had no effect on NOD or PPI. Importantly, no long-term neurotoxicity was detected following repeated mephedrone alone or when co-administered with caffeine. In conclusion, the study suggests a potentially dangerous effect of concomitant caffeine and mephedrone, and highlights the importance of taking polydrug use into consideration when investigating the acute adverse effect profile of popular recreational drugs.

  6. Caffeine alters the behavioural and body temperature responses to mephedrone without causing long-term neurotoxicity in rats.

    PubMed

    Shortall, Sinead E; Green, A Richard; Fone, Kevin Cf; King, Madeleine V

    2016-07-01

    Administration of caffeine with 3,4-methylenedioxymethamphetamine (MDMA) alters the pharmacological properties of MDMA in rats. The current study examined whether caffeine alters the behavioural and neurochemical effects of mephedrone, which has similar psychoactive effects to MDMA. Rats received either saline, mephedrone (10 mg/kg), caffeine (10 mg/kg) or combined caffeine and mephedrone intraperitoneally twice weekly on consecutive days for three weeks. Locomotor activity (days 1 and 16), novel object discrimination (NOD, day 2), elevated plus maze (EPM) exploration (day 8), rectal temperature changes (day 9) and pre-pulse inhibition (PPI) of acoustic startle response (day 15) were assessed. Seven days after the final injection, brain regions were collected for the measurement of 5-hydroxytryptamine (5-HT), dopamine and their metabolites. Combined caffeine and mephedrone further enhanced the locomotor response observed following either drug administered alone, and converted mephedrone-induced hypothermia to hyperthermia. Co-administration also abolished mephedrone-induced anxiogenic response on the EPM, but had no effect on NOD or PPI. Importantly, no long-term neurotoxicity was detected following repeated mephedrone alone or when co-administered with caffeine. In conclusion, the study suggests a potentially dangerous effect of concomitant caffeine and mephedrone, and highlights the importance of taking polydrug use into consideration when investigating the acute adverse effect profile of popular recreational drugs. PMID:27257032

  7. Long-term plasticity determines the postsynaptic response to correlated afferents with multivesicular short-term synaptic depression

    PubMed Central

    Bird, Alex D.; Richardson, Magnus J. E.

    2014-01-01

    Synchrony in a presynaptic population leads to correlations in vesicle occupancy at the active sites for neurotransmitter release. The number of independent release sites per presynaptic neuron, a synaptic parameter recently shown to be modified during long-term plasticity, will modulate these correlations and therefore have a significant effect on the firing rate of the postsynaptic neuron. To understand how correlations from synaptic dynamics and from presynaptic synchrony shape the postsynaptic response, we study a model of multiple release site short-term plasticity and derive exact results for the crosscorrelation function of vesicle occupancy and neurotransmitter release, as well as the postsynaptic voltage variance. Using approximate forms for the postsynaptic firing rate in the limits of low and high correlations, we demonstrate that short-term depression leads to a maximum response for an intermediate number of presynaptic release sites, and that this leads to a tuning-curve response peaked at an optimal presynaptic synchrony set by the number of neurotransmitter release sites per presynaptic neuron. These effects arise because, above a certain level of correlation, activity in the presynaptic population is overly strong resulting in wastage of the pool of releasable neurotransmitter. As the nervous system operates under constraints of efficient metabolism it is likely that this phenomenon provides an activity-dependent constraint on network architecture. PMID:24523691

  8. Association of Clinical Response and Long-term Outcome Among Patients With Biopsied Orbital Pseudotumor Receiving Modern Radiation Therapy

    SciTech Connect

    Prabhu, Roshan S.; Kandula, Shravan; Liebman, Lang; Wojno, Ted H.; Hayek, Brent; Hall, William A.; Shu, Hui-Kuo; Crocker, Ian

    2013-03-01

    Purpose: To retrospectively evaluate institutional outcomes for patients treated with modern radiation therapy (RT) for biopsied orbital pseudotumor (OP). Methods and Materials: Twenty patients (26 affected orbits) with OP were treated with RT between January 2002 and December 2011. All patients underwent biopsy with histopathologic exclusion of other disease processes. Sixteen patients (80%) were treated with intensity modulated RT, 3 (15%) with opposed lateral beams, and 1 (5%) with electrons. Median RT dose was 27 Gy (range 25.2-30.6 Gy). Response to RT was evaluated at 4 months post-RT. Partial response (PR) was defined as improvement in orbital symptoms without an increase in steroid dose. Complete response (CR) 1 and CR 2 were defined as complete resolution of orbital symptoms with reduction in steroid dose (CR 1) or complete tapering of steroids (CR 2). The median follow-up period was 18.6 months (range 4-81.6 months). Results: Seventeen patients (85%) demonstrated response to RT, with 7 (35%), 1 (5%), and 9 (45%) achieving a PR, CR 1, and CR 2, respectively. Of the 17 patients who had ≥PR at 4 months post-RT, 6 (35%) experienced recurrence of symptoms. Age (>46 years vs ≤46 years, P=.04) and clinical response to RT (CR 2 vs CR 1/PR, P=.05) were significantly associated with pseudotumor recurrence. Long-term complications were seen in 7 patients (35%), including 4 with cataract formation, 1 with chronic dry eye, 1 with enophthalmos, and 1 with keratopathy. Conclusions: RT is an effective treatment for improving symptoms and tapering steroids in patients with a biopsy supported diagnosis of OP. Older age and complete response to RT were associated with a significantly reduced probability of symptom recurrence. The observed late complications may be related to RT, chronic use of steroids/immunosuppressants, medical comorbidities, or combination of factors.

  9. Long-term effects of warming and ocean acidification are modified by seasonal variation in species responses and environmental conditions.

    PubMed

    Godbold, Jasmin A; Solan, Martin

    2013-01-01

    Warming of sea surface temperatures and alteration of ocean chemistry associated with anthropogenic increases in atmospheric carbon dioxide will have profound consequences for a broad range of species, but the potential for seasonal variation to modify species and ecosystem responses to these stressors has received little attention. Here, using the longest experiment to date (542 days), we investigate how the interactive effects of warming and ocean acidification affect the growth, behaviour and associated levels of ecosystem functioning (nutrient release) for a functionally important non-calcifying intertidal polychaete (Alitta virens) under seasonally changing conditions. We find that the effects of warming, ocean acidification and their interactions are not detectable in the short term, but manifest over time through changes in growth, bioturbation and bioirrigation behaviour that, in turn, affect nutrient generation. These changes are intimately linked to species responses to seasonal variations in environmental conditions (temperature and photoperiod) that, depending upon timing, can either exacerbate or buffer the long-term directional effects of climatic forcing. Taken together, our observations caution against over emphasizing the conclusions from short-term experiments and highlight the necessity to consider the temporal expression of complex system dynamics established over appropriate timescales when forecasting the likely ecological consequences of climatic forcing.

  10. Long-term responses of rainforest erosional systems at different spatial scales to selective logging and climatic change.

    PubMed

    Walsh, R P D; Bidin, K; Blake, W H; Chappell, N A; Clarke, M A; Douglas, I; Ghazali, R; Sayer, A M; Suhaimi, J; Tych, W; Annammala, K V

    2011-11-27

    Long-term (21-30 years) erosional responses of rainforest terrain in the Upper Segama catchment, Sabah, to selective logging are assessed at slope, small and large catchment scales. In the 0.44 km(2) Baru catchment, slope erosion measurements over 1990-2010 and sediment fingerprinting indicate that sediment sources 21 years after logging in 1989 are mainly road-linked, including fresh landslips and gullying of scars and toe deposits of 1994-1996 landslides. Analysis and modelling of 5-15 min stream-suspended sediment and discharge data demonstrate a reduction in storm-sediment response between 1996 and 2009, but not yet to pre-logging levels. An unmixing model using bed-sediment geochemical data indicates that 49 per cent of the 216 t km(-2) a(-1) 2009 sediment yield comes from 10 per cent of its area affected by road-linked landslides. Fallout (210)Pb and (137)Cs values from a lateral bench core indicate that sedimentation rates in the 721 km(2) Upper Segama catchment less than doubled with initially highly selective, low-slope logging in the 1980s, but rose 7-13 times when steep terrain was logged in 1992-1993 and 1999-2000. The need to keep steeplands under forest is emphasized if landsliding associated with current and predicted rises in extreme rainstorm magnitude-frequency is to be reduced in scale.

  11. Long-term effects of warming and ocean acidification are modified by seasonal variation in species responses and environmental conditions

    PubMed Central

    Godbold, Jasmin A.; Solan, Martin

    2013-01-01

    Warming of sea surface temperatures and alteration of ocean chemistry associated with anthropogenic increases in atmospheric carbon dioxide will have profound consequences for a broad range of species, but the potential for seasonal variation to modify species and ecosystem responses to these stressors has received little attention. Here, using the longest experiment to date (542 days), we investigate how the interactive effects of warming and ocean acidification affect the growth, behaviour and associated levels of ecosystem functioning (nutrient release) for a functionally important non-calcifying intertidal polychaete (Alitta virens) under seasonally changing conditions. We find that the effects of warming, ocean acidification and their interactions are not detectable in the short term, but manifest over time through changes in growth, bioturbation and bioirrigation behaviour that, in turn, affect nutrient generation. These changes are intimately linked to species responses to seasonal variations in environmental conditions (temperature and photoperiod) that, depending upon timing, can either exacerbate or buffer the long-term directional effects of climatic forcing. Taken together, our observations caution against over emphasizing the conclusions from short-term experiments and highlight the necessity to consider the temporal expression of complex system dynamics established over appropriate timescales when forecasting the likely ecological consequences of climatic forcing. PMID:23980249

  12. Long-term responses of rainforest erosional systems at different spatial scales to selective logging and climatic change

    PubMed Central

    Walsh, R. P. D.; Bidin, K.; Blake, W. H.; Chappell, N. A.; Clarke, M. A.; Douglas, I.; Ghazali, R.; Sayer, A. M.; Suhaimi, J.; Tych, W.; Annammala, K. V.

    2011-01-01

    Long-term (21–30 years) erosional responses of rainforest terrain in the Upper Segama catchment, Sabah, to selective logging are assessed at slope, small and large catchment scales. In the 0.44 km2 Baru catchment, slope erosion measurements over 1990–2010 and sediment fingerprinting indicate that sediment sources 21 years after logging in 1989 are mainly road-linked, including fresh landslips and gullying of scars and toe deposits of 1994–1996 landslides. Analysis and modelling of 5–15 min stream-suspended sediment and discharge data demonstrate a reduction in storm-sediment response between 1996 and 2009, but not yet to pre-logging levels. An unmixing model using bed-sediment geochemical data indicates that 49 per cent of the 216 t km−2 a−1 2009 sediment yield comes from 10 per cent of its area affected by road-linked landslides. Fallout 210Pb and 137Cs values from a lateral bench core indicate that sedimentation rates in the 721 km2 Upper Segama catchment less than doubled with initially highly selective, low-slope logging in the 1980s, but rose 7–13 times when steep terrain was logged in 1992–1993 and 1999–2000. The need to keep steeplands under forest is emphasized if landsliding associated with current and predicted rises in extreme rainstorm magnitude-frequency is to be reduced in scale. PMID:22006973

  13. Long-term responses of rainforest erosional systems at different spatial scales to selective logging and climatic change.

    PubMed

    Walsh, R P D; Bidin, K; Blake, W H; Chappell, N A; Clarke, M A; Douglas, I; Ghazali, R; Sayer, A M; Suhaimi, J; Tych, W; Annammala, K V

    2011-11-27

    Long-term (21-30 years) erosional responses of rainforest terrain in the Upper Segama catchment, Sabah, to selective logging are assessed at slope, small and large catchment scales. In the 0.44 km(2) Baru catchment, slope erosion measurements over 1990-2010 and sediment fingerprinting indicate that sediment sources 21 years after logging in 1989 are mainly road-linked, including fresh landslips and gullying of scars and toe deposits of 1994-1996 landslides. Analysis and modelling of 5-15 min stream-suspended sediment and discharge data demonstrate a reduction in storm-sediment response between 1996 and 2009, but not yet to pre-logging levels. An unmixing model using bed-sediment geochemical data indicates that 49 per cent of the 216 t km(-2) a(-1) 2009 sediment yield comes from 10 per cent of its area affected by road-linked landslides. Fallout (210)Pb and (137)Cs values from a lateral bench core indicate that sedimentation rates in the 721 km(2) Upper Segama catchment less than doubled with initially highly selective, low-slope logging in the 1980s, but rose 7-13 times when steep terrain was logged in 1992-1993 and 1999-2000. The need to keep steeplands under forest is emphasized if landsliding associated with current and predicted rises in extreme rainstorm magnitude-frequency is to be reduced in scale. PMID:22006973

  14. Biochemical responses and mitochondrial mediated activation of apoptosis on long-term effect of aspartame in rat brain.

    PubMed

    Ashok, Iyaswamy; Sheeladevi, Rathinasamy

    2014-01-01

    Aspartame, an artificial sweetener, is very widely used in many foods and beverages. But there are controversies about its metabolite which is marked for its toxicity. Hence it is believed to be unsafe for human use. Previous studies have reported on methanol exposure with involvements of free radicals on excitotoxicity of neuronal apoptosis. Hence, this present study is proposed to investigate whether or not chronic aspartame (FDA approved Daily Acceptable Intake (ADI),40 mg/kg bwt) administration could release methanol, and whether or not it can induce changes in brain oxidative stress status and gene and protein expression of anti-apoptotic Bcl-2 and pro-apoptotic Bax and caspase-3 in the rat brain region. To mimic the human methanol metabolism, Methotrexate (MTX)-treated Wistar strain male albino rats were used and after the oral administration of aspartame, the effects were studied along with controls and MTX-treated controls. Aspartame exposure resulted with a significant increase in the enzymatic activity in protein carbonyl, lipid peroxidation levels, superoxide dismutase, glutathione-S-transferase, glutathione peroxidase and catalase activity in (aspartame MTX)-treated animals and with a significant decrease in reduced glutathione, glutathione reductase and protein thiol, pointing out the generation of free radicals. The gene and protein expression of pro apoptotic marker Bax showed a marked increase whereas the anti-apoptotic marker Bcl-2 decreased markedly indicating the aspartame is harmful at cellular level. It is clear that long term aspartame exposure could alter the brain antioxidant status, and can induce apoptotic changes in brain.

  15. Long-term survival correlates with immunological responses in renal cell carcinoma patients treated with mRNA-based immunotherapy.

    PubMed

    Rittig, Susanne M; Haentschel, Maik; Weimer, Katrin J; Heine, Annkristin; Müller, Martin R; Brugger, Wolfram; Horger, Marius S; Maksimovic, Olga; Stenzl, Arnulf; Hoerr, Ingmar; Rammensee, Hans-Georg; Holderried, Tobias A; Kanz, Lothar; Pascolo, Steve; Brossart, Peter

    2016-05-01

    Renal cell carcinoma (RCC) is an immunogenic tumor for which immunotherapeutic approaches could be associated with clinically relevant responses. It was recently shown, that induction of T-cell responses against multiple tumor-associated antigen (TAA) epitopes results in prolonged overall survival in RCC patients. In 2003-2005, we performed a phase I/II trial testing an mRNA-based vaccine formulation consisting of a mixture of in vitro transcribed RNA coding for six different TAAs (MUC1, CEA, Her2/neu, telomerase, survivin, MAGE-A1) in 30 metastatic RCC (mRCC) patients. In the first 14 patients, vaccinations were applied i.d. on days 0, 14, 28, and 42. In the consecutive 16 patients, an intensified protocol consisting of i.d. injections (daily on days 0-3, 7-10, 28, and 42) was used. After the respective induction periods, patients in both cohorts were vaccinated monthly until tumor progression. At survival update performed in July 2015, one of the 30 patients was still alive. One patient was lost to follow-up. Median survival of 24.5 mo (all patients) and 89 mo (favorable risk patients) exceeded predicted survival according to Memorial Sloan Kettering Cancer Center (MSKCC) risk score. Impressively, long-term survivors displayed immunological responses to the applied antigens while vice versa no patient without detectable immune response had survived more than 33 mo. The current survival update shows a clear correlation between survival and immunological responses to TAAs encoded by the naked mRNA vaccine. This is one of the first vaccination studies and the only RNA trial that reports on safety and efficacy after a follow-up of more than 10 y. PMID:27467913

  16. Biochemical Response to Androgen Deprivation Therapy Before External Beam Radiation Therapy Predicts Long-term Prostate Cancer Survival Outcomes

    SciTech Connect

    Zelefsky, Michael J.; Gomez, Daniel R.; Polkinghorn, William R.; Pei, Xin; Kollmeier, Marisa

    2013-07-01

    Purpose: To determine whether the response to neoadjuvant androgen deprivation therapy (ADT) defined by a decline in prostate-specific antigen (PSA) to nadir values is associated with improved survival outcomes after external beam radiation therapy (EBRT) for prostate cancer. Methods and Materials: One thousand forty-five patients with localized prostate cancer were treated with definitive EBRT in conjunction with neoadjuvant and concurrent ADT. A 6-month course of ADT was used (3 months during the neoadjuvant phase and 2 to 3 months concurrently with EBRT). The median EBRT prescription dose was 81 Gy using a conformal-based technique. The median follow-up time was 8.5 years. Results: The 10-year PSA relapse-free survival outcome among patients with pre-radiation therapy PSA nadirs of ≤0.3 ng/mL was 74.3%, compared with 57.7% for patients with higher PSA nadir values (P<.001). The 10-year distant metastases-free survival outcome among patients with pre-radiation therapy PSA nadirs of ≤0.3 ng/mL was 86.1%, compared with 78.6% for patients with higher PSA nadir values (P=.004). In a competing-risk analysis, prostate cancer-related deaths were also significantly reduced among patients with pre-radiation therapy PSA nadirs of <0.3 ng/mL compared with higher values (7.8% compared with 13.7%; P=.009). Multivariable analysis demonstrated that the pre-EBRT PSA nadir value was a significant predictor of long-term biochemical tumor control, distant metastases-free survival, and cause-specific survival outcomes. Conclusions: Pre-radiation therapy nadir PSA values of ≤0.3 ng/mL after neoadjuvant ADT were associated with improved long-term biochemical tumor control, reduction in distant metastases, and prostate cancer-related death. Patients with higher nadir values may require alternative adjuvant therapies to improve outcomes.

  17. Long-term change of site response after the M W 9.0 Tohoku earthquake in Japan

    NASA Astrophysics Data System (ADS)

    Wu, Chunquan; Peng, Zhigang

    2012-12-01

    The recent M W 9.0 off the Pacific coast of Tohoku earthquake is the largest recorded earthquake in Japan's history. The Tohoku main shock and its aftershocks generated widespread strong shakings as large as ~3000 Gal along the east coast of Japan. Wu and Peng (2011) found clear drop of resonant frequency of up to 70% during the Tohoku main shock at 6 sites and correlation of resonance (peak) frequency and peak ground acceleration (PGA) during the main shock. Here we follow that study and systematically analyze long-term changes of material properties in the shallow crust from one year before to 5 months after the Tohoku main shock, using seismic data recorded by the Japanese Strong Motion Network KiK-Net. We use sliding window spectral ratios computed from a pair of surface and borehole stations to track the temporal changes in the site response of 6 sites. Our results show two stages of logarithmic recovery after a sharp drop of resonance frequency during the Tohoku main shock. The first stage is a rapid recovery within several hundred seconds to several hours, and the second stage is a slow recovery of more than five months. We also investigate whether the damage caused by the Tohoku main shock could make the near surface layers more susceptible to further damages, but we do not observe clear changes in susceptibility to further damage before and after the Tohoku main shock.

  18. Extracting the Weather Response from Long-Term Hourly Electricity Load Data in an Eastern Region of the United States

    NASA Astrophysics Data System (ADS)

    Wang, Y.; Bielicki, J. M.

    2015-12-01

    Understanding climate change impacts on the energy sector requires understanding how electricity consumption responds to weather conditions, such as temperature. This study applied a state-space model to 22 years (1993-2014) of publicly available hourly load data from the Pennsylvania-New Jersey-Maryland (PJM) Interconnection. Prior to our analysis, we removed long-term trends which are usually considered to be related to socio-economic and demographic factors, in the various sub-regions of the PJM interconnection to focus on the response to weather. The state-space models were comprised of weekly cycle, autoregressive-moving average components, and regressions on temperature, relative humidity, and wind speed variables. A separate model was fitted for each hour of the day. We found that the best relationship between temperature and electricity load may occur with a lag depending on the time of the day. The base temperature giving optimal mean squared residual magnitude was found to be lower than the 65 oF (18.3 oC) value traditionally used for cooling- and heating-degree days calculations. Relative humidity, wind speed, and sometimes a past temperature-variability term also increased the predicative power of the model. A few outliers existed in the hourly load dataset, which were not predicted well by the model, but the other residuals of the models were <=5% of the observed values. Removal of the outliers did not significantly impact the estimated model structure or parameters.

  19. Prior Exposure to Interpersonal Violence and Long-term Treatment Response for Boys with a Disruptive Behavior Disorder

    PubMed Central

    Shenk, Chad E.; Dorn, Lorah D.; Kolko, David J.; Rausch, Joseph R.; Insana, Salvatore P.

    2016-01-01

    Interpersonal violence (IPV) is common in children with a disruptive behavior disorder (DBD) and increases the risk for greater DBD symptom severity, callous-unemotional (CU) traits, and neuroendocrine disruption. Thus, IPV may make it difficult to change symptom trajectories for families receiving DBD interventions given these relationships. The current study examined whether IPV prior to receiving treatment for a DBD predicted trajectories of a variety of associated outcomes, specifically DBD symptoms, CU traits, and cortisol concentrations. Boys with a DBD diagnosis (N = 66; age range = 6-11 years; 54.5% of whom experienced IPV prior to treatment) of either oppositional defiant disorder or conduct disorder participated in a randomized clinical trial and were assessed 3 years following treatment. Multilevel modeling demonstrated that prior IPV predicted smaller rates of change in DBD symptoms, CU traits, and cortisol trajectories, indicating less benefit from intervention. The effect size magnitudes of IPV were large for each outcome (d = 0.88 – 1.07). These results suggest that IPV is a predictor of the long-term treatment response for boys with a DBD. Including trauma-focused components into existing DBD interventions may be worth testing to improve treatment effectiveness for boys with a prior history of IPV. PMID:25270151

  20. Response of peatland ecosystem to climatic changes in Central-Eastern Europe: a long-term ecological approach

    NASA Astrophysics Data System (ADS)

    Slowinska, S.; Marcisz, K.; Slowinski, M. M.; Lamentowicz, M.; Lamentowicz, L.; Mitchell, E. A.

    2013-12-01

    Northern peatlands play a major role in the global carbon cycle, and they are valuable archives of the past environmental change. The functioning of these ecosystems depends on the feedback between biotic and abiotic factors that are still not fully understood. In our study we investigated relationships between hydrological (groundwater level fluctuations, hydrochemistry), meteorological conditions near the ground (air temperature and humidity, photosynthetically active radiation, leaf wetness, temperature and moisture of Sphagnum) and biological factors: vegetation patterns, Sphagnum mosses growth and testate amoebae (Protists) composition. We designed a long-term ecological study site in a Sphagnum mire in Northern Poland that consisted of five meteorological micro stations and eleven piezometers located in two transects at 5,95 ha area. During the growing season 2012 we observed significant differences between plots in terms of micrometeorological and hydrological conditions that resulted in different Sphagnum increments and seasonal dynamics of testate amoebae communities. Our study is very important to better understand how temperate peatlands react to the climatic change and recent warming. Obtained results revealed a high sensitivity of bog ecosystem to e.g. short-term heat waves. Further research will be conducted to model a potential response of Sphagnum peatland to the future climate change. Project supported by Polish National Science Centre grant No. NN306060940 and the grant PSPB-013/2010 from Switzerland through the Swiss Contribution to the enlarged European Union.

  1. Dose-response efficacy and long-term effect of the hypocholesterolemic effect of octadecylpectinamide in rats.

    PubMed

    Marounek, Milan; Volek, Zdeněk; Dušková, Dagmar; Tůma, Jan; Taubner, Tomáš

    2013-09-12

    The dose-response efficiency and long-term effect of the hypocholesterolemic effect of octadecylpectinamide was examined in female rats fed diets containing cholesterol at 10 g/kg. In our first experiment, amidated pectin supplied at 20 g/kg, 40 g/kg and 60 g/kg significantly decreased serum cholesterol from 3.32 μmol/ml (control) to 1.23 μmol/ml in a dose-dependent manner. In a second experiment, the hypocholesterolemic effect of amidated pectin supplied at 20 g/kg persisted after 3 months of feeding. In both experiments, the amidated pectin significantly decreased the concentrations of cholesterol in hepatic tissue and triacylglycerols in serum. The serum concentration of aspartate aminotransferase significantly increased in rats fed amidated pectin at 60 g/kg for 4 weeks, and at 20 g/kg for 3 months. In conclusion, amidated pectin at a low dose and used for a period shorter than 3 months might be considered as an effective hypocholesterolemic and lipid-lowering agent that may substitute typical antilipidemic drugs.

  2. Long-term monitoring at multiple trophic levels suggests heterogeneity in responses to climate change in the Canadian Arctic tundra

    PubMed Central

    Gauthier, Gilles; Bêty, Joël; Cadieux, Marie-Christine; Legagneux, Pierre; Doiron, Madeleine; Chevallier, Clément; Lai, Sandra; Tarroux, Arnaud; Berteaux, Dominique

    2013-01-01

    Arctic wildlife is often presented as being highly at risk in the face of current climate warming. We use the long-term (up to 24 years) monitoring records available on Bylot Island in the Canadian Arctic to examine temporal trends in population attributes of several terrestrial vertebrates and in primary production. Despite a warming trend (e.g. cumulative annual thawing degree-days increased by 37% and snow-melt date advanced by 4–7 days over a 23-year period), we found little evidence for changes in the phenology, abundance or productivity of several vertebrate species (snow goose, foxes, lemmings, avian predators and one passerine). Only primary production showed a response to warming (annual above-ground biomass of wetland graminoids increased by 123% during this period). We nonetheless found evidence for potential mismatches between herbivores and their food plants in response to warming as snow geese adjusted their laying date by only 3.8 days on average for a change in snow-melt of 10 days, half of the corresponding adjustment shown by the timing of plant growth (7.1 days). We discuss several reasons (duration of time series, large annual variability, amplitude of observed climate change, nonlinear dynamic or constraints imposed by various rate of warming with latitude in migrants) to explain the lack of response by herbivores and predators to climate warming at our study site. We also show how length and intensity of monitoring could affect our ability to detect temporal trends and provide recommendations for future monitoring. PMID:23836788

  3. Long-term monitoring at multiple trophic levels suggests heterogeneity in responses to climate change in the Canadian Arctic tundra.

    PubMed

    Gauthier, Gilles; Bêty, Joël; Cadieux, Marie-Christine; Legagneux, Pierre; Doiron, Madeleine; Chevallier, Clément; Lai, Sandra; Tarroux, Arnaud; Berteaux, Dominique

    2013-08-19

    Arctic wildlife is often presented as being highly at risk in the face of current climate warming. We use the long-term (up to 24 years) monitoring records available on Bylot Island in the Canadian Arctic to examine temporal trends in population attributes of several terrestrial vertebrates and in primary production. Despite a warming trend (e.g. cumulative annual thawing degree-days increased by 37% and snow-melt date advanced by 4-7 days over a 23-year period), we found little evidence for changes in the phenology, abundance or productivity of several vertebrate species (snow goose, foxes, lemmings, avian predators and one passerine). Only primary production showed a response to warming (annual above-ground biomass of wetland graminoids increased by 123% during this period). We nonetheless found evidence for potential mismatches between herbivores and their food plants in response to warming as snow geese adjusted their laying date by only 3.8 days on average for a change in snow-melt of 10 days, half of the corresponding adjustment shown by the timing of plant growth (7.1 days). We discuss several reasons (duration of time series, large annual variability, amplitude of observed climate change, nonlinear dynamic or constraints imposed by various rate of warming with latitude in migrants) to explain the lack of response by herbivores and predators to climate warming at our study site. We also show how length and intensity of monitoring could affect our ability to detect temporal trends and provide recommendations for future monitoring.

  4. Long-term monitoring at multiple trophic levels suggests heterogeneity in responses to climate change in the Canadian Arctic tundra.

    PubMed

    Gauthier, Gilles; Bêty, Joël; Cadieux, Marie-Christine; Legagneux, Pierre; Doiron, Madeleine; Chevallier, Clément; Lai, Sandra; Tarroux, Arnaud; Berteaux, Dominique

    2013-08-19

    Arctic wildlife is often presented as being highly at risk in the face of current climate warming. We use the long-term (up to 24 years) monitoring records available on Bylot Island in the Canadian Arctic to examine temporal trends in population attributes of several terrestrial vertebrates and in primary production. Despite a warming trend (e.g. cumulative annual thawing degree-days increased by 37% and snow-melt date advanced by 4-7 days over a 23-year period), we found little evidence for changes in the phenology, abundance or productivity of several vertebrate species (snow goose, foxes, lemmings, avian predators and one passerine). Only primary production showed a response to warming (annual above-ground biomass of wetland graminoids increased by 123% during this period). We nonetheless found evidence for potential mismatches between herbivores and their food plants in response to warming as snow geese adjusted their laying date by only 3.8 days on average for a change in snow-melt of 10 days, half of the corresponding adjustment shown by the timing of plant growth (7.1 days). We discuss several reasons (duration of time series, large annual variability, amplitude of observed climate change, nonlinear dynamic or constraints imposed by various rate of warming with latitude in migrants) to explain the lack of response by herbivores and predators to climate warming at our study site. We also show how length and intensity of monitoring could affect our ability to detect temporal trends and provide recommendations for future monitoring. PMID:23836788

  5. Transient Shifts of Incubation Temperature Reveal Immediate and Long-Term Transcriptional Response in Chicken Breast Muscle Underpinning Resilience and Phenotypic Plasticity.

    PubMed

    Naraballobh, Watcharapong; Trakooljul, Nares; Murani, Eduard; Brunner, Ronald; Krischek, Carsten; Janisch, Sabine; Wicke, Michael; Ponsuksili, Siriluck; Wimmers, Klaus

    2016-01-01

    Variations in egg incubation temperatures can have acute or long-term effects on gene transcription in avian species. Altered gene expression may, in turn, affect muscle traits in poultry and indirectly influence commercial production. To determine how changes in eggshell temperature affect gene expression, incubation temperatures were varied [36.8°C (low), 37.8°C (control), 38.8°C (high)] at specific time periods reflecting two stages of myogenesis [embryonic days (ED) 7-10 and 10-13]. Gene expression was compared between interventions and matching controls by microarrays in broiler breast muscle at ED10 or ED13 and post-hatch at day 35. Early (ED7-10) high incubation temperature (H10ΔC) resulted in 1370 differentially expressed genes (DEGs) in embryos. Ingenuity pathway analysis revealed temporary activation of cell maintenance, organismal development, and survival ability genes, but these effects were not maintained in adults. Late high incubation temperature (ED10-13) (H13ΔC) had slightly negative impacts on development of cellular components in embryos, but a cumulative effect was observed in adults, in which tissue development and nutrition metabolism were affected. Early low incubation temperature (L10ΔC) produced 368 DEGs, most of which were down-regulated and involved in differentiation and formation of muscle cells. In adults, this treatment down-regulated pathways of transcriptional processes, but up-regulated cell proliferation. Late low temperature incubation (L13ΔC) produced 795 DEGs in embryos, and activated organismal survival and post-transcriptional regulation pathways. In adults this treatment activated cellular and organ development, nutrition and small molecule activity, and survival rate, but deactivated size of body and muscle cells. Thermal interventions during incubation initiate immediate and delayed transcriptional responses that are specific for timing and direction of treatment. Interestingly, the transcriptional response to

  6. Transient Shifts of Incubation Temperature Reveal Immediate and Long-Term Transcriptional Response in Chicken Breast Muscle Underpinning Resilience and Phenotypic Plasticity

    PubMed Central

    Naraballobh, Watcharapong; Trakooljul, Nares; Murani, Eduard; Brunner, Ronald; Krischek, Carsten; Janisch, Sabine; Ponsuksili, Siriluck

    2016-01-01

    Variations in egg incubation temperatures can have acute or long-term effects on gene transcription in avian species. Altered gene expression may, in turn, affect muscle traits in poultry and indirectly influence commercial production. To determine how changes in eggshell temperature affect gene expression, incubation temperatures were varied [36.8°C (low), 37.8°C (control), 38.8°C (high)] at specific time periods reflecting two stages of myogenesis [embryonic days (ED) 7–10 and 10–13]. Gene expression was compared between interventions and matching controls by microarrays in broiler breast muscle at ED10 or ED13 and post-hatch at day 35. Early (ED7-10) high incubation temperature (H10ΔC) resulted in 1370 differentially expressed genes (DEGs) in embryos. Ingenuity pathway analysis revealed temporary activation of cell maintenance, organismal development, and survival ability genes, but these effects were not maintained in adults. Late high incubation temperature (ED10-13) (H13ΔC) had slightly negative impacts on development of cellular components in embryos, but a cumulative effect was observed in adults, in which tissue development and nutrition metabolism were affected. Early low incubation temperature (L10ΔC) produced 368 DEGs, most of which were down-regulated and involved in differentiation and formation of muscle cells. In adults, this treatment down-regulated pathways of transcriptional processes, but up-regulated cell proliferation. Late low temperature incubation (L13ΔC) produced 795 DEGs in embryos, and activated organismal survival and post-transcriptional regulation pathways. In adults this treatment activated cellular and organ development, nutrition and small molecule activity, and survival rate, but deactivated size of body and muscle cells. Thermal interventions during incubation initiate immediate and delayed transcriptional responses that are specific for timing and direction of treatment. Interestingly, the transcriptional response to

  7. Transient Shifts of Incubation Temperature Reveal Immediate and Long-Term Transcriptional Response in Chicken Breast Muscle Underpinning Resilience and Phenotypic Plasticity.

    PubMed

    Naraballobh, Watcharapong; Trakooljul, Nares; Murani, Eduard; Brunner, Ronald; Krischek, Carsten; Janisch, Sabine; Wicke, Michael; Ponsuksili, Siriluck; Wimmers, Klaus

    2016-01-01

    Variations in egg incubation temperatures can have acute or long-term effects on gene transcription in avian species. Altered gene expression may, in turn, affect muscle traits in poultry and indirectly influence commercial production. To determine how changes in eggshell temperature affect gene expression, incubation temperatures were varied [36.8°C (low), 37.8°C (control), 38.8°C (high)] at specific time periods reflecting two stages of myogenesis [embryonic days (ED) 7-10 and 10-13]. Gene expression was compared between interventions and matching controls by microarrays in broiler breast muscle at ED10 or ED13 and post-hatch at day 35. Early (ED7-10) high incubation temperature (H10ΔC) resulted in 1370 differentially expressed genes (DEGs) in embryos. Ingenuity pathway analysis revealed temporary activation of cell maintenance, organismal development, and survival ability genes, but these effects were not maintained in adults. Late high incubation temperature (ED10-13) (H13ΔC) had slightly negative impacts on development of cellular components in embryos, but a cumulative effect was observed in adults, in which tissue development and nutrition metabolism were affected. Early low incubation temperature (L10ΔC) produced 368 DEGs, most of which were down-regulated and involved in differentiation and formation of muscle cells. In adults, this treatment down-regulated pathways of transcriptional processes, but up-regulated cell proliferation. Late low temperature incubation (L13ΔC) produced 795 DEGs in embryos, and activated organismal survival and post-transcriptional regulation pathways. In adults this treatment activated cellular and organ development, nutrition and small molecule activity, and survival rate, but deactivated size of body and muscle cells. Thermal interventions during incubation initiate immediate and delayed transcriptional responses that are specific for timing and direction of treatment. Interestingly, the transcriptional response to

  8. Embryonic response to long-term exposure of the marine crustacean Nephrops norvegicus to ocean acidification and elevated temperature

    PubMed Central

    Styf, Hannah K; Nilsson Sköld, Helen; Eriksson, Susanne P

    2013-01-01

    Due to anthropogenic CO2 emissions, our oceans have gradually become warmer and more acidic. To better understand the consequences of this, there is a need for long-term (months) and multistressor experiments. Earlier research demonstrates that the effects of global climate change are specific to species and life stages. We exposed berried Norway lobsters (Nephrops norvegicus), during 4 months to the combination of six ecologically relevant temperatures (5–18°C) and reduced pH (by 0.4 units). Embryonic responses were investigated by quantifying proxies for development rate and fitness including: % yolk consumption, mean heart rate, rate of oxygen consumption, and oxidative stress. We found no interactions between temperature and pH, and reduced pH only affected the level of oxidative stress significantly, with a higher level of oxidative stress in the controls. Increased temperature and % yolk consumed had positive effects on all parameters except on oxidative stress, which did not change in response to temperature. There was a difference in development rate between the ranges of 5–10°C (Q10: 5.4) and 10–18°C (Q10: 2.9), implicating a thermal break point at 10°C or below. No thermal limit to a further increased development rate was found. The insensitivity of N. norvegicus embryos to low pH might be explained by adaptation to a pH-reduced external habitat and/or internal hypercapnia during incubation. Our results thus indicate that this species would benefit from global warming and be able to withstand the predicted decrease in ocean pH in the next century during their earliest life stages. However, future studies need to combine low pH and elevated temperature treatments with hypoxia as hypoxic events are frequently and increasingly occurring in the habitat of benthic species. PMID:24455136

  9. Vesicular Monoamine Transporter 2 and the Acute and Long-Term Response to 3,4-(±)-Methylenedioxymethamphetamine

    PubMed Central

    Lizarraga, Lucina E.; Cholanians, Aram B.; Phan, Andy V.; Herndon, Joseph M.; Lau, Serrine S.; Monks, Terrence J.

    2015-01-01

    3,4-(±)-Methylenedioxymethamphetamine (MDMA, Ecstasy) is a ring-substituted amphetamine derivative with potent psychostimulant properties. The neuropharmacological effects of MDMA are biphasic in nature, initially causing synaptic monoamine release, primarily of serotonin (5-HT). Conversely, the long-term effects of MDMA manifest as prolonged depletions in 5-HT, and reductions in 5-HT reuptake transporter (SERT), indicative of serotonergic neurotoxicity. MDMA-induced 5-HT efflux relies upon disruption of vesicular monoamine storage, which increases cytosolic 5-HT concentrations available for release via a carrier-mediated mechanism. The vesicular monoamine transporter 2 (VMAT2) is responsible for packaging monoamine neurotransmitters into cytosolic vesicles. Thus, VMAT2 is a molecular target for a number of psychostimulant drugs, including methamphetamine and MDMA. We investigated the effects of depressed VMAT2 activity on the adverse responses to MDMA, via reversible inhibition of the VMAT2 protein with Ro4-1284. A single dose of MDMA (20 mg/kg, subcutaneous) induced significant hyperthermia in rats. Ro4-1284 (10 mg/kg, intraperitoneal) pretreatment prevented the thermogenic effects of MDMA, instead causing a transient decrease in body temperature. MDMA-treated rats exhibited marked increases in horizontal velocity and rearing behavior. In the presence of Ro4-1284, MDMA-mediated horizontal hyperlocomotion was delayed and attenuated, whereas rearing activity was abolished. Finally, Ro4-1284 prevented deficits in 5-HT content in rat cortex and striatum, and reduced depletions in striatal SERT staining, 7 days after MDMA administration. In summary, acute inhibition of VMAT2 by Ro4-1284 protected against MDMA-mediated hyperthermia, hyperactivity, and serotonergic neurotoxicity. The data suggest the involvement of VMAT2 in the thermoregulatory, behavioral, and neurotoxic effects of MDMA. PMID:25370842

  10. Long-term water quality and biological responses to multiple best management practices in Rock Creek, Idaho

    USGS Publications Warehouse

    Maret, T.R.; MacCoy, D.E.; Carlisle, D.M.

    2008-01-01

    Water quality and macroinvertebrate assemblage data from 1981 to 2005 were assessed to evaluate the water quality and biological responses of a western trout stream to the implementation of multiple best management practices (BMPs) on irrigated cropland. Data from Rock Creek near Twin Falls, Idaho, a long-term monitoring site, were assembled from state and federal sources to provide the evaluation. Seasonal loads of the nonpoint source pollutants suspended sediment (SS), total phosphorus (TP), and nitrate-nitrite (NN) were estimated using a regression model with time-series streamflow data and constituent concentrations. Trends in the macroinvertebrate assemblages were evaluated using a number of biological metrics and nonmetric multidimensional scaling ordination. Regression analysis found significant annual decreases in TP and SS flow-adjusted concentrations during the BMP implementation period from 1983 to 1990 of about 7 and 10%, respectively. These results are coincident with the implementation of multiple BMPs on about 75% of the irrigated cropland in the watershed. Macroinvertebrate assemblages during this time also responded with a change in taxa composition resulting in improved biotic index scores. Taxon specific TP and SS optima, empirically derived from a large national dataset, predicted a decrease in SS concentrations of about 37% (52 to 33 mg/l) and a decrease in TP concentrations of about 50% (0.20 to 0.10 mg/l) from 1981 to 1987. Decreasing trends in TP, SS, and NN pollutant loads were primarily the result of naturally low streamflow conditions during the BMP post-implementation period from 1993 to 2005. Trends in macroinvertebrate responses during 1993 to 2005 were confounded by the introduction of the New Zealand mudsnail (Potamopyrgus antipodarum), which approached densities of 100,000 per m 2 in riffle habitat. The occurrence of this invasive species appears to have caused a major shift in composition and function of the macroinvertebrate

  11. Long-term dynamics of tropical walking sticks in response to multiple large-scale and intense disturbances.

    PubMed

    Willig, Michael R; Presley, Steven J; Bloch, Christopher P

    2011-02-01

    Understanding the effects of disturbance and secondary succession on spatio-temporal patterns in the abundance of species is stymied by a lack of long-term demographic data, especially in response to infrequent and high intensity disturbances, such as hurricanes. Moreover, resistance and resilience to hurricane-induced disturbance may be mediated by legacies of previous land use, although such interactive effects are poorly understood, especially in tropical environments. We address these central issues in disturbance ecology by analyzing an extensive dataset, spanning the impacts of Hurricanes Hugo and Georges, on the abundance of a Neotropical walking stick, Lamponius portoricensis, in tabonuco rainforest of Puerto Rico during the wet and dry seasons from 1991 to 2007. By synthesizing data from two proximate sites in tabonuco forest, we show that resistance to Hurricane Hugo (97% reduction in abundance) was much less than resistance to Hurricane Georges (21% reduction in abundance). Based on a powerful statistical approach (generalized linear mixed-effects models with Poisson error terms), we documented that the temporal trajectories of abundance during secondary succession (i.e., patterns of resilience) differed between hurricanes and among historical land use categories, but that the effects of hurricanes and land use histories were independent of each other. These complex results likely arise because of differences in the intensities of the two hurricanes with respect to microclimatic effects (temperature and moisture) in the forest understory, as well as to time-lags in the response of L. portoricensis to changes in the abundance and distribution of preferred food plants (Piper) in post-hurricane environments.

  12. Responses of a marine red tide alga Skeletonema costatum (Bacillariophyceae) to long-term UV radiation exposures.

    PubMed

    Wu, Hongyan; Gao, Kunshan; Wu, Haiyan

    2009-02-01

    UV radiation (280-400 nm) is known to affect phytoplankton in negative, neutral and positive ways depending on the species or levels of irradiation energy. However, little has been documented on how photosynthetic physiology and growth of red tide alga respond to UVR in a long-term period. We exposed the cells of the marine red tide diatom Skeletonema costatum for 6 days to simulated solar radiations with UV-A (320-400 nm) or UV-A+UV-B (295-400 nm) and examined their changes in photosynthesis and growth. Presence of UV-B continuously reduced the effective photosynthetic quantum yield of PSII, and resulted in complete growth inhibition and death of cells. When UV-B or UV-B+UV-A was screened off, the growth rate decreased initially but regained thereafter. UV-absorbing compounds and carotenoids increased in response to the exposures with UVR. However, mechanisms for photoprotection associated with the increased carotenoids or UV-absorbing compounds were not adequate under the continuous exposure to a constant level of UV-B (0.09 Wm(-2), DNA-weighted). In contrast, under solar radiation screened off UV-B, the photoprotection was first accomplished by an initial increase of carotenoids and a later increase in UV-absorbing compounds. The overall response of this red tide alga to prolonged UV exposures indicates that S. costatum is a UV-B-sensitive species and increased UV-B irradiance would influence the formation of its blooms.

  13. The relationship of initial clinical parameters to the long-term response in 112 cases of periodontal disease.

    PubMed

    Wasserman, B; Hirschfeld, L

    1988-01-01

    The purpose of the present study was to determine whether any of the clinical parameters recorded during an initial periodontal examination would relate to the course of periodontal cases maintained for long periods of time. Based on available documentation, cases which had a downhill course were assembled from a population previously studied. In addition, long-term cases currently under maintenance care were drawn from our private practice. On average, the patients had been under care for 23 years. The study population was heavily weighted toward downhill cases to better compare these cases with those usually found in periodontal practice. Positive statistical correlations were found between the amount of subgingival calculus and the degree of gingival inflammation at initial examination. Disease severity initially was positively correlated to long-term course of disease. The amount of subgingival calculus did not relate to the long-term result. There was a strong correlation between inflammatory gingival hyperplasia initially and good long-term maintenance. The results suggest that, in combination, initial characteristics of periodontal cases coupled with long-term results of treatment may aid in further subclassifying the periodontal diseases.

  14. Nitrifying moving bed biofilm reactor (MBBR) biofilm and biomass response to long term exposure to 1 °C.

    PubMed

    Hoang, V; Delatolla, R; Abujamel, T; Mottawea, W; Gadbois, A; Laflamme, E; Stintzi, A

    2014-02-01

    This study aims to investigate moving bed biofilm reactor (MBBR) nitrification rates, nitrifying biofilm morphology, biomass viability as well as bacterial community shifts during long-term exposure to 1 °C. Long-term exposure to 1 °C is the key operational condition for potential ammonia removal upgrade units to numerous northern region treatment systems. The average laboratory MBBR ammonia removal rate after long-term exposure to 1 °C was measured to be 18 ± 5.1% as compared to the average removal rate at 20 °C. Biofilm morphology and specifically the thickness along with biomass viability at various depths in the biofilm were investigated using variable pressure electron scanning microscope (VPSEM) imaging and confocal laser scanning microscope (CLSM) imaging in combination with viability live/dead staining. The biofilm thickness along with the number of viable cells showed significant increases after long-term exposure to 1 °C. Hence, this study observed nitrifying bacteria with higher activities at warm temperatures and a slightly greater quantity of nitrifying bacteria with lower activities at cold temperatures in nitrifying MBBR biofilms. Using DNA sequencing analysis, Nitrosomonas and Nitrosospira (ammonia oxidizers) as well as Nitrospira (nitrite oxidizer) were identified and no population shift was observed between 20 °C and after long-term exposure to 1 °C.

  15. Reduced Irregularity of Ventricular Response During Atrial Fibrillation and Long-term Outcome in Patients With Heart Failure.

    PubMed

    Cygankiewicz, Iwona; Corino, Valentina; Vazquez, Rafael; Bayes-Genis, Antoni; Mainardi, Luca; Zareba, Wojciech; de Luna, Antoni Bayes; Platonov, Pyotr G

    2015-10-01

    Reduced heart rate variability (HRV) is associated with poor outcome in patients with heart failure (HF). However, the data on predictive value of RR variability during atrial fibrillation (AF) are limited. Therefore, the aim of this study was to evaluate the association between ventricular response characteristics and long-term clinical outcome in the population of ambulatory patients with mild-to-moderate HF and AF at baseline. The study included 155 patients (mean age 69 ± 10 years) with AF at 20-minute Holter electrocardiographic (ECG) recordings at enrollment. HRV analysis included SDNN, rMSSD, and pNN50, whereas irregularity indexes included 2 nonlinear parameters: approximate entropy (ApEn) and Shannon entropy. After median 41 months of follow-up, 54 patients died, including 21 HF related and 16 sudden deaths. Patients with ApEn ≤1.68 (lower tertile) had 40% mortality versus 12% in others (p <0.001) at 2 years of follow-up. Only nonlinear HRV parameters (irregularity but not variability indexes) identified patients at higher risk during follow-up. Decreased ApEn ≤1.68 was an independent predictor of total mortality (hazard ratio [HR] 2.81, 95% confidence interval [CI] 1.61 to 4.89, p <0.001), sudden cardiac death (HR 3.83, 95% CI 1.31 to 11.25, p = 0.014), and HF death (HR 3.45, 95% CI 1.42 to 8.38, p = 0.006) in a multivariate Cox analysis. In conclusion, in a post hoc analysis of Muerte Subita en Insufficiencia Cardiaca study AF cohort, reduced irregularity of RR intervals during AF, likely caused by autonomic dysfunction, was an independent predictor of all-cause mortality and sudden death and HF progression in patients with mild-to-moderate HF, whereas traditional HRV indexes did not predict outcome.

  16. Long-term power generation expansion planning with short-term demand response: Model, algorithms, implementation, and electricity policies

    NASA Astrophysics Data System (ADS)

    Lohmann, Timo

    Electric sector models are powerful tools that guide policy makers and stakeholders. Long-term power generation expansion planning models are a prominent example and determine a capacity expansion for an existing power system over a long planning horizon. With the changes in the power industry away from monopolies and regulation, the focus of these models has shifted to competing electric companies maximizing their profit in a deregulated electricity market. In recent years, consumers have started to participate in demand response programs, actively influencing electricity load and price in the power system. We introduce a model that features investment and retirement decisions over a long planning horizon of more than 20 years, as well as an hourly representation of day-ahead electricity markets in which sellers of electricity face buyers. This combination makes our model both unique and challenging to solve. Decomposition algorithms, and especially Benders decomposition, can exploit the model structure. We present a novel method that can be seen as an alternative to generalized Benders decomposition and relies on dynamic linear overestimation. We prove its finite convergence and present computational results, demonstrating its superiority over traditional approaches. In certain special cases of our model, all necessary solution values in the decomposition algorithms can be directly calculated and solving mathematical programming problems becomes entirely obsolete. This leads to highly efficient algorithms that drastically outperform their programming problem-based counterparts. Furthermore, we discuss the implementation of all tailored algorithms and the challenges from a modeling software developer's standpoint, providing an insider's look into the modeling language GAMS. Finally, we apply our model to the Texas power system and design two electricity policies motivated by the U.S. Environment Protection Agency's recently proposed CO2 emissions targets for the

  17. Changing forest water yields in response to climate warming: results from long-term experimental watershed sites across North America

    PubMed Central

    Creed, Irena F; Spargo, Adam T; Jones, Julia A; Buttle, Jim M; Adams, Mary B; Beall, Fred D; Booth, Eric G; Campbell, John L; Clow, Dave; Elder, Kelly; Green, Mark B; Grimm, Nancy B; Miniat, Chelcy; Ramlal, Patricia; Saha, Amartya; Sebestyen, Stephen; Spittlehouse, Dave; Sterling, Shannon; Williams, Mark W; Winkler, Rita; Yao, Huaxia

    2014-01-01

    Climate warming is projected to affect forest water yields but the effects are expected to vary. We investigated how forest type and age affect water yield resilience to climate warming. To answer this question, we examined the variability in historical water yields at long-term experimental catchments across Canada and the United States over 5-year cool and warm periods. Using the theoretical framework of the Budyko curve, we calculated the effects of climate warming on the annual partitioning of precipitation (P) into evapotranspiration (ET) and water yield. Deviation (d) was defined as a catchment's change in actual ET divided by P [AET/P; evaporative index (EI)] coincident with a shift from a cool to a warm period – a positive d indicates an upward shift in EI and smaller than expected water yields, and a negative d indicates a downward shift in EI and larger than expected water yields. Elasticity was defined as the ratio of interannual variation in potential ET divided by P (PET/P; dryness index) to interannual variation in the EI – high elasticity indicates low d despite large range in drying index (i.e., resilient water yields), low elasticity indicates high d despite small range in drying index (i.e., nonresilient water yields). Although the data needed to fully evaluate ecosystems based on these metrics are limited, we were able to identify some characteristics of response among forest types. Alpine sites showed the greatest sensitivity to climate warming with any warming leading to increased water yields. Conifer forests included catchments with lowest elasticity and stable to larger water yields. Deciduous forests included catchments with intermediate elasticity and stable to smaller water yields. Mixed coniferous/deciduous forests included catchments with highest elasticity and stable water yields. Forest type appeared to influence the resilience of catchment water yields to climate warming, with conifer and deciduous catchments more susceptible to

  18. Changing forest water yields in response to climate warming: results from long-term experimental watershed sites across North America.

    PubMed

    Creed, Irena F; Spargo, Adam T; Jones, Julia A; Buttle, Jim M; Adams, Mary B; Beall, Fred D; Booth, Eric G; Campbell, John L; Clow, Dave; Elder, Kelly; Green, Mark B; Grimm, Nancy B; Miniat, Chelcy; Ramlal, Patricia; Saha, Amartya; Sebestyen, Stephen; Spittlehouse, Dave; Sterling, Shannon; Williams, Mark W; Winkler, Rita; Yao, Huaxia

    2014-10-01

    Climate warming is projected to affect forest water yields but the effects are expected to vary. We investigated how forest type and age affect water yield resilience to climate warming. To answer this question, we examined the variability in historical water yields at long-term experimental catchments across Canada and the United States over 5-year cool and warm periods. Using the theoretical framework of the Budyko curve, we calculated the effects of climate warming on the annual partitioning of precipitation (P) into evapotranspiration (ET) and water yield. Deviation (d) was defined as a catchment's change in actual ET divided by P [AET/P; evaporative index (EI)] coincident with a shift from a cool to a warm period - a positive d indicates an upward shift in EI and smaller than expected water yields, and a negative d indicates a downward shift in EI and larger than expected water yields. Elasticity was defined as the ratio of interannual variation in potential ET divided by P (PET/P; dryness index) to interannual variation in the EI - high elasticity indicates low d despite large range in drying index (i.e., resilient water yields), low elasticity indicates high d despite small range in drying index (i.e., nonresilient water yields). Although the data needed to fully evaluate ecosystems based on these metrics are limited, we were able to identify some characteristics of response among forest types. Alpine sites showed the greatest sensitivity to climate warming with any warming leading to increased water yields. Conifer forests included catchments with lowest elasticity and stable to larger water yields. Deciduous forests included catchments with intermediate elasticity and stable to smaller water yields. Mixed coniferous/deciduous forests included catchments with highest elasticity and stable water yields. Forest type appeared to influence the resilience of catchment water yields to climate warming, with conifer and deciduous catchments more susceptible to

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

    PubMed Central

    Bliss, Timothy V.P.; Cooke, Sam F

    2011-01-01

    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. PMID:21779718

  20. Long-term survival and T-cell kinetics in relapsed/refractory ALL patients who achieved MRD response after blinatumomab treatment

    PubMed Central

    Gökbuget, Nicola; Klinger, Matthias; Viardot, Andreas; Stelljes, Matthias; Neumann, Svenja; Horst, Heinz-A.; Marks, Reinhard; Faul, Christoph; Diedrich, Helmut; Reichle, Albrecht; Brüggemann, Monika; Holland, Chris; Schmidt, Margit; Einsele, Hermann; Bargou, Ralf C.; Topp, Max S.

    2015-01-01

    This long-term follow-up analysis evaluated overall survival (OS) and relapse-free survival (RFS) in a phase 2 study of the bispecific T-cell engager antibody construct blinatumomab in 36 adults with relapsed/refractory B-precursor acute lymphoblastic leukemia (ALL). In the primary analysis, 25 (69%) patients with relapsed/refractory ALL achieved complete remission with full (CR) or partial (CRh) hematologic recovery of peripheral blood counts within the first 2 cycles. Twenty-five patients (69%) had a minimal residual disease (MRD) response (<10−4 blasts), including 22 CR/CRh responders, 2 patients with hypocellular bone marrow, and 1 patient with normocellular bone marrow but low peripheral counts. Ten of the 36 patients (28%) were long-term survivors (OS ≥30 months). Median OS was 13.0 months (median follow-up, 32.6 months). MRD response was associated with significantly longer OS (Mantel-Byar P = .009). All 10 long-term survivors had an MRD response. Median RFS was 8.8 months (median follow-up, 28.9 months). A plateau for RFS was reached after ∼18 months. Six of the 10 long-term survivors remained relapse-free, including 4 who received allogeneic stem cell transplantation (allo-SCT) as consolidation for blinatumomab and 2 who received 3 additional cycles of blinatumomab instead of allo-SCT. Three long-term survivors had neurologic events or cytokine release syndrome, resulting in temporary blinatumomab discontinuation; all restarted blinatumomab successfully. Long-term survivors had more pronounced T-cell expansion than patients with OS <30 months. PMID:26480933

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

    ERIC Educational Resources Information Center

    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…

  2. Student Response Systems in the College Classroom: An Investigation of Short-Term, Intermediate, and Long-Term Recall of Facts

    ERIC Educational Resources Information Center

    Blood, Erika

    2012-01-01

    The effects of student response system (SRS) use during lecture-style instruction on short-term, intermediate, and long-term retention of facts was investigated in an undergraduate teacher preparation course. Participants were undergraduate students enrolled in a special education initial certification program. Student performance on quizzes and…

  3. Can a Robot Be Perceived as a Developing Creature? Effects of a Robot's Long-Term Cognitive Developments on Its Social Presence and People's Social Responses toward It

    ERIC Educational Resources Information Center

    Lee, Kwan Min; Park, Namkee; Song, Hayeon

    2005-01-01

    This study tests the effect of long-term artificial development of a robot on users' feelings of social presence and social responses toward the robot. The study is a 2 (developmental capability: developmental versus fully matured) x 2 (number of participants: individual versus group) between-subjects experiment (N = 40) in which participants…

  4. Potential of the solid-Earth response for limiting long-term West Antarctic Ice Sheet retreat

    NASA Astrophysics Data System (ADS)

    Konrad, Hannes; Sasgen, Ingo; Pollard, David; Klemann, Volker

    2016-04-01

    for asthenosphere viscosities of 3x10^20 Pa s or higher. References Gomez, N., Pollard, D., Mitrovica, J. X., Huybers, P., & Clark, P. U. (2012). Evolution of a coupled marine ice sheet-sea level model. J. Geophys. Res. 117(F1). Konrad, H., Sasgen, I., Pollard, D. & Klemann, V. (2015). Potential of the solid-Earth response for limiting long-term West Antarctic Ice Sheet retreat in a warming climate. Earth Planet. Sci. Lett. 432, 2015.

  5. Reduced Irregularity of Ventricular Response During Atrial Fibrillation and Long-term Outcome in Patients With Heart Failure.

    PubMed

    Cygankiewicz, Iwona; Corino, Valentina; Vazquez, Rafael; Bayes-Genis, Antoni; Mainardi, Luca; Zareba, Wojciech; de Luna, Antoni Bayes; Platonov, Pyotr G

    2015-10-01

    Reduced heart rate variability (HRV) is associated with poor outcome in patients with heart failure (HF). However, the data on predictive value of RR variability during atrial fibrillation (AF) are limited. Therefore, the aim of this study was to evaluate the association between ventricular response characteristics and long-term clinical outcome in the population of ambulatory patients with mild-to-moderate HF and AF at baseline. The study included 155 patients (mean age 69 ± 10 years) with AF at 20-minute Holter electrocardiographic (ECG) recordings at enrollment. HRV analysis included SDNN, rMSSD, and pNN50, whereas irregularity indexes included 2 nonlinear parameters: approximate entropy (ApEn) and Shannon entropy. After median 41 months of follow-up, 54 patients died, including 21 HF related and 16 sudden deaths. Patients with ApEn ≤1.68 (lower tertile) had 40% mortality versus 12% in others (p <0.001) at 2 years of follow-up. Only nonlinear HRV parameters (irregularity but not variability indexes) identified patients at higher risk during follow-up. Decreased ApEn ≤1.68 was an independent predictor of total mortality (hazard ratio [HR] 2.81, 95% confidence interval [CI] 1.61 to 4.89, p <0.001), sudden cardiac death (HR 3.83, 95% CI 1.31 to 11.25, p = 0.014), and HF death (HR 3.45, 95% CI 1.42 to 8.38, p = 0.006) in a multivariate Cox analysis. In conclusion, in a post hoc analysis of Muerte Subita en Insufficiencia Cardiaca study AF cohort, reduced irregularity of RR intervals during AF, likely caused by autonomic dysfunction, was an independent predictor of all-cause mortality and sudden death and HF progression in patients with mild-to-moderate HF, whereas traditional HRV indexes did not predict outcome. PMID:26298305

  6. Indigenous Knowledge and Long-term Ecological Change: Detection, Interpretation, and Responses to Changing Ecological Conditions in Pacific Island Communities

    PubMed Central

    Aswani, Shankar

    2010-01-01

    When local resource users detect, understand, and respond to environmental change they can more effectively manage environmental resources. This article assesses these abilities among artisanal fishers in Roviana Lagoon, Solomon Islands. In a comparison of two villages, it documents local resource users’ abilities to monitor long-term ecological change occurring to seagrass meadows near their communities, their understandings of the drivers of change, and their conceptualizations of seagrass ecology. Local observations of ecological change are compared with historical aerial photography and IKONOS satellite images that show 56 years of actual changes in seagrass meadows from 1947 to 2003. Results suggest that villagers detect long-term changes in the spatial cover of rapidly expanding seagrass meadows. However, for seagrass meadows that showed no long-term expansion or contraction in spatial cover over one-third of respondents incorrectly assumed changes had occurred. Examples from a community-based management initiative designed around indigenous ecological knowledge and customary sea tenure governance show how local observations of ecological change shape marine resource use and practices which, in turn, can increase the management adaptability of indigenous or hybrid governance systems. PMID:20336296

  7. Response of soil carbon dioxide efflux to fire disturbance in a long-term grassland global change experiment

    NASA Astrophysics Data System (ADS)

    Strong, A. L.; Chiariello, N.; Tobeck, T.; Field, C. B.

    2012-12-01

    How terrestrial biosphere-atmosphere carbon dioxide exchange responds to global change is an important component to understanding global feedbacks of the carbon cycle. Soils represent a global store of organic carbon on the order of 3000 Pg C. Increased carbon dioxide release from increased respiration of soil C in response to climate warming and other direct and indirect anthropogenic factors could create a positive carbon cycle feedback to climate change. Numerous studies have demonstrated that soil respiration increases under experimental warming and elevated CO2, although the long-term, multi-year dynamics of this feedback remain poorly constrained. Punctuated disturbances, such as fire, are also likely to affect soil C responses, and understanding how fire and other global change factors interact in their influence on soil respiration is important in order to fully characterize climate-carbon cycle feedbacks. Previous studies have found that fire disturbance in semi-arid grasslands reduces soil CO2. The Jasper Ridge Global Change Experiment is a thirteen-year continuous full-factorial global change manipulation (elevated carbon dioxide, temperature, precipitation, and nitrogen deposition) located in a clay-loam soil grassland in central coastal California. In summer 2011, an additional treatment condition -- a controlled burn -- was applied to half the experimental plots to provide a fire treatment, and in the following growing season, soil carbon dioxide effluxes were measured at peak aboveground plant biomass (April 2012) and after summer senescence (June 2012) using a LiCOR-6400 soil respiration chamber and infrared gas analyzer. Across all plots and other treatments, CO2 fluxes were greater in burned grassland soils than in non-burned grassland soils (p < 0.01). CO2 fluxes were also greater in grassland plots with N addition than in grassland plots without additional nutrients (p < 0.01). These two effects appear to be additive, as CO2 fluxes were greater

  8. Long-Term Citalopram Treatment Alters the Stress Responses of the Cortical Dopamine and Noradrenaline Systems: the Role of Cortical 5-HT1A Receptors

    PubMed Central

    Kaneko, Fumi; Kishikawa, Yuki; Hanada, Yuuki; Yamada, Makiko; Kakuma, Tatsuyuki; Kawahara, Hiroshi; Nishi, Akinori

    2016-01-01

    Background: Cortical dopamine and noradrenaline are involved in the stress response. Citalopram, a selective serotonin reuptake inhibitor, has direct and indirect effects on the serotonergic system. Furthermore, long-term treatment with citalopram affects the dopamine and noradrenaline systems, which could contribute to the therapeutic action of antidepressants. Methods: The effects of long-term treatment with citalopram on the responses of the dopamine and noradrenaline systems in the rat prefrontal cortex to acute handling stress were evaluated using in vivo microdialysis. Results: Acute handling stress increased dopamine and noradrenaline levels in the prefrontal cortex. The dopamine and noradrenaline responses were suppressed by local infusion of a 5-HT1A receptor agonist, 7-(Dipropylamino)-5,6,7,8-tetrahydronaphthalen-1-ol;hydrobromide, into the prefrontal cortex. The dopamine response was abolished by long-term treatment with citalopram, and the abolished dopamine response was reversed by local infusion of a 5-HT1A receptor antagonist, (Z)-but-2-enedioic acid;N-[2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl]-N-pyridin-2-ylcyclohexanecarboxamide into the prefrontal cortex. On the other hand, long-term treatment with citalopram reduced the basal noradrenaline levels (approximately 40% of the controls), but not the basal dopamine levels. The noradrenaline response was maintained despite the low basal noradrenaline levels. Signaling from the 5-HT1A receptors and α2-adrenoceptors was not involved in the decrease in the basal noradrenaline levels but partially affected the noradrenaline response. Conclusions: Chronic citalopram treatment differentially suppresses the dopamine and noradrenaline systems in the prefrontal cortex, and the dopamine stress response was preferentially controlled by upregulating 5-HT1A receptor signaling. Our findings provide insight into how antidepressants modulate the dopamine and noradrenaline systems to overcome acute stress. PMID

  9. Long-term results after intentional tooth reimplantation in monkeys.

    PubMed

    Caffesse, R G; Nasjleti, C E; Castelli, W A

    1977-11-01

    The purpose of this study was to evaluate histologically the long-term response to intentional tooth reimplantation in six rhesus monkeys. The study revealed that cervical and apical root resorption is a universal complication after tooth reimplantation and that arrested areas of resorption will show repair by deposition of cementum. A highly cellular periodontal membrane usually will develop. Periodontal fibers will reattach to reparative bone and cementum but seldom regain functional orientation. Partial or complete ankylosis may result. A further complication is progressive undermining resorption of the ankylosed teeth. Long-term studies are mandatory to evaluate the response to intentional tooth reimplantation.

  10. Do managerial efficiency and social responsibility drive long-term financial performance of not-for-profit hospitals before acquisition?

    PubMed

    Phillips, J F

    1999-01-01

    Due to steep declines in charitable support and reduced demand for traditional hospital services, economic goals are increasingly important to not-for-profit hospitals. Effects of efficient management and effective pursuit of not-for-profit status (for example, levels of Medicare, indigent patients, and unprofitable services) on financial viability are explored. While previous research compared hospitals of different ownership status, not-for-profit hospital operations before acquisition by for-profit hospital chains are investigated--"neutral ground" relative to ownership. Results suggest minor links between efficiency and long-term profitability despite effectiveness in pursuit of non taxable status.

  11. Dendritic excitability microzones and occluded long-term depression after classical conditioning of the rabbit's nictitating membrane response.

    PubMed

    Schreurs, B G; Tomsic, D; Gusev, P A; Alkon, D L

    1997-01-01

    underwent a long-term (> 20 min) reduction in peak amplitude (-24%) in cells (n = 12) from animals given unpaired stimulus presentations but to a far less extent (-9%) in cells (n = 20) from animals given in vivo paired training. Whereas 92% of cells from unpaired animals showed pairing-specific depression, 50% of cells from paired animals showed no depression and in several cases showed potentiation. Our data establish that there are localized learning-specific changes in membrane and synaptic excitability of Purkinje cells in rabbit lobule HVI that can be detected in slices 24 h after classical conditioning. Long-term changes within Purkinje cells that effect this enhanced excitability may occlude pairing-specific long-term depression.

  12. Long-term change in a meso-predator community in response to prolonged and heterogeneous human impact

    PubMed Central

    Ferretti, Francesco; Osio, Giacomo C.; Jenkins, Chris J.; Rosenberg, Andrew A.; Lotze, Heike K.

    2013-01-01

    Sharks and rays' abundance can decline considerably with fishing. Community changes, however, are more complex because of species interactions, and variable vulnerability and exposure to fishing. We evaluated long-term changes in the elasmobranch community of the Adriatic Sea, a heavily exploited Mediterranean basin where top-predators have been strongly depleted historically, and fishing developed unevenly between the western and eastern side. Combining and standardizing catch data from five trawl surveys from 1948–2005, we estimated abundance trends and explained community changes using life histories, fish-market and effort data, and historical information. We identified a highly depleted elasmobranch community. Since 1948, catch rates have declined by >94% and 11 species ceased to be detected. The exploitation history and spatial gradients in fishing pressure explained most patterns in abundance and diversity, including the absence of strong compensatory increases. Ecological corridors and large-scale protected areas emerged as potential management options for elasmobranch conservation. PMID:23308344

  13. Satellite tagging and biopsy sampling of killer whales at subantarctic Marion Island: effectiveness, immediate reactions and long-term responses.

    PubMed

    Reisinger, Ryan R; Oosthuizen, W Chris; Péron, Guillaume; Cory Toussaint, Dawn; Andrews, Russel D; de Bruyn, P J Nico

    2014-01-01

    Remote tissue biopsy sampling and satellite tagging are becoming widely used in large marine vertebrate studies because they allow the collection of a diverse suite of otherwise difficult-to-obtain data which are critical in understanding the ecology of these species and to their conservation and management. Researchers must carefully consider their methods not only from an animal welfare perspective, but also to ensure the scientific rigour and validity of their results. We report methods for shore-based, remote biopsy sampling and satellite tagging of killer whales Orcinus orca at Subantarctic Marion Island. The performance of these methods is critically assessed using 1) the attachment duration of low-impact minimally percutaneous satellite tags; 2) the immediate behavioural reactions of animals to biopsy sampling and satellite tagging; 3) the effect of researcher experience on biopsy sampling and satellite tagging; and 4) the mid- (1 month) and long- (24 month) term behavioural consequences. To study mid- and long-term behavioural changes we used multievent capture-recapture models that accommodate imperfect detection and individual heterogeneity. We made 72 biopsy sampling attempts (resulting in 32 tissue samples) and 37 satellite tagging attempts (deploying 19 tags). Biopsy sampling success rates were low (43%), but tagging rates were high with improved tag designs (86%). The improved tags remained attached for 26±14 days (mean ± SD). Individuals most often showed no reaction when attempts missed (66%) and a slight reaction-defined as a slight flinch, slight shake, short acceleration, or immediate dive-when hit (54%). Severe immediate reactions were never observed. Hit or miss and age-sex class were important predictors of the reaction, but the method (tag or biopsy) was unimportant. Multievent trap-dependence modelling revealed considerable variation in individual sighting patterns; however, there were no significant mid- or long-term changes following

  14. Responses of absolute and specific soil enzyme activities to long term additions of organic and mineral fertilizer.

    PubMed

    Zhang, Xinyu; Dong, Wenyi; Dai, Xiaoqin; Schaeffer, Sean; Yang, Fengting; Radosevich, Mark; Xu, Lili; Liu, Xiyu; Sun, Xiaomin

    2015-12-01

    Long-term phosphorus (P) and nitrogen (N) applications may seriously affect soil microbial activity. A long-term field fertilizer application trial was established on reddish paddy soils in the subtropical region of southern China in 1998. We assessed the effects of swine manure and seven different rates or ratios of NPK fertilizer treatments on (1) the absolute and specific enzyme activities per unit of soil organic carbon (SOC) or microbial biomass carbon (MBC) involved in C, N, and P transformations and (2) their relationships with soil environmental factors and soil microbial community structures. The results showed that manure applications led to increases in the absolute and specific activities of soil β-1,4-glucosidase(βG), β-1,4-N-acetylglucosaminidase (NAG), and leucine aminopeptidase (LAP). The absolute and specific acid phosphatase (AP) activities decreased as mineral P fertilizer application rates and ratios increased. Redundancy analysis (RDA) showed that there were negative correlations between absolute and specific AP activities, pH, and total P contents, while there were positive correlations between soil absolute and specific βG, NAG, and LAP enzyme activities, and SOC and total N contents. RDA showed that the contents of actinomycete and Gram-positive bacterium PLFA biomarkers are more closely related to the absolute and specific enzyme activities than the other PLFA biomarkers (P<0.01). Our results suggest that both the absolute and specific enzyme activities could be used as sensitive soil quality indicators that provide useful linkages with the microbial community structures and environmental factors. To maintain microbial activity and to minimize environmental impacts, P should be applied as a combination of inorganic and organic forms, and total P fertilizer application rates to subtropical paddy soils should not exceed 44 kg P ha(-1) year(-1). PMID:26196069

  15. Response of organic and inorganic carbon and nitrogen to long-term grazing of the shortgrass steppe.

    PubMed

    Reeder, Jean D; Schuman, Gerald E; Morgan, Jack A; Lecain, Daniel R

    2004-04-01

    We investigated the influence of long-term (56 years) grazing on organic and inorganic carbon (C) and nitrogen (N) contents of the plant-soil system (to 90 cm depth) in shortgrass steppe of northeastern Colorado. Grazing treatments included continuous season-long (May-October) grazing by yearling heifers at heavy (60-75% utilization) and light (20-35% utilization) stocking rates, and nongrazed exclosures. The heavy stocking rate resulted in a plant community that was dominated (75% of biomass production) by the C4 grass blue grama (Bouteloua gracilis), whereas excluding livestock grazing increased the production of C3 grasses and prickly pear cactus (Opuntia polycantha). Soil organic C (SOC) and organic N were not significantly different between the light grazing and nongrazed treatments, whereas the heavy grazing treatment was 7.5 Mg ha(-1) higher in SOC than the nongrazed treatment. Lower ratios of net mineralized N to total organic N in both grazed compared to nongrazed treatments suggest that long-term grazing decreased the readily mineralizable fraction of soil organic matter. Heavy grazing affected soil inorganic C (SIC) more than the SOC. The heavy grazing treatment was 23.8 Mg ha(-1) higher in total soil C (0-90 cm) than the nongrazed treatment, with 68% (16.3 Mg ha(-1)) attributable to higher SIC, and 32% (7.5 Mg ha(-1)) to higher SOC. These results emphasize the importance in semiarid and arid ecosystems of including inorganic C in assessments of the mass and distribution of plant-soil C and in evaluations of the impacts of grazing management on C sequestration.

  16. Satellite tagging and biopsy sampling of killer whales at subantarctic Marion Island: effectiveness, immediate reactions and long-term responses.

    PubMed

    Reisinger, Ryan R; Oosthuizen, W Chris; Péron, Guillaume; Cory Toussaint, Dawn; Andrews, Russel D; de Bruyn, P J Nico

    2014-01-01

    Remote tissue biopsy sampling and satellite tagging are becoming widely used in large marine vertebrate studies because they allow the collection of a diverse suite of otherwise difficult-to-obtain data which are critical in understanding the ecology of these species and to their conservation and management. Researchers must carefully consider their methods not only from an animal welfare perspective, but also to ensure the scientific rigour and validity of their results. We report methods for shore-based, remote biopsy sampling and satellite tagging of killer whales Orcinus orca at Subantarctic Marion Island. The performance of these methods is critically assessed using 1) the attachment duration of low-impact minimally percutaneous satellite tags; 2) the immediate behavioural reactions of animals to biopsy sampling and satellite tagging; 3) the effect of researcher experience on biopsy sampling and satellite tagging; and 4) the mid- (1 month) and long- (24 month) term behavioural consequences. To study mid- and long-term behavioural changes we used multievent capture-recapture models that accommodate imperfect detection and individual heterogeneity. We made 72 biopsy sampling attempts (resulting in 32 tissue samples) and 37 satellite tagging attempts (deploying 19 tags). Biopsy sampling success rates were low (43%), but tagging rates were high with improved tag designs (86%). The improved tags remained attached for 26±14 days (mean ± SD). Individuals most often showed no reaction when attempts missed (66%) and a slight reaction-defined as a slight flinch, slight shake, short acceleration, or immediate dive-when hit (54%). Severe immediate reactions were never observed. Hit or miss and age-sex class were important predictors of the reaction, but the method (tag or biopsy) was unimportant. Multievent trap-dependence modelling revealed considerable variation in individual sighting patterns; however, there were no significant mid- or long-term changes following

  17. Satellite Tagging and Biopsy Sampling of Killer Whales at Subantarctic Marion Island: Effectiveness, Immediate Reactions and Long-Term Responses

    PubMed Central

    Reisinger, Ryan R.; Oosthuizen, W. Chris; Péron, Guillaume; Cory Toussaint, Dawn; Andrews, Russel D.; de Bruyn, P. J. Nico

    2014-01-01

    Remote tissue biopsy sampling and satellite tagging are becoming widely used in large marine vertebrate studies because they allow the collection of a diverse suite of otherwise difficult-to-obtain data which are critical in understanding the ecology of these species and to their conservation and management. Researchers must carefully consider their methods not only from an animal welfare perspective, but also to ensure the scientific rigour and validity of their results. We report methods for shore-based, remote biopsy sampling and satellite tagging of killer whales Orcinus orca at Subantarctic Marion Island. The performance of these methods is critically assessed using 1) the attachment duration of low-impact minimally percutaneous satellite tags; 2) the immediate behavioural reactions of animals to biopsy sampling and satellite tagging; 3) the effect of researcher experience on biopsy sampling and satellite tagging; and 4) the mid- (1 month) and long- (24 month) term behavioural consequences. To study mid- and long-term behavioural changes we used multievent capture-recapture models that accommodate imperfect detection and individual heterogeneity. We made 72 biopsy sampling attempts (resulting in 32 tissue samples) and 37 satellite tagging attempts (deploying 19 tags). Biopsy sampling success rates were low (43%), but tagging rates were high with improved tag designs (86%). The improved tags remained attached for 26±14 days (mean ± SD). Individuals most often showed no reaction when attempts missed (66%) and a slight reaction–defined as a slight flinch, slight shake, short acceleration, or immediate dive–when hit (54%). Severe immediate reactions were never observed. Hit or miss and age-sex class were important predictors of the reaction, but the method (tag or biopsy) was unimportant. Multievent trap-dependence modelling revealed considerable variation in individual sighting patterns; however, there were no significant mid- or long-term changes following

  18. Responses of absolute and specific soil enzyme activities to long term additions of organic and mineral fertilizer.

    PubMed

    Zhang, Xinyu; Dong, Wenyi; Dai, Xiaoqin; Schaeffer, Sean; Yang, Fengting; Radosevich, Mark; Xu, Lili; Liu, Xiyu; Sun, Xiaomin

    2015-12-01

    Long-term phosphorus (P) and nitrogen (N) applications may seriously affect soil microbial activity. A long-term field fertilizer application trial was established on reddish paddy soils in the subtropical region of southern China in 1998. We assessed the effects of swine manure and seven different rates or ratios of NPK fertilizer treatments on (1) the absolute and specific enzyme activities per unit of soil organic carbon (SOC) or microbial biomass carbon (MBC) involved in C, N, and P transformations and (2) their relationships with soil environmental factors and soil microbial community structures. The results showed that manure applications led to increases in the absolute and specific activities of soil β-1,4-glucosidase(βG), β-1,4-N-acetylglucosaminidase (NAG), and leucine aminopeptidase (LAP). The absolute and specific acid phosphatase (AP) activities decreased as mineral P fertilizer application rates and ratios increased. Redundancy analysis (RDA) showed that there were negative correlations between absolute and specific AP activities, pH, and total P contents, while there were positive correlations between soil absolute and specific βG, NAG, and LAP enzyme activities, and SOC and total N contents. RDA showed that the contents of actinomycete and Gram-positive bacterium PLFA biomarkers are more closely related to the absolute and specific enzyme activities than the other PLFA biomarkers (P<0.01). Our results suggest that both the absolute and specific enzyme activities could be used as sensitive soil quality indicators that provide useful linkages with the microbial community structures and environmental factors. To maintain microbial activity and to minimize environmental impacts, P should be applied as a combination of inorganic and organic forms, and total P fertilizer application rates to subtropical paddy soils should not exceed 44 kg P ha(-1) year(-1).

  19. Biochemical and physiological responses in liver and muscle of rainbow trout after long-term exposure to propiconazole.

    PubMed

    Li, Zhi-Hua; Zlabek, Vladimir; Li, Ping; Grabic, Roman; Velisek, Josef; Machova, Jana; Randak, Tomas

    2010-09-01

    In this study, the chronic toxic effects of PCZ, a triazole fungicide commonly present in surface and ground water, on morphological indices, ROS generation and RNA/DNA ratio in liver and white muscle of rainbow trout were investigated. Fish were exposed at sublethal concentrations of PCZ (0.2, 50 and 500 microg L(-1)) for 7, 20 and 30d. Compared with the control, there were significant lower CF and HSI in fish exposed at the highest concentration of PCZ. ROS levels in both tissues increased significantly at higher PCZ concentrations (50 and 500 microg L(-1)) after 20 d and above, as well as in muscle of fish exposed at lowest PCZ concentration (0.2 microg L(-1)) after 30 d. The hepatic antioxidant enzymes (SOD and CAT) activities were induced significantly at higher concentrations (50, 500 microg L(-1)) of PCZ after 20 d and at 50 microg L(-1) after 30 d. Additional, hepatic SOD activity was significantly induced at 0.2 microg L(-1) after 30 d. Compared with the hepatic antioxidant enzymes activities in fish exposed to 50 microg L(-1) of PCZ, there was a decreasing trend in those exposed to 500 microg L(-1) after 30 d exposure. However, both the antioxidant enzymes activities were significantly inhibited in muscle of fish exposed to 500 microg L(-1) PCZ after 30 d. Moreover there was significant lower RNA/DNA ratio in both tissues after long-term exposure to higher concentration of PCZ. In short, environmental concentrations of PCZ could not induce obvious impacts on fish, but long-term exposure to higher concentrations of CBZ could affect seriously the health status of fish.

  20. The effects of short-term and long-term learning on the responses of lateral intraparietal neurons to visually presented objects

    PubMed Central

    Sigurdardottir, Heida M.; Sheinberg, David L.

    2015-01-01

    The lateral intraparietal area (LIP) of the dorsal visual stream is thought to play an important role in visually directed orienting, or the guidance of where to look and pay attention. LIP can also respond selectively to differently shaped objects. We sought to understand how and to what extent short-term and long-term experience with visual orienting can determine the nature of responses of LIP neurons to objects of different shapes. We taught monkeys to arbitrarily associate centrally presented objects of various shapes with orienting either toward or away from a preferred peripheral spatial location of a neuron. For some objects the training lasted for less than a single day, while for other objects the training lasted for several months. We found that neural responses to visual objects are affected both by such short-term and long-term experience, but that the length of the learning period determines exactly how this neural plasticity manifests itself. Short-term learning over the course of a single training session affects neural responses to objects, but these effects are only seen relatively late after visual onset; at this time, the neural responses to newly learned objects start to resemble those of familiar over-learned objects that share their meaning or arbitrary association. Long-term learning, on the other hand, affects the earliest and apparently bottom-up responses to visual objects. These responses tend to be greater for objects that have repeatedly been associated with looking toward, rather than away from, LIP neurons’ preferred spatial locations. Responses to objects can nonetheless be distinct even though the objects have both been similarly acted on in the past and will lead to the same orienting behavior in the future. Our results therefore also indicate that a complete experience-driven override of LIP object responses is difficult or impossible. PMID:25633647

  1. Divergent responses of soil buffering capacity to long-term N deposition in three typical tropical forests with different land-use history.

    PubMed

    Lu, Xiankai; Mao, Qinggong; Mo, Jiangming; Gilliam, Frank S; Zhou, Guoyi; Luo, Yiqi; Zhang, Wei; Huang, Juan

    2015-04-01

    Elevated anthropogenic nitrogen (N) deposition has become an important driver of soil acidification at both regional and global scales. It remains unclear, however, how long-term N deposition affects soil buffering capacity in tropical forest ecosystems and in ecosystems of contrasting land-use history. Here, we expand on a long-term N deposition experiment in three tropical forests that vary in land-use history (primary, secondary, and planted forests) in Southern China, with N addition as NH4NO3 of 0, 50, 100, and 150 kg N ha(-1) yr(-1), respectively. Results showed that all three forests were acid-sensitive ecosystems with poor soil buffering capacity, while the primary forest had higher base saturation and cation exchange capacity than others. However, long-term N addition significantly accelerated soil acidification and decreased soil buffering capacity in the primary forest, but not in the degraded secondary and planted forests. We suggest that ecosystem N status, influenced by different land-use history, is primarily responsible for these divergent responses. N-rich primary forests may be more sensitive to external N inputs than others with low N status, and should be given more attention under global changes in the future, because lack of nutrient cations is irreversible. PMID:25741588

  2. Divergent responses of soil buffering capacity to long-term N deposition in three typical tropical forests with different land-use history.

    PubMed

    Lu, Xiankai; Mao, Qinggong; Mo, Jiangming; Gilliam, Frank S; Zhou, Guoyi; Luo, Yiqi; Zhang, Wei; Huang, Juan

    2015-04-01

    Elevated anthropogenic nitrogen (N) deposition has become an important driver of soil acidification at both regional and global scales. It remains unclear, however, how long-term N deposition affects soil buffering capacity in tropical forest ecosystems and in ecosystems of contrasting land-use history. Here, we expand on a long-term N deposition experiment in three tropical forests that vary in land-use history (primary, secondary, and planted forests) in Southern China, with N addition as NH4NO3 of 0, 50, 100, and 150 kg N ha(-1) yr(-1), respectively. Results showed that all three forests were acid-sensitive ecosystems with poor soil buffering capacity, while the primary forest had higher base saturation and cation exchange capacity than others. However, long-term N addition significantly accelerated soil acidification and decreased soil buffering capacity in the primary forest, but not in the degraded secondary and planted forests. We suggest that ecosystem N status, influenced by different land-use history, is primarily responsible for these divergent responses. N-rich primary forests may be more sensitive to external N inputs than others with low N status, and should be given more attention under global changes in the future, because lack of nutrient cations is irreversible.

  3. Responses of bacterial and archaeal ammonia oxidizers to soil organic and fertilizer amendments under long-term management

    SciTech Connect

    Wessen, E.; Nyberg, K.; Jansson, J.K.; Hallin, S.

    2010-05-01

    Ammonia-oxidizing bacteria (AOB) and ammonia-oxidizing archaea (AOA) co-exist in soil, but their relative distribution may vary depending on the environmental conditions. Effects of changes in soil organic matter and nutrient content on the AOB and AOA are poorly understood. Our aim was to compare effects of long-term soil organic matter depletion and amendments with labile (straw) and more recalcitrant (peat) organic matter, with and without easily plant-available nitrogen, on the activities, abundances and community structures of AOB and AOA. Soil was sampled from a long-term field site in Sweden that was established in 1956. The potential ammonia oxidation rates, the AOB and AOA amoA gene abundances and the community structures of both groups based on T-RFLP of amoA genes were determined. Straw amendment during 50 years had not altered any of the measured soil parameters, while the addition of peat resulted in a significant increase of soil organic carbon as well as a decrease in pH. Nitrogen fertilization alone resulted in a small decrease in soil pH, organic carbon and total nitrogen, but an increase in primary production. Type and amount of organic matter had an impact on the AOB and AOA community structures and the AOA abundance. Our findings confirmed that AOA are abundant in soil, but showed that under certain conditions the AOB dominate, suggesting niche differentiation between the two groups at the field site. The large differences in potential rates between treatments correlated to the AOA community size, indicating that they were functionally more important in the nitrification process than the AOB. The AOA abundance was positively related to addition of labile organic carbon, which supports the idea that AOA could have alternative growth strategies using organic carbon. The AOB community size varied little in contrast to that of the AOA. This indicates that the bacterial ammonia oxidizers as a group have a greater ecophysiological diversity and

  4. Preoperative Chemoradiotherapy (CRT) Followed by Laparoscopic Surgery for Rectal Cancer: Predictors of the Tumor Response and the Long-Term Oncologic Outcomes

    SciTech Connect

    Lee, Jong Hoon; Kim, Sung Hwan; Kim, Jun-Gi; Cho, Hyun Min; Shim, Byoung Yong

    2011-10-01

    Purpose: We have evaluated the predictors of a tumor response to chemoradiotherapy (CRT) and the long-term oncologic outcomes of preoperative CRT and laparoscopic surgery for patients who suffer from rectal cancer. Methods and Materials: The study involved 274 patients with locally advanced rectal cancer and who had been treated with preoperative CRT and curative laparoscopic total mesorectal excision between January 2003 and January 2009. We assessed the long-term oncologic outcomes, in terms of recurrence and survival, of the treated patients. Results: Forty-two (15.3%) of the 274 patients had complete pathologic responses (pCR). The pre-CRT carcinoembryonic antigen level was the only significant predictor of a pCR on the multivariate analysis (p = 0.01). The overall survival at 5 years was 73.1%, with a mean survival period of 59.7 months (95% CI, 57.1-62.3). The disease-free survival at 5 years was 67.3% with a mean survival period of 54.7 months (95% CI, 51.7-57.8). The pCR group had a higher rate of overall survival at 5 years than did the non-pCR group, and the difference was significant (86.0% vs. 71.2%; hazard ratio = 0.87; 95% CI, 0.78-0.96; p = 0.03). The cumulative incidences of local and distant recurrences at 5 years were 5.8% and 28.3%, respectively. A total of 84.5% (234 of 274) of the patients had their anal sphincters preserved. Grade 3 or 4 acute and long-term toxic effects occurred in 22.2% and 8.4% of the patients, respectively. Conclusion: Preoperative CRT and laparoscopic surgery seems safe and feasible with favorable long-term outcomes and a high rate of sphincter preservation for the patients with low-lying tumors of the rectum.

  5. Characterization of basal and re-inflammation-associated long-term alteration in pain responsivity following short-lasting neonatal local inflammatory insult.

    PubMed

    Ren, K; Anseloni, V; Zou, S-P; Wade, E B; Novikova, S I; Ennis, M; Traub, R J; Gold, M S; Dubner, R; Lidow, M S

    2004-08-01

    Recently, several studies have suggested that neonatal noxious insult could alter future responses to painful stimuli. However, the manifestations, mechanisms, and even developmental nature of these alterations remain a matter of controversy. In part, this is due to the lack of detailed information on the neonatal sensitive period(s) during which noxious stimulation influences future nociception, and the time-course and distribution of the resultant abnormalities. The present paper describes these parameters in a rat model of short-lasting ( approximately 24 h) neonatal local inflammation of a hindpaw produced by injection of 0.25% carrageenan (1 microl/g). Examinations of paw withdrawal responses to thermal and mechanical stimulations in adult animals, which as neonates were subjected to this insult, showed that the previously-reported long-term hypoalgesia and hyperalgesia are not mutually exclusive outcomes of early noxious experience. Long-term hypoalgesia was apparent at the basal conditions and was equally strong in the previously injured and uninjured paws, which suggests a globally-driven deficit. In contrast, long-term excessive hyperalgesia had the strongest manifestation in the neonatally-injured paw after re-inflammation, indicating significant segmental involvement in its generation. The differences between mechanisms underlying the observed hypoalgesia and hyperalgesia are further underscored by the finding that, while the former is detectable only after animals reach the second month of life, the latter is elicitable immediately upon cessation of the initial neonatal inflammation. Nevertheless, we detected a significant overlap in the neonatal sensitive periods for generation of these effects (both occurring within the first postnatal week). Also, neither the basal hypoalgesia nor excessive re-inflammation-associated hyperalgesia subsided with age and were detectable in 120-125-day-old rats. These finding provide a framework within which the entire

  6. Two phases of response to long-term moderate heat: Variation in thermotolerance between Arabidopsis thaliana and its relative Arabis paniculata.

    PubMed

    Tang, Ting; Liu, Peile; Zheng, Guowei; Li, Weiqi

    2016-02-01

    Long-term moderate heat is often experienced by plants and will become even more common in the future due to global warming. However, the responses of plants to this stress have not been characterised. In the present study, growth between Arabidopsis thaliana and its relative Arabis paniculata upon long-term exposure to moderate heat was compared. It was found that the latter was more tolerant than the former, and the patterns of physiological and biochemical responses of both plants presented two phases. The early phase involved no significant visible morphological and physiological changes. It occurred during the first third of the heat treatment and was extended when the stress was attenuated. During the later phase, the plants died or were damaged. Heat shock proteins were dramatically induced at the early phase and gradually decreased at the later phase in A. thaliana. By contrast, the levels were induced and maintained in A. paniculata. Profiling of membrane lipids found that the two plants exhibited opposite patterns of lipid remodelling at the early phase: A. paniculata synthesised phosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine and phosphatidylinositol and showed a rapid decrease in the degree of lipid unsaturation, while A. thaliana degraded its lipids at the early phase and showed an accelerated degradation at the later phase. These biochemical adjustments during the early phase could favor the thermotolerance of A. paniculata. These results suggest that this species could thus be a model for the study of resistance to long-term moderate heat, through a strategy by which plants can adapt to long-term moderate heat.

  7. Two phases of response to long-term moderate heat: Variation in thermotolerance between Arabidopsis thaliana and its relative Arabis paniculata.

    PubMed

    Tang, Ting; Liu, Peile; Zheng, Guowei; Li, Weiqi

    2016-02-01

    Long-term moderate heat is often experienced by plants and will become even more common in the future due to global warming. However, the responses of plants to this stress have not been characterised. In the present study, growth between Arabidopsis thaliana and its relative Arabis paniculata upon long-term exposure to moderate heat was compared. It was found that the latter was more tolerant than the former, and the patterns of physiological and biochemical responses of both plants presented two phases. The early phase involved no significant visible morphological and physiological changes. It occurred during the first third of the heat treatment and was extended when the stress was attenuated. During the later phase, the plants died or were damaged. Heat shock proteins were dramatically induced at the early phase and gradually decreased at the later phase in A. thaliana. By contrast, the levels were induced and maintained in A. paniculata. Profiling of membrane lipids found that the two plants exhibited opposite patterns of lipid remodelling at the early phase: A. paniculata synthesised phosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine and phosphatidylinositol and showed a rapid decrease in the degree of lipid unsaturation, while A. thaliana degraded its lipids at the early phase and showed an accelerated degradation at the later phase. These biochemical adjustments during the early phase could favor the thermotolerance of A. paniculata. These results suggest that this species could thus be a model for the study of resistance to long-term moderate heat, through a strategy by which plants can adapt to long-term moderate heat. PMID:26782026

  8. Loss of serum HCV RNA at week 4 of interferon-alpha therapy is associated with more favorable long-term response in patients with chronic hepatitis C.

    PubMed

    Orito, E; Mizokami, M; Suzuki, K; Ohba, K; Ohno, T; Mori, M; Hayashi, K; Kato, K; Iino, S; Lau, J Y

    1995-06-01

    To determine the virological factors associated with a favorable long-term response to interferon-alpha (IFN) therapy in chronic hepatitis C virus (HCV) infection, 61 Japanese patients with chronic HCV infection were treated with IFN for 24 weeks (780 million units in total) and followed for 8 to 16 months after cessation of therapy. Ten patients dropped out because of severe side effects. Of the 51 patients who completed IFN therapy, 23 showed complete and sustained response (CR --> SR), 13 complete response with early relapse (CR --> Rel), and 15 no response to IFN (NR). For the pretreatment serum HCV RNA level, 20/23 who had CR --> SR had < 10(6) eq/ml compared to 3/13 CR --> Rel and 1/15 NR (P < 0.01). Serologically defined HCV type 2 infection was also associated with a better opportunity to develop CR --> SR compared to CR --> Rel of NR (P < 0.01). Loss of serum HCV RNA at week 4 of IFN therapy was also associated with a more favorable long-term response [17/19 CR --> SR were HCV RNA negative compared to 3/11 CR --> Rel (P < 0.01) and 2/13 NR (P < 0.01)]. In contrast, normalization of serum alanine aminotransferase (ALT) levels at week 4 was found in 9/19 CR --> SR compared to 8/11 CR --> Rel (P = NS), and 0/13 in NR (P < 0.01). Six months after cessation of IFN therapy, 3/25 CR --> SR patients were HCV RNA positive despite normalization of serum ALT levels. These data indicated that in addition to pretreatment serum HCV RNA levels and HCV type, the kinetics of response to IFN (at week 4) were also predictive of subsequent long-term response to IFN in patients with chronic HCV infection.

  9. Soil ionomic and enzymatic responses and correlations to fertilizations amended with and without organic fertilizer in long-term experiments.

    PubMed

    Feng, Xumeng; Ling, Ning; Chen, Huan; Zhu, Chen; Duan, Yinghua; Peng, Chang; Yu, Guanghui; Ran, Wei; Shen, Qirong; Guo, Shiwei

    2016-01-01

    To investigate potential interactions between the soil ionome and enzyme activities affected by fertilization with or without organic fertilizer, soil samples were collected from four long-term experiments over China. Irrespective of variable interactions, fertilization type was the major factor impacting soil ionomic behavior and accounted for 15.14% of the overall impact. Sampling site was the major factor affecting soil enzymatic profile and accounted for 34.25% of the overall impact. The availabilities of Pb, La, Ni, Co, Fe and Al were significantly higher in soil with only chemical fertilizer than the soil with organic amendment. Most of the soil enzyme activities, including α-glucosidase activity, were significantly activated by organic amendment. Network analysis between the soil ionome and the soil enzyme activities was more complex in the organic-amended soils than in the chemical fertilized soils, whereas the network analysis among the soil ions was less complex with organic amendment. Moreover, α-glucosidase was revealed to generally harbor more corrections with the soil ionic availabilities in network. We concluded that some of the soil enzymes activated by organic input can make the soil more vigorous and stable and that the α-glucosidase revealed by this analysis might help stabilize the soil ion availability. PMID:27079657

  10. Long-term exposure of rapeseed (Brassica napus L.) to ZnO nanoparticles: anatomical and ultrastructural responses.

    PubMed

    Mousavi Kouhi, Seyed Mousa; Lahouti, Mehrdad; Ganjeali, Ali; Entezari, Mohammad H

    2015-07-01

    Rapid development of nanotechnology in recent years has raised concerns about nanoparticle (NPs) release into the environment and its adverse effects on living organisms. The present study is the first comprehensive report on the anatomical and ultrastructural changes of a variety of cells after long-term exposure of plant to NPs or bulk material particles (BPs). Light and electron microscopy revealed some anatomical and ultrastructural modifications of the different types of cell in the root and leaf, induced by both types of treatment. Zinc oxide (ZnO) BPs-induced modifications were surprisingly more than those induced by ZnO NPs. The modifications induced by ZnO BPs or ZnO NPs were almost similar to those induced by excess Zn. Zn content of the root and leaf of both ZnO NPs- and ZnO BPs-treated plants was severely increased, where the increase was greater in the plants treated with ZnO BPs. Overall, these results indicate that the modifications induced by ZnO particles can be attributed, at least partly, to the Zn(2+) dissolution by ZnO particles rather than their absorption by root and their subsequent effects.

  11. Soil ionomic and enzymatic responses and correlations to fertilizations amended with and without organic fertilizer in long-term experiments.

    PubMed

    Feng, Xumeng; Ling, Ning; Chen, Huan; Zhu, Chen; Duan, Yinghua; Peng, Chang; Yu, Guanghui; Ran, Wei; Shen, Qirong; Guo, Shiwei

    2016-01-01

    To investigate potential interactions between the soil ionome and enzyme activities affected by fertilization with or without organic fertilizer, soil samples were collected from four long-term experiments over China. Irrespective of variable interactions, fertilization type was the major factor impacting soil ionomic behavior and accounted for 15.14% of the overall impact. Sampling site was the major factor affecting soil enzymatic profile and accounted for 34.25% of the overall impact. The availabilities of Pb, La, Ni, Co, Fe and Al were significantly higher in soil with only chemical fertilizer than the soil with organic amendment. Most of the soil enzyme activities, including α-glucosidase activity, were significantly activated by organic amendment. Network analysis between the soil ionome and the soil enzyme activities was more complex in the organic-amended soils than in the chemical fertilized soils, whereas the network analysis among the soil ions was less complex with organic amendment. Moreover, α-glucosidase was revealed to generally harbor more corrections with the soil ionic availabilities in network. We concluded that some of the soil enzymes activated by organic input can make the soil more vigorous and stable and that the α-glucosidase revealed by this analysis might help stabilize the soil ion availability.

  12. Soil ionomic and enzymatic responses and correlations to fertilizations amended with and without organic fertilizer in long-term experiments

    NASA Astrophysics Data System (ADS)

    Feng, Xumeng; Ling, Ning; Chen, Huan; Zhu, Chen; Duan, Yinghua; Peng, Chang; Yu, Guanghui; Ran, Wei; Shen, Qirong; Guo, Shiwei

    2016-04-01

    To investigate potential interactions between the soil ionome and enzyme activities affected by fertilization with or without organic fertilizer, soil samples were collected from four long-term experiments over China. Irrespective of variable interactions, fertilization type was the major factor impacting soil ionomic behavior and accounted for 15.14% of the overall impact. Sampling site was the major factor affecting soil enzymatic profile and accounted for 34.25% of the overall impact. The availabilities of Pb, La, Ni, Co, Fe and Al were significantly higher in soil with only chemical fertilizer than the soil with organic amendment. Most of the soil enzyme activities, including α-glucosidase activity, were significantly activated by organic amendment. Network analysis between the soil ionome and the soil enzyme activities was more complex in the organic-amended soils than in the chemical fertilized soils, whereas the network analysis among the soil ions was less complex with organic amendment. Moreover, α-glucosidase was revealed to generally harbor more corrections with the soil ionic availabilities in network. We concluded that some of the soil enzymes activated by organic input can make the soil more vigorous and stable and that the α-glucosidase revealed by this analysis might help stabilize the soil ion availability.

  13. Soil ionomic and enzymatic responses and correlations to fertilizations amended with and without organic fertilizer in long-term experiments

    PubMed Central

    Feng, Xumeng; Ling, Ning; Chen, Huan; Zhu, Chen; Duan, Yinghua; Peng, Chang; Yu, Guanghui; Ran, Wei; Shen, Qirong; Guo, Shiwei

    2016-01-01

    To investigate potential interactions between the soil ionome and enzyme activities affected by fertilization with or without organic fertilizer, soil samples were collected from four long-term experiments over China. Irrespective of variable interactions, fertilization type was the major factor impacting soil ionomic behavior and accounted for 15.14% of the overall impact. Sampling site was the major factor affecting soil enzymatic profile and accounted for 34.25% of the overall impact. The availabilities of Pb, La, Ni, Co, Fe and Al were significantly higher in soil with only chemical fertilizer than the soil with organic amendment. Most of the soil enzyme activities, including α-glucosidase activity, were significantly activated by organic amendment. Network analysis between the soil ionome and the soil enzyme activities was more complex in the organic-amended soils than in the chemical fertilized soils, whereas the network analysis among the soil ions was less complex with organic amendment. Moreover, α-glucosidase was revealed to generally harbor more corrections with the soil ionic availabilities in network. We concluded that some of the soil enzymes activated by organic input can make the soil more vigorous and stable and that the α-glucosidase revealed by this analysis might help stabilize the soil ion availability. PMID:27079657

  14. Long-term exposure of rapeseed (Brassica napus L.) to ZnO nanoparticles: anatomical and ultrastructural responses.

    PubMed

    Mousavi Kouhi, Seyed Mousa; Lahouti, Mehrdad; Ganjeali, Ali; Entezari, Mohammad H

    2015-07-01

    Rapid development of nanotechnology in recent years has raised concerns about nanoparticle (NPs) release into the environment and its adverse effects on living organisms. The present study is the first comprehensive report on the anatomical and ultrastructural changes of a variety of cells after long-term exposure of plant to NPs or bulk material particles (BPs). Light and electron microscopy revealed some anatomical and ultrastructural modifications of the different types of cell in the root and leaf, induced by both types of treatment. Zinc oxide (ZnO) BPs-induced modifications were surprisingly more than those induced by ZnO NPs. The modifications induced by ZnO BPs or ZnO NPs were almost similar to those induced by excess Zn. Zn content of the root and leaf of both ZnO NPs- and ZnO BPs-treated plants was severely increased, where the increase was greater in the plants treated with ZnO BPs. Overall, these results indicate that the modifications induced by ZnO particles can be attributed, at least partly, to the Zn(2+) dissolution by ZnO particles rather than their absorption by root and their subsequent effects. PMID:25752639

  15. Prognostic value of intra-operative abnormal muscle response monitoring during microvascular decompression for long-term outcome of hemifacial spasm.

    PubMed

    Li, Jiping; Zhang, Yuqing; Zhu, Hongwei; Li, Yongjie

    2012-01-01

    The reliability of intra-operative abnormal muscle response (AMR) monitoring as an indicator of post-operative outcome in patients with hemifacial spasm (HFS) is under debate. The primary aim of this study was to evaluate the correlation between intra-operative AMR changes and long-term post-operative outcome. We monitored intra-operative AMR during microvascular decompression (MVD) in consecutive patients with HFS (n = 104). Patients in this study were divided into two groups based on whether their AMR disappeared or persisted following MVD. Ninety patients were followed-up, and the mean duration from surgery to final follow-up examination was 3.7 years. Fourteen patients were lost to follow-up. AMR disappeared during surgery for 80 patients; of these, 74 achieved complete resolution of HFS, five had persistent HFS, and one patient developed a recurrence of HFS. Of the 10 patients with persistent AMR despite effective MVD, eight patients achieved complete resolution, one patient had persistent HFS, and one developed recurrent HFS. The long-term clinical outcome of HFS after MVD did not significantly correlate with intra-operative AMR changes (p = 0.791). Therefore, we suggest that intra-operative AMR monitoring may not be a reliable indicator of long-term post-operative outcome for HFS.

  16. Muscle-Specific Myosin Heavy Chain Shifts in Response to a Long-Term High Fat/High Sugar Diet and Resveratrol Treatment in Nonhuman Primates

    PubMed Central

    Hyatt, Jon-Philippe K.; Nguyen, Lisa; Hall, Allison E.; Huber, Ashley M.; Kocan, Jessica C.; Mattison, Julie A.; de Cabo, Rafael; LaRocque, Jeannine R.; Talmadge, Robert J.

    2016-01-01

    Shifts in myosin heavy chain (MHC) expression within skeletal muscle can be induced by a host of stimuli including, but not limited to, physical activity, alterations in neural activity, aging, and diet or obesity. Here, we hypothesized that both age and a long-term (2 year) high fat/high sugar diet (HFS) would induce a slow to fast MHC shift within the plantaris, soleus, and extensor digitorum longus (EDL) muscles from rhesus monkeys. Furthermore, we tested whether supplementation with resveratrol, a naturally occurring compound that has been attributed with augmenting aerobic potential through mitochondrial proliferation, would counteract any diet-induced MHC changes by promoting a fast to slow isoform switch. In general, we found that MHC isoforms were not altered by aging during mid-life. The HFS diet had the largest impact within the soleus muscle where the greatest slow to fast isoform shifts were observed in both mRNA and protein indicators. As expected, long-term resveratrol treatment counteracted, or blunted, these diet-induced shifts within the soleus muscle. The plantaris muscle also demonstrated a fast-to-slow phenotypic response to resveratrol treatment. In conclusion, diet or resveratrol treatment impacts skeletal muscle phenotype in a muscle-specific manner and resveratrol supplementation may be one approach for promoting the fatigue-resistant MHC (type I) isoform especially if its expression is blunted as a result of a long-term high fat/sugar diet. PMID:26973542

  17. Understanding Ecosystem Response to Perturbation: The Need to Combine Long-Term Monitoring with Process-Based Research Across Spatial and Temporal Scales

    NASA Astrophysics Data System (ADS)

    Laudon, H.

    2014-12-01

    The societal needs for understanding ecosystems response to environmental perturbation have never been greater. Most research on the mechanisms that regulate long-term changes in water quality is based either on individual well-studied catchments, or regional monitoring datasets. While the advantage of research catchments often is the large amount of ancillary information that can provide mechanistic explanations, the results are often difficult to extrapolate because of limited statistical and geographic representation. Conversely, environmental monitoring sites often lack the process-based designed data collection, which instead makes it difficult to infer causal relationships. Here I will discuss the value of field research infrastructures sites that combine the best of long-term monitoring time-series with the exclusivity of process-based research infrastructures across multiple spatial and temporal scales. The basis for this presentation will be on the Krycklan Catchment Study (www.slu.se/Krycklan) located in northern Sweden that provides a unique field experimental platform for hillslope to landscape-scale research on long-term ecosystem dynamics in the boreal landscape. The site is designed for processes-based research needed to assess the role of external drivers such as forest management, climate change, and long-range transport of pollutants on forests, mires, soils, streams, lakes and groundwater. In my presentation I will discuss some examples of how Krycklan has succeeded to construct a state-of-the-art field infrastructure for experimental and hypothesis driven research, maintain the long-term climatic, biogeochemical, hydrological and environmental data collection of highest quality, and how this has supported the development of new models and guidelines for research, policy and management.

  18. Differences in the Responses of Photosystems I and II in Cymbidium sinense and C. tracyanum to Long-Term Chilling Stress

    PubMed Central

    Li, Jia-Wei; Zhang, Shi-Bao

    2016-01-01

    The susceptibility of photosystem I (PSI) and photosystem II (PSII) to chilling stress depends on plant species, and cyclic electron flow (CEF) plays an important role in photoprotection for some species under short stress periods. However, little is known about the responses of PSI and PSII to long-term chilling stress. We studied two orchid species—Cymbidium sinense and C. tracyanum— that differ in their capacity to adapt to low temperature, and exposed plants for 19 d to stress conditions that included 4°C and a light intensity of 250 to 350 μmol photons m-2 s-1. Meanwhile, we investigated their dynamic variations in Chl fluorescence and P700 parameters. After exposure to 4°C and 250 μmol photons m-2 s-1 for 6 h, PSI activity was maintained stable in both species, but stronger PSII photoinhibition was observed in C. sinense. During the long-term treatment, the maximum quantum yield of PSII was significantly reduced, with that decrease being greater in C. sinense. After 19 d of chilling treatment, the maximum photo-oxidizable P700 declined only slightly in C. tracyanum but dropped significantly in C. sinense. Linear electron flow was largely depressed during the long-term chilling treatment, especially in C. sinense. Meanwhile, C. tracyanum showed higher CEF activity than C. sinense. These results indicate that PSII is more sensitive to chilling-light stress than PSI in both species. The rate of PSII photodamage at chilling-light stress is higher in C. sinense than C. tracyanum, and CEF contributes to photoprotection for PSI and PSII under long-term chilling stress in C. tracyanum. PMID:26779201

  19. Shifts and dynamics of greenhouse gas fluxes in coastal marshes: Responses to short- and long-term nitrogen additions (Invited)

    NASA Astrophysics Data System (ADS)

    Moseman-Valtierra, S.; Kroeger, K. D.; Tang, J.; Fisher, K.; Bratton, J. F.; Crusius, J.

    2010-12-01

    Coastal wetlands are estimated to sequester carbon at faster rates than most ecosystems, and thus they are appealing targets for efforts to ameliorate climate change through biological C storage. However, to accurately estimate the climatic impact of such strategies, we must simultaneously consider fluxes of greenhouse gases from these ecosystems, including CH4 and N2O. Coastal salt marshes are currently thought to represent minor sources of greenhouse gases relative to freshwater wetlands, but the few measurements that exist for N2O and CH4 fluxes in these systems have not spanned the range of their dynamic environmental conditions. Further, multiple anthropogenic sources have disproportionately increased nitrogen loads in coastal ecosystems, which we hypothesized may significantly enhance N2O emissions from salt marshes. We tested this hypothesis with short- and long-term manipulative experiments at low to moderate nitrogen loads in pristine temperate Spartina patens marshes at Plum Island (MA). In July 2009, we compared background greenhouse gas fluxes with those measured immediately after either a single addition of nitrate (equivalent to 1.4g N m -2) or a control solution of artificial seawater. Prior to manipulations, the salt marsh sediments represented small sinks of N2O, as fluxes averaged -33 μmol N2O m-2 day-1. Yet, within one hour of manipulations, the plots with nitrate additions became sources of N2O, with fluxes averaging 42 and 108 μmol N2O m-2 day-1 in light and dark chambers, respectively. These exceeded fluxes in control plots by more than an order of magnitude. Respiratory CO2 fluxes were also significantly higher in nitrate-enriched plots (4.4 +/- 1 μmol CO2 m-2 s-1) than in controls (2.4 +/- 0.3 μmol CO2 m-2 s-1) immediately following the nitrate additions. Methane fluxes were not affected by nitrogen, but they varied spatially, ranging from 7.5 to 2200 μmol CH4 m-2 day-1. Although the enhanced N2O fluxes did not persist after 2 days, the

  20. Long-term bone mineral density response to enzyme replacement therapy in a retrospective pediatric cohort of Gaucher patients.

    PubMed

    Ciana, Giovanni; Deroma, Laura; Franzil, Anna Martina; Dardis, Andrea; Bembi, Bruno

    2012-11-01

    Osteopenia is described as a relevant sign of bone involvement in Gaucher disease (GD) both in pediatric and adult patients. Furthermore, abnormal bone metabolism is considered to play a role in growth and pubertal delay. To analyze the long-term effect of enzyme replacement therapy (ERT) on bone mineral density (BMD), a retrospective observational study was conducted in a cohort of 18 GD pediatric patients (13 males, 5 females; median age 9.2 years). They received biweekly infusions of 20-60 IU/kg of alglucerase/imiglucerase. Clinical, laboratory and imaging parameters were evaluated every 2 years. According to the International Society of Clinical Densitometry guidelines, a Z-score ≤ -2.0 was considered pathological. Nine patients (group P0) began ERT during infancy and nine (group P1) during puberty. At baseline, in three patients (16.6 %; 1P0, 2P1) Z-score was ≤ -2.0 (range -2.47 to -2.25). In patient P0 it normalized after 2 years, while in the 2P1 patients (splenectomized siblings) it persisted abnormal. The remaining 15 patients (83.4 %) always presented a normal value. In group P0, Z-score improved in infancy but showed a significant decrease during puberty, on the contrary it constantly improved in group P1. Furthermore, at baseline group P0 showed a higher median Z-score than group P1: 0.79 (0.38; 1.50) and -1.61 (-2.25; -1.56) respectively. The use of correct BMD standards to interpret bone loss during pediatric age suggests a limited significance of bone loss in these patients. Moreover, the persistence of residual disease activity may affect normal bone growth during puberty in GD populations. PMID:22441841

  1. [Responses of soil nematode communities to long-term application of inorganic fertilizers in upland red soil].

    PubMed

    Zhang, Wei; Liu, Man-Qiang; He, Yuan-Qiu; Fan, Jian-Bo; Chen, Yan

    2014-08-01

    Soil biota plays a key role in ecosystem functioning of red soil. Based on the long-term inorganic fertilization field experiment (25-year) in an upland red soil, the impacts of different inorganic fertilization managements, including NPK (nitrogen, phosphorus and potassium fertilizers), NPKCaS (NPK plus gypsum fertilizers), NP (nitrogen and phosphorus fertilizers), NK (nitrogen and potassium fertilizers) and PK (phosphorus and potassium fertilizers), on the assemblage of soil nematodes during the growing period of peanut were investigated. Significant differences among the treatments were observed for total nematode abundance, trophic groups and ecological indices (P < 0.01). The total nematode abundance decreased in the order of PK > NPKCaS > NPK > NP > NK. The total number of nematodes was significantly higher in NPKCaS and PK than in NPK, NP and NK except in May. Plant parasitic nematodes were the dominant trophic group in all treatments excepted in NPKCaS, and their proportion ranged between 38% and 65%. The dominant trophic group in NPKCaS was bacterivores and represented 42.1%. Furthermore, the higher values of maturity index, Wasilewska index and structure index in NPKCaS indicated that the combined application of NPK and gypsum could remarkably relieve soil acidification, resulting in a more mature and stable soil food web structure. While, that of the NK had the opposite effect. In conclusion, our study suggested that the application of both gypsum and phosphate is an effective practice to improve soil quality. Moreover, the analysis of nematode assemblage is relevant to reflect the impact of different inorganic fertilizer on the red soil ecosystem. PMID:25509090

  2. [Responses of soil nematode communities to long-term application of inorganic fertilizers in upland red soil].

    PubMed

    Zhang, Wei; Liu, Man-Qiang; He, Yuan-Qiu; Fan, Jian-Bo; Chen, Yan

    2014-08-01

    Soil biota plays a key role in ecosystem functioning of red soil. Based on the long-term inorganic fertilization field experiment (25-year) in an upland red soil, the impacts of different inorganic fertilization managements, including NPK (nitrogen, phosphorus and potassium fertilizers), NPKCaS (NPK plus gypsum fertilizers), NP (nitrogen and phosphorus fertilizers), NK (nitrogen and potassium fertilizers) and PK (phosphorus and potassium fertilizers), on the assemblage of soil nematodes during the growing period of peanut were investigated. Significant differences among the treatments were observed for total nematode abundance, trophic groups and ecological indices (P < 0.01). The total nematode abundance decreased in the order of PK > NPKCaS > NPK > NP > NK. The total number of nematodes was significantly higher in NPKCaS and PK than in NPK, NP and NK except in May. Plant parasitic nematodes were the dominant trophic group in all treatments excepted in NPKCaS, and their proportion ranged between 38% and 65%. The dominant trophic group in NPKCaS was bacterivores and represented 42.1%. Furthermore, the higher values of maturity index, Wasilewska index and structure index in NPKCaS indicated that the combined application of NPK and gypsum could remarkably relieve soil acidification, resulting in a more mature and stable soil food web structure. While, that of the NK had the opposite effect. In conclusion, our study suggested that the application of both gypsum and phosphate is an effective practice to improve soil quality. Moreover, the analysis of nematode assemblage is relevant to reflect the impact of different inorganic fertilizer on the red soil ecosystem.

  3. Cellular immune responses to HIV

    NASA Astrophysics Data System (ADS)

    McMichael, Andrew J.; Rowland-Jones, Sarah L.

    2001-04-01

    The cellular immune response to the human immunodeficiency virus, mediated by T lymphocytes, seems strong but fails to control the infection completely. In most virus infections, T cells either eliminate the virus or suppress it indefinitely as a harmless, persisting infection. But the human immunodeficiency virus undermines this control by infecting key immune cells, thereby impairing the response of both the infected CD4+ T cells and the uninfected CD8+ T cells. The failure of the latter to function efficiently facilitates the escape of virus from immune control and the collapse of the whole immune system.

  4. Modulation of long-term memory and extinction responses induced by growth hormone (GH) and growth hormone releasing hormone (GHRH) in rats.

    PubMed

    Schneider-Rivas, S; Rivas-Arancibia, S; Vázquez-Pereyra, F; Vázquez-Sandoval, R; Borgonio-Pérez, G

    1995-01-01

    The purpose of this work is to study the participation of growth hormone (GH) and growth hormone releasing hormone (GHRH) in the modulation of long-term memory and the extinction response of a passive avoidance task in rats. However, the effect on memory vary according to the age of the animals due to plasma levels of either hormone being modified during the aging process. Male Wistar rats were divided according to age into two experimental blocks (young rats 3 months old and aged rats 24 months old at the start of the experiment) where each block received the same treatment. Each experimental block was then divided randomly into three groups where two were experimental and the other served as control. The animals were then submitted to a one-trial passive avoidance conditioning and tested for memory retention 24 hrs after as well as twice a week until the extinction response occurred. The control group received an isotonic saline solution and the other two groups received 0.8 U.I. of GH or 4 mcg of GHRH respectively. All substances were in a 0.08 ml volume and applied 24 hrs before training as well as 24 hrs before each retention session. The results indicate that GH and GHRH modulate long-term memory as well as the extinction response and in either case the response seems to vary with age. GH and GHRH facilitates long-term memory in young rats but not in aged rats. Finally, whereas GH delays the extinction response in both groups, GHRH retards the extinction only in aged rats.

  5. Sustained long-term immune responses after in situ gene therapy combined with radiotherapy and hormonal therapy in prostate cancer patients

    SciTech Connect

    Fujita, Tetsuo; Teh, Bin S.; Mai, W.-Y.; Kusaka, Nobuyuki; Naruishi, Koji; Fattah, Elmoataz Abdel; Aguilar-Cordova, Estuardo; Butler, E. Brian; Thompson, Timothy C.

    2006-05-01

    Purpose: To explore long-term immune responses after combined radio-gene-hormonal therapy. Methods and Materials: Thirty-three patients with prostate specific antigen 10 or higher or Gleason score of 7 or higher or clinical stage T2b to T3 were treated with gene therapy that consisted of 3 separate intraprostatic injections of AdHSV-tk on Days 0, 56, and 70. Each injection was followed by 2 weeks of valacyclovir. Intensity-modulated radiation therapy was delivered 2 days after the second AdHSV-tk injection for 7 weeks. Hormonal therapy was initiated on Day 0 and continued for 4 months or 2.3 years. Blood samples were taken before, during, and after treatment. Lymphocytes were analyzed by fluorescent antibody cell sorting (FACS). Results: Median follow-up was 26 months (range, 4-48 months). The mean percentages of DR{sup +}CD8{sup +} T cells were increased at all timepoints up to 8 months. The mean percentages of DR{sup +}CD4{sup +} T cells were increased later and sustained longer until 12 months. Long-term (2.3 years) use of hormonal therapy did not affect the percentage of any lymphocyte population. Conclusions: Sustained long-term (up to 8 to 12 months) systemic T-cell responses were noted after combined radio-gene-hormonal therapy for prostate cancer. Prolonged use of hormonal therapy does not suppress this response. These results suggest the potential for sustained activation of cell-mediated immune responses against cancer.

  6. Convergent ecosystem responses to 23-year ambient and manipulated warming link advancing snowmelt and shrub encroachment to transient and long-term climate-soil carbon feedback.

    PubMed

    Harte, John; Saleska, Scott R; Levy, Charlotte

    2015-06-01

    Ecosystem responses to climate change can exert positive or negative feedbacks on climate, mediated in part by slow-moving factors such as shifts in vegetation community composition. Long-term experimental manipulations can be used to examine such ecosystem responses, but they also present another opportunity: inferring the extent to which contemporary climate change is responsible for slow changes in ecosystems under ambient conditions. Here, using 23 years of data, we document a shift from nonwoody to woody vegetation and a loss of soil carbon in ambient plots and show that these changes track previously shown similar but faster changes under experimental warming. This allows us to infer that climate change is the cause of the observed shifts in ambient vegetation and soil carbon and that the vegetation responses mediate the observed changes in soil carbon. Our findings demonstrate the realism of an experimental manipulation, allow attribution of a climate cause to observed ambient ecosystem changes, and demonstrate how a combination of long-term study of ambient and experimental responses to warming can identify mechanistic drivers needed for realistic predictions of the conditions under which ecosystems are likely to become carbon sources or sinks over varying timescales.

  7. Financing long-term care in Canada.

    PubMed

    Jacobs, P; Mills, C; Hollander, M

    1997-06-01

    Financial policies relating to long-term care in Canada are changing rapidly in response to demands for health care reform. This chapter focuses on the financial structure of institutional care, primarily nursing homes, in the western provinces of Alberta and British Columbia. Community-based long-term care is discussed briefly.

  8. The inherent properties of enzymes can only lead to a negative temperature response of soil C decomposition on the long-term.

    NASA Astrophysics Data System (ADS)

    Alvarez, Gaël; Fontaine, Sébastien

    2015-04-01

    More than one century after the pioneer work of Arrhenius on the temperature dependence of chemical reactions, the response of soil C decomposition to global warming remains uncertain. The majority of lab experiments, generally conducted at short term (months to years), suggest that the decomposition of soil C accelerates with temperature. In contrast, long-term (> 5 years) ecosystem warming experiments show that stimulation of soil respiration is only transitory. Moreover, studies on ecosystem C fluxes along a latitudinal gradient even suggest that, for a given amount of C fixed by the ecosystem, the decomposition flux decreases with temperature leading to higher C storage in warmer ecosystems (Giardina and Ryan, 2000; Sanderman, 2003). To understand this discrepancy between short-term and long-term temperature responses of C decomposition, we re-analysed the thermo-dependence of decomposition in a theory distinguishing enzyme-limited and substrate-limited reactions. Indeed, it is increasingly recognized that decomposition of the largest pool of soil C (humified organic C, HOC) is limited by the amount of soil (extracellular) enzymes. The substrate-limited reaction and its dependence to temperature were classically modelled with the first order kinetics dC/dt=-kC where reaction velocity k is modelled by an Arrhenius equation. The thermo-dependence of enzyme-limited reactions was studied in models where the reaction velocity depends on the specific activity of enzymes and the dynamics of enzyme pool, each of which may display distinct temperature sensitivities. The dynamics of the enzyme pool depended on (1) the inactivation of enzymes and its dependence to time and temperature and (2) the microbial production of enzymes, which is limited by the energy available to soil microorganisms. These models were analysed mathematically and through simulations using data on thermodynamics properties of enzymes (activation energies) and ecosystem C fluxes. Our results show

  9. Long-term monitoring of creep rate along the Hayward fault and evidence for a lasting creep response to 1989 Loma Prieta earthquake

    USGS Publications Warehouse

    Lienkaemper, J.J.; Galehouse, J.S.; Simpson, R.W.

    2001-01-01

    We present results from over 30 yr of precise surveys of creep along the Hayward fault. Along most of the fault, spatial variability in long-term creep rates is well determined by these data and can help constrain 3D-models of the depth of the creeping zone. However, creep at the south end of the fault stopped completely for more than 6 years after the M7 1989 Loma Prieta Earthquake (LPEQ), perhaps delayed by stress drop imposed by this event. With a decade of detailed data before LPEQ and a decade after it, we report that creep response to that event does indeed indicate the expected deficit in creep.

  10. Microbial Community Structure Responses to Long-Term Acid-Mine Drainage Contamination in a Coastal Salt Marsh

    NASA Astrophysics Data System (ADS)

    Moreau, J. W.; Zierenberg, R. A.; Banfield, J. F.

    2004-12-01

    Constructed wetlands for in situ bioremediation of metals and acid mine drainage (AMD) require the activity of sulfate-reducing bacteria (SRB) to sequester dissolved metals into metal-sulfide precipitates (e.g. Webb et al. 1998). Factors such as low pH and high dissolved [Cu] will constrain the growth of SRB (Sani et al. 2001). Unintentional stimulation of the growth of sulfuric acid-generating microbes, such as Thiomicrospira, would also decrease bioremediation efficiency. Few studies of natural wetlands under long-term forcing by AMD and metals have been performed. We characterized the microbial diversity, mineralogy and geochemistry of a contaminated salt marsh at the Richmond Field Station along the East San Francisco Bay. For over 50 years, this marsh has received pH ˜2, metal-rich groundwaters from near-surface pyrite tailings and paint and explosives manufacturers. Sediment cores (30-40 cm long) were taken from contaminated sites with pH ˜2 and ˜8. Whole-sediment analyses showed As, Cd, Cu, Se, Zn, and Pb are present at 100s of ppm (URS Corp. 2001). ICP-AES analyses of pore waters showed 10-50 ppb As. All cores contained fine-grained black muds and exhibited a noticeable sulfide odor. Transmission electron microscope studies of marsh sediments support the sequestration of metals into aggregates of nanocrystalline sulfides. Isotopic analyses of pore-water sulfate taken at several depths within cores of AMD pool (SMR-1) and tidal slough sediments (SM148-1) at pHs 2-3 and 7-8, respectively, all yielded significant negative δ 34S values (-25 to -35 ‰ ) consistent with bacterial sulfate reduction. However, values of the upper 10 cm of SMR-1 are roughly 10 ‰ heavier than seawater and support a significant contribution of dissolved sulfate from direct oxidation of pyrite tailings. 16S gene clone libraries revealed significantly different microbial community structures in cores SMR-1 and SM148-1. Roughly 40% of the library from SMR-1 consisted of

  11. Long-term response of a Mojave Desert winter annual plant community to a whole-ecosystem atmospheric CO2 manipulation (FACE).

    PubMed

    Smith, Stanley D; Charlet, Therese N; Zitzer, Stephen F; Abella, Scott R; Vanier, Cheryl H; Huxman, Travis E

    2014-03-01

    Desert annuals are a critically important component of desert communities and may be particularly responsive to increasing atmospheric (CO2 ) because of their high potential growth rates and flexible phenology. During the 10-year life of the Nevada Desert FACE (free-air CO2 enrichment) Facility, we evaluated the productivity, reproductive allocation, and community structure of annuals in response to long-term elevated (CO2 ) exposure. The dominant forb and grass species exhibited accelerated phenology, increased size, and higher reproduction at elevated (CO2 ) in a wet El Niño year near the beginning of the experiment. However, a multiyear dry cycle resulted in no increases in productivity or reproductive allocation for the remainder of the experiment. At the community level, early indications of increased dominance of the invasive Bromus rubens at elevated (CO2 ) gave way to an absence of Bromus in the community during a drought cycle, with a resurgence late in the experiment in response to higher rainfall and a corresponding high density of Bromus in a final soil seed bank analysis, particularly at elevated (CO2 ). This long-term experiment resulted in two primary conclusions: (i) elevated (CO2 ) does not increase productivity of annuals in most years; and (ii) relative stimulation of invasive grasses will likely depend on future precipitation, with a wetter climate favoring invasive grasses but currently predicted greater aridity favoring native dicots.

  12. Long-term acclimatory response to excess excitation energy: evidence for a role of hydrogen peroxide in the regulation of photosystem II antenna size.

    PubMed

    Borisova-Mubarakshina, Maria M; Ivanov, Boris N; Vetoshkina, Daria V; Lubimov, Valeriy Y; Fedorchuk, Tatyana P; Naydov, Ilya A; Kozuleva, Marina A; Rudenko, Natalia N; Dall'Osto, Luca; Cazzaniga, Stefano; Bassi, Roberto

    2015-12-01

    Higher plants possess the ability to trigger a long-term acclimatory response to different environmental light conditions through the regulation of the light-harvesting antenna size of photosystem II. The present study provides an insight into the molecular nature of the signal which initiates the high light-mediated response of a reduction in antenna size. Using barley (Hordeum vulgare) plants, it is shown (i) that the light-harvesting antenna size is not reduced in high light with a low hydrogen peroxide content in the leaves; and (ii) that a decrease in the antenna size is observed in low light in the presence of an elevated concentration of hydrogen peroxide in the leaves. In particular, it has been demonstrated that the ability to reduce the antenna size of photosystem II in high light is restricted to photosynthetic apparatus with a reduced level of the plastoquinone pool and with a low hydrogen peroxide content. Conversely, the reduction of antenna size in low light is induced in photosynthetic apparatus possessing elevated hydrogen peroxide even when the reduction level of the plastoquinone pool is low. Hydrogen peroxide affects the relative abundance of the antenna proteins that modulate the antenna size of photosystem II through a down-regulation of the corresponding lhcb mRNA levels. This work shows that hydrogen peroxide contributes to triggering the photosynthetic apparatus response for the reduction of the antenna size of photosystem II by being the molecular signal for the long-term acclimation of plants to high light.

  13. Prophylactic mRNA Vaccination against Allergy Confers Long-Term Memory Responses and Persistent Protection in Mice

    PubMed Central

    Hattinger, E.; Scheiblhofer, S.; Roesler, E.; Thalhamer, T.; Thalhamer, J.; Weiss, R.

    2015-01-01

    Recently, mRNA vaccines have been introduced as a safety-optimized alternative to plasmid DNA-based vaccines for protection against allergy. However, it remained unclear whether the short persistence of this vaccine type would limit memory responses and whether the protective immune response type would be maintained during recurrent exposure to allergen. We tested the duration of protective memory responses in mice vaccinated with mRNA encoding the grass pollen allergen Phl p 5 by challenging them with recombinant allergen, 3.5, 6, and 9 months after vaccination. In a second experiment, vaccinated mice were repeatedly challenged monthly with aerosolized allergen over a period of 7 months. Antibody and cytokine responses as well as lung inflammation and airway hyperresponsiveness were assessed. mRNA vaccination induced robust TH1 memory responses for at least 9 months. Vaccination efficiently suppressed TH2 cytokines, IgE responses, and lung eosinophilia. Protection was maintained after repeated exposure to aerosolized allergen and no TH1 associated pathology was observed. Lung function remained improved compared to nonvaccinated controls. Our data clearly indicate that mRNA vaccination against Phl p 5 induces robust, long-lived memory responses, which can be recalled by allergen exposure without side effects. mRNA vaccines fulfill the requirements for safe prophylactic vaccination without the need for booster immunizations. PMID:26557723

  14. Inter and intra-specific variation in photosynthetic acclimation response to long term exposure of elevated carbon dioxide

    SciTech Connect

    Wilkinson, M. |

    1996-08-01

    The response of intra and interspecific variation in photosynthetic acclimation to growth at elevated atmospheric CO{sub 2} concentration (600{micro}mol mol-l) in six important grassland species was investigated. Plants were grown in a background sward of Lolium perenne and measurements were made after four years of growth at elevated C{sub a}. Elevated CO{sub 2} was maintained using a FACE (Free-Air Carbon Enrichment) system. Significant intra and interspecific variation in acclimation response was demonstrated. The response of adaxial and abaxial stomatal conductance to elevated CO{sub 2} was also investigated. The stomatal conductance of both the adaxial and abaxial leaf surfaces was found to be reduced by elevated C{sub a}. Significant asymmetric responses in stomatal conductance was demonstrated in D. glomerata and T. pratense. Analysis of stomatal indices and densities indicated that the observed reductions in stomatal conductance were probably the result of changes in stomatal aperture.

  15. Predicting the long-term effects of human-robot interaction: a reflection on responsibility in medical robotics.

    PubMed

    Datteri, Edoardo

    2013-03-01

    This article addresses prospective and retrospective responsibility issues connected with medical robotics. It will be suggested that extant conceptual and legal frameworks are sufficient to address and properly settle most retrospective responsibility problems arising in connection with injuries caused by robot behaviours (which will be exemplified here by reference to harms occurred in surgical interventions supported by the Da Vinci robot, reported in the scientific literature and in the press). In addition, it will be pointed out that many prospective responsibility issues connected with medical robotics are nothing but well-known robotics engineering problems in disguise, which are routinely addressed by roboticists as part of their research and development activities: for this reason they do not raise particularly novel ethical issues. In contrast with this, it will be pointed out that novel and challenging prospective responsibility issues may emerge in connection with harmful events caused by normal robot behaviours. This point will be illustrated here in connection with the rehabilitation robot Lokomat.

  16. Contrasts in short- and long-term responses of Mediterranean reptile species to fire and habitat structure.

    PubMed

    Santos, Xavier; Badiane, Arnaud; Matos, Cátia

    2016-01-01

    Changes in habitat structure constitute a major factor explaining responses of reptiles to fire. However, few studies have examined habitat factors that covary with fire-history variables to explain reptile responses. We hypothesise that more complex habitats should support richer reptile communities, and that species-specific relative abundance should be related to particular habitat features. From spring 2012-2014, twenty-five transects were surveyed in the Albera Region (north-east Iberia). The vegetation structure was measured and the extent of habitat types in a 1000-m buffer around each transect calculated. Reptile-community metrics (species richness and reptile abundance) were related to fire history, vegetation structure, and habitat types, using generalized additive models. These metrics correlated with habitat-structure variables but not with fire history. The number of species increased with more complex habitats but decreased with pine-plantation abundance in the 1000-m buffer. We found contrasting responses among reptiles in terms of time since fire and those responses differed according to vegetation variables and habitat types. An unplanned fire in August 2012 provided the opportunity to compare reptile abundance values between pre-fire and the short term (1-2 years) after the fire. Most species exhibited a negative short-term response to the 2012 fire except Tarentola mauritanica, a gecko that inhabits large rocks, as opposed to other ground-dwelling species. In the reptiles studied, contrasting responses to time since fire are consistent with the habitat-accommodation model of succession. These differences are linked to specific microhabitat preferences and suggest that functional traits can be used to predict species-specific responses to fire.

  17. Contrasts in short- and long-term responses of Mediterranean reptile species to fire and habitat structure.

    PubMed

    Santos, Xavier; Badiane, Arnaud; Matos, Cátia

    2016-01-01

    Changes in habitat structure constitute a major factor explaining responses of reptiles to fire. However, few studies have examined habitat factors that covary with fire-history variables to explain reptile responses. We hypothesise that more complex habitats should support richer reptile communities, and that species-specific relative abundance should be related to particular habitat features. From spring 2012-2014, twenty-five transects were surveyed in the Albera Region (north-east Iberia). The vegetation structure was measured and the extent of habitat types in a 1000-m buffer around each transect calculated. Reptile-community metrics (species richness and reptile abundance) were related to fire history, vegetation structure, and habitat types, using generalized additive models. These metrics correlated with habitat-structure variables but not with fire history. The number of species increased with more complex habitats but decreased with pine-plantation abundance in the 1000-m buffer. We found contrasting responses among reptiles in terms of time since fire and those responses differed according to vegetation variables and habitat types. An unplanned fire in August 2012 provided the opportunity to compare reptile abundance values between pre-fire and the short term (1-2 years) after the fire. Most species exhibited a negative short-term response to the 2012 fire except Tarentola mauritanica, a gecko that inhabits large rocks, as opposed to other ground-dwelling species. In the reptiles studied, contrasting responses to time since fire are consistent with the habitat-accommodation model of succession. These differences are linked to specific microhabitat preferences and suggest that functional traits can be used to predict species-specific responses to fire. PMID:26408003

  18. Long-term complete response of antiandrogen withdrawal syndrome in a patient with metastatic prostate cancer: A case report

    PubMed Central

    Sano, Masayuki; Yamamoto, Shinya; Uehara, Sho; Yuasa, Takeshi; Masuda, Hitoshi; Fukui, Iwao; Yonese, Junji

    2016-01-01

    Antiandrogen withdrawal syndrome (AWS) is a well-established phenomenon in prostate cancer treated with combined androgen blockade (CAB). AWS is generally defined as subjective and/or objective improvement following discontinuation of an antiandrogen. However, the duration of the AWS response is usually limited. In addition, a complete response is quite rare. We herein present the case of a patient who achieved complete response from AWS, with the duration of this response lasting for >6 years. A 72-year-old man with metastatic prostate cancer received CAB with a luteinizing hormone-releasing hormone analog and bicalutamide. In addition, for local cancer control, external beam radiation therapy (70 Gy) to the prostate was performed. Subsequently, the serum prostate-specific antigen (PSA) level reached a nadir (undetectable level). Four years later, the patient's serum PSA level started to rise, and bicalutamide was discontinued to confirm AWS at a serum PSA level of 0.34 ng/ml. The PSA level immediately decreased again to an undetectable level (0.00 ng/ml), where it has been remained for 6 years. Bone scintigraphy and computed tomography scans have shown no evidence of bone or other metastases since the introduction of AWS. To the best of our knowledge, there have been no reports of such a long duration of complete response from AWS. Therefore, this phenomenon should always be considered, even in patients with advanced disease. PMID:27588183

  19. Short- and long-term response of deteriorating brackish marshes and open-water ponds to sediment enhancement by thin-layer dredge disposal

    USGS Publications Warehouse

    La Peyre, M.K.; Gossman, B.; Piazza, Bryan P.

    2009-01-01

    Artificial sediment enhancement using a thin layer of dredged material has been suggested as a means to increase elevation and create soil conditions conducive to increased marsh structure and function in deteriorating marshes. Using a chronosequence approach, we examined the effects of sediment enhancement in deteriorating marsh and open-water pond habitats located in six brackish marshes. Sediment enhancement of both marsh and interior pond sites had significant, immediate, and long-lasting effects on physical soil properties and nutrient status with increased bulk density and inorganic nitrogen. Vegetative cover and productivity response were minimal for deteriorating vegetated marshes with the short-term response data showing no significant impact of sediment enhancement and long-term trends indicating decreasing productivity over time. In contrast, trajectory models of vegetative cover and productivity in interior pond sites showed increases over time indicating that, for restoration of interior ponds, sediment enhancement may prove valuable. The use of trajectory models emphasizes the need for long-term monitoring to determine restoration success of projects. ?? 2008 U.S. Government.

  20. Evaluation of Neural Response Telemetry (NRT™) with focus on long-term rate adaptation over a wide range of stimulation rates.

    PubMed

    Huarte, Alicia; Ramos, Angel; Morera, Constantino; Garcia-Ibáñez, Luis; Battmer, Rolf; Dillier, Norbert; Wesarg, Thomas; Müller-Deile, Joachim; Hey, Mattias; Offeciers, Erwin; von Wallenberg, Ernst; Coudert, Chrystelle; Killian, Matthijs

    2014-05-01

    Custom Sound EP™ (CSEP) is an advanced flexible software tool dedicated to recording of electrically evoked compound action potentials (ECAPs) in Nucleus® recipients using Neural Response Telemetry™ (NRT™). European multi-centre studies of the Freedom™ cochlear implant system confirmed that CSEP offers tools to effectively record ECAP thresholds, amplitude growth functions, recovery functions, spread of excitation functions, and rate adaptation functions and an automated algorithm (AutoNRT™) to measure threshold profiles. This paper reports on rate adaptation measurements. Rate adaptation of ECAP amplitudes can successfully be measured up to rates of 495 pulses per second (pps) by repeating conventional ECAP measurements and over a wide range of rates up to 8000 pps using the masked response extraction technique. Rate adaptation did not show a predictable relationship with speech perception and coding strategy channel rate preference. The masked response extraction method offers opportunities to study long-term rate adaptation with well-defined and controlled stimulation paradigms. PMID:24559068

  1. Infant Long-Term Memory for a Conditioned Response and Intelligence Test Performance at 2 Years of Age.

    ERIC Educational Resources Information Center

    Fagen, Jeffrey W.; And Others

    To find predictive relations between measures taken in infancy and later scores on intelligence tests, a study was made that measured in the infant those cognitive processes examined later in life. Operant conditioning tasks were employed which required 3-, 7-, and 11-month-old infants to execute some response to produce an environmental…

  2. Deep molecular responses achieved in patients with CML-CP who are switched to nilotinib after long-term imatinib.

    PubMed

    Hughes, Timothy P; Lipton, Jeffrey H; Spector, Nelson; Cervantes, Francisco; Pasquini, Ricardo; Clementino, Nelma Cristina D; Dorlhiac Llacer, Pedro Enrique; Schwarer, Anthony P; Mahon, Francois-Xavier; Rea, Delphine; Branford, Susan; Purkayastha, Das; Collins, LaTonya; Szczudlo, Tomasz; Leber, Brian

    2014-07-31

    Patients in complete cytogenetic response (CCyR) with detectable BCR-ABL1 after ≥2 years on imatinib were randomized to nilotinib (400 mg twice daily, n = 104) or continued imatinib (n = 103) in the Evaluating Nilotinib Efficacy and Safety in clinical Trials-Complete Molecular Response (ENESTcmr) trial. By 1 and 2 years, confirmed undetectable BCR-ABL1 was achieved by 12.5% vs 5.8% (P = .108) and 22.1% vs 8.7% of patients in the nilotinib and imatinib arms, respectively (P = .0087). Among patients without molecular response 4.5 (BCR-ABL1(IS) ≤0.0032%; MR(4.5)) and those without major molecular response at study start, MR(4.5) by 2 years was achieved by 42.9% vs 20.8% and 29.2% vs 3.6% of patients in the nilotinib and imatinib arms, respectively. No patient in the nilotinib arm lost CCyR, vs 3 in the imatinib arm. Adverse events were more common in the nilotinib arm, as expected with the introduction of a new drug vs remaining on a well-tolerated drug. The safety profile of nilotinib was consistent with other reported studies. In summary, switching to nilotinib enabled more patients with chronic myeloid leukemia in chronic phase (CML-CP) to sustain lower levels of disease burden vs remaining on imatinib. This trial was registered at www.clinicaltrials.gov as #NCT00760877.

  3. Aqueous exposure to Aroclor 1254 modulates the mitogenic response of Atlantic salmon anterior kidney T-cells: Indications of short- and long-term immunomodulation

    USGS Publications Warehouse

    Iwanowicz, L.R.; Lerner, D.T.; Blazer, V.S.; McCormick, S.D.

    2005-01-01

    Polychlorinated biphenyls (PCBs) exist as persistent organic pollutants in numerous river systems in the United States. Unfortunately, some of these rivers are sites of active Atlantic salmon restoration programs, and polychlorinated biphenyls have been implicated as ancillary factors contributing to failed salmon restoration. Here, we investigate the immediate and chronic effects of intermediate duration aqueous PCB exposure (1 or 10 ??g L-1 Aroclor 1254) on the mitogen-stimulated lymphoproliferative response of Atlantic salmon anterior kidney leukocytes (AKLs). A short-term study was designed to examine immunomodulation in Atlantic salmon smolts immediately following 21 days of aqueous exposure, while a long-term study evaluated chronic impacts in the mitogen response in parr 15 months post-exposure as larvae. The proliferative response of AKLs to the mitogens concanavalin A (CON A), phytohemaglutinnin-P (PHA-P), pokeweed mitogen (PWM), and lipopolysaccharide were used as an indice of immunomodulation. The proliferative response to the T-cell mitogens CON A and PHA-P was significantly increased in the 10 ??g L-1 group (n = 10; P = 0.043 and 0.002, respectively) immediately following exposure of smolts. Additionally, The PHA-P response was significantly increased in the 1 ??g L-1 exposure group (n = 10, P = 0.036). In fish treated as larvae and tested 15 months later, the PHA-P sensitive populations exhibited elevated proliferation in the 1 and 10 ??g L-1 groups (n = 12, P < 0.04) relative to the vehicle control while the PWM response was significantly increased (n = 12, P = 0.036) only in the 10 ??g L-1 treated groups. These results demonstrate an immunomodulatory effect of PCBs on T-cell mitogen sensitive populations of lymphocytes in Atlantic salmon as well as long-term immunomodulation in PHA-P and PWM sensitive populations. ?? 2005 Elsevier B.V. All rights reserved.

  4. Bivalent response to long-term storage in liquid-preserved boar semen: a flow cytometric analysis.

    PubMed

    Henning, Heiko; Petrunkina, Anna M; Harrison, Robin A P; Waberski, Dagmar

    2012-07-01

    The fertility of liquid-preserved boar semen declines during storage at 17°C, insemination trials even indicating early losses in fertilizing ability within the first 24-48 h of storage. Standard semen parameters barely reflect these changes in semen quality, and new approaches for assessment of functional changes in stored spermatozoa are needed. Capacitation, the essential prefertilization step for spermatozoa in the female genital tract, is specifically induced in vitro by bicarbonate. Therefore, we have investigated changes in responsiveness of boar spermatozoa to bicarbonate during storage. Ejaculates of 14 boars were diluted in Beltsville thawing solution, cooled to 17°C and stored for 12, 24, 72, 120, and 168 h before investigation. At each time, basic semen quality was characterized by sperm motility and viability. Subsequently, washed subsamples were incubated in variants of an in vitro fertilization (IVF) medium and assessed for kinetic changes of viability (plasma membrane integrity) and intracellular calcium concentration using flow cytometry in combination with propidium iodide and Fluo-3. By this means, it was possible to determine specific effects of bicarbonate and calcium on sperm subpopulations over incubation time. During storage, standard semen parameters remained on a high level. However, flow cytometric analysis of sperm responses to capacitating and control media revealed two opposing effects of storage. There was a loss of response to bicarbonate in part of the live sperm population but an increasing degree of instability in the rest. Assessment of response to capacitating media by flow cytometry appears a markedly more sensitive way of monitoring sperm functionality during storage than the standard semen parameters of motility and viability. PMID:22573481

  5. Exposure–response model for sibutramine and placebo: suggestion for application to long-term weight-control drug development

    PubMed Central

    Han, Seunghoon; Jeon, Sangil; Hong, Taegon; Lee, Jongtae; Bae, Soo Hyeon; Park, Wan-su; Park, Gab-jin; Youn, Sunil; Jang, Doo Yeon; Kim, Kyung-Soo; Yim, Dong-Seok

    2015-01-01

    No wholly successful weight-control drugs have been developed to date, despite the tremendous demand. We present an exposure–response model of sibutramine mesylate that can be applied during clinical development of other weight-control drugs. Additionally, we provide a model-based evaluation of sibutramine efficacy. Data from a double-blind, randomized, placebo-controlled, multicenter study were used (N=120). Subjects in the treatment arm were initially given 8.37 mg sibutramine base daily, and those who lost <2 kg after 4 weeks’ treatment were escalated to 12.55 mg. The duration of treatment was 24 weeks. Drug concentration and body weight were measured predose and at 4 weeks, 8 weeks, and 24 weeks after treatment initiation. Exposure and response to sibutramine, including the placebo effect, were modeled using NONMEM 7.2. An asymptotic model approaching the final body weight was chosen to describe the time course of weight loss. Extent of weight loss was described successfully using a sigmoidal exposure–response relationship of the drug with a constant placebo effect in each individual. The placebo effect was influenced by subjects’ sex and baseline body mass index. Maximal weight loss was predicted to occur around 1 year after treatment initiation. The difference in mean weight loss between the sibutramine (daily 12.55 mg) and placebo groups was predicted to be 4.5% in a simulation of 1 year of treatment, with considerable overlap of prediction intervals. Our exposure–response model, which included the placebo effect, is the first example of a quantitative model that can be used to predict the efficacy of weight-control drugs. Similar approaches can help decision-making during clinical development of novel weight-loss drugs. PMID:26392753

  6. Predicting long-term carbon sequestration in response to CO2 enrichment: How and why do current ecosystem models differ?

    DOE PAGESBeta

    Walker, Anthony P.; Zaehle, Sönke; Medlyn, Belinda E.; De Kauwe, Martin G.; Asao, Shinichi; Hickler, Thomas; Parton, William; Ricciuto, Daniel M.; Wang, Ying -Ping; Wårlind, David; et al

    2015-04-27

    Large uncertainty exists in model projections of the land carbon (C) sink response to increasing atmospheric CO2. Free-Air CO2 Enrichment (FACE) experiments lasting a decade or more have investigated ecosystem responses to a step change in atmospheric CO2 concentration. To interpret FACE results in the context of gradual increases in atmospheric CO2 over decades to centuries, we used a suite of seven models to simulate the Duke and Oak Ridge FACE experiments extended for 300 years of CO2 enrichment. We also determine key modeling assumptions that drive divergent projections of terrestrial C uptake and evaluate whether these assumptions can bemore » constrained by experimental evidence. All models simulated increased terrestrial C pools resulting from CO2 enrichment, though there was substantial variability in quasi-equilibrium C sequestration and rates of change. In two of two models that assume that plant nitrogen (N) uptake is solely a function of soil N supply, the net primary production response to elevated CO2 became progressively N limited. In four of five models that assume that N uptake is a function of both soil N supply and plant N demand, elevated CO2 led to reduced ecosystem N losses and thus progressively relaxed nitrogen limitation. Many allocation assumptions resulted in increased wood allocation relative to leaves and roots which reduced the vegetation turnover rate and increased C sequestration. Additionally, self-thinning assumptions had a substantial impact on C sequestration in two models. As a result, accurate representation of N process dynamics (in particular N uptake), allocation, and forest self-thinning is key to minimizing uncertainty in projections of future C sequestration in response to elevated atmospheric CO2.« less

  7. Arsenic downregulates gene expression at the postsynaptic density in mouse cerebellum, including genes responsible for long-term potentiation and depression.

    PubMed

    Zhang, Cong; Li, Sheng; Sun, Yahui; Dong, Wei; Piao, Fengyuan; Piao, Yongjun; Liu, Shuang; Guan, Huai; Yu, Shengbo

    2014-08-01

    Arsenic (As) is a neurotoxin induces dysfunction of learning and memory. Research has indicated that cerebellum may be involved in arsenic-induced impairment of learning and memory. However, the molecular mechanisms that underlie these effects remain unclear. This study screened for the differentially expressed genes related to the long-term potentiation and long-term depression (LTP and LTD) at the cerebellar postsynaptic density (PSD) of mice following exposure to arsenic, and we provide evidence of the mechanism by which arsenic adversely affects the functions of learning and memory. Here, SPF mice were exposed to 1ppm, 2ppm and 4ppm As2O3 for 60 days. The ultrastructure of the synapses in cerebella of these mice was observed via transmission electron microscopy. The cerebellum global gene expression of mice exposed to 4ppm As2O3 was determined through GeneChip analysis. We used the web tool DAVID to analyze the Gene Ontology (GO) and KEGG pathways that were significantly enriched among the differentially expressed genes. Our observations of synaptic ultrastructure showed that the thickness of the cerebellar PSD was reduced in mice exposed to arsenic. Go analysis revealed the PSD as a significantly altered cellular component. KEGG pathway analysis showed that LTP and LTD were affected by arsenic with highest statistical significance, and 20 differentially expressed genes were associated with them. Among these differentially expressed genes, significant decreases in the mRNA expressions of CaMKII, Gria1, Gria2, Grin1, Itpr1, Grm1 and PLCβ4 related to the LTP and LTD were found at the PSD of mouse cerebellum exposed to arsenic. The downregulation of these genes was further confirmed via real-time reverse transcription PCR or Western blot at 1ppm, 2ppm and 4ppm As2O3. Our results indicate that the 7 genes with in cerebellar PSDs may be involved in arsenic-induced neurotoxicity, including impairment of learning and memory.

  8. Long-term antibody response and immunologic memory in children immunized with hepatitis B vaccine at birth.

    PubMed

    Saffar, M J; Rezai, M S

    2004-12-01

    Four hundred and fifty three healthy children immunized with a course of hepatitis B vaccine beginning at birth were tested at 10-11 years of age for persistence of anti-hepatitis B-S antigen antibody (anti-HBs); and responses of children without protective antibody to different doses of hepatitis B vaccine booster were evaluated. Although nearly 42% of them were not seroprotected, but most of boosted subjects (87.3%) retained robust immunologic memory and rapidly retained a protective anti-HBs antibody titer of at least 10 IU/L after booster vaccination.

  9. Two doses of bovine viral diarrhea virus DNA vaccine delivered by electroporation induce long-term protective immune responses.

    PubMed

    van Drunen Littel-van den Hurk, Sylvia; Lawman, Zoe; Snider, Marlene; Wilson, Don; van den Hurk, Jan V; Ellefsen, Barry; Hannaman, Drew

    2013-02-01

    Bovine viral diarrhea virus (BVDV) is a pathogen of major importance in cattle, so there is a need for new effective vaccines. DNA vaccines induce balanced immune responses and are relatively inexpensive and thus promising for both human and veterinary applications. In this study, newborn calves with maternal antibodies were vaccinated intramuscularly (i.m.) with a BVDV E2 DNA vaccine with the TriGrid Delivery System for i.m. delivery (TDS-IM). Two doses of this vaccine spaced 6 or 12 weeks apart were sufficient to induce significant virus-neutralizing antibody titers, numbers of activated T cells, and reduction in viral shedding and clinical presentations after BVDV-2 challenge. In contrast to the placebo-treated animals, the vaccinated calves did not lose any weight, which is an excellent indicator of the well-being of an animal and has a significant economic impact. Furthermore, the interval between the two vaccinations did not influence the magnitude of the immune responses or degree of clinical protection, and a third immunization was not necessary or beneficial. Since electroporation may enhance not only the magnitude but also the duration of immunity after DNA immunization, the interval between vaccination and challenge was extended in a second trial, which showed that two doses of this E2 DNA vaccine again significantly reduced clinical disease against BVDV for several months. These results are promising and support this technology for use against infectious diseases in cattle and large species, including humans, in general.

  10. Responses of barley root and shoot proteomes to long-term nitrogen deficiency, short-term nitrogen starvation and ammonium.

    PubMed

    Møller, Anders L B; Pedas, Pai; Andersen, Birgit; Svensson, Birte; Schjoerring, Jan K; Finnie, Christine

    2011-12-01

    Cereals are major crops worldwide, and improvement of their nitrogen use efficiency is a crucial challenge. In this study proteins responding to N supply in barley roots and shoots were analysed using a proteomics approach, to provide insight into mechanisms of N uptake and assimilation. Control plants grown hydroponically for 33 d with 5 mm nitrate, plants grown under N deficiency (0.5 mm nitrate, 33 d) or short-term N starvation (28 d with 5 mm nitrate followed by 5 d with no N source) were compared. N deficiency caused changes in C and N metabolism and ascorbate-glutathione cycle enzymes in shoots and roots. N starvation altered proteins of amino acid metabolism in roots. Both treatments caused proteome changes in roots that could affect growth. Shoots of plants grown with ammonium as N source (28 d with 5 mm nitrate followed by 5 d with 5 mm ammonium) showed responses similar to N deficient shoots, characterized by turnover of ribulose 1·5-bisphosphate carboxylase/oxygenase (Rubisco) and increases in proteins of the chloroplastic transcription and translation machinery. Identified proteins in 67 and 49 varying spots in roots and shoots respectively, corresponded to 62 functions and over 80 gene products, considerably advancing knowledge of N responses in barley.

  11. Systems-wide analysis of acclimation responses to long-term heat stress and recovery in the photosynthetic model organism Chlamydomonas reinhardtii.

    PubMed

    Hemme, Dorothea; Veyel, Daniel; Mühlhaus, Timo; Sommer, Frederik; Jüppner, Jessica; Unger, Ann-Katrin; Sandmann, Michael; Fehrle, Ines; Schönfelder, Stephanie; Steup, Martin; Geimer, Stefan; Kopka, Joachim; Giavalisco, Patrick; Schroda, Michael

    2014-11-01

    We applied a top-down systems biology approach to understand how Chlamydomonas reinhardtii acclimates to long-term heat stress (HS) and recovers from it. For this, we shifted cells from 25 to 42°C for 24 h and back to 25°C for ≥8 h and monitored abundances of 1856 proteins/protein groups, 99 polar and 185 lipophilic metabolites, and cytological and photosynthesis parameters. Our data indicate that acclimation of Chlamydomonas to long-term HS consists of a temporally ordered, orchestrated implementation of response elements at various system levels. These comprise (1) cell cycle arrest; (2) catabolism of larger molecules to generate compounds with roles in stress protection; (3) accumulation of molecular chaperones to restore protein homeostasis together with compatible solutes; (4) redirection of photosynthetic energy and reducing power from the Calvin cycle to the de novo synthesis of saturated fatty acids to replace polyunsaturated ones in membrane lipids, which are deposited in lipid bodies; and (5) when sinks for photosynthetic energy and reducing power are depleted, resumption of Calvin cycle activity associated with increased photorespiration, accumulation of reactive oxygen species scavengers, and throttling of linear electron flow by antenna uncoupling. During recovery from HS, cells appear to focus on processes allowing rapid resumption of growth rather than restoring pre-HS conditions.

  12. Short- versus long-term responses to changing CO2 in a coastal dinoflagellate bloom: implications for interspecific competitive interactions and community structure.

    PubMed

    Tatters, Avery O; Schnetzer, Astrid; Fu, Feixue; Lie, Alle Y A; Caron, David A; Hutchins, David A

    2013-07-01

    Increasing pCO2 (partial pressure of CO2 ) in an "acidified" ocean will affect phytoplankton community structure, but manipulation experiments with assemblages briefly acclimated to simulated future conditions may not accurately predict the long-term evolutionary shifts that could affect inter-specific competitive success. We assessed community structure changes in a natural mixed dinoflagellate bloom incubated at three pCO2 levels (230, 433, and 765 ppm) in a short-term experiment (2 weeks). The four dominant species were then isolated from each treatment into clonal cultures, and maintained at all three pCO2 levels for approximately 1 year. Periodically (4, 8, and 12 months), these pCO2 -conditioned clones were recombined into artificial communities, and allowed to compete at their conditioning pCO2 level or at higher and lower levels. The dominant species in these artificial communities of CO2 -conditioned clones differed from those in the original short-term experiment, but individual species relative abundance trends across pCO2 treatments were often similar. Specific growth rates showed no strong evidence for fitness increases attributable to conditioning pCO2 level. Although pCO2 significantly structured our experimental communities, conditioning time and biotic interactions like mixotrophy also had major roles in determining competitive outcomes. New methods of carrying out extended mixed species experiments are needed to accurately predict future long-term phytoplankton community responses to changing pCO2 . PMID:23815646

  13. Systems-Wide Analysis of Acclimation Responses to Long-Term Heat Stress and Recovery in the Photosynthetic Model Organism Chlamydomonas reinhardtii[W][OPEN

    PubMed Central

    Hemme, Dorothea; Veyel, Daniel; Mühlhaus, Timo; Sommer, Frederik; Jüppner, Jessica; Unger, Ann-Katrin; Sandmann, Michael; Fehrle, Ines; Schönfelder, Stephanie; Steup, Martin; Geimer, Stefan; Kopka, Joachim; Giavalisco, Patrick; Schroda, Michael

    2014-01-01

    We applied a top-down systems biology approach to understand how Chlamydomonas reinhardtii acclimates to long-term heat stress (HS) and recovers from it. For this, we shifted cells from 25 to 42°C for 24 h and back to 25°C for ≥8 h and monitored abundances of 1856 proteins/protein groups, 99 polar and 185 lipophilic metabolites, and cytological and photosynthesis parameters. Our data indicate that acclimation of Chlamydomonas to long-term HS consists of a temporally ordered, orchestrated implementation of response elements at various system levels. These comprise (1) cell cycle arrest; (2) catabolism of larger molecules to generate compounds with roles in stress protection; (3) accumulation of molecular chaperones to restore protein homeostasis together with compatible solutes; (4) redirection of photosynthetic energy and reducing power from the Calvin cycle to the de novo synthesis of saturated fatty acids to replace polyunsaturated ones in membrane lipids, which are deposited in lipid bodies; and (5) when sinks for photosynthetic energy and reducing power are depleted, resumption of Calvin cycle activity associated with increased photorespiration, accumulation of reactive oxygen species scavengers, and throttling of linear electron flow by antenna uncoupling. During recovery from HS, cells appear to focus on processes allowing rapid resumption of growth rather than restoring pre-HS conditions. PMID:25415976

  14. Variability in the intraspecific response of Pinus ponderosa seedlings subjected to long-term exposure to elevated CO{sub 2}

    SciTech Connect

    Houpis, J.L.J.; Anschel, D.J.; Pushnik, J.C.; Anderson, P.D.

    1995-01-01

    The authors are investigating the effects of elevated CO{sub 2} and intraspecific variability on Pinus ponderosa. To analyze intraspecific variability, they included seedling source (family) as an additional treatment, using a split-plot experimental design. The three elevated CO{sub 2} treatments were ambient (approx. 350 ppm CO{sub 2}), ambient + 175 ppm CO{sub 2} and ambient +350 ppm CO{sub 2}. Their study uses the source/sink control framework at several key integrating steps, incorporating the long-term effects of elevated CO{sub 2} (insuring sufficient time for the expression of any long-term physiological and biochemical acclimation to occur) and genetics (using multiple species and multiple known genetic sources) in an attempt to ascertain the extent of overall regulation contributed by selected independent regulatory process at the physiological, biochemical and structural level. In order to assess intraspecific variability, this paper reports on the integration of measurements of photosynthesis, chlorophyll fluorescence, pigmentation, RuBPCase, SPSase to quantify the effects of elevated CO{sub 2} on the growth response of various families of the same species.

  15. Long-term experiment on physiological responses to synergetic effects of ocean acidification and photoperiod in the Antarctic sea ice algae Chlamydomonas sp. ICE-L.

    PubMed

    Xu, Dong; Wang, Yitao; Fan, Xiao; Wang, Dongsheng; Ye, Naihao; Zhang, Xiaowen; Mou, Shanli; Guan, Zheng; Zhuang, Zhimeng

    2014-07-15

    Studies on ocean acidification have mostly been based on short-term experiments of low latitude with few investigations of the long-term influence on sea ice communities. Here, the combined effects of ocean acidification and photoperiod on the physiological response of the Antarctic sea ice microalgae Chlamydomonas sp. ICE-L were examined. There was a general increase in growth, PSII photosynthetic parameters, and N and P uptake in continuous light, compared to those exposed to regular dark and light cycles. Elevated pCO2 showed no consistent effect on growth rate (p=0.8) and N uptake (p=0.38) during exponential phrase, depending on the photoperiod but had a positive effect on PSII photosynthetic capacity and P uptake. Continuous dark reduced growth, photosynthesis, and nutrient uptake. Moreover, intracellular lipid, mainly in the form of PUFA, was consumed at 80% and 63% in low and high pCO2 in darkness. However, long-term culture under high pCO2 gave a more significant inhibition of growth and Fv/Fm to high light stress. In summary, ocean acidification may have significant effects on Chlamydomonas sp. ICE-L survival in polar winter. The current study contributes to an understanding of how a sea ice algae-based community may respond to global climate change at high latitudes. PMID:24922067

  16. Long-term experiment on physiological responses to synergetic effects of ocean acidification and photoperiod in the Antarctic sea ice algae Chlamydomonas sp. ICE-L.

    PubMed

    Xu, Dong; Wang, Yitao; Fan, Xiao; Wang, Dongsheng; Ye, Naihao; Zhang, Xiaowen; Mou, Shanli; Guan, Zheng; Zhuang, Zhimeng

    2014-07-15

    Studies on ocean acidification have mostly been based on short-term experiments of low latitude with few investigations of the long-term influence on sea ice communities. Here, the combined effects of ocean acidification and photoperiod on the physiological response of the Antarctic sea ice microalgae Chlamydomonas sp. ICE-L were examined. There was a general increase in growth, PSII photosynthetic parameters, and N and P uptake in continuous light, compared to those exposed to regular dark and light cycles. Elevated pCO2 showed no consistent effect on growth rate (p=0.8) and N uptake (p=0.38) during exponential phrase, depending on the photoperiod but had a positive effect on PSII photosynthetic capacity and P uptake. Continuous dark reduced growth, photosynthesis, and nutrient uptake. Moreover, intracellular lipid, mainly in the form of PUFA, was consumed at 80% and 63% in low and high pCO2 in darkness. However, long-term culture under high pCO2 gave a more significant inhibition of growth and Fv/Fm to high light stress. In summary, ocean acidification may have significant effects on Chlamydomonas sp. ICE-L survival in polar winter. The current study contributes to an understanding of how a sea ice algae-based community may respond to global climate change at high latitudes.

  17. The Effects of Iron Complexing Ligands on the Long Term Ecosystem Response to Iron Enrichment of HNLC waters

    SciTech Connect

    Mark L. Wells; Mary Jane Perry; William P. Cochlan; Charles G. Trick

    2006-11-18

    The central hypothesis of this project is that natural iron-complexing organic ligands in seawater differentially regulate iron availability to large (microplankton) and small (nano and picoplankton) class of phytoplankton and thereby strongly influence the potential carbon sequestration in High Nitrate Low Chlorophyll (HNLC) regions of the ocean. The primary project goals are to: 1) determine how different natural and synthetic Fe chelators affect Fe availability to phytoplankton species that are representative of offshore HNLC waters, 2) elucidate how the changes in absolute concentrations of these chelators affect the longer-term ecosystem response to alleviation of Fe limitation, and 3) ascertain how changes in the ligand composition affect rates of cell sinking and aggregation - representative measures of the efficiency of carbon sequestration to the deep.

  18. Long-term responses to treatment in UK veterans with military-related PTSD: an observational study

    PubMed Central

    Murphy, Dominic; Spencer-Harper, Lucy; Carson, Carron; Palmer, Emily; Hill, Kate; Sorfleet, Nicola; Wessely, Simon; Busuttil, Walter

    2016-01-01

    Objectives Military-related trauma can be difficult to treat. Evaluating longer term responses to treatment and identifying which individuals may need additional support could inform clinical practice. We assessed 1-year outcomes in UK veterans treated for post-traumatic stress disorder (PTSD). Design Within-participant design. Setting The intervention was offered by Combat Stress, a mental health charity for veterans in the UK. Participants The sample included 401 veterans who completed a standardised 6-week residential treatment. Of these, 268 (67%) were successfully followed up a year after the end of treatment. Methods A range of health outcomes were collected pretreatment and repeated at standard intervals post-treatment. The primary outcome was severity of PTSD symptoms, and secondary outcomes included measures of other mental health difficulties (depression, anxiety and anger), problems with alcohol, and social and occupational functioning. Results Significant reductions in PTSD severity were observed a year after treatment (PSS-I: −11.9, 95% CI −13.1 to −10.7). Reductions in the secondary outcomes were also reported. Higher levels of post-treatment functional impairment (0.24, 95% CI 0.08 to 0.41) and alcohol problems (0.18, 95% CI 0.03 to 0.32) were associated with poorer PTSD treatment response at 12 months. Conclusions This uncontrolled study suggests the longer term benefits of a structured programme to treat UK veterans with PTSD. Our findings point to the importance of continued support targeted for particular individuals post-treatment to improve longer term outcomes. PMID:27638494

  19. Long-term activation of the pro-coagulant response after neoadjuvant chemoradiation and major cancer surgery

    PubMed Central

    Byrne, M; Reynolds, J V; O'Donnell, J S; Keogan, M; White, B; Byrne, M; Murphy, S; Maher, S G; Pidgeon, G P

    2009-01-01

    Background: The association between cancer, major surgery and venous thromboembolism (VTE) is well established. Multimodal therapy is increasingly being used as standard treatment for localised gastrointestinal cancer. The aim of this study was to examine the markers of pro-coagulation response and VTE risk in an exemplar multimodal model of pre-operative combination chemotherapy and radiation therapy, followed by complex cancer surgery. Methods: Consecutive patients (n=36) with localised oesophageal cancer were studied at baseline after the first and second cycles of chemoradiation, and on post-operative days 1–28, and at 3, 6 and 9 months. Factors regulating the pro- and anti-coagulant response, as well as pro-inflammatory markers including NFκB activation in peripheral blood mononuclear cells, were examined. All patients received enoxaparin 40 mg s.c. postoperatively up to discharge, and underwent pulmonary CT-pulmonary angiography and venography on day 10 postoperatively. Results: Four (11%) non-fatal thromboembolic events were documented, all after hospital discharge. Neoadjuvant therapy before surgery activated factor VIII (FVIII) and pro-inflammatory NFκB, and increased D-dimers, pro-thrombin fragment 1+2 (F1+2) and the thrombin-anti-thrombin complex (TAT). Surgery significantly (P<0.05) increased pro-thrombin time (PT), activated partial thromboplastin time, fibrinogen, D-dimers, TAT, F1+2 and FVIII up to 6 months. Conclusion: These data highlight the linked pro-coagulant and immunoinflammatory pathways in the multimodal management of oesophageal cancer, and suggest that the duration of current standard thromboprophylaxis regimens warrants further study. PMID:19953092

  20. Long-term hydrodynamic response induced by past climatic and geomorphologic forcing: The case of the Paris basin, France

    NASA Astrophysics Data System (ADS)

    Jost, A.; Violette, S.; Gonçalvès, J.; Ledoux, E.; Guyomard, Y.; Guillocheau, F.; Kageyama, M.; Ramstein, G.; Suc, J.-P.

    In the framework of safe underground storage of radioactive waste in low-permeability layers, it is essential to evaluate the mobility of deep groundwaters over timescales of several million years. On these timescales, the environmental evolution of a repository should depend upon a range of natural processes that are primarily driven by climate and geomorphologic variations. In this paper, the response of the Paris basin groundwater system to variations in its hydrodynamic boundary conditions induced by past climate and geodynamic changes over the last five million years is investigated. A three-dimensional transient modelling of the Paris basin aquifer/aquitard system was developed using the code NEWSAM (Ecole des Mines de Paris, ENSMP). The geometry and hydrodynamic parameters of the model originate from a basin model, NEWBAS (ENSMP), built to simulate the geological history of the basin. Geomorphologic evolution is deduced from digital elevation model analysis, which allows to estimate river-valley incision and alpine surrection. Climate forcing results from palaeoclimate modelling experiments using the LMDz atmospheric general circulation model (Institut Pierre Simon Laplace) with a refined spatial resolution, for the present, the Last Glacial Maximum (21 ka) and the Middle Pliocene Warmth (∼3 Ma). The water balance is computed by the distributed hydrological model MODSUR (ENSMP). Results about the simulated evolution of piezometric heads in the system in response to the altered boundary conditions are presented, in particular in the vicinity of ANDRA’s Bure potential repository site within the Callovo-Oxfordian argillaceous layer. For the present, the comparison of head patterns between steady state and time dependent simulation shows little differences for aquifer layers close to the surface but suggests a transient state of the current system in the main aquitards of the basin and in the deep aquifers, characterized by abnormally low fluid potentials

  1. Long-term stability of an subsurface ocean in Ganymede and its effect to tidal response, toward future altimetry measurement

    NASA Astrophysics Data System (ADS)

    Kimura, J.; Kamata, S.; Vance, S.; Hussmann, H.

    2015-12-01

    The outer solar system provides potential habitats for extra-terrestrial life. Previous spacecraft's and telescopic observations support that the Jovian icy moons may harbor water oceans beneath the icy crusts. However evidence for oceans is not definitive and awaits confirmation measurements. Also their depth and composition remain unclear, as do their stability and variability with time. Here we focus on Ganymede, the primary target of the Jupiter Icy Moons Explorer (JUICE). To investigate the lifetime of an ocean (thickness change through time), we perform numerical simulations for the internal thermal evolution using a one-dimensional spherically symmetric model for the convective and conductive heat transfer, with radial dependences of viscosity, heat source distribution, and other material properties. We assume an initially entirely liquid H2O layer which is an end-member case, and take into account the energy production due to decay of long-lived radioactive elements and also evaluate the effect of tidal heating. To see the temporal change of the boundary position between solid ice layers including ice shell and high-pressure ice mantle, we also evaluate the energy balance at the phase boundaries between the solid and liquid H2O layer, and the movements of the positions of these boundaries are calculated by evaluating the heat balance between incoming and outgoing flux at the boundaries considering with latent heat (classically known as a Stefan problem). In addition, the existence of a subsurface ocean and internal rheological structure (essentially based on thermal structure) would determine Ganymede's tidal response. JUICE mission,measurements of tidal deformation of Ganymede using laser altimetry will provide key information about its interior. We investigate the parameter dependence (e.g., elastic/rheological properties of ice and depth/thickness of the ocean, etc.) of Ganymede's tidal response, adopting a depth-dependent viscosity prole assuming a

  2. Food viscosity as determinant for adaptive growth responses in rat intestine: long-term feeding of different hydroxyethyl celluloses.

    PubMed

    Elsenhans, B; Caspary, W F

    2000-07-01

    Carbohydrate gelling agents can be regarded as being representative for the soluble and viscous fractions of dietary fibre. Their dietary concentration affects the consistency of the ingested food as well as the dilution of nutrients and energy. By feeding hydroxyethyl cellulose (HEC) differing in molecular mass, and thus in its viscosity properties, only the consistency of the diet was modified. Three HEC (of low (LV), medium (MV) and high viscosity (HV)) were employed in a 6-week feeding study with female rats to evaluate the effect of the viscosity on adaptive responses of intestinal growth variables. Each of the HEC was added in three increasing concentrations (8, 16, and 32%, w/w) to a fibre-free control diet to yield nine test groups besides a fibre-free and an additional, fibre-rich, cereal-based control group. Except for the highest concentration of the high viscosity product (32% HV-HEC), the dilution of the energy density of the diet was almost completely compensated by an increased food intake. With the same exception, energy utilisation was not impaired and, therefore, body-weight gains in the test groups were not significantly different from that in the control. Most other changes, e.g. increases in small intestinal length, mucosal DNA content, caecal and colonic weight, not only depended on the dietary concentration but also on the viscosity of HEC in a manner that either increasing the viscosity at a given dietary concentration or increasing the dietary concentration at a given viscosity led to the same results. These findings clearly prove the important role of the viscosity of the lumen content, as a mere physico-chemical factor, in determining adaptative growth responses in the intestinal tract of rats.

  3. Clinical Outcome of HIV-Infected Patients with Sustained Virologic Response to Antiretroviral Therapy: Long-Term Follow-Up of a Multicenter Cohort

    PubMed Central

    Gutierrez, Félix; Padilla, Sergio; Masiá, Mar; Iribarren, José A.; Moreno, Santiago; Viciana, Pompeyo; Muñoz, Leopoldo; Sirvent, José L. Gómez; Vidal, Francesc; López-Aldeguer, José; Blanco, José R.; Leal, Manuel; Rodríguez-Arenas, María Angeles; Hoyos, Santiago Perez

    2006-01-01

    Background Limited information exists on long-term prognosis of patients with sustained virologic response to antiretroviral therapy. We aimed to assess predictors of unfavorable clinical outcome in patients who maintain viral suppression with HAART. Methods Using data collected from ten clinic-based cohorts in Spain, we selected all antiretroviral-naive adults who initiated HAART and maintained plasma HIV-1 RNA levels <500 copies/mL throughout follow-up. Factors associated with disease progression were determined by Cox proportional-hazards models. Results Of 2,613 patients who started HAART, 757 fulfilled the inclusion criteria. 61% of them initiated a protease inhibitor-based HAART regimen, 29.7% a nonnucleoside reverse-transcriptase inhibitor-based regimen, and 7.8% a triple-nucleoside regimen. During 2,556 person-years of follow-up, 22 (2.9%) patients died (mortality rate 0.86 per 100 person-years), and 40 (5.3%) died or developed a new AIDS-defining event. The most common causes of death were neoplasias and liver failure. Mortality was independently associated with a CD4-T cell response <50 cells/L after 12 months of HAART (adjusted hazard ratio [AHR], 4.26 [95% confidence interval {CI}, 1.68–10.83]; P = .002), and age at initiation of HAART (AHR, 1.06 per year; 95% CI, 1.02–1.09; P = .001). Initial antiretroviral regimen chosen was not associated with different risk of clinical progression. Conclusions Patients with sustained virologic response on HAART have a low mortality rate over time. Long-term outcome of these patients is driven by immunologic response at the end of the first year of therapy and age at the time of HAART initiation, but not by the initial antiretroviral regimen selected. PMID:17183720

  4. Multivariate and phylogenetic analyses assessing the response of bacterial mat communities from an ancient oligotrophic aquatic ecosystem to different scenarios of long-term environmental disturbance.

    PubMed

    Pajares, Silvia; Souza, Valeria; Eguiarte, Luis E

    2015-01-01

    Understanding the response of bacterial communities to environmental change is extremely important in predicting the effect of biogeochemical modifications in ecosystem functioning. The Cuatro Cienegas Basin is an ancient oasis in the Mexican Chihuahuan desert that hosts a wide diversity of microbial mats and stromatolites that have survived in extremely oligotrophic pools with nearly constant conditions. However, thus far, the response of these unique microbial communities to long-term environmental disturbances remains unexplored. We therefore studied the compositional stability of these bacterial mat communities by using a replicated (3x) mesocosm experiment: a) Control; b) Fluct: fluctuating temperature; c) 40C: increase to 40 ºC; d) UVplus: artificial increase in UV radiation; and f) UVmin: UV radiation protection. In order to observe the changes in biodiversity, we obtained 16S rRNA gene clone libraries from microbial mats at the end of the experiment (eight months) and analyzed them using multivariate and phylogenetic tools. Sequences were assigned to 13 major lineages, among which Cyanobacteria (38.8%) and Alphaproteobacteria (25.5%) were the most abundant. The less extreme treatments (Control and UVmin) had a more similar composition and distribution of the phylogenetic groups with the natural pools than the most extreme treatments (Fluct, 40C, and UVplus), which showed drastic changes in the community composition and structure, indicating a different community response to each environmental disturbance. An increase in bacterial diversity was found in the UVmin treatment, suggesting that protected environments promote the establishment of complex bacterial communities, while stressful environments reduce diversity and increase the dominance of a few Cyanobacterial OTUs (mainly Leptolyngbya sp) through environmental filtering. Mesocosm experiments using complex bacterial communities, along with multivariate and phylogenetic analyses of molecular data, can

  5. Multivariate and Phylogenetic Analyses Assessing the Response of Bacterial Mat Communities from an Ancient Oligotrophic Aquatic Ecosystem to Different Scenarios of Long-Term Environmental Disturbance

    PubMed Central

    Pajares, Silvia; Souza, Valeria; Eguiarte, Luis E.

    2015-01-01

    Understanding the response of bacterial communities to environmental change is extremely important in predicting the effect of biogeochemical modifications in ecosystem functioning. The Cuatro Cienegas Basin is an ancient oasis in the Mexican Chihuahuan desert that hosts a wide diversity of microbial mats and stromatolites that have survived in extremely oligotrophic pools with nearly constant conditions. However, thus far, the response of these unique microbial communities to long-term environmental disturbances remains unexplored. We therefore studied the compositional stability of these bacterial mat communities by using a replicated (3x) mesocosm experiment: a) Control; b) Fluct: fluctuating temperature; c) 40C: increase to 40 ºC; d) UVplus: artificial increase in UV radiation; and f) UVmin: UV radiation protection. In order to observe the changes in biodiversity, we obtained 16S rRNA gene clone libraries from microbial mats at the end of the experiment (eight months) and analyzed them using multivariate and phylogenetic tools. Sequences were assigned to 13 major lineages, among which Cyanobacteria (38.8%) and Alphaproteobacteria (25.5%) were the most abundant. The less extreme treatments (Control and UVmin) had a more similar composition and distribution of the phylogenetic groups with the natural pools than the most extreme treatments (Fluct, 40C, and UVplus), which showed drastic changes in the community composition and structure, indicating a different community response to each environmental disturbance. An increase in bacterial diversity was found in the UVmin treatment, suggesting that protected environments promote the establishment of complex bacterial communities, while stressful environments reduce diversity and increase the dominance of a few Cyanobacterial OTUs (mainly Leptolyngbya sp) through environmental filtering. Mesocosm experiments using complex bacterial communities, along with multivariate and phylogenetic analyses of molecular data, can

  6. Long-term sustained release of salicylic acid from cross-linked biodegradable polyester induces a reduced foreign body response in mice.

    PubMed

    Chandorkar, Yashoda; Bhaskar, Nitu; Madras, Giridhar; Basu, Bikramjit

    2015-02-01

    There has been a continuous surge toward developing new biopolymers that exhibit better in vivo biocompatibility properties in terms of demonstrating a reduced foreign body response (FBR). One approach to mitigate the undesired FBR is to develop an implant capable of releasing anti-inflammatory molecules in a sustained manner over a long time period. Implants causing inflammation are also more susceptible to infection. In this article, the in vivo biocompatibility of a novel, biodegradable salicylic acid releasing polyester (SAP) has been investigated by subcutaneous implantation in a mouse model. The tissue response to SAP was compared with that of a widely used biodegradable polymer, poly(lactic acid-co-glycolic acid) (PLGA), as a control over three time points: 2, 4, and 16 weeks postimplantation. A long-term in vitro study illustrates a continuous, linear (zero order) release of salicylic acid with a cumulative mass percent release rate of 7.34 × 10(-4) h(-1) over ∼1.5-17 months. On the basis of physicochemical analysis, surface erosion for SAP and bulk erosion for PLGA have been confirmed as their dominant degradation modes in vivo. On the basis of the histomorphometrical analysis of inflammatory cell densities and collagen distribution as well as quantification of proinflammatory cytokine levels (TNF-α and IL-1β), a reduced foreign body response toward SAP with respect to that generated by PLGA has been unambiguously established. The favorable in vivo tissue response to SAP, as manifest from the uniform and well-vascularized encapsulation around the implant, is consistent with the decrease in inflammatory cell density and increase in angiogenesis with time. The above observations, together with the demonstration of long-term and sustained release of salicylic acid, establish the potential use of SAP for applications in improved matrices for tissue engineering and chronic wound healing.

  7. Population-level Consequences of Breeding Phenology in Response to Climate Variability in Seabirds and Landbirds: Two Long-term Studies From California

    NASA Astrophysics Data System (ADS)

    Warzybok, P.; Nur, N.; Bradley, R.; Sydeman, W. J.; Abraham, C.; Chase, M. K.

    2007-12-01

    Long-term studies conducted on breeding populations on the Farallon Islands (1971 to 2007) and in the Point Reyes National Seashore (1980 to 2007), provide the means to characterize breeding phenology of seabird and landbird species and determine how that has changed over multiple temporal scales (variation among years, among decades, shifts in ocean regimes, etc.). However, to interpret phenological patterns and shifts requires information on the demography and ecological context of these species. Here we describe studies on three seabird species (Common Murre Uria aalge, Cassin's Auklet Ptychoramphus aleuticus, Brandt's Cormorant, Phalacrocorax penicillatus) where we have tied changes in breeding phenology, within a year, and among years, to demographic consequences (reproductive success, proportion of the population that breeds, adult survival, etc.). In addition, for these species we have information on diet choice of parents feeding chicks and how that has varied within and among years, as well as oceanographic correlates (sea surface temperature, upwelling indices, etc). Results reveal marked variation among the species in their response to oceanographic and climate variability, reflecting their different ecologies. We describe how these results can be used to forecast response to future climate change, as well as to interpret year by response to climate variability. We also summarize results from a long-term study of Song Sparrows (Melospiza melodia), where we have investigated onset and termination of breeding and the climate factors that may influence it, while identifying the population-level responses associated with phenological shifts. We close by making recommendations for large-scale monitoring of phenology based on these more localized studies.

  8. Predcition of Long term Water table Trends in Response to Groundwater Irrigation and Climate Change in an Indian Context

    NASA Astrophysics Data System (ADS)

    Thekkemeppilly Sivakumar, I.; Steenhuis, T. S.; Walter, M. F.; Ghosh, S.; Salvi, K. A.

    2015-12-01

    Intensified groundwater irrigation is a major factor that contributes to water table decline. This phenomenon has been documented in many parts of the world. This study investigates trends in water table in response to agriculture intensification to meet increasing food demand, water management practices and climate change. A shallow-aquifer model based on the extended Thornthwaite-Mather procedure is used to predict groundwater levels in response to precipitation, evapotranspiration, and groundwater pumping for irrigation. Krishna district in the state of Andhra Pradesh in southern India which has a sub-humid, monsoon climate and Calicut district of Kerala state with a wet tropical monsoon climate have been chosen as sites for this study. The effect of increasing food demand by a growing population is investigated by increasing the number of crops per year from one to three. We consider three climate scenarios and two water management practices in this study. The three climate scenarios are the ones those envisaged by the Intergovernmental Panel for Climate Change (IPCC). The two water management practices considered are the traditional flooded agriculture and the system of rice intensification method which does not use total flooding. The results show that single crop agriculture in Krishna district is sustainable for all climate scenarios and water management practices with a maximum depth to water table around 6 - 7 m at the end of dry season and the water table recovers to the surface most of the time. Increasing crop production with two or three crops per year with groundwater irrigation is unsustainable with the water table levels dropping potentially to 200 - 1000 m at the end of 21st century. We found that climate change and better irrigation water management practices affected ground water levels only minimally compared to the growing more than one crop per year. Our study leads to the conclusion that ground water irrigated rice can only be sustainable

  9. Effects of Long-Term Flutamide Treatment During Development on Sexual Behaviour and Hormone Responsiveness in Rams.

    PubMed

    Roselli, C E; Meaker, M; Stormshak, F; Estill, C T

    2016-05-01

    Testosterone exposure during midgestation differentiates neural circuits controlling sex-specific behaviours and patterns of gonadotrophin secretion in male sheep. Testosterone acts through androgen receptors (AR) and/or after aromatisation to oestradiol and binding to oestrogen receptors. The present study assessed the role of AR activation in male sexual differentiation. We compared rams that were exposed to the AR antagonist flutamide (Flu) throughout the critical period (i.e. days 30-90 of gestation) to control rams and ewes that received no prenatal treatments. The external genitalia of all Flu rams were phenotypically female. Testes were positioned s.c. in the inguinal region of the abdomen, exhibited seasonally impaired androgen secretion and were azospermic. Flu rams displayed male-typical precopulatory and mounting behaviours but could not intromit or ejaculate because they lacked a penis. Flu rams exhibited greater mounting behaviour than control rams and, similar to controls, showed sexual partner preferences for oestrous ewes. Neither control, nor Flu rams responded to oestradiol treatments with displays of female-typical receptive behaviour or LH surge responses, whereas all control ewes responded as expected. The ovine sexually dimorphic nucleus in Flu rams was intermediate in volume between control rams and ewes and significantly different from both. These results indicate that prenatal anti-androgen exposure is not able to block male sexual differentiation in sheep and suggest that compensatory mechanisms intervene to maintain sufficient androgen stimulation during development.

  10. Effects of Long-Term Flutamide Treatment During Development on Sexual Behaviour and Hormone Responsiveness in Rams.

    PubMed

    Roselli, C E; Meaker, M; Stormshak, F; Estill, C T

    2016-05-01

    Testosterone exposure during midgestation differentiates neural circuits controlling sex-specific behaviours and patterns of gonadotrophin secretion in male sheep. Testosterone acts through androgen receptors (AR) and/or after aromatisation to oestradiol and binding to oestrogen receptors. The present study assessed the role of AR activation in male sexual differentiation. We compared rams that were exposed to the AR antagonist flutamide (Flu) throughout the critical period (i.e. days 30-90 of gestation) to control rams and ewes that received no prenatal treatments. The external genitalia of all Flu rams were phenotypically female. Testes were positioned s.c. in the inguinal region of the abdomen, exhibited seasonally impaired androgen secretion and were azospermic. Flu rams displayed male-typical precopulatory and mounting behaviours but could not intromit or ejaculate because they lacked a penis. Flu rams exhibited greater mounting behaviour than control rams and, similar to controls, showed sexual partner preferences for oestrous ewes. Neither control, nor Flu rams responded to oestradiol treatments with displays of female-typical receptive behaviour or LH surge responses, whereas all control ewes responded as expected. The ovine sexually dimorphic nucleus in Flu rams was intermediate in volume between control rams and ewes and significantly different from both. These results indicate that prenatal anti-androgen exposure is not able to block male sexual differentiation in sheep and suggest that compensatory mechanisms intervene to maintain sufficient androgen stimulation during development. PMID:27005749

  11. Microbial lipid and amino sugar responses to long-term simulated global environmental changes in a California annual grassland.

    PubMed

    Liang, Chao; Gutknecht, Jessica L M; Balser, Teri C

    2015-01-01

    Global environmental change is predicted to have major consequences for carbon cycling and the functioning of soil ecosystems. However, we have limited knowledge about its impacts on the microorganisms, which act as a "valve" between carbon sequestered in soils versus released into the atmosphere. In this study we examined microbial response to continuous 9-years manipulation of three global change factors (elevated CO2, warming, and nitrogen deposition), singly and in combination using two methods: lipid and amino sugar biomarkers at the Jasper Ridge Global Change Experiment (JRGCE). The two methods yielded important distinctions. There were limited microbial lipid differences, but many significant effects for microbial amino sugars. We found that CO2 was not a direct factor influencing soil carbon and major amino sugar pools, but had a positive impact on bacterial-derived muramic acid. Likewise, warming and nitrogen deposition appeared to enrich residues specific to bacteria despite an overall depletion in total amino sugars. The results indicate that elevated CO2, warming, and nitrogen deposition all appeared to increase bacterial-derived residues, but this accumulation effect was far offset by a corresponding decline in fungal residues. The sensitivity of microbial residue biomarker amino sugars to warming and nitrogen deposition may have implications for our predictions of global change impacts on soil stored carbon. PMID:25999926

  12. Host Biomarkers Are Associated With Response to Therapy and Long-Term Mortality in Pediatric Severe Malaria

    PubMed Central

    Conroy, Andrea L.; Hawkes, Michael; McDonald, Chloe R.; Kim, Hani; Higgins, Sarah J.; Barker, Kevin R.; Namasopo, Sophie; Opoka, Robert O.; John, Chandy C.; Liles, W. Conrad; Kain, Kevin C.

    2016-01-01

    Background. Host responses to infection are critical determinants of disease severity and clinical outcome. The development of tools to risk stratify children with malaria is needed to identify children most likely to benefit from targeted interventions. Methods. This study investigated the kinetics of candidate biomarkers of mortality associated with endothelial activation and dysfunction (angiopoietin-2 [Ang-2], soluble FMS-like tyrosine kinase-1 [sFlt-1], and soluble intercellular adhesion molecule-1 [sICAM-1]) and inflammation (10 kDa interferon γ-induced protein [CXCL10/IP-10] and soluble triggering receptor expressed on myeloid cells-1 [sTREM-1]) in the context of a randomized, double-blind, placebo-controlled, parallel-arm trial evaluating inhaled nitric oxide versus placebo as adjunctive therapy to parenteral artesunate for severe malaria. One hundred eighty children aged 1–10 years were enrolled at Jinja Regional Referral Hospital in Uganda and followed for up to 6 months. Results. There were no differences between the 2 study arms in the rate of biomarker recovery. Median levels of Ang-2, CXCL10, and sFlt-1 were higher at admission in children who died in-hospital (n = 15 of 180; P < .001, P = .027, and P = .004, respectively). Elevated levels of Ang-2, sTREM-1, CXCL10, and sICAM-1 were associated with prolonged clinical recovery times in survivors. The Ang-2 levels were also associated with postdischarge mortality (P < .0001). No biomarkers were associated with neurodisability. Conclusions. Persistent endothelial activation and dysfunction predict survival in children admitted with severe malaria.

  13. Modeling aeolian transport in response to succession, disturbance and future climate: Dynamic long-term risk assessment for contaminant redistribution

    USGS Publications Warehouse

    Breshears, D.D.; Kirchner, T.B.; Whicker, J.J.; Field, J.P.; Allen, C.D.

    2012-01-01

    Aeolian sediment transport is a fundamental process redistributing sediment, nutrients, and contaminants in dryland ecosystems. Over time frames of centuries or longer, horizontal sediment fluxes and associated rates of contaminant transport are likely to be influenced by succession, disturbances, and changes in climate, yet models of horizontal sediment transport that account for these fundamental factors are lacking, precluding in large part accurate assessment of human health risks associated with persistent soil-bound contaminants. We present a simple model based on empirical measurements of horizontal sediment transport (predominantly saltation) to predict potential contaminant transport rates for recently disturbed sites such as a landfill cover. Omnidirectional transport is estimated within vegetation that changes using a simple Markov model that simulates successional trajectory and considers three types of short-term disturbances (surface fire, crown fire, and drought-induced plant mortality) under current and projected climates. The model results highlight that movement of contaminated soil is sensitive to vegetation dynamics and increases substantially (e.g., > fivefold) when disturbance and/or future climate are considered. The time-dependent responses in horizontal sediment fluxes and associated contaminant fluxes were sensitive to variability in the timing of disturbance, with longer intervals between disturbance allowing woody plants to become dominant and crown fire and drought abruptly reducing woody plant cover. Our results, which have direct implications for contaminant transport and landfill management in the specific context of our assessment, also have general relevance because they highlight the need to more fully account for vegetation dynamics, disturbance, and changing climate in aeolian process studies. ?? 2011.

  14. Modeling aeolian transport in response to succession, disturbance and future climate: Dynamic long-term risk assessment for contaminant redistribution

    NASA Astrophysics Data System (ADS)

    Breshears, David D.; Kirchner, Thomas B.; Whicker, Jeffrey J.; Field, Jason P.; Allen, Craig D.

    2012-01-01

    Aeolian sediment transport is a fundamental process redistributing sediment, nutrients, and contaminants in dryland ecosystems. Over time frames of centuries or longer, horizontal sediment fluxes and associated rates of contaminant transport are likely to be influenced by succession, disturbances, and changes in climate, yet models of horizontal sediment transport that account for these fundamental factors are lacking, precluding in large part accurate assessment of human health risks associated with persistent soil-bound contaminants. We present a simple model based on empirical measurements of horizontal sediment transport (predominantly saltation) to predict potential contaminant transport rates for recently disturbed sites such as a landfill cover. Omnidirectional transport is estimated within vegetation that changes using a simple Markov model that simulates successional trajectory and considers three types of short-term disturbances (surface fire, crown fire, and drought-induced plant mortality) under current and projected climates. The model results highlight that movement of contaminated soil is sensitive to vegetation dynamics and increases substantially (e.g., > fivefold) when disturbance and/or future climate are considered. The time-dependent responses in horizontal sediment fluxes and associated contaminant fluxes were sensitive to variability in the timing of disturbance, with longer intervals between disturbance allowing woody plants to become dominant and crown fire and drought abruptly reducing woody plant cover. Our results, which have direct implications for contaminant transport and landfill management in the specific context of our assessment, also have general relevance because they highlight the need to more fully account for vegetation dynamics, disturbance, and changing climate in aeolian process studies.

  15. Satellite-driven predictions of animal migrations in response to short and long-term environmental change

    NASA Astrophysics Data System (ADS)

    Beck, P. S.; Bohrer, G.; Wethington, S.; Bartlam-Brooks, H. L.; Powers, D. R.; Goetz, S. J.; Graham, C. H.

    2012-12-01

    Animal migrations have evolved in response to spatio-temporal heterogeneity in resources, habitats, predation, and competition. Their reliance on disjunct habitats makes migratory animals potentially more vulnerable to extreme climate events or phenological changes at other trophic levels. The advent of affordable satellite-based tracking technology has revolutionized the study of animal movement in the past two decades. Understanding internal and external drivers of migratory behavior, and how they interact, is critical for migration ecology to move beyond solely the measurement and description of organism-level movement and to predict how environmental change might affect migrations. To achieve this, it is necessary to not only measure animals' movement but also their reliance on prevailing external, i.e. environmental, conditions prior to, and during migration. An increasingly wide array of satellite and model-derived gridded data sets that map environmental conditions at regular temporal intervals are now readily accessible because of standardized processing and data formats, as well as a variety of online portals that provide host data archives and/or on-demand processing free-of-charge. While they are often of coarser spatial resolution, these data can overcome many limitations of in situ measurements with regard to spatial extent and temporal frequency. We demonstrate the use of global gridded environmental time-series in the study of animal migrations through case studies. First we show how inter-annual weather variation in wintering habitats affects migratory behavior of broad-tailed hummingbirds and investigate how it carries over to their reproductive success and survival in summer habitats. To do so, we use vegetation indices as proxies of resource availability, and the NCEP Climate Forecast System Reanalysis (CFSR) to map known physiological constraints on the birds. Secondly, we investigated the effects of long as well as short-term variations in

  16. Rapid Eye Movement Sleep Deprivation Produces Long-Term Detrimental Effects in Spatial Memory and Modifies the Cellular Composition of the Subgranular Zone

    PubMed Central

    Soto-Rodriguez, Sofia; Lopez-Armas, Gabriela; Luquin, Sonia; Ramos-Zuñiga, Rodrigo; Jauregui-Huerta, Fernando; Gonzalez-Perez, Oscar; Gonzalez-Castañeda, Rocio E.

    2016-01-01

    . Highlight Sleep deprivation affects spatial memory and proliferation in the dentate gyrus. To date it is unknown whether these deleterious effects are persistent over a long period of time. We analyzed the effects of sleep deprivation in the hippocampus after 21 days of recovery sleep. Our findings indicate that after sleep recovery, the detrimental effects of SD can be observed for at least 2 weeks, as shown by a reduction in memory performance, changes in the hippocampal cellular composition and higher apoptotic rate over a long period of time. PMID:27303266

  17. Rapid Eye Movement Sleep Deprivation Produces Long-Term Detrimental Effects in Spatial Memory and Modifies the Cellular Composition of the Subgranular Zone.

    PubMed

    Soto-Rodriguez, Sofia; Lopez-Armas, Gabriela; Luquin, Sonia; Ramos-Zuñiga, Rodrigo; Jauregui-Huerta, Fernando; Gonzalez-Perez, Oscar; Gonzalez-Castañeda, Rocio E

    2016-01-01

    . Highlight Sleep deprivation affects spatial memory and proliferation in the dentate gyrus. To date it is unknown whether these deleterious effects are persistent over a long period of time. We analyzed the effects of sleep deprivation in the hippocampus after 21 days of recovery sleep. Our findings indicate that after sleep recovery, the detrimental effects of SD can be observed for at least 2 weeks, as shown by a reduction in memory performance, changes in the hippocampal cellular composition and higher apoptotic rate over a long period of time.

  18. Rapid Eye Movement Sleep Deprivation Produces Long-Term Detrimental Effects in Spatial Memory and Modifies the Cellular Composition of the Subgranular Zone.

    PubMed

    Soto-Rodriguez, Sofia; Lopez-Armas, Gabriela; Luquin, Sonia; Ramos-Zuñiga, Rodrigo; Jauregui-Huerta, Fernando; Gonzalez-Perez, Oscar; Gonzalez-Castañeda, Rocio E

    2016-01-01

    . Highlight Sleep deprivation affects spatial memory and proliferation in the dentate gyrus. To date it is unknown whether these deleterious effects are persistent over a long period of time. We analyzed the effects of sleep deprivation in the hippocampus after 21 days of recovery sleep. Our findings indicate that after sleep recovery, the detrimental effects of SD can be observed for at least 2 weeks, as shown by a reduction in memory performance, changes in the hippocampal cellular composition and higher apoptotic rate over a long period of time. PMID:27303266

  19. Long-term environmental exposure to metals (Cu, Cd, Pb, Zn) activates the immune cell stress response in the common European sea star (Asterias rubens).

    PubMed

    Matranga, V; Pinsino, A; Randazzo, D; Giallongo, A; Dubois, P

    2012-05-01

    The common sea star Asterias rubens represents a key-species of the North-Eastern Atlantic macro benthic community. The cells of their immune system, known as coelomocytes, are the first line of defence against environmental hazards. Here, we report the results of investigations on the immune cells response of sea stars exposed to marine environmental pollution for long periods. We show that levels of the heat shock cognate protein 70 (HSC70) in coelomocytes from A. rubens, which were collected during a field study in the Sǿrfjord (North Sea, SW coast of Norway) along a contamination gradient, are directly associated with the long-term accumulation of Cd, Cu heavy metals exclusively in the tegument. Conversely, Pb and Zn accumulation in the tegument did not relate to HSC70 levels and none of the metals were found accumulated in the pyloric coeca. In addition the coelomocytes from A. rubens, collected in high and low metal impacted stations were examined by a proteomic approach using two-dimensional electrophoresis (2DE). By comparison of the proteomic maps, we observed that 31 protein spots differed in their relative abundance, indicating a gene expression response to the metal mixture exposure. All together, our results confirm that the echinoderm immune cells are a suitable model for the assessment of long-term exposure to environmental pollution, moreover that the increased level of HSC70 can be considered a signal of an acquired tolerance within a large spectrum of protein profile changes occurring in response to metal contamination.

  20. Comparison between short-term response and long-term outcomes after initial systemic treatment of chronic graft-versus-host disease

    PubMed Central

    Martin, Paul J.; Storer, Barry E.; Carpenter, Paul A.; Couriel, Daniel R.; Flowers, Mary E.D.; Gupta, Vikas; Hsu, Jack W.; Jagasia, Madan; Kitko, Carrie L.; Maziarz, Richard T.; Rowley, Scott D.; Shaughnessy, Paul J.; van Besien, Koen; Weisdorf, Daniel; Lee, Stephanie J.

    2010-01-01

    Chronic GVHD clinical trials often use early endpoints, such as clinical response at 3 or 6 months as the primary endpoint, instead of measures of long-term treatment success, such as the ability to discontinue immunosuppressive treatment after development of immune tolerance and resolution of active disease. We evaluated the ability of defined overall and organ-specific response categories at 3 and 6 months to predict subsequent success or failure of primary treatment. The analysis included 116 patients who were evaluated at 3 months and 94 patients who were evaluated at 6 months after enrollment. Success was identified as withdrawal of systemic treatment after resolution of chronic GVHD without secondary therapy. Failure was identified as secondary systemic treatment, or death or development of bronchiolitis obliterans during primary treatment. With most definitions, response at 3 and 6 months did not show statistically significant correlation with subsequent success of primary treatment. With some definitions, the absence of response at 6 months showed statistically significant correlation with subsequent failure of primary treatment. These results suggest that early response to agents currently used for primary treatment does not necessarily predict subsequent tolerance, an important endpoint in the management of chronic GVHD. Rigorously defined clinical response is an appropriate primary endpoint for studies of chronic GVHD, but future clinical trials should provide for extended follow-up in order to ascertain late outcomes that are not necessarily predictable by evaluation of response before 6 months. PMID:20601033

  1. Long-term tolerability and maintenance of therapeutic response to sodium oxybate in an open-label extension study in patients with fibromyalgia

    PubMed Central

    2013-01-01

    Introduction The long-term safety and therapeutic response of sodium oxybate (SXB) in fibromyalgia syndrome (FM) patients were assessed for a combined period of up to 1 year in a prospective, multicenter, open-label, extension study in patients completing 1 of 2 phase 3 randomized, double-blind, controlled, 14-week trials that examined the efficacy and safety of SXB 4.5 g, SXB 6 g, and placebo for treatment of FM. Methods This extension study comprised an additional 38 weeks of treatment and was carried out at 130 clinical sites in 7 countries. Initial entry criteria for the previous 2 double-blind clinical trials required that patients aged ≥ 18 years met the American College of Rheumatology 1990 criteria for FM, had a body mass index (BMI) < 40 kg/m2, and had a score ≥ 50 on a 100-mm pain visual analog scale (VAS) at baseline. All patients began treatment in the extension study with SXB 4.5 g/night (administered in 2 equally divided doses) for at least 1 week, followed by possible serial 1.5 g/night dose increases to 9 g/night (maximum) or reductions to 4.5 g/night (minimum). Results Of the 560 FM patients enrolled in this extension study, 319 (57.0%) completed the study. The main reason for early discontinuation was adverse events (AEs; 23.0% of patients). Patients were primarily middle-aged (mean 46.9 ± 10.8 years), female (91.1%), white (91.4%), with a mean duration of FM symptoms of 9.9 ± 8.7 years. Serious AEs were experienced by 3.6% of patients. The most frequently reported AEs (incidence ≥ 5% at any dose or overall) were nausea, headache, dizziness, nasopharyngitis, vomiting, sinusitis, diarrhea, anxiety, insomnia, influenza, somnolence, upper respiratory tract infection, muscle spasms, urinary tract infection, and gastroenteritis viral. Maintenance of SXB therapeutic response was demonstrated with continued improvement from controlled-study baseline in pain VAS, Fibromyalgia Impact Questionnaire (FIQ) total scores, and other measures

  2. Using Time Series of Landsat Data to Improve Understanding of Short- and Long-Term Changes to Vegetation Phenology in Response to Climate Change

    NASA Astrophysics Data System (ADS)

    Friedl, M. A.; Melaas, E. K.; Sulla-menashe, D. J.; Gray, J. M.

    2014-12-01

    Phenology, the seasonal progression of organisms through stages of dormancy, active growth, and senescence is a key regulator of ecosystem processes and is widely used as an indicator of vegetation responses to climate change. This is especially true in temperate forests, where seasonal dynamics in canopy development and senescence are tightly coupled to the climate system. Despite this, understanding of climate-phenology interactions is incomplete. A key impediment to improving this understanding is that available datasets are geographically sparse, and in most cases include relatively short time series. Remote sensing has been widely promoted as a useful tool for studies of large-scale phenology, but long-term studies from remote sensing have been limited to AVHRR data, which suffers from limitations related to its coarse spatial resolution and uncertainties in atmospheric corrections and radiometric adjustments that are used to create AVHRR time series. In this study, we used 30 years of Landsat data to quantify the nature and magnitude of long-term trends and short-term variability in the timing of spring leaf emergence and fall senescence. Our analysis focuses on temperate forest locations in the Northeastern United States that are co-located with surface meteorological observations, where we have estimated the timing of leaf emergence and leaf senescence at annual time steps using atmospherically corrected surface reflectances from Landsat TM and ETM+ imagery. Comparison of results from Landsat against ground observations demonstrates that phenological events can be reliably estimated from Landsat time series. More importantly, results from this analysis suggest two main conclusions related to the nature of climate change impacts on temperate forest phenology. First, there is clear evidence of trends towards longer growing seasons in the Landsat record. Second, interannual variability is large, with average year-to-year variability exceeding the magnitude of

  3. [Long-term complete response of multiple lung metastases from renal cell carcinoma induced by combination therapy with interferon alpha and UFT: a case report].

    PubMed

    Terachi, T; Okada, Y; Takeuchi, H; Yoshida, O

    1993-04-01

    We report a case of long-term complete response of multiple lung metastases of renal cell carcinoma (RCC) by the combination therapy with interferon alpha (IFN alpha) and UFT. A 38 year-old man having left RCC with lung metastases underwent radical left nephrectomy and extended lymph node dissection, the pathological stage being pT2N2. Although metastatic lung tumors increased in size and number against intravenously admitted interferon gamma (IFN gamma) therapy after the surgery, they completely disappeared following the subsequent combination therapy with intramuscularly admitted interferon alpha (IFN alpha) and oral intake of UFT in about 2 years. The patient has been disease-free for 5 years after cessation of the treatment. Combination therapy with IFN alpha and UFT might be more effective on metastases of RCC than single use of IFN alpha or IFN gamma.

  4. TRAIL and TRAIL receptors splice variants during long-term interferon β treatment of patients with multiple sclerosis: evaluation as biomarkers for therapeutic response

    PubMed Central

    López-Gómez, Carlos; Oliver-Martos, Begoña; Pinto-Medel, María-Jesús; Suardiaz, Margarita; Reyes-Garrido, Virginia; Urbaneja, Patricia; Fernández, Óscar; Leyva, Laura

    2016-01-01

    Objective We aimed to assess the effects of interferon β (IFNβ) treatment on the expression of the splice variants of the Tumour necrosis factor-Related Apoptosis Inducing Ligand (TRAIL) and its receptors in different cell subpopulations (CD14+, CD4+ and CD8+) from patients with multiple sclerosis (MS), and to determine whether this expression discriminated responders from non-responders to IFNβ therapy. Methods We examined mRNA expression of the TRAIL and TRAIL receptors variants in patients with MS, at baseline and after one year of IFNβ therapy, according to responsiveness to this drug. Results Long-term therapy with IFNβ increased the expression of TRAIL-α in T cell subsets exclusively from responders and decreased the expression of the isoform 2 of TRAILR-2 in monocytes from responders as well as non-responders. Lower expression of TRAIL-α, and higher expression of TRAIL-β in monocytes and T cells, was found before the onset of IFNβ therapy in patients who will subsequently become responders. Baseline expression of TRAILR-1 was also significantly higher in monocytes and CD4+ T cells from responders. Conclusions The present study shows that long-term IFNβ treatment has a direct influence on TRAIL-α and TRAILR-2 isoform 2 expression. Besides, receiver operating characteristic analysis revealed that the baseline expression of TRAIL-α in monocytes and T cells, and that of TRAILR-1 in monocytes and CD4+ T cells, showed a predictive value of the clinical response to IFNβ therapy, pointing to a role of TRAIL system in the mechanism of action of IFNβ in MS that will need further investigation. PMID:25736057

  5. Performance of a Predictive Model for Long-Term Hemoglobin Response to Darbepoetin and Iron Administration in a Large Cohort of Hemodialysis Patients

    PubMed Central

    Barbieri, Carlo; Bolzoni, Elena; Mari, Flavio; Cattinelli, Isabella; Bellocchio, Francesco; Martin, José D.; Amato, Claudia; Stopper, Andrea; Gatti, Emanuele; Macdougall, Iain C.; Stuard, Stefano; Canaud, Bernard

    2016-01-01

    Anemia management, based on erythropoiesis stimulating agents (ESA) and iron supplementation, has become an increasingly challenging problem in hemodialysis patients. Maintaining hemodialysis patients within narrow hemoglobin targets, preventing cycling outside target, and reducing ESA dosing to prevent adverse outcomes requires considerable attention from caregivers. Anticipation of the long-term response (i.e. at 3 months) to the ESA/iron therapy would be of fundamental importance for planning a successful treatment strategy. To this end, we developed a predictive model designed to support decision-making regarding anemia management in hemodialysis (HD) patients treated in center. An Artificial Neural Network (ANN) algorithm for predicting hemoglobin concentrations three months into the future was developed and evaluated in a retrospective study on a sample population of 1558 HD patients treated with intravenous (IV) darbepoetin alfa, and IV iron (sucrose or gluconate). Model inputs were the last 90 days of patients’ medical history and the subsequent 90 days of darbepoetin/iron prescription. Our model was able to predict individual variation of hemoglobin concentration 3 months in the future with a Mean Absolute Error (MAE) of 0.75 g/dL. Error analysis showed a narrow Gaussian distribution centered in 0 g/dL; a root cause analysis identified intercurrent and/or unpredictable events associated with hospitalization, blood transfusion, and laboratory error or misreported hemoglobin values as the main reasons for large discrepancy between predicted versus observed hemoglobin values. Our ANN predictive model offers a simple and reliable tool applicable in daily clinical practice for predicting the long-term response to ESA/iron therapy of HD patients. PMID:26939055

  6. Relation between the persistence of an abnormal muscle response and the long-term clinical course after microvascular decompression for hemifacial spasm.

    PubMed

    Tobishima, Hana; Hatayama, Toru; Ohkuma, Hiroki

    2014-06-17

    Mentalis muscle responses to electrical stimulation of the zygomatic branch of the facial nerve are considered abnormal muscle responses (AMRs) and can be used to monitor the success of decompression in microvascular decompression (MVD) surgery. The aim of this study was to compare the long-term outcome of MVD surgery in which the AMR disappeared to the outcome of surgery in which the AMR persisted. From 2005 to 2009, 131 patients with hemifacial spasm received MVD surgery with intraoperative monitoring of AMR. At 1 week postsurgery, spasms had resolved in 82% of cases in the AMR-disappearance group and 46% of cases in the persistent-AMR group, mild spasms were present in 10% of cases in the AMR-disappearance group and 31% of cases in the persistent-AMR group, and moderate were present spasms in 8% of cases in the AMR-disappearance group and 23% of cases in the persistent-AMR group (P < 0.05). At 1 year postsurgery, spasms had resolved in 92% of cases in the AMR-disappearance group and 84% of cases in the persistent-AMR group, mild spasms were present in 6% of cases in the AMR-disappearance group and 8% of cases in the persistent-AMR group, and moderate spasms were present in 3% of cases in the AMR-disappearance group and 8% of the cases in the persistent-AMR group (P = 0.56). These results indicate that the long-term outcome of MVD surgery in which the AMR persisted was no different to that of MVD surgery in which the AMR disappeared.

  7. Performance of a Predictive Model for Long-Term Hemoglobin Response to Darbepoetin and Iron Administration in a Large Cohort of Hemodialysis Patients.

    PubMed

    Barbieri, Carlo; Bolzoni, Elena; Mari, Flavio; Cattinelli, Isabella; Bellocchio, Francesco; Martin, José D; Amato, Claudia; Stopper, Andrea; Gatti, Emanuele; Macdougall, Iain C; Stuard, Stefano; Canaud, Bernard

    2016-01-01

    Anemia management, based on erythropoiesis stimulating agents (ESA) and iron supplementation, has become an increasingly challenging problem in hemodialysis patients. Maintaining hemodialysis patients within narrow hemoglobin targets, preventing cycling outside target, and reducing ESA dosing to prevent adverse outcomes requires considerable attention from caregivers. Anticipation of the long-term response (i.e. at 3 months) to the ESA/iron therapy would be of fundamental importance for planning a successful treatment strategy. To this end, we developed a predictive model designed to support decision-making regarding anemia management in hemodialysis (HD) patients treated in center. An Artificial Neural Network (ANN) algorithm for predicting hemoglobin concentrations three months into the future was developed and evaluated in a retrospective study on a sample population of 1558 HD patients treated with intravenous (IV) darbepoetin alfa, and IV iron (sucrose or gluconate). Model inputs were the last 90 days of patients' medical history and the subsequent 90 days of darbepoetin/iron prescription. Our model was able to predict individual variation of hemoglobin concentration 3 months in the future with a Mean Absolute Error (MAE) of 0.75 g/dL. Error analysis showed a narrow Gaussian distribution centered in 0 g/dL; a root cause analysis identified intercurrent and/or unpredictable events associated with hospitalization, blood transfusion, and laboratory error or misreported hemoglobin values as the main reasons for large discrepancy between predicted versus observed hemoglobin values. Our ANN predictive model offers a simple and reliable tool applicable in daily clinical practice for predicting the long-term response to ESA/iron therapy of HD patients. PMID:26939055

  8. A novel function for the Hox gene Abd-B in the male accessory gland regulates the long-term female post-mating response in Drosophila.

    PubMed

    Gligorov, Dragan; Sitnik, Jessica L; Maeda, Robert K; Wolfner, Mariana F; Karch, François

    2013-03-01

    In insects, products of the male reproductive tract are essential for initiating and maintaining the female post-mating response (PMR). The PMR includes changes in egg laying, receptivity to courting males, and sperm storage. In Drosophila, previous studies have determined that the main cells of the male accessory gland produce some of the products required for these processes. However, nothing was known about the contribution of the gland's other secretory cell type, the secondary cells. In the course of investigating the late functions of the homeotic gene, Abdominal-B (Abd-B), we discovered that Abd-B is specifically expressed in the secondary cells of the Drosophila male accessory gland. Using an Abd-B BAC reporter coupled with a collection of genetic deletions, we discovered an enhancer from the iab-6 regulatory domain that is responsible for Abd-B expression in these cells and that apparently works independently from the segmentally regulated chromatin domains of the bithorax complex. Removal of this enhancer results in visible morphological defects in the secondary cells. We determined that mates of iab-6 mutant males show defects in long-term egg laying and suppression of receptivity, and that products of the secondary cells are influential during sperm competition. Many of these phenotypes seem to be caused by a defect in the storage and gradual release of sex peptide in female mates of iab-6 mutant males. We also found that Abd-B expression in the secondary cells contributes to glycosylation of at least three accessory gland proteins: ovulin (Acp26Aa), CG1656, and CG1652. Our results demonstrate that long-term post-mating changes observed in mated females are not solely induced by main cell secretions, as previously believed, but that secondary cells also play an important role in male fertility by extending the female PMR. Overall, these discoveries provide new insights into how these two cell types cooperate to produce and maintain a robust female PMR.

  9. Allocation of recent photoassimilates in mature European beech and Norway spruce - seasonal variability and responses to experimentally increased tropospheric O3 concentration and long-term drought

    NASA Astrophysics Data System (ADS)

    Grams, Thorsten

    2016-04-01

    respiration is exclusively supplied by recently fixed C was rejected for both species. After long-term (7 years) exposure to elevated (i.e. twice-ambient) O3 concentrations, allocation of recently fixed C to stems was distinctly affected when studied during later summer. In correspondence with significantly lowered woody biomass development in beech (- 40 %), C allocation to stems was reduced in response to O3 exposure. Conversely in spruce, photoassimilate allocation to stems and coarse root respiration was hardly affected, reflecting the overall lower sensitivity of spruce to elevated O3 concentrations. Compartmental modeling characterized functional properties of substrate pools supplying respiratory C demands. Stem respiration of spruce appeared to be largely supplied by recent photoassimilates. Conversely in beech, stored C, putatively located in stem parenchyma cells, was a major source for respiration, reflecting the fundamental anatomical disparity between angiosperm beech and gymnosperm spruce. Overall, the observed differences in C allocation between the two study species reflect the high plasticity of beech trees in response to seasons and stressors such as drought and elevated O3, whereas spruce displayed much lower responsiveness to the applied stressors and along the seasonal course of the year.

  10. Long-term decrease of CD4+CD45RA+ T cells and impaired primary immune response after post-traumatic splenectomy.

    PubMed

    Wolf, H M; Eibl, M M; Georgi, E; Samstag, A; Spatz, M; Uranüs, S; Passl, R

    1999-10-01

    Congenital or acquired absence of the spleen and functional hyposplenism are associated with abnormalities of host defence such as an increased susceptibility to infection with encapsulated bacteria. The effects of the lack of the spleen on cell-mediated immunity are largely unknown. In the present study we have investigated peripheral blood lymphocyte subpopulations in healthy adults who had undergone splenectomy because of severe abdominal trauma > 4 years before the study. The results show a significant reduction in the percentage of CD4+ T cells due to a selective and long-term decrease in the percentage of CD4+CD45RA+ lymphocytes, the CD4+ T-cell subset mainly involved in primary immune responses to newly encountered antigens. Levels of the reciprocal CD45RO+CD4+ T-cell subset were comparable between splenectomized and control individuals, as were lymphoproliferative responses and IFN-gamma production to recall antigens. Decreased levels of CD4+CD45RA+ cells were accompanied by an impairment in primary immune responsiveness, as assessed by investigating T-cell proliferation to stimulation with keyhole limpet haemocyanin and by measuring antibody responses following primary immunization with a clinically relevant T-dependent antigen, hepatitis A vaccine, in vivo. These findings suggest a possible role of the spleen in the generation, maintenance and/or differentiation of naive, unprimed T cells or their precursors, which might have a possible functional relevance for primary immune responses following splenectomy. PMID:10520025

  11. Long-term effects of neonatal alcohol exposure on photic reentrainment and phase-shifting responses of the activity rhythm in adult rats

    PubMed Central

    Allen, Gregg C.; Farnell, Yuhua Z.; Maeng, Ji-ung; West, James R.; Chen, Wei-Jung A.; Earnest, David J.

    2009-01-01

    In rats, neonatal alcohol (EtOH) exposure coinciding with the period of rapid brain growth produces structural damage in some brain regions that often persists into adulthood and thus may have long-term consequences in the neural regulation of behavior. Because recent findings indicate that the circadian clock located in the rat suprachiasmatic nucleus is vulnerable to alcohol-induced insults during development, the present study examined the long-term effects of neonatal alcohol exposure on the photic regulation of circadian behavior in adult rats. Rat pups were exposed to alcohol (3.0, 4.5, or 6.0 g·kg-1·day-1) or isocaloric milk formula on postnatal days 4-9 using artificial-rearing methods. At 2 months of age, animals were housed individually and circadian wheel-running behavior was continuously analyzed to determine the effects of neonatal alcohol treatment on the rate of reentrainment to a 6-h advance in the 12-h light:12-h dark photoperiod and the phase-shifting properties of free-running rhythms in response to discrete light pulses on a background of constant darkness. For all doses, neonatal alcohol exposure had a significant effect in reducing the time for reentrainment such that EtOH-treated rats required four to five fewer days than control animals for stable realignment of the activity rhythm to the shifted light-dark cycle. Coupled with the accelerated rate of reentrainment, the amplitude of light-evoked phase delays at circadian time 14 and advances at circadian time 22 in the 4.5 and 6.0 g·kg-1·day-1 EtOH groups was almost twofold greater than that observed in control animals. The present observations indicate that the mechanisms by which photic signals regulate circadian behavior are permanently altered following alcohol exposure during the period of rapid brain development. These long-term alterations in the photic regulation of circadian rhythms may account, at least partially, for some neurobehavioral consequences of prenatal alcohol

  12. Long-term trends of changes in pine and oak foliar nitrogen metabolism in response to chronic nitrogen amendments at Harvard Forest, MA.

    PubMed

    Minocha, Rakesh; Turlapati, Swathi A; Long, Stephanie; McDowell, William H; Minocha, Subhash C

    2015-08-01

    We evaluated the long-term (1995-2008) trends in foliar and sapwood metabolism, soil solution chemistry and tree mortality rates in response to chronic nitrogen (N) additions to pine and hardwood stands at the Harvard Forest Long Term Ecological Research (LTER) site. Common stress-related metabolites like polyamines (PAs), free amino acids (AAs) and inorganic elements were analyzed for control, low N (LN, 50 kg NH4NO3 ha(-1) year(-1)) and high N (HN, 150 kg NH4NO3 ha(-1) year(-1)) treatments. In the pine stands, partitioning of excess N into foliar PAs and AAs increased with both N treatments until 2002. By 2005, several of these effects on N metabolites disappeared for HN, and by 2008 they were mostly observed for LN plot. A significant decline in foliar Ca and P was observed mostly with HN for a few years until 2005. However, sapwood data actually showed an increase in Ca, Mg and Mn and no change in PAs in the HN plot for 2008, while AAs data revealed trends that were generally similar to foliage for 2008. Concomitant with these changes, mortality data revealed a large number of dead trees in HN pine plots by 2002; the mortality rate started to decline by 2005. Oak trees in the hardwood plot did not exhibit any major changes in PAs, AAs, nutrients and mortality rate with LN treatment, indicating that oak trees were able to tolerate the yearly doses of 50 kg NH4NO3 ha(-1) year(-1). However, HN trees suffered from physiological and nutritional stress along with increased mortality in 2008. In this case also, foliar data were supported by the sapwood data. Overall, both low and high N applications resulted in greater physiological stress to the pine trees than the oaks. In general, the time course of changes in metabolic data are in agreement with the published reports on changes in soil chemistry and microbial community structure, rates of soil carbon sequestration and production of woody biomass for this chronic N study. This correspondence of selected metabolites

  13. Long-term trends of changes in pine and oak foliar nitrogen metabolism in response to chronic nitrogen amendments at Harvard Forest, MA.

    PubMed

    Minocha, Rakesh; Turlapati, Swathi A; Long, Stephanie; McDowell, William H; Minocha, Subhash C

    2015-08-01

    We evaluated the long-term (1995-2008) trends in foliar and sapwood metabolism, soil solution chemistry and tree mortality rates in response to chronic nitrogen (N) additions to pine and hardwood stands at the Harvard Forest Long Term Ecological Research (LTER) site. Common stress-related metabolites like polyamines (PAs), free amino acids (AAs) and inorganic elements were analyzed for control, low N (LN, 50 kg NH4NO3 ha(-1) year(-1)) and high N (HN, 150 kg NH4NO3 ha(-1) year(-1)) treatments. In the pine stands, partitioning of excess N into foliar PAs and AAs increased with both N treatments until 2002. By 2005, several of these effects on N metabolites disappeared for HN, and by 2008 they were mostly observed for LN plot. A significant decline in foliar Ca and P was observed mostly with HN for a few years until 2005. However, sapwood data actually showed an increase in Ca, Mg and Mn and no change in PAs in the HN plot for 2008, while AAs data revealed trends that were generally similar to foliage for 2008. Concomitant with these changes, mortality data revealed a large number of dead trees in HN pine plots by 2002; the mortality rate started to decline by 2005. Oak trees in the hardwood plot did not exhibit any major changes in PAs, AAs, nutrients and mortality rate with LN treatment, indicating that oak trees were able to tolerate the yearly doses of 50 kg NH4NO3 ha(-1) year(-1). However, HN trees suffered from physiological and nutritional stress along with increased mortality in 2008. In this case also, foliar data were supported by the sapwood data. Overall, both low and high N applications resulted in greater physiological stress to the pine trees than the oaks. In general, the time course of changes in metabolic data are in agreement with the published reports on changes in soil chemistry and microbial community structure, rates of soil carbon sequestration and production of woody biomass for this chronic N study. This correspondence of selected metabolites

  14. The long term effect of age and maternally derived antibodies against foot and mouth disease on the serological response following vaccination in young dairy calves.

    PubMed

    Elnekave, Ehud; Dekker, Aldo; Eble, Phaedra; van Hemert-Kluitenberg, Froukje; Gelman, Boris; Storm, Nick; Klement, Eyal

    2016-09-22

    In Israel, occurrence of foot and mouth disease (FMD) in dairy farms is rare. However, when FMD outbreaks occur, dairy calves are the most affected, despite routine vaccination. Contradictory findings exist regarding the effect of age and maternally derived antibodies (MDA) on the serological response following vaccinations against FMD in dairy calves. Furthermore, the long term effect of FMD vaccination regimen during early life was rarely assessed. This study was conducted in order to assess both the short and long term effects. In total 44 non-vaccinated calves were divided into four groups of different age. Calves were vaccinated up to four times and 484 serum samples were collected on 11 time points in a period of 70weeks. Virus neutralizing tests were performed in order to determine the neutralizing antibody titers (NAT) against the vaccine strains (homologous serotypes): O-4625, O-Manisa, ASIA-1-Shamir and the heterologous serotype A-Turkey-20/2006. A similar NAT pattern was observed to all serotypes and therefore statistical analysis was restricted to O-4625 serotype. The MDA titer was negatively associated with the age of the calves and the MDA half-life was 22days. We demonstrated that early vaccination of calves (younger than three months) resulted in low NAT, even after four repeated vaccinations, compared with vaccination of calves older than three months. The percentage of time in which these calves had a NAT above 2.0 (log10) between the age of six months and 1.5years was significantly lower compared to older calves (older than three months). Additionally, we found that by increasing the frequency of vaccination in calves older than three months, it is possible to reach high NAT by the age of one year. Adoption of such a vaccination regimen in Israel as well as other FMD endemic countries may allow better protection against FMD in dairy calves and reduction in FMD incidence. PMID:27521229

  15. Quantifying long-term stress in brown bears with the hair cortisol concentration: a biomarker that may be confounded by rapid changes in response to capture and handling.

    PubMed

    Cattet, Marc; Macbeth, Bryan J; Janz, David M; Zedrosser, Andreas; Swenson, Jon E; Dumond, Mathieu; Stenhouse, Gordon B

    2014-01-01

    The measurement of cortisol in hair is becoming important in studying the role of stress in the life history, health and ecology of wild mammals. The hair cortisol concentration (HCC) is generally believed to be a reliable indicator of long-term stress that can reflect frequent or prolonged activation of the hypothalamic-pituitary-adrenal axis over weeks to months through passive diffusion from the blood supply to the follicular cells that produce the hair. Diffusion of cortisol from tissues surrounding the follicle and glandular secretions (sebum and sweat) that coat the growing hair may also affect the HCC, but the extent of these effects is thought to be minimal. In this study, we report on a range of factors that are associated with, and possibly influence, cortisol concentrations in the hair of free-ranging brown bears (Ursus arctos). Through two levels of analyses that differed in sample sizes and availability of predictor variables, we identified the presence or absence of capture, restraint and handling, as well as different methods of capture, as significant factors that appeared to influence HCC in a time frame that was too short (minutes to hours) to be explained by passive diffusion from the blood supply alone. Furthermore, our results suggest that HCC was altered after hair growth had ceased and blood supply to the hair follicle was terminated. However, we also confirmed that HCC was inversely associated with brown bear body condition and was, therefore, responsive to diminished food availability/quality and possibly other long-term stressors that affect body condition. Collectively, our findings emphasize the importance of further elucidating the mechanisms of cortisol accumulation in hair and the influence of long- and short-term stressors on these mechanisms. PMID:27293647

  16. The long term effect of age and maternally derived antibodies against foot and mouth disease on the serological response following vaccination in young dairy calves.

    PubMed

    Elnekave, Ehud; Dekker, Aldo; Eble, Phaedra; van Hemert-Kluitenberg, Froukje; Gelman, Boris; Storm, Nick; Klement, Eyal

    2016-09-22

    In Israel, occurrence of foot and mouth disease (FMD) in dairy farms is rare. However, when FMD outbreaks occur, dairy calves are the most affected, despite routine vaccination. Contradictory findings exist regarding the effect of age and maternally derived antibodies (MDA) on the serological response following vaccinations against FMD in dairy calves. Furthermore, the long term effect of FMD vaccination regimen during early life was rarely assessed. This study was conducted in order to assess both the short and long term effects. In total 44 non-vaccinated calves were divided into four groups of different age. Calves were vaccinated up to four times and 484 serum samples were collected on 11 time points in a period of 70weeks. Virus neutralizing tests were performed in order to determine the neutralizing antibody titers (NAT) against the vaccine strains (homologous serotypes): O-4625, O-Manisa, ASIA-1-Shamir and the heterologous serotype A-Turkey-20/2006. A similar NAT pattern was observed to all serotypes and therefore statistical analysis was restricted to O-4625 serotype. The MDA titer was negatively associated with the age of the calves and the MDA half-life was 22days. We demonstrated that early vaccination of calves (younger than three months) resulted in low NAT, even after four repeated vaccinations, compared with vaccination of calves older than three months. The percentage of time in which these calves had a NAT above 2.0 (log10) between the age of six months and 1.5years was significantly lower compared to older calves (older than three months). Additionally, we found that by increasing the frequency of vaccination in calves older than three months, it is possible to reach high NAT by the age of one year. Adoption of such a vaccination regimen in Israel as well as other FMD endemic countries may allow better protection against FMD in dairy calves and reduction in FMD incidence.

  17. Spatial and Temporal Patterns of Nutrient Limitation, Plant Biomass and Productivity, and Stream Metabolism Vary in Response to Short- and Long-Term Hydrological Regime Shifts

    NASA Astrophysics Data System (ADS)

    Grimm, N. B.; Sabo, J. L.; Dong, X.; Ruhí, A.

    2014-12-01

    Climate and hydrology are strong drivers of ecosystem structure and function in arid landscapes. Arid regions are characterized by high interannual variation in precipitation, and these climate patterns drive the overall hydrologic disturbance regime (in terms of flooding and drying), which influences geomorphic structure, biotic distributions, and nutrient status of desert stream ecosystems. We analyzed the long-term pattern of discharge in a desert stream in Arizona to identify hydrologic regime shifts, i.e., abrupt transitions between sequences of floods and droughts at periods of months to decades. We used wavelet analysis to identify time intervals over a 50-year time series that were negatively correlated with one another, reflecting a shift from wet to dry phases. We also looked with finer resolution at the most recent 10-year period, when wetlands have come to dominate the ecosystem owing to a management change, and at individual flood and drought events within years. In space, there is high site fidelity of wetland plant cover, corresponding to reliable water sources. Comparing five-year patterns of plant distribution and stream metabolism between wet and dry years suggested the primacy of geomorphic controls in drought periods. Nutrient limitation of algal production varied from moderate to very strong N limitation, with only one year when there was a (weak) suggestion of secondary P limitation. Over the longer period of record, we identified times characterized by hydrological regime shifts and asked whether ecosystem variables would have changed over that time period. We hypothesized, in particular, that the changes in nutrient status of the stream ecosystem would result from these regime shifts. We used our most complete long-term dataset on stream nitrogen (N) and phosphorus (P) concentrations and N:P ratios as a proxy for nutrient limitation. However, N:P varied primarily at fine scales in response to individual flood events.

  18. Long-term response in high-grade optic glioma treated with medically induced hypothyroidism and carboplatin: a case report and review of the literature.

    PubMed

    Ashur-Fabian, Osnat; Blumenthal, Deborah T; Bakon, Mati; Nass, Dvora; Davis, Paul J; Hercbergs, Aleck

    2013-03-01

    Glioblastoma multiforme (GBM) is the most malignant and frequent brain tumor, with an aggressive growth pattern and poor prognosis despite best treatment modalities. Long-term survival of patients with GBM is rare. Optic glioma represents 0.6-1.2% of all brain tumors. Unlike low-grade optic gliomas in children, optic gliomas in adults are highly aggressive and death usually occurs in less than a year. Prolonged progression-free survival and survival rates have been reported in association with induced hypothyroidism in two clinical trials for recurrent GBM. We present the clinical, radiological, and pathological findings in a patient with inoperable GBM of the optic chiasm. Following failure of initial, standard radiation and temozolomide therapy, chemical hypothyroidism was induced using the antithyroid thioamide, propylthiouracil, followed by carboplatin chemotherapy. Initial thyroid stimulating hormone, free T4, and free T3 analysis was carried out and then monthly. This patient responded rapidly to treatment (clinically and with tumor regression within 4 weeks) on two separate occasions with an extended remission period (2.5 years) and prolonged overall survival (4.5 years). We report the successful long-term tumor response to medically induced chemical hypothyroidism in conjunction with carboplatinum chemotherapy of an adult patient with grade IV GBM of the optic chiasm. These clinical observations find mechanistic support from the recent identification of potent mitogenic actions of the thyroid hormone, L-thyroxine, in malignant glioma through binding to a cognate thyroid hormone receptor on the αvβ3 integrin. Approaches to block its activity are now explored in preclinical studies. PMID:23348245

  19. Quantifying long-term stress in brown bears with the hair cortisol concentration: a biomarker that may be confounded by rapid changes in response to capture and handling

    PubMed Central

    Cattet, Marc; Macbeth, Bryan J.; Janz, David M.; Zedrosser, Andreas; Swenson, Jon E.; Dumond, Mathieu; Stenhouse, Gordon B.

    2014-01-01

    The measurement of cortisol in hair is becoming important in studying the role of stress in the life history, health and ecology of wild mammals. The hair cortisol concentration (HCC) is generally believed to be a reliable indicator of long-term stress that can reflect frequent or prolonged activation of the hypothalamic–pituitary–adrenal axis over weeks to months through passive diffusion from the blood supply to the follicular cells that produce the hair. Diffusion of cortisol from tissues surrounding the follicle and glandular secretions (sebum and sweat) that coat the growing hair may also affect the HCC, but the extent of these effects is thought to be minimal. In this study, we report on a range of factors that are associated with, and possibly influence, cortisol concentrations in the hair of free-ranging brown bears (Ursus arctos). Through two levels of analyses that differed in sample sizes and availability of predictor variables, we identified the presence or absence of capture, restraint and handling, as well as different methods of capture, as significant factors that appeared to influence HCC in a time frame that was too short (minutes to hours) to be explained by passive diffusion from the blood supply alone. Furthermore, our results suggest that HCC was altered after hair growth had ceased and blood supply to the hair follicle was terminated. However, we also confirmed that HCC was inversely associated with brown bear body condition and was, therefore, responsive to diminished food availability/quality and possibly other long-term stressors that affect body condition. Collectively, our findings emphasize the importance of further elucidating the mechanisms of cortisol accumulation in hair and the influence of long- and short-term stressors on these mechanisms. PMID:27293647

  20. Responses of Plant Community Composition to Long-term Changes in Snow Depth at the Great Basin Desert - Sierra Nevada ecotone.

    NASA Astrophysics Data System (ADS)

    Loik, M. E.

    2015-12-01

    Snowfall is the dominant hydrologic input for many high-elevation ecosystems of the western United States. Many climate models envision changes in California's Sierra Nevada snow pack characteristics, which would severely impact the storage and release of water for one of the world's largest economies. Given the importance of snowfall for future carbon cycling in high elevation ecosystems, how will these changes affect seedling recruitment, plant mortality, and community composition? To address this question, experiments utilize snow fences to manipulate snow depth and melt timing at a desert-montane ecotone in eastern California, USA. Long-term April 1 snow pack depth averages 1344 mm (1928-2015) but is highly variable from year to year. Snow fences increased equilibrium drift snow depth by 100%. Long-term changes in snow depth and melt timing are associated with s shift from shurbs to graminoids where snow depth was increased for >50 years. Changes in snow have impacted growth for only three plant species. Moreover, annual growth ring increments of the conifers Pinus jeffreyi and Pi. contorta were not equally sensitive to snow depth. There were over 8000 seedlings of the shrubs Artemisia tridentata and Purshia tridentata found in 6300 m2 in summer 2009, following about 1400 mm of winter snow and spring rain. The frequency of seedlings of A. tridentata and P. tridentata were much lower on increased-depth plots compared to ambient-depth, and reduced-depth plots. Survival of the first year was lowest for A. tridentata. Survival of seedlings from the 2008 cohort was much higher for P. tridentata than A. tridentata during the 2011-2015 drought. Results indicate complex interactions between snow depth and plant community characteristics, and that responses of plants at this ecotone may not respond similarly to increases vs. decreases in snow depth. These changes portend altered carbon uptake in this region under future snowfall scenarios.

  1. Arsenic downregulates gene expression at the postsynaptic density in mouse cerebellum, including genes responsible for long-term potentiation and depression.

    PubMed

    Zhang, Cong; Li, Sheng; Sun, Yahui; Dong, Wei; Piao, Fengyuan; Piao, Yongjun; Liu, Shuang; Guan, Huai; Yu, Shengbo

    2014-08-01

    Arsenic (As) is a neurotoxin induces dysfunction of learning and memory. Research has indicated that cerebellum may be involved in arsenic-induced impairment of learning and memory. However, the molecular mechanisms that underlie these effects remain unclear. This study screened for the differentially expressed genes related to the long-term potentiation and long-term depression (LTP and LTD) at the cerebellar postsynaptic density (PSD) of mice following exposure to arsenic, and we provide evidence of the mechanism by which arsenic adversely affects the functions of learning and memory. Here, SPF mice were exposed to 1ppm, 2ppm and 4ppm As2O3 for 60 days. The ultrastructure of the synapses in cerebella of these mice was observed via transmission electron microscopy. The cerebellum global gene expression of mice exposed to 4ppm As2O3 was determined through GeneChip analysis. We used the web tool DAVID to analyze the Gene Ontology (GO) and KEGG pathways that were significantly enriched among the differentially expressed genes. Our observations of synaptic ultrastructure showed that the thickness of the cerebellar PSD was reduced in mice exposed to arsenic. Go analysis revealed the PSD as a significantly altered cellular component. KEGG pathway analysis showed that LTP and LTD were affected by arsenic with highest statistical significance, and 20 differentially expressed genes were associated with them. Among these differentially expressed genes, significant decreases in the mRNA expressions of CaMKII, Gria1, Gria2, Grin1, Itpr1, Grm1 and PLCβ4 related to the LTP and LTD were found at the PSD of mouse cerebellum exposed to arsenic. The downregulation of these genes was further confirmed via real-time reverse transcription PCR or Western blot at 1ppm, 2ppm and 4ppm As2O3. Our results indicate that the 7 genes with in cerebellar PSDs may be involved in arsenic-induced neurotoxicity, including impairment of learning and memory. PMID:24831965

  2. Physiological maturation and drug responses of human induced pluripotent stem cell-derived cortical neuronal networks in long-term culture

    PubMed Central

    Odawara, A.; Katoh, H.; Matsuda, N.; Suzuki, I.

    2016-01-01

    The functional network of human induced pluripotent stem cell (hiPSC)-derived neurons is a potentially powerful in vitro model for evaluating disease mechanisms and drug responses. However, the culture time required for the full functional maturation of individual neurons and networks is uncertain. We investigated the development of spontaneous electrophysiological activity and pharmacological responses for over 1 year in culture using multi-electrode arrays (MEAs). The complete maturation of spontaneous firing, evoked responses, and modulation of activity by glutamatergic and GABAergic receptor antagonists/agonists required 20–30 weeks. At this stage, neural networks also demonstrated epileptiform synchronized burst firing (SBF) in response to pro-convulsants and SBF suppression using clinical anti-epilepsy drugs. Our results reveal the feasibility of long-term MEA measurements from hiPSC-derived neuronal networks in vitro for mechanistic analyses and drug screening. However, developmental changes in electrophysiological and pharmacological properties indicate the necessity for the international standardization of culture and evaluation procedures. PMID:27188845

  3. Long-Term Monitoring of Physical Behavior Reveals Different Cardiac Responses to Physical Activity among Subjects with and without Chronic Neck Pain

    PubMed Central

    Hallman, David M.; Mathiassen, Svend Erik; Lyskov, Eugene

    2015-01-01

    Background. We determined the extent to which heart rate variability (HRV) responses to daily physical activity differ between subjects with and without chronic neck pain. Method. Twenty-nine subjects (13 women) with chronic neck pain and 27 age- and gender-matched healthy controls participated. Physical activity (accelerometry), HRV (heart rate monitor), and spatial location (Global Positioning System (GPS)) were recorded for 74 hours. GPS data were combined with a diary to identify periods of work and of leisure at home and elsewhere. Time- and frequency-domain HRV indices were calculated and stratified by period and activity type (lying/sitting, standing, or walking). ANCOVAs with multiple adjustments were used to disclose possible group differences in HRV. Results. The pain group showed a reduced HRV response to physical activity compared with controls (p = .001), according to the sympathetic-baroreceptor HRV index (LF/HF, ratio between low- and high-frequency power), even after adjustment for leisure time physical activity, work stress, sleep quality, mental health, and aerobic capacity (p = .02). The parasympathetic response to physical activity did not differ between groups. Conclusions. Relying on long-term monitoring of physical behavior and heart rate variability, we found an aberrant sympathetic-baroreceptor response to daily physical activity among subjects with chronic neck pain. PMID:26557711

  4. Report to the Nuclear energy Research Advisory Committee (NERAC) Subcommittee on "Long-Term Isotope Research and Productions Plan" - Responses to Questions

    SciTech Connect

    Ammoniums

    1999-07-01

    This report presents responses to two series of questions that were raised by a subcommittee of the Nuclear Energy Research Advisory Committee (NERAC) that has been charged with producing a ''Long-Term Isotope Research and Production Plan.'' The NERAC subcommittee is chaired by Dr. Richard Reba, and the Hanford Site Visit team, which comprises a subset of the subcommittee members, is chaired by Dr. Thomas Ruth. The first set of questions raised by the subcommittee on isotope production at the Hanford Site was received from Dr. Ruth on May 10, 1999, and the second set was received from him on July 5, 1999. Responses to the first set of questions were prepared as part of a June 1999 report entitled ''Isotope Production at the Hanford Site in Richland, Washington'' (PNNL 1999a). The responses to these questions are summarized in this document, with frequent references to the June 1999 report for additional details. Responses to the second set of questions from the NERAC subcommittee are presented in this document for the first time.

  5. Physiological maturation and drug responses of human induced pluripotent stem cell-derived cortical neuronal networks in long-term culture.

    PubMed

    Odawara, A; Katoh, H; Matsuda, N; Suzuki, I

    2016-05-18

    The functional network of human induced pluripotent stem cell (hiPSC)-derived neurons is a potentially powerful in vitro model for evaluating disease mechanisms and drug responses. However, the culture time required for the full functional maturation of individual neurons and networks is uncertain. We investigated the development of spontaneous electrophysiological activity and pharmacological responses for over 1 year in culture using multi-electrode arrays (MEAs). The complete maturation of spontaneous firing, evoked responses, and modulation of activity by glutamatergic and GABAergic receptor antagonists/agonists required 20-30 weeks. At this stage, neural networks also demonstrated epileptiform synchronized burst firing (SBF) in response to pro-convulsants and SBF suppression using clinical anti-epilepsy drugs. Our results reveal the feasibility of long-term MEA measurements from hiPSC-derived neuronal networks in vitro for mechanistic analyses and drug screening. However, developmental changes in electrophysiological and pharmacological properties indicate the necessity for the international standardization of culture and evaluation procedures.

  6. Does reduced gravity alter cellular response to ionizing radiation?

    PubMed

    Manti, Lorenzo

    2006-05-01

    This review addresses the purported interplay between actual or simulated weightlessness and cellular response to ionizing radiation. Although weightlessness is known to alter several cellular functions and to affect signaling pathways implicated in cell proliferation, differentiation and death, its influence on cellular radiosensitivity has so far proven elusive. Renewed controversy as to whether reduced gravity enhances long-term radiation risk is fueled by recently published data that claim either overall enhancement of genomic damage or no increase of radiation-induced clastogenicity by modeled microgravity in irradiated human cells. In elucidating this crucial aspect of space radiation protection, ground-based experiments, such as those based on rotating-wall bioreactors, will increasingly be used and represent a more reproducible alternative to in-flight experiments. These low-shear vessels also make three-dimensional cellular co-cultures possible and thus allow to study the gravisensitivity of radioresponse in a context that better mimics cell-to-cell communication and hence in vivo cellular behavior.

  7. Flexible modeling of exposure-response relationship between long-term average levels of particulate air pollution and mortality in the American Cancer Society study.

    PubMed

    Abrahamowicz, Michal; Schopflocher, Tom; Leffondré, Karen; du Berger, Roxane; Krewski, Daniel

    Accurate estimation of the exposure-response relationship between environmental particulate air pollution and mortality is important from both an etiologic and regulatory perspective. However, little is known about the actual shapes of these exposure-response curves. The objective of this study was to estimate the exposure-response relationships between mortality and long-term average city-specific levels of sulfates and fine particulate matter (PM(2.5)). We reanalyzed the data derived from the American Cancer Society (ACS) Cancer Prevention Study II, a large prospective study conducted in the United States between 1982 and 1989. Exposure to particulate air pollution was assessed prior to entry into the cohort. Mean sulfate concentrations for 1980 were available in 151 cities, and median PM(2.5) levels between 1979 and 1983 were available in 50 cities. Two sampling strategies were employed to reduce the computational burden. The modified case-cohort approach combined a random subcohort of 1200 individuals with an additional 1300 cases (i.e., deaths). The second strategy involved pooling the results of separate analyses of 10 disjoint random subsets, each with about 2200 participants. To assess the independent effect of the particulate levels on all-causes mortality, we relied on flexible, nonparametric survival analytical methods. To eliminate potentially restrictive assumptions underlying the conventional models, we employed a flexible regression spline generalization of the Cox proportional-hazards (PH) model. The regression spline method allowed us to model simultaneously the time-dependent changes in the effect of particulate matter on the hazard and a possibly nonlinear exposure-response relationship. The PH and linearity hypotheses were tested using likelihood ratio tests. In all analyses, we stratified by age and 5-yr age groups and adjusted for the subject's age, lifetime smoking exposure, obesity, and education. For both fine particles (PM(2.5)) and

  8. Living on the edge: adaptive and plastic responses of the tree Nothofagus pumilio to a long-term transplant experiment predict rear-edge upward expansion.

    PubMed

    Mathiasen, Paula; Premoli, Andrea C

    2016-06-01

    Current climate change affects the competitive ability and reproductive success of many species, leading to local extinctions, adjustment to novel local conditions by phenotypic plasticity or rapid adaptation, or tracking their optima through range shifts. However, many species have limited ability to expand to suitable areas. Altitudinal gradients, with abrupt changes in abiotic conditions over short distances, represent "natural experiments" for the evaluation of ecological and evolutionary responses under scenarios of climate change. Nothofagus pumilio is the tree species which dominates as pure stands the montane forests of Patagonia. We evaluated the adaptive value of variation in quantitative traits of N. pumilio under contrasting conditions of the altitudinal gradient with a long-term reciprocal transplant experimental design. While high-elevation plants show little response in plant, leaf, and phenological traits to the experimental trials, low-elevation ones show greater plasticity in their responses to changing environments, particularly at high elevation. Our results suggest a relatively reduced potential for evolutionary adaptation of high-elevation genotypes, and a greater evolutionary potential of low-elevation ones. Under global warming scenarios of forest upslope migration, high-elevation variants may be outperformed by low-elevation ones during this process, leading to the local extinction and/or replacement of these genotypes. These results challenge previous models and predictions expected under global warming for altitudinal gradients, on which the leading edge is considered to be the upper treeline forests. PMID:26868524

  9. Using an optimality model to understand medium and long-term responses of vegetation water use to elevated atmospheric CO2 concentrations

    PubMed Central

    Schymanski, Stanislaus J.; Roderick, Michael L.; Sivapalan, Murugesu

    2015-01-01

    Vegetation has different adjustable properties for adaptation to its environment. Examples include stomatal conductance at short time scale (minutes), leaf area index and fine root distributions at longer time scales (days–months) and species composition and dominant growth forms at very long time scales (years–decades–centuries). As a result, the overall response of evapotranspiration to changes in environmental forcing may also change at different time scales. The vegetation optimality model simulates optimal adaptation to environmental conditions, based on the assumption that different vegetation properties are optimized to maximize the long-term net carbon profit, allowing for separation of different scales of adaptation, without the need for parametrization with observed responses. This paper discusses model simulations of vegetation responses to today's elevated atmospheric CO2 concentrations (eCO2) at different temporal scales and puts them in context with experimental evidence from free-air CO2 enrichment (FACE) experiments. Without any model tuning or calibration, the model reproduced general trends deduced from FACE experiments, but, contrary to the widespread expectation that eCO2 would generally decrease water use due to its leaf-scale effect on stomatal conductance, our results suggest that eCO2 may lead to unchanged or even increased vegetation water use in water-limited climates, accompanied by an increase in perennial vegetation cover. PMID:26019228

  10. Seasonal and annual variations in physiological and biochemical responses from transplanted marine bioindicator species Mytilus spp. during a long term field exposure experiment.

    PubMed

    Helmholz, Heike; Ruhnau, Christiane; Pröfrock, Daniel; Erbslöh, Hans-Burkhard; Prange, Andreas

    2016-09-15

    In a pilot field study the long term response of transplanted bioindicator organisms Mytilus spp. was analyzed on the basis of physiological indices and biochemical measurements related to the energy budget. Three different time series with deployment times of eight to twelve months were compared according to seasonality and repeatability of the responses. Test organisms were incubated at a coastal station in the anthropogenically impacted estuary of the river Elbe and at a North Sea station located in vicinity to the Island of Helgoland in the German Bight. The stations differ in their hydrological as well as chemical characteristics. They can be discriminated by statistical factor analysis based on the measured biochemical parameter. Levels of all energy budget biomarker varied between seasons; however, the degree of variation of the specific response was differently expressed. The mussels deployed at Helgoland showed a reproducible high Condition Index in each sampling series and an oscillating Gonadosomatic Index representing the reproduction cycle. The lowest available energy was recorded in mussels at the estuarine sampling station compared to the off-shore station. This may be caused by the energetically costly maintenance of osmotic balance and consequently result in a lower amount of energy available for defense again chemical stress, growth and reproduction. PMID:27203523

  11. Using an optimality model to understand medium and long-term responses of vegetation water use to elevated atmospheric CO2 concentrations.

    PubMed

    Schymanski, Stanislaus J; Roderick, Michael L; Sivapalan, Murugesu

    2015-05-27

    Vegetation has different adjustable properties for adaptation to its environment. Examples include stomatal conductance at short time scale (minutes), leaf area index and fine root distributions at longer time scales (days-months) and species composition and dominant growth forms at very long time scales (years-decades-centuries). As a result, the overall response of evapotranspiration to changes in environmental forcing may also change at different time scales. The vegetation optimality model simulates optimal adaptation to environmental conditions, based on the assumption that different vegetation properties are optimized to maximize the long-term net carbon profit, allowing for separation of different scales of adaptation, without the need for parametrization with observed responses. This paper discusses model simulations of vegetation responses to today's elevated atmospheric CO2 concentrations (eCO2) at different temporal scales and puts them in context with experimental evidence from free-air CO2 enrichment (FACE) experiments. Without any model tuning or calibration, the model reproduced general trends deduced from FACE experiments, but, contrary to the widespread expectation that eCO2 would generally decrease water use due to its leaf-scale effect on stomatal conductance, our results suggest that eCO2 may lead to unchanged or even increased vegetation water use in water-limited climates, accompanied by an increase in perennial vegetation cover.

  12. Chronic hepatitis C virus infections in brazilian patients: association with genotypes, clinical parameters and response to long term alpha interferon therapy

    PubMed

    Bassit; Da Silva LC; Ribeiro-Dos-Santos; Maertens; Carrilho; Fonseca; Alves; Gayotto; Pereira; Takei; Chamone; Saez-Alquezar

    1999-05-01

    The present study assessed the clinical significance of hepatitis C virus (HCV) genotypes and their influence on response to long term recombinant-interferon-alpha (r-IFN-alpha) therapy in Brazilian patients. One hundred and thirty samples from patients previously genotyped for the HCV and with histologically confirmed chronic hepatitis C (CH-C) were evaluated for clinical and epidemiological parameters (sex, age, time of HCV infection and transmission routes). No difference in disease activity, sex, age or mode and time of transmission were seen among patients infected with HCV types 1, 2 or 3. One hundred and thirteen of them were treated with 3 million units of r-IFN-alpha, 3 times a week for 12 months. Initial response (IR) was significantly better in patients with genotype 2 (100%) and 3 (46%) infections than in patients with genotype 1 (29%) (p < 0. 005). Among subtypes, difference in IR was observed between 1b and 2 (p < 0.005), and between 1b and 3a (p < 0.05). Sustained response (SR) was observed in 12% for (sub)type 1a, 13% for 1b, 19% for 3a, and 40% for type 2; significant differences were found between 1b and 2 (p < 0.001), and between 1b and 3a (p < 0.05). Moreover, presence of cirrhosis was significantly associated with non response and response with relapse (p < 0.05). In conclusion, non-1 HCV genotype and lack of histological diagnosis of cirrhosis were the only baseline features associated with sustained response to treatment. These data indicate that HCV genotyping may have prognostic relevance in the responsiveness to r-IFN-alpha therapy in Brazilian patients with chronic HCV infection, as seen in other reports worldwide. PMID:10529839

  13. Modulation of Long-Term Potentiation of Cortico-Amygdala Synaptic Responses and Auditory Fear Memory by Dietary Polyunsaturated Fatty Acid

    PubMed Central

    Yamada, Daisuke; Wada, Keiji; Sekiguchi, Masayuki

    2016-01-01

    Converging evidence suggests that an imbalance of ω3 to ω6 polyunsaturated fatty acid (PUFA) in the brain is involved in mental illnesses such as anxiety disorders. However, the underlying mechanism is unknown. We previously reported that the dietary ratio of ω3 to ω6 PUFA alters this ratio in the brain, and influences contextual fear memory. In addition to behavioral change, enhancement of cannabinoid CB1 receptor-mediated short-term synaptic plasticity and facilitation of the agonist sensitivity of CB1 receptors have been observed in excitatory synaptic responses in the basolateral nucleus of the amygdala (BLA). However, it is not known whether long-term synaptic plasticity in the amygdala is influenced by the dietary ratio of ω3 to ω6 PUFA. In the present study, we examined long-term potentiation (LTP) of optogenetically-evoked excitatory synaptic responses in synapses between the terminal of the projection from the auditory cortex (ACx) and the pyramidal cells in the lateral nucleus of the amygdala. We found that LTP in this pathway was attenuated in mice fed with a high ω3 to ω6 PUFA ratio diet (0.97), compared with mice fed with a low ω3 to ω6 PUFA ratio diet (0.14). Furthermore, mice in the former condition showed reduced fear responses in an auditory fear conditioning test, compared with mice in the latter condition. In both electrophysiological and behavioral experiments, the effect of a diet with a high ω3 to ω6 PUFA diet ratio was completely blocked by treatment with a CB1 receptor antagonist. Furthermore, a significant reduction was observed in cholesterol content, but not in the level of an endogenous CB1 receptor agonist, 2-arachidonoylglycerol (2-AG), in brain samples containing the amygdala. These results suggest that the balance of ω3 to ω6 PUFA has an impact on fear memory and cortico-amygdala synaptic plasticity, both in a CB1 receptor–dependent manner.

  14. Modulation of Long-Term Potentiation of Cortico-Amygdala Synaptic Responses and Auditory Fear Memory by Dietary Polyunsaturated Fatty Acid

    PubMed Central

    Yamada, Daisuke; Wada, Keiji; Sekiguchi, Masayuki

    2016-01-01

    Converging evidence suggests that an imbalance of ω3 to ω6 polyunsaturated fatty acid (PUFA) in the brain is involved in mental illnesses such as anxiety disorders. However, the underlying mechanism is unknown. We previously reported that the dietary ratio of ω3 to ω6 PUFA alters this ratio in the brain, and influences contextual fear memory. In addition to behavioral change, enhancement of cannabinoid CB1 receptor-mediated short-term synaptic plasticity and facilitation of the agonist sensitivity of CB1 receptors have been observed in excitatory synaptic responses in the basolateral nucleus of the amygdala (BLA). However, it is not known whether long-term synaptic plasticity in the amygdala is influenced by the dietary ratio of ω3 to ω6 PUFA. In the present study, we examined long-term potentiation (LTP) of optogenetically-evoked excitatory synaptic responses in synapses between the terminal of the projection from the auditory cortex (ACx) and the pyramidal cells in the lateral nucleus of the amygdala. We found that LTP in this pathway was attenuated in mice fed with a high ω3 to ω6 PUFA ratio diet (0.97), compared with mice fed with a low ω3 to ω6 PUFA ratio diet (0.14). Furthermore, mice in the former condition showed reduced fear responses in an auditory fear conditioning test, compared with mice in the latter condition. In both electrophysiological and behavioral experiments, the effect of a diet with a high ω3 to ω6 PUFA diet ratio was completely blocked by treatment with a CB1 receptor antagonist. Furthermore, a significant reduction was observed in cholesterol content, but not in the level of an endogenous CB1 receptor agonist, 2-arachidonoylglycerol (2-AG), in brain samples containing the amygdala. These results suggest that the balance of ω3 to ω6 PUFA has an impact on fear memory and cortico-amygdala synaptic plasticity, both in a CB1 receptor–dependent manner. PMID:27601985

  15. Modulation of Long-Term Potentiation of Cortico-Amygdala Synaptic Responses and Auditory Fear Memory by Dietary Polyunsaturated Fatty Acid.

    PubMed

    Yamada, Daisuke; Wada, Keiji; Sekiguchi, Masayuki

    2016-01-01

    Converging evidence suggests that an imbalance of ω3 to ω6 polyunsaturated fatty acid (PUFA) in the brain is involved in mental illnesses such as anxiety disorders. However, the underlying mechanism is unknown. We previously reported that the dietary ratio of ω3 to ω6 PUFA alters this ratio in the brain, and influences contextual fear memory. In addition to behavioral change, enhancement of cannabinoid CB1 receptor-mediated short-term synaptic plasticity and facilitation of the agonist sensitivity of CB1 receptors have been observed in excitatory synaptic responses in the basolateral nucleus of the amygdala (BLA). However, it is not known whether long-term synaptic plasticity in the amygdala is influenced by the dietary ratio of ω3 to ω6 PUFA. In the present study, we examined long-term potentiation (LTP) of optogenetically-evoked excitatory synaptic responses in synapses between the terminal of the projection from the auditory cortex (ACx) and the pyramidal cells in the lateral nucleus of the amygdala. We found that LTP in this pathway was attenuated in mice fed with a high ω3 to ω6 PUFA ratio diet (0.97), compared with mice fed with a low ω3 to ω6 PUFA ratio diet (0.14). Furthermore, mice in the former condition showed reduced fear responses in an auditory fear conditioning test, compared with mice in the latter condition. In both electrophysiological and behavioral experiments, the effect of a diet with a high ω3 to ω6 PUFA diet ratio was completely blocked by treatment with a CB1 receptor antagonist. Furthermore, a significant reduction was observed in cholesterol content, but not in the level of an endogenous CB1 receptor agonist, 2-arachidonoylglycerol (2-AG), in brain samples containing the amygdala. These results suggest that the balance of ω3 to ω6 PUFA has an impact on fear memory and cortico-amygdala synaptic plasticity, both in a CB1 receptor-dependent manner. PMID:27601985

  16. Importance of early and deeper responses to long-term survival in CML patients: Implications of BCR-ABL testing in management of CML in Indian setting

    PubMed Central

    Agarwal, Mohan B.

    2014-01-01

    The prognosis of patients with chronic myeloid leukemia (CML) has changed radically since the advent of imatinib mesylate, a selective inhibitor of BCR-ABL tyrosine kinase. Shortly thereafter, more potent BCR-ABL inhibitors (dasatinib and nilotinib) were introduced for use in patients resistant to or intolerant of imatinib. All three drugs are now approved for initial therapy for chronic phase CML. Response to tyrosine kinase inhibitor (TKI) treatment is assessed with standardized quantitative reverse transcriptase polymerase chain reaction (Q-RTPCR) and/or cytogenetics at 3, 6 and 12 months. Clinical trials have clearly demonstrated that early and deeper cytogenetic and molecular response to TKI therapy is associated with lower rate of disease progression and improved long-term outcomes. In recent times, molecular response as determined by BCR-ABL transcript levels at defined time points is rapidly gaining popularity as a predictive marker for subsequent outcomes in CML. Optimal response is defined as BCR-ABL transcript levels of ≤10% at 3 months, <1% at 6 months, and ≤0.1% from 12 months onward while >10% at 6 months and >1% from 12 months onward define failure. Patients who do not achieve molecular milestones at 3 or 6 months with 3 months being highly predictive are less likely to achieve cytogenetic responses eventually; early identification of such patients who have a low probability of achieving an adequate response are thus candidates for alternative treatment. Review of literature by electronic search of MEDline, Google Scholar was done using keywords and data was identified and systematically evaluated. PMID:25006277

  17. Long-term environmental stewardship.

    SciTech Connect

    Nagy, Michael David

    2010-08-01

    The purpose of this Supplemental Information Source Document is to effectively describe Long-Term Environmental Stewardship (LTES) at Sandia National Laboratories/New Mexico (SNL/NM). More specifically, this document describes the LTES and Long-Term Stewardship (LTS) Programs, distinguishes between the LTES and LTS Programs, and summarizes the current status of the Environmental Restoration (ER) Project.

  18. Glucose-6-phosphate dehydrogenase plays a central role in the response of tomato (Solanum lycopersicum) plants to short and long-term drought.

    PubMed

    Landi, Simone; Nurcato, Roberta; De Lillo, Alessia; Lentini, Marco; Grillo, Stefania; Esposito, Sergio

    2016-08-01

    The present study was undertaken to investigate the expression, occurrence and activity of glucose 6 phosphate dehydrogenase (G6PDH - EC 1.1.1.49), the key-enzyme of the Oxidative Pentose Phosphate Pathway (OPPP), in tomato plants (Solanum lycopersicum cv. Red Setter) exposed to short- and long-term drought stress. For the first time, drought effects have been evaluated in plants under different growth conditions: in hydroponic laboratory system, and in greenhouse pots under controlled conditions; and in open field, in order to evaluate drought response in a representative agricultural environment. Interestingly, changes observed appear strictly associated to the induction of well known stress response mechanisms, such as the increase of proline synthesis, accumulation of chaperone Hsp70, and ascorbate peroxidase. Results show significant increase in total activity of G6PDH, and specifically in expression and occurrence of cytosolic isoform (cy-G6PDH) in plants grown in any cultivation system upon drought. Intriguingly, the results clearly suggest that abscissic acid (ABA) pathway and signaling cascade (protein phosphatase 2C PP2C) could be strictly related to increased G6PDH expression, occurrence and activities. We hypothesized for G6PDH a specific role as one of the main reductants' suppliers to counteract the effects of drought stress, in the light of converging evidences given by young and adult tomato plants under stress of different duration and intensity. PMID:27085599

  19. Adjuvanting an inactivated influenza vaccine with flagellin improves the function and quantity of the long-term antibody response in a nonhuman primate neonate model.

    PubMed

    Holbrook, Beth C; D'Agostino, Ralph B; Parks, Griffith D; Alexander-Miller, Martha A

    2016-09-01

    Young infants are at significantly increased risk of developing severe disease following infection with influenza virus. At present there is no approved vaccine for individuals below the age of six months given previous studies showing a failure of these individuals to efficiently seroconvert. Given the major impact of influenza on infant health, it is critical that we develop vaccines that will be safe and effective in this population. Using a nonhuman primate (NHP) model, we have evaluated the ability of an inactivated influenza virus vaccine adjuvanted with flagellin to result in long term immune responses in neonates. To evaluate this critical attribute, neonate NHP were vaccinated and boosted with inactivated influenza virus in combination with either flagellin or a mutant inactive flagellin control. Our studies show that inclusion of flagellin resulted in a significant increase (5-fold, p=0.04) in influenza virus-specific IgG antibody at 6months post-vaccination. In addition, the antibody present at this late time was of higher affinity (2.4-fold, p=0.02). Finally a greater percentage of infants had detectable neutralizing antibody. These results support the use of flagellin in neonates as an adjuvant that promotes long-lived, high affinity antibody responses. PMID:27516064

  20. A BTLA-mediated bait and switch strategy permits Listeria expansion in CD8α(+) DCs to promote long-term T cell responses.

    PubMed

    Yang, Xuanming; Zhang, Xunmin; Sun, Yonglian; Tu, Tony; Fu, May Lynne; Miller, Mendy; Fu, Yang-Xin

    2014-07-01

    Listeria monocytogenes infected CD8α(+) DCs in the spleen are essential for CD8(+) T cell generation. CD8α(+) DCs are also necessary for Listeria expansion and dissemination within the host. The mechanisms that regulate CD8α(+) DCs to allow Listeria expansion are unclear. We find that activating the B and T lymphocyte attenuator (BTLA), a coinhibitory receptor for T cells, suppresses, while blocking BTLA enhances, both the primary and memory CD8 T cell responses against Listeria. Btla(-/-) mice have lower effector and memory CD8(+) T cells while paradoxically also being more resistant to Listeria. Although bacterial entry into Btla(-/-) CD8α(+) DCs is unaffected, Listeria fails to expand within these cells. BTLA signaling limits Fas/FasL-mediated suppression of Listeria expansion within CD8α(+) DCs to more effectively alert adaptive immune cells. This study uncovers a BTLA-mediated strategy used by the host that permits Listeria proliferation to enable increasing T cell responses for long-term protection.

  1. Bone geometry in response to long-term tennis playing and its relationship with muscle volume: a quantitative magnetic resonance imaging study in tennis players.

    PubMed

    Ducher, G; Courteix, D; Même, S; Magni, C; Viala, J F; Benhamou, C L

    2005-10-01

    The benefit of impact-loading activity for bone strength depends on whether the additional bone mineral content (BMC) accrued at loaded sites is due to an increased bone size, volumetric bone mineral density (vBMD) or both. Using magnetic resonance imaging (MRI) and dual energy X-ray absorptiometry (DXA), the aim of this study was to characterize the geometric changes of the dominant radius in response to long-term tennis playing and to assess the influence of muscle forces on bone tissue by investigating the muscle-bone relationship. Twenty tennis players (10 men and 10 women, mean age: 23.1+/-4.7 years, with 14.3+/-3.4 years of playing) were recruited. The total bone volume, cortical volume, sub-cortical volume and muscle volume were measured at both distal radii by MRI. BMC was assessed by DXA and was divided by the total bone volume to derive vBMD. Grip strength was evaluated with a dynamometer. Significant side-to-side differences (P<0.0001) were found in muscle volume (+9.7%), grip strength (+13.3%), BMC (+13.5%), total bone volume (+10.3%) and sub-cortical volume (+20.6%), but not in cortical volume (+2.6%, ns). The asymmetry in total bone volume explained 75% of the variance in BMC asymmetry (P<0.0001). vBMD was slightly higher on the dominant side (+3.3%, P<0.05). Grip strength and muscle volume correlated with all bone variables (except vBMD) on both sides (r=0.48-0.86, P<0.05-0.0001) but the asymmetries in muscle parameters did not correlate with those in bone parameters. After adjustment for muscle volume or grip strength, BMC was still greater on the dominant side. This study showed that the greater BMC induced by long-term tennis playing at the dominant radius was associated to a marked increase in bone size and a slight improvement in volumetric BMD, thereby improving bone strength. In addition to the muscle contractions, other mechanical stimuli seemed to exert a direct effect on bone tissue, contributing to the specific bone response to tennis

  2. Soil mineral composition matters: response of microbial communities to phenanthrene and plant litter addition in long-term matured artificial soils.

    PubMed

    Babin, Doreen; Vogel, Cordula; Zühlke, Sebastian; Schloter, Michael; Pronk, Geertje Johanna; Heister, Katja; Spiteller, Michael; Kögel-Knabner, Ingrid; Smalla, Kornelia

    2014-01-01

    The fate of polycyclic aromatic hydrocarbons (PAHs) in soil is determined by a suite of biotic and abiotic factors, and disentangling their role in the complex soil interaction network remains challenging. Here, we investigate the influence of soil composition on the microbial community structure and its response to the spiked model PAH compound phenanthrene and plant litter. We used long-term matured artificial soils differing in type of clay mineral (illite, montmorillonite) and presence of charcoal or ferrihydrite. The soils received an identical soil microbial fraction and were incubated for more than two years with two sterile manure additions. The matured artificial soils and a natural soil were subjected to the following spiking treatments: (I) phenanthrene, (II) litter, (III) litter + phenanthrene, (IV) unspiked control. Total community DNA was extracted from soil sampled on the day of spiking, 7, 21, and 63 days after spiking. Bacterial 16S rRNA gene and fungal internal transcribed spacer amplicons were quantified by qPCR and subjected to denaturing gradient gel electrophoresis (DGGE). DGGE analysis revealed that the bacterial community composition, which was strongly shaped by clay minerals after more than two years of incubation, changed in response to spiked phenanthrene and added litter. DGGE and qPCR showed that soil composition significantly influenced the microbial response to spiking. While fungal communities responded only in presence of litter to phenanthrene spiking, the response of the bacterial communities to phenanthrene was less pronounced when litter was present. Interestingly, microbial communities in all artificial soils were more strongly affected by spiking than in the natural soil, which might indicate the importance of higher microbial diversity to compensate perturbations. This study showed the influence of soil composition on the microbiota and their response to phenanthrene and litter, which may increase our understanding of

  3. Soil Mineral Composition Matters: Response of Microbial Communities to Phenanthrene and Plant Litter Addition in Long-Term Matured Artificial Soils

    PubMed Central

    Babin, Doreen; Vogel, Cordula; Zühlke, Sebastian; Schloter, Michael; Pronk, Geertje Johanna; Heister, Katja; Spiteller, Michael; Kögel-Knabner, Ingrid; Smalla, Kornelia

    2014-01-01

    The fate of polycyclic aromatic hydrocarbons (PAHs) in soil is determined by a suite of biotic and abiotic factors, and disentangling their role in the complex soil interaction network remains challenging. Here, we investigate the influence of soil composition on the microbial community structure and its response to the spiked model PAH compound phenanthrene and plant litter. We used long-term matured artificial soils differing in type of clay mineral (illite, montmorillonite) and presence of charcoal or ferrihydrite. The soils received an identical soil microbial fraction and were incubated for more than two years with two sterile manure additions. The matured artificial soils and a natural soil were subjected to the following spiking treatments: (I) phenanthrene, (II) litter, (III) litter + phenanthrene, (IV) unspiked control. Total community DNA was extracted from soil sampled on the day of spiking, 7, 21, and 63 days after spiking. Bacterial 16S rRNA gene and fungal internal transcribed spacer amplicons were quantified by qPCR and subjected to denaturing gradient gel electrophoresis (DGGE). DGGE analysis revealed that the bacterial community composition, which was strongly shaped by clay minerals after more than two years of incubation, changed in response to spiked phenanthrene and added litter. DGGE and qPCR showed that soil composition significantly influenced the microbial response to spiking. While fungal communities responded only in presence of litter to phenanthrene spiking, the response of the bacterial communities to phenanthrene was less pronounced when litter was present. Interestingly, microbial communities in all artificial soils were more strongly affected by spiking than in the natural soil, which might indicate the importance of higher microbial diversity to compensate perturbations. This study showed the influence of soil composition on the microbiota and their response to phenanthrene and litter, which may increase our understanding of

  4. Sex differences in the long-term repeatability of the acute stress response in long-lived, free-living Florida scrub-jays (Aphelocoma coerulescens).

    PubMed

    Small, Thomas W; Schoech, Stephan J

    2015-01-01

    There is increasing evidence that individual differences in the physiological stress response are persistent traits in many animals. To test the hypothesis that the stress-induced CORT (SI-CORT) response is repeatable over the adult life span of Florida scrub-jays (Aphelocoma coerulescens), we sampled 32 male and 25 female free-living scrub-jays (aged 2-13 years) during a 9-year period (2004-2012). Each individual was sampled two to five times and samples were collected one or more years apart during the pre-breeding season (Jan-March). In addition, individuals sampled over the greatest time period (6-8 years) were analyzed separately to more closely assess long-term repeatability. SI-CORT was repeatable in females, but not males, when values were not corrected for confounding variables (agreement repeatability). However, when the year and time of day of sample collection were controlled (adjusted repeatability), SI-CORT was repeatable in both sexes. SI-CORT was also repeatable in the males and females sampled 6-8 years apart. Finally, baseline CORT levels of males, but not females, exhibited low but significant repeatability when adjusted for year. The results of this study demonstrate that differences in SI-CORT levels were repeatable within adult scrub-jays sampled up to 8 years apart. Further, the female SI-CORT response was more consistent between pre-breeding seasons than males, which may have resulted from males having higher SI-CORT plasticity in response to environmental conditions. These data support the hypothesis that the SI-CORT response of Florida scrub-jays develops before adulthood and persists throughout much, if not all, of their natural adult life span.

  5. Photodynamic dose does not correlate with long-term tumor response to mTHPC-PDT performed at several drug-light intervals

    SciTech Connect

    Wang, Ken Kang-Hsin; Mitra, Soumya; Foster, Thomas H.

    2008-08-15

    Meso-tetra-hydroxyphenyl-chlorin (mTHPC, Foscan registered ), a promising photosensitizer for photodynamic therapy (PDT), is approved in Europe for the palliative treatment of head and neck cancer. Based on work in mice that investigated optimal tumor accumulation, clinical protocols with Foscan registered typically employ an interval of 96 h between systemic sensitizer administration and irradiation. However, recent studies in mouse tumor models have demonstrated significantly improved long-term tumor response when irradiation is performed at shorter drug-light intervals of 3 and 6 h. Using a previously published theoretical model of microscopic PDT dosimetry and informed by experimentally determined photophysical properties and intratumor sensitizer concentrations and distributions, we calculated photodynamic dose depositions following mTHPC-PDT for drug-light intervals of 3, 6, 24, and 96 h. Our results demonstrate that the singlet oxygen dose to the tumor volume does not track even qualitatively with tumor responses for these four drug-light intervals. Further, microscopic analysis of simulated singlet oxygen deposition shows that in no case do any subpopulations of tumor cells receive a threshold dose. Indeed, under the conditions of these simulations more than 90% of the tumor volume receives a dose that is approximately 20-fold lower than the threshold dose for mTHPC. Thus, in this evaluation of mTHPC-PDT at various drug-light intervals, any PDT dose metric that is proportional to singlet oxygen creation and/or deposition would fail to predict the tumor response. In situations like this one, other reporters of biological response to therapy would be necessary.

  6. Application of Long-term cultured Interferon-γ Enzyme-linked Immunospot Assay for Assessing Effector and Memory T Cell Responses in Cattle.

    PubMed

    Maggioli, Mayara F; Palmer, Mitchell V; Vordermeier, H Martin; Whelan, Adam O; Fosse, James M; Nonnecke, Brian J; Waters, W Ray

    2015-01-01

    Effector and memory T cells are generated through developmental programing of naïve cells following antigen recognition. If the infection is controlled up to 95 % of the T cells generated during the expansion phase are eliminated (i.e., contraction phase) and memory T cells remain, sometimes for a lifetime. In humans, two functionally distinct subsets of memory T cells have been described based on the expression of lymph node homing receptors. Central memory T cells express C-C chemokine receptor 7 and CD45RO and are mainly located in T-cell areas of secondary lymphoid organs. Effector memory T cells express CD45RO, lack CCR7 and display receptors associated with lymphocyte homing to peripheral or inflamed tissues. Effector T cells do not express either CCR7 or CD45RO but upon encounter with antigen produce effector cytokines, such as interferon-γ. Interferon-γ release assays are used for the diagnosis of bovine and human tuberculosis and detect primarily effector and effector memory T cell responses. Central memory T cell responses by CD4(+) T cells to vaccination, on the other hand, may be used to predict vaccine efficacy, as demonstrated with simian immunodeficiency virus infection of non-human primates, tuberculosis in mice, and malaria in humans. Several studies with mice and humans as well as unpublished data on cattle, have demonstrated that interferon-γ ELISPOT assays measure central memory T cell responses. With this assay, peripheral blood mononuclear cells are cultured in decreasing concentration of antigen for 10 to 14 days (long-term culture), allowing effector responses to peak and wane; facilitating central memory T cells to differentiate and expand within the culture. PMID:26275095

  7. Application of Long-term cultured Interferon-γ Enzyme-linked Immunospot Assay for Assessing Effector and Memory T Cell Responses in Cattle.

    PubMed

    Maggioli, Mayara F; Palmer, Mitchell V; Vordermeier, H Martin; Whelan, Adam O; Fosse, James M; Nonnecke, Brian J; Waters, W Ray

    2015-07-11

    Effector and memory T cells are generated through developmental programing of naïve cells following antigen recognition. If the infection is controlled up to 95 % of the T cells generated during the expansion phase are eliminated (i.e., contraction phase) and memory T cells remain, sometimes for a lifetime. In humans, two functionally distinct subsets of memory T cells have been described based on the expression of lymph node homing receptors. Central memory T cells express C-C chemokine receptor 7 and CD45RO and are mainly located in T-cell areas of secondary lymphoid organs. Effector memory T cells express CD45RO, lack CCR7 and display receptors associated with lymphocyte homing to peripheral or inflamed tissues. Effector T cells do not express either CCR7 or CD45RO but upon encounter with antigen produce effector cytokines, such as interferon-γ. Interferon-γ release assays are used for the diagnosis of bovine and human tuberculosis and detect primarily effector and effector memory T cell responses. Central memory T cell responses by CD4(+) T cells to vaccination, on the other hand, may be used to predict vaccine efficacy, as demonstrated with simian immunodeficiency virus infection of non-human primates, tuberculosis in mice, and malaria in humans. Several studies with mice and humans as well as unpublished data on cattle, have demonstrated that interferon-γ ELISPOT assays measure central memory T cell responses. With this assay, peripheral blood mononuclear cells are cultured in decreasing concentration of antigen for 10 to 14 days (long-term culture), allowing effector responses to peak and wane; facilitating central memory T cells to differentiate and expand within the culture.

  8. Long-term Pulmonary Responses to Quadweekly Intermittent Intratracheal Spray Instillations of Magnetite (Fe3O4) Nanoparticles for 52 Weeks in Fischer 344 Rats

    PubMed Central

    Tada, Yukie; Yano, Norio; Takahashi, Hiroshi; Yuzawa, Katsuhiro; Ando, Hiroshi; Kubo, Yoshikazu; Nagasawa, Akemichi; Inomata, Akiko; Ogata, Akio; Nakae, Dai

    2013-01-01

    Information about potential risks of iron nanomaterials is still limited, while a wide variety of applications are expected. We recently reported acute phase responses of male and female Fischer 344 rats after a single intratracheal spray instillation of Fe3O4 nanoparticles (magnetite), clearly showing dose-dependent pulmonary inflammatory changes (Tada et al., J Toxicol Pathol 25, 233–239, 2012). The present study assessed long-term responses of male and female Fischer 344 rats to multiple administrations of magnetite. Ten-week-old male and female Fischer 344 rats (n=20/group) were exposed to a total of 13 quadweekly intermittent intratracheal spray instillations of magnetite during the experimental period of 52 weeks, at doses of 0, 0.2 (low), 1.0 (medium) and 5.0 (high-dose) mg/kg body weight per administration. Absolute and relative lung weights of the high-dose group were significantly higher than those of the control group. Macroscopically, slight enlargement and scattered black patches were recognized in the lungs and the lung-associated lymph nodes of the high-dose group. Histopathologically, infiltration of macrophages phagocytosing magnetite (all dose groups) and of chronic inflammatory cells (medium- and high-dose males and high-dose females), alveolar bronchiolization and granuloma (high-dose group) were observed. In addition, alveolar hyperplasias were observed in some rats of the high-dose group, and cytoplasmic overexpression of β-catenin protein was immunohistochemically found in such lesions. The present results clearly show that instilled magnetite causes chronic inflammatory responses in the lung. These responses occur in a dose-dependent manner without apparent differences among sexes PMID:24526812

  9. Long-Term Hepatitis B Virus (HBV) Response to Lamivudine-Containing Highly Active Antiretroviral Therapy in HIV-HBV Co-Infected Patients in Thailand

    PubMed Central

    Khamduang, Woottichai; Gaudy-Graffin, Catherine; Ngo-Giang-Huong, Nicole; Jourdain, Gonzague; Moreau, Alain; Luekamlung, Nuananong; Halue, Guttiga; Buranawanitchakorn, Yuwadee; Kunkongkapan, Sura; Buranabanjasatean, Sudanee; Lallemant, Marc; Sirirungsi, Wasna; Goudeau, Alain

    2012-01-01

    Background Approximately 4 million of people are co-infected with HIV and Hepatitis B virus (HBV). In resource-limited settings, the majority of HIV-infected patients initiate first-line highly active antiretroviral therapy containing lamivudine (3TC-containing-HAART) and long-term virological response of HBV to lamivudine-containing HAART in co-infected patients is not well known. Methodology/Principal Finding HIV-HBV co-infected patients enrolled in the PHPT cohort (ClinicalTrials.gov NCT00433030) and initiating a 3TC-containing-HAART regimen were included. HBV-DNA, HIV-RNA, CD4+ T-cell counts and alanine transaminase were measured at baseline, 3 months, 12 months and then every 6 months up to 5 years. Kaplan-Meier analysis was used to estimate the cumulative rates of patients who achieved and maintained HBV-DNA suppression. Of 30 co-infected patients, 19 were positive for HBe antigen (HBeAg). At initiation of 3TC-containing-HAART, median HBV DNA and HIV RNA levels were 7.35 log10 IU/mL and 4.47 log10 copies/mL, respectively. At 12 months, 67% of patients achieved HBV DNA suppression: 100% of HBeAg-negative patients and 47% of HBeAg-positive. Seventy-three percent of patients had HIV RNA below 50 copies/mL. The cumulative rates of maintained HBV-DNA suppression among the 23 patients who achieved HBV-DNA suppression were 91%, 87%, and 80% at 1, 2, and 4 years respectively. Of 17 patients who maintained HBV-DNA suppression while still on 3TC, 4 (24%) lost HBsAg and 7 of 8 (88%) HBeAg-positive patients lost HBeAg at their last visit (median duration, 59 months). HBV breakthrough was observed only in HBeAg-positive patients and 6 of 7 patients presenting HBV breakthrough had the rtM204I/V mutations associated with 3TC resistance along with rtL180M and/or rtV173L. Conclusions All HBeAg-negative patients and 63% of HBeAg-positive HIV-HBV co-infected patients achieved long-term HBV DNA suppression while on 3TC-containing-HAART. This study provides information useful for

  10. Metabolite Profiling of Diverse Rice Germplasm and Identification of Conserved Metabolic Markers of Rice Roots in Response to Long-Term Mild Salinity Stress

    PubMed Central

    Nam, Myung Hee; Bang, Eunjung; Kwon, Taek Yun; Kim, Yuran; Kim, Eun Hee; Cho, Kyungwon; Park, Woong June; Kim, Beom-Gi; Yoon, In Sun

    2015-01-01

    The sensitivity of rice to salt stress greatly depends on growth stages, organ types and cultivars. Especially, the roots of young rice seedlings are highly salt-sensitive organs that limit plant growth, even under mild soil salinity conditions. In an attempt to identify metabolic markers of rice roots responding to salt stress, metabolite profiling was performed by 1H-NMR spectroscopy in 38 rice genotypes that varied in biomass accumulation under long-term mild salinity condition. Multivariate statistical analysis showed separation of the control and salt-treated rice roots and rice genotypes with differential growth potential. By quantitative analyses of 1H-NMR data, five conserved salt-responsive metabolic markers of rice roots were identified. Sucrose, allantoin and glutamate accumulated by salt stress, whereas the levels of glutamine and alanine decreased. A positive correlation of metabolite changes with growth potential and salt tolerance of rice genotypes was observed for allantoin and glutamine. Adjustment of nitrogen metabolism in rice roots is likely to be closely related to maintain the growth potential and increase the stress tolerance of rice. PMID:26378525

  11. Response to: “Long-term effectiveness and consequences of carbon dioxide sequestration” by Gary Shaffer, published in Nature Geosciences, 27 June 2010.

    SciTech Connect

    Dooley, James J.

    2010-07-12

    Shaffer’s (2010) article reports on the long term impact of less than perfect retention of anthropogenic CO2 stored in deep geologic reservoirs and in the ocean. The central thesis of this article is predicated on two deeply flawed assumptions. The first and most glaring is the implicit assumption that society has only one means of reducing greenhouse gas emissions, carbon dioxide capture and storage (CCS). Secondly, there is absolutely no geophysical nor geomechanical basis for assuming an exponential decay of CO2 stored in deep geologic formations as done by Schaffer. Shaffer’s analysis of the impact of leakage from anthropogenic CO2 stored in deep geologic reservoirs are based upon two fundamentally flawed assumptions and therefore the reported results as well as the public policy conclusions presented in the paper need to be read with this understanding in mind as far less CO2 stored below ground because society drew upon a broad portfolio of advanced energy technologies over the coming century coupled with a more technically accurate conceptualization of CO2 storage in the deep subsurface and the important role of secondary and tertiary trapping mechanisms would have yield a far less pessimistic view of the potential role that CCS can play in a broader portfolio of societal responses to the very serious threat posed by climate change.

  12. ESR dosimetry of fossil enamel: some comments about measurement precision, long-term signal fading and dose-response curve fitting.

    PubMed

    Duval, M; Guilarte Moreno, V; Grün, R

    2013-12-01

    This work deals with the specific studies of three main sources of uncertainty in electron spin resonance (ESR) dosimetry/dating of fossil tooth enamel: (1) the precision of the ESR measurements, (2) the long-term signal fading the selection of the fitting function. They show a different influence on the equivalent dose (D(E)) estimates. Repeated ESR measurements were performed on 17 different samples: results show a mean coefficient of variation of the ESR intensities of 1.20 ± 0.23 %, inducing a mean relative variability of 3.05 ± 2.29 % in the D(E) values. ESR signal fading over 5 y was also observed: its magnitude seems to be quite sample dependant but is nevertheless especially important for the most irradiated aliquots. This fading has an apparent random effect on the D(E) estimates. Finally, the authors provide new insights and recommendations about the fitting of ESR dose-response curves of fossil enamel with a double saturating exponential (DSE) function. The potential of a new variation of the DSE was also explored. Results of this study also show that the choice of the fitting function is of major importance, maybe more than the other sources previously mentioned, in order to get accurate final D(E) values.

  13. Long-term boron-deficiency-responsive genes revealed by cDNA-AFLP differ between Citrus sinensis roots and leaves

    PubMed Central

    Lu, Yi-Bin; Qi, Yi-Ping; Yang, Lin-Tong; Lee, Jinwook; Guo, Peng; Ye, Xin; Jia, Meng-Yang; Li, Mei-Li; Chen, Li-Song

    2015-01-01

    Seedlings of Citrus sinensis (L.) Osbeck were supplied with boron (B)-deficient (without H3BO3) or -sufficient (10 μM H3BO3) nutrient solution for 15 weeks. We identified 54 (38) and 38 (45) up (down)-regulated cDNA-AFLP bands (transcript-derived fragments, TDFs) from B-deficient leaves and roots, respectively. These TDFs were mainly involved in protein and amino acid metabolism, carbohydrate and energy metabolism, nucleic acid metabolism, cell transport, signal transduction, and stress response and defense. The majority of the differentially expressed TDFs were isolated only from B-deficient roots or leaves, only seven TDFs with the same GenBank ID were isolated from the both. In addition, ATP biosynthesis-related TDFs were induced in B-deficient roots, but unaffected in B-deficient leaves. Most of the differentially expressed TDFs associated with signal transduction and stress defense were down-regulated in roots, but up-regulated in leaves. TDFs related to protein ubiquitination and proteolysis were induced in B-deficient leaves except for one TDF, while only two down-regulated TDFs associated with ubiquitination were detected in B-deficient roots. Thus, many differences existed in long-term B-deficiency-responsive genes between roots and leaves. In conclusion, our findings provided a global picture of the differential responses occurring in B-deficient roots and leaves and revealed new insight into the different adaptive mechanisms of C. sinensis roots and leaves to B-deficiency at the transcriptional level. PMID:26284101

  14. Long-term boron-deficiency-responsive genes revealed by cDNA-AFLP differ between Citrus sinensis roots and leaves.

    PubMed

    Lu, Yi-Bin; Qi, Yi-Ping; Yang, Lin-Tong; Lee, Jinwook; Guo, Peng; Ye, Xin; Jia, Meng-Yang; Li, Mei-Li; Chen, Li-Song

    2015-01-01

    Seedlings of Citrus sinensis (L.) Osbeck were supplied with boron (B)-deficient (without H3BO3) or -sufficient (10 μM H3BO3) nutrient solution for 15 weeks. We identified 54 (38) and 38 (45) up (down)-regulated cDNA-AFLP bands (transcript-derived fragments, TDFs) from B-deficient leaves and roots, respectively. These TDFs were mainly involved in protein and amino acid metabolism, carbohydrate and energy metabolism, nucleic acid metabolism, cell transport, signal transduction, and stress response and defense. The majority of the differentially expressed TDFs were isolated only from B-deficient roots or leaves, only seven TDFs with the same GenBank ID were isolated from the both. In addition, ATP biosynthesis-related TDFs were induced in B-deficient roots, but unaffected in B-deficient leaves. Most of the differentially expressed TDFs associated with signal transduction and stress defense were down-regulated in roots, but up-regulated in leaves. TDFs related to protein ubiquitination and proteolysis were induced in B-deficient leaves except for one TDF, while only two down-regulated TDFs associated with ubiquitination were detected in B-deficient roots. Thus, many differences existed in long-term B-deficiency-responsive genes between roots and leaves. In conclusion, our findings provided a global picture of the differential responses occurring in B-deficient roots and leaves and revealed new insight into the different adaptive mechanisms of C. sinensis roots and leaves to B-deficiency at the transcriptional level. PMID:26284101

  15. Patients Lacking Sustainable Long-Term Weight Loss after Gastric Bypass Surgery Show Signs of Decreased Inhibitory Control of Prepotent Responses

    PubMed Central

    Hogenkamp, Pleunie S.; Sundbom, Magnus; Nilsson, Victor C.; Benedict, Christian; Schiöth, Helgi B.

    2015-01-01

    Background A considerable number of bariatric patients report poor long-term weight loss after Roux-en-Y gastric bypass (RYGB) surgery. One possibility for an underlying cause is an impairment of cognitive control that impedes this patient group’s dietary efforts. Objective To investigate if patients having either poor or good weight loss response, ~12 years after RYGB-surgery, differ in their ability to inhibit prepotent responses when processing food cues during attentional operations—as measure of cognitive control. Methods In terms of weight loss following RYGB-surgery, 15 ‘poor responders’ and 15 ‘good responders’, matched for gender, age, education, preoperative body mass index, and years since surgery, were administered two tasks that measure sustained attention and response control: a go/no-go task and a Stroop interference task; both of which are associated with maladaptive eating behaviours. Results The poor responders (vs. good responders) needed significantly more time when conducting a go/no-go task (603±134 vs. 519±44 msec, p = 0.03), but the number of errors did not differ between groups. When conducting a Stroop interference task, poor responders read fewer inks than good responders (68±16 vs. 85±10 words, p = 0.002). Conclusion Patients lacking sustainable weight loss after RYGB-surgery showed poorer inhibitory control than patients that successfully lost weight. In the authors’ view, these results suggest that cognitive behavioral therapies post-RYGB-surgery may represent a promising behavioral adjuvant to achieve sustainable weight loss in patients undergoing this procedure. Future studies should examine whether these control deficits in poor responders are food-specific or not. PMID:25774526

  16. Long-term boron-deficiency-responsive genes revealed by cDNA-AFLP differ between Citrus sinensis roots and leaves.

    PubMed

    Lu, Yi-Bin; Qi, Yi-Ping; Yang, Lin-Tong; Lee, Jinwook; Guo, Peng; Ye, Xin; Jia, Meng-Yang; Li, Mei-Li; Chen, Li-Song

    2015-01-01

    Seedlings of Citrus sinensis (L.) Osbeck were supplied with boron (B)-deficient (without H3BO3) or -sufficient (10 μM H3BO3) nutrient solution for 15 weeks. We identified 54 (38) and 38 (45) up (down)-regulated cDNA-AFLP bands (transcript-derived fragments, TDFs) from B-deficient leaves and roots, respectively. These TDFs were mainly involved in protein and amino acid metabolism, carbohydrate and energy metabolism, nucleic acid metabolism, cell transport, signal transduction, and stress response and defense. The majority of the differentially expressed TDFs were isolated only from B-deficient roots or leaves, only seven TDFs with the same GenBank ID were isolated from the both. In addition, ATP biosynthesis-related TDFs were induced in B-deficient roots, but unaffected in B-deficient leaves. Most of the differentially expressed TDFs associated with signal transduction and stress defense were down-regulated in roots, but up-regulated in leaves. TDFs related to protein ubiquitination and proteolysis were induced in B-deficient leaves except for one TDF, while only two down-regulated TDFs associated with ubiquitination were detected in B-deficient roots. Thus, many differences existed in long-term B-deficiency-responsive genes between roots and leaves. In conclusion, our findings provided a global picture of the differential responses occurring in B-deficient roots and leaves and revealed new insight into the different adaptive mechanisms of C. sinensis roots and leaves to B-deficiency at the transcriptional level.

  17. Cellular response of titanium and its alloys as implants.

    PubMed

    Bhola, Rahul; Bhola, Shaily M; Mishra, Brajendra; Ayers, Reed; Olson, David L; Ohno, Timothy

    2011-08-01

    The cellular response of osteocytes to commercially pure titanium (α) and its alloys (α + β and β) has been tested in a culture media, and the results have been supplemented by analyses from various techniques such as inductively coupled plasma atomic emission spectroscopic (ICP-AES) analysis, X-ray photoemission spectroscopy (XPS), scanning electron microscopy (SEM), metallography, and electrochemical measurements. These results have been correlated with respect to the presence of various alloying elements in these alloys to qualify them for human application. The newer β alloys have been examined for their potential use as implants. These results serve as a preliminary baseline to characterize the best alloy system for a comprehensive long-term investigation.

  18. Long term complications of diabetes

    MedlinePlus

    ... this page: //medlineplus.gov/ency/patientinstructions/000327.htm Long term complications of diabetes To use the sharing ... sores and infections. If it goes on too long, your toes, foot, or leg may need to ...

  19. Abdominal Pain, Long-Term

    MedlinePlus

    MENU Return to Web version Abdominal Pain, Long-term See complete list of charts. Ongoing or recurrent abdominal pain, also called chronic pain, may be difficult to diagnose, causing frustration for ...

  20. Long-term biomass research

    SciTech Connect

    Not Available

    1981-03-01

    Some of DOE's long term R and D programs for biomass are summarized in this article. These include research efforts in the fields of anaerobic digestion, energy farming, short rotation cultivation and aquatic farming. (DMC)

  1. Localization of health systems in low- and middle-income countries in response to long-term increases in energy prices.

    PubMed

    Dalglish, Sarah L; Poulsen, Melissa N; Winch, Peter J

    2013-01-01

    External challenges to health systems, such as those caused by global economic, social and environmental changes, have received little attention in recent debates on health systems' performance in low-and middle-income countries (LMICs). One such challenge in coming years will be increasing prices for petroleum-based products as production from conventional petroleum reserves peaks and demand steadily increases in rapidly-growing LMICs. Health systems are significant consumers of fossil fuels in the form of petroleum-based medical supplies; transportation of goods, personnel and patients; and fuel for lighting, heating, cooling and medical equipment. Long-term increases in petroleum prices in the global market will have potentially devastating effects on health sectors in LMICs who already struggle to deliver services to remote parts of their catchment areas. We propose the concept of "localization," originating in the environmental sustainability literature, as one element of response to these challenges. Localization assigns people at the local level a greater role in the production of goods and services, thereby decreasing reliance on fossil fuels and other external inputs. Effective localization will require changes to governance structures within the health sector in LMICs, empowering local communities to participate in their own health in ways that have remained elusive since this goal was first put forth in the Alma-Ata Declaration on Primary Health Care in 1978. Experiences with decentralization policies in the decades following Alma-Ata offer lessons on defining roles and responsibilities, building capacity at the local level, and designing appropriate policies to target inequities, all of which can guide health systems to adapt to a changing environmental and energy landscape.

  2. Characterizing the Long-Term PM2.5 Concentration-Response Function: Comparing the Strengths and Weaknesses of Research Synthesis Approaches.

    PubMed

    Fann, Neal; Gilmore, Elisabeth A; Walker, Katherine

    2016-09-01

    The magnitude, shape, and degree of certainty in the association between long-term population exposure to ambient fine particulate matter (PM2.5 ) and the risk of premature death is one of the most intensely studied issues in environmental health. For regulatory risk analysis, this relationship is described quantitatively by a concentration-response (C-R) function that relates exposure to ambient concentrations with the risk of premature mortality. Four data synthesis techniques develop the basis for, and derive, this function: systematic review, expert judgment elicitation, quantitative meta-analysis, and integrated exposure-response (IER) assessment. As part of an academic workshop aiming to guide the use of research synthesis approaches, we developed criteria with which to evaluate and select among the approaches for their ability to inform policy choices. These criteria include the quality and extent of scientific support for the method, its transparency and verifiability, its suitability to the policy problem, and the time and resources required for its application. We find that these research methods are both complementary and interdependent. A systematic review of the multidisciplinary evidence is a starting point for all methods, providing the broad conceptual basis for the nature, plausibility, and strength of the associations between PM exposure and adverse health effects. Further, for a data-rich application like PM2.5 and premature mortality, all three quantitative approaches can produce estimates that are suitable for regulatory and benefit analysis. However, when fewer data are available, more resource-intensive approaches such as expert elicitation may be more important for understanding what scientists know, where they agree or disagree, and what they believe to be the most important areas of uncertainty. Whether implicitly or explicitly, all require considerable judgment by scientists. Finding ways for all these methods to acknowledge

  3. Mental health response in Haiti in the aftermath of the 2010 earthquake: a case study for building long-term solutions.

    PubMed

    Raviola, Giuseppe; Eustache, Eddy; Oswald, Catherine; Belkin, Gary S

    2012-01-01

    Significant challenges exist in providing safe, effective, and culturally sound mental health and psychosocial services when an unforeseen disaster strikes in a low-resource setting. We present here a case study describing the experience of a transnational team in expanding mental health and psychosocial services delivered by two health care organizations, one local (Zanmi Lasante) and one international (Partners in Health), acting collaboratively as part of the emergency response to the 2010 Haiti earthquake. In the year and a half following the earthquake, Zanmi Lasante and Partners in Health provided 20,000 documented individual and group appointments for mental health and psychosocial needs. During the delivery of disaster response services, the collaboration led to the development of a model to guide the expansion and scaling up of community-based mental health services in the Zanmi Lasante health care system over the long-term, with potential for broader scale-up in Haiti. This model identifies key skill packages and implementation rules for developing evidence-based pathways and algorithms for treating common mental disorders. Throughout the collaboration, efforts were made to coordinate planning with multiple organizations interested in supporting the development of mental health programs following the disaster, including national governmental bodies, nongovernmental organizations, universities, foreign academic medical centers, and corporations. The collaborative interventions are framed here in terms of four overarching categories of action: direct service delivery, research, training, and advocacy. This case study exemplifies the role of psychiatrists working in low-resource settings as public health program implementers and as members of multidisciplinary teams.

  4. Localization of health systems in low- and middle-income countries in response to long-term increases in energy prices

    PubMed Central

    2013-01-01

    External challenges to health systems, such as those caused by global economic, social and environmental changes, have received little attention in recent debates on health systems’ performance in low-and middle-income countries (LMICs). One such challenge in coming years will be increasing prices for petroleum-based products as production from conventional petroleum reserves peaks and demand steadily increases in rapidly-growing LMICs. Health systems are significant consumers of fossil fuels in the form of petroleum-based medical supplies; transportation of goods, personnel and patients; and fuel for lighting, heating, cooling and medical equipment. Long-term increases in petroleum prices in the global market will have potentially devastating effects on health sectors in LMICs who already struggle to deliver services to remote parts of their catchment areas. We propose the concept of “localization,” originating in the environmental sustainability literature, as one element of response to these challenges. Localization assigns people at the local level a greater role in the production of goods and services, thereby decreasing reliance on fossil fuels and other external inputs. Effective localization will require changes to governance structures within the health sector in LMICs, empowering local communities to participate in their own health in ways that have remained elusive since this goal was first put forth in the Alma-Ata Declaration on Primary Health Care in 1978. Experiences with decentralization policies in the decades following Alma-Ata offer lessons on defining roles and responsibilities, building capacity at the local level, and designing appropriate policies to target inequities, all of which can guide health systems to adapt to a changing environmental and energy landscape. PMID:24199690

  5. Mental Health Response in Haiti in the Aftermath of the 2010 Earthquake: A Case Study for Building Long-Term Solutions

    PubMed Central

    Raviola, Giuseppe; Eustache, Eddy; Oswald, Catherine; Belkin, Gary S

    2012-01-01

    Significant challenges exist in providing safe, effective, and culturally sound mental health and psychosocial services when an unforeseen disaster strikes in a low-resource setting. We present here a case study describing the experience of a transnational team in expanding mental health and psychosocial services delivered by two health care organizations, one local (Zanmi Lasante) and one international (Partners in Health), acting collaboratively as part of the emergency response to the 2010 Haiti earthquake. In the year and a half following the earthquake, Zanmi Lasante and Partners in Health provided 20,000 documented individual and group appointments for mental health and psychosocial needs. During the delivery of disaster response services, the collaboration led to the development of a model to guide the expansion and scaling up of community-based mental health services in the Zanmi Lasante health care system over the long-term, with potential for broader scale-up in Haiti. This model identifies key skill packages and implementation rules for developing evidence-based pathways and algorithms for treating common mental disorders. Throughout the collaboration, efforts were made to coordinate planning with multiple organizations interested in supporting the development of mental health programs following the disaster, including national governmental bodies, nongovernmental organizations, universities, foreign academic medical centers, and corporations. The collaborative interventions are framed here in terms of four overarching categories of action: direct service delivery, research, training, and advocacy. This case study exemplifies the role of psychiatrists working in low-resource settings as public health program implementers and as members of multidisciplinary teams. (Harv Rev Psychiatry 2012;20:68–77.) PMID:22335184

  6. Short- and long-term responses and recovery of mussels Mytilus edulis exposed to heavy fuel oil no. 6 and styrene.

    PubMed

    Ruiz, Pamela; Ortiz-Zarragoitia, Maren; Orbea, Amaia; Vingen, Sjur; Hjelle, Anne; Baussant, Thierry; Cajaraville, Miren P

    2014-07-01

    Biomarkers have the potential to be used to assess the impact of anthropogenic discharges in marine waters. We have used a suite of biomarkers spanning from enzymatic to histopathological alterations and general stress responses to assess the short- and long-term impact on mussels Mytilus edulis of heavy fuel oil no. 6 and styrene. Mussels were exposed for 5 months, with a refilling of the exposure system, to a water soluble fraction of heavy fuel and, then, kept for a month in clean water for recovery. In a second experiment, mussels were exposed to styrene for 19 days and maintained in clean water for up to 4 months. Chemical body tissue levels reflected the weathering processes of these compounds. Acyl-CoA oxidase activity was induced in oil-exposed mussels after refilling, whereas styrene inhibited it after 19 days of exposure and after 2 weeks in clean water. Gamete development and alkali-labile phosphate levels suggest that neither oil nor styrene behaved as endocrine disruptors. Neutral red retention time was lower in treated groups than in controls. Lysosomal membrane stability was significantly reduced in exposed groups and recovered after withdrawal of oil but not after removal of styrene. Neither oil nor styrene exposure affected the condition index except for the reduction seen in mussels exposed to oil for 1 month. Biomarker response index discriminated exposed mussels, which showed higher values, and returned to control levels after recovery. Results obtained from these pilot experiments can help to identify relevant monitoring tools to assess the impact of oil and chemicals in marine spill scenarios.

  7. Long-term persistence of systemic and mucosal immune response to HPV-16/18 AS04-adjuvanted vaccine in preteen/adolescent girls and young women.

    PubMed

    Petäjä, Tiina; Pedersen, Court; Poder, Airi; Strauss, Gitte; Catteau, Gregory; Thomas, Florence; Lehtinen, Matti; Descamps, Dominique

    2011-11-01

    Vaccination against oncogenic human papillomavirus (HPV) types is one key intervention for cervical cancer prevention. This follow-up study assessed the persistence of the systemic and mucosal immune responses together with the safety profile of the HPV-16/18 AS04-adjuvanted vaccine administered to young women aged 10-25 years. Serum and cervicovaginal secretion (CVS) samples were collected at prespecified time-points during the 48-month follow-up period. Anti-HPV-16/18 antibody levels in serum and CVS were measured by enzyme-linked immunosorbent assay (ELISA). At Month 48, all subjects remained seropositive for serum anti-HPV-16 and -18 antibodies. As previously observed, anti-HPV-16 and -18 antibodies levels (ELISA Units/mL) were higher in subjects vaccinated at the age of 10-14 years (2862.2 and 940.8) compared to subjects vaccinated at the age of 15-25 years (1186.2 and 469.8). Moreover, anti-HPV-16 and -18 antibodies in CVS were still detectable for subjects aged 15-25 years (84.1% and 69.7%, respectively). There was a strong correlation between serum and CVS anti-HPV-16 and -18 antibodies levels (correlation coefficients = 0.84 and 0.90 at Month 48, respectively) supporting the hypothesis of transudation or exudation of serum immunoglobulin G antibodies through the cervical epithelium. The HPV-16/18 AS04-adjuvanted vaccine had a clinically acceptable safety profile. In conclusion, this follow-up study shows that the HPV-16/18 AS04-adjuvanted vaccine administered to preteen/adolescents girls and young women induces long-term systemic and mucosal immune response and has a clinically acceptable safety profile up to 4 years after the first vaccine dose. PMID:21190190

  8. Risk factors, CD4 long-term evolution and mortality of HIV-infected patients who persistently maintain low CD4 counts, despite virological response to HAART.

    PubMed

    Pacheco, Yolanda M; Jarrín, Inmaculada; Del Amo, Julia; Moreno, Santiago; Iribarren, José A; Viciana, Pompeyo; Parra, Jorge; Gomez-Sirvent, Juan L; Gutierrez, Félix; Blanco, José R; Vidal, Francesc; Leal, Manuel

    2009-11-01

    A proportion of HIV-patients does not normally restore their CD4 counts despite virological response to HAART. Those whose CD4 counts persistently remain closed to the critical threshold for opportunistic infections deserve special interest. To study the risk factors, the long-term CD4 counts evolution, and the risk of death of patients who persistently maintain low CD4 counts, despite virological response to HAART, within a multicenter, hospital-based cohort study. A total of 147 patients were selected from CoRIS-MD and classified into a "Low-Group" or a "High-Group", depending on their CD4 counts after two-years of effective HAART (threshold 250 cells/microL). Associated risk factors were analysed by logistic regression, the CD4 dynamics were evaluated over a total period of 7.70 years (IQR, 6.70-9.00), and mortality was estimated by Cox proportional hazard. A total of 40 patients (27%) were classified into the "Low-Group". The odds ratio for this group increased with age, being 4.56 (2.23-9.33) for over 40, and was also higher among IDU, 3.63 (1.04-12.68). Six years thereafter, among these patients, only a 30% exceeded 350 CD4 cells/microL and a 12% exceeded 500 CD4 cells/microL. Furthermore, the "Low-Group" had a death rate of 2.42 per 100 persons/year (95%CI, 1.01-5.81), although once adjusted by age the estimates were no longer significant [4.14 (0.87-19.72)]. Our results suggest that those HIV patients who have not overcome the critical threshold of 250 CD4 cells/microL after a two years period of virologically effective HAART do persist with the aforementioned failure of CD4 restoration for a much longer time.

  9. Long-term response to first-line trabectedin in an elderly female patient with a metastatic leiomyosarcoma unfit for anthracycline

    PubMed Central

    Maruzzo, Marco; Brunello, Antonella; Diminutto, Alberto; Rastrelli, Marco

    2016-01-01

    Systemic chemotherapy comprising anthracycline monotherapy is the standard regimen for metastatic soft tissue sarcomas, particularly leiomyosarcomas, which have limited sensitivity to ifosfamide. However, the optimal chemotherapy regimen for elderly patients, especially those considered unfit for anthracyclines, is undefined. Trabectedin is a potent marine-derived antineoplastic drug with documented activity in liposarcomas and leiomyosarcomas. It is registered in Europe for the treatment of adult patients with advanced soft tissue sarcoma, after failure of anthracyclines and ifosfamide, or who are unsuited to receive these agents. We report the long-term response to first-line trabectedin therapy in an elderly patient with metastatic leiomyosarcoma unfit for standard therapy. A 66-year-old woman underwent resection of a pelvic epithelioid leiomyosarcoma with positive margins in December 2002, followed by postoperative radiotherapy. In February 2012, she was diagnosed with multiple lung lesions and local relapse in the pelvis. As she was considered unsuitable for both anthracycline and ifosfamide because of cardiovascular comorbidities and because she was highly anxious at the prospect of developing alopecia, vomiting, and fatigue, we commenced treatment with trabectedin at 75% of the standard dose of 1.5 mg/m2 every 3 weeks. Treatment was well tolerated, and the patient continued treatment for 25 cycles, with disease stabilization according to the RECIST criteria and a partial response according to the Choi criteria. Disease progression was observed in November 2013 and the patient died 20 months after the diagnosis of metastases. Trabectedin may represent an alternative option for highly selected elderly patients with metastatic sarcoma and unfit for anthracyclines; careful monitoring of toxicities is strongly recommended. PMID:26629769

  10. [Taiwan long-term care insurance and the evolution of long-term care in Japan].

    PubMed

    Huang, Hui-Wen; Liu, Shu-Hui; Pai, Yu-Chu

    2010-08-01

    The proportion of elderly (65 years of age and older) in Taiwan has exceeded 10% since 2008. With more elderly, the number of patients suffering from dementia and disabilities has also been rapidly increasing. Japan also has been facing increasing demand for long-term care due to an aging society. Prior to 2000, social welfare programs in Japan, working to cope with changing needs, typically provided insufficient services, and geriatric patients were hospitalized unnecessarily, wasting medical resources and causing undue patient hardship. In response, Japan launched its long-term care insurance program in April 2000. Under the program, city, town and village-based organizations should take responsibility for providing care to the elderly in their place of residence. The program significantly improved previous financial shortfalls and long-term care supply and demand has been met by existing social welfare organization resources. In Taiwan, the provision of long-term care by county / city authorities has proven inconsistent, with performance deemed poor after its first decade of long-term care operations. Service was found to be affected by differences in available resources and insufficient long-term care administration. The cultures of Taiwan and Japan are similar. The authors visited the Japan Long-Term Care Insurance Institute in August 2009. Main issues involved in the implementation and evolution of the Japan long-term Care Insurance are reported on in this paper. We hope such may be useful information to those working to develop long-term care programs in Taiwan. PMID:20661859

  11. Phenology of species interactions in response to climate change: two case studies of plant-pollinator interactions using long-term data

    NASA Astrophysics Data System (ADS)

    McKinney, A. M.; Inouye, D. W.

    2012-12-01

    Climate change may alter the temporal overlap among interacting taxa with potential demographic consequences. Evidence of mistimed interactions in response to climate change, especially between plants and pollinators, is mixed, and few long-term datasets exist to test for changes in synchrony. Furthermore, advancements in flowering driven by climate change are especially pronounced at higher latitudes, so that migratory pollinators from lower latitudes may increasingly arrive at breeding grounds after the appearance of floral resources. We explored long-term shifts in phenological synchrony in two plant-pollinator systems:1) syrphid fly and flowering phenology in the Colorado Rocky Mountains, USA (1992-2011) and 2) hummingbird arrival relative to onset of early-season nectar resources in the Colorado Rocky Mountains (1975-2011) and the Santa Catalina Mountains, Arizona, USA (1984-2010). We investigated the abiotic cues associated with the phenology of the activity period of syrphid flies and their floral resources, including degree days above freezing, precipitation, and timing of snowmelt as potential explanatory variables. Timing of snowmelt was the best predictor of the onset of flowering and syrphid emergence. Snowmelt was also the best predictor of the end of flowering, while temperature and precipitation best predicted the end of the syrphid period. Both the onset and end of flowering advanced more rapidly than syrphids in response to earlier snowmelt. These different rates of phenological advancement resulted in increased temporal overlap between the flower and syrphid community in years of early snowmelt, because of longer flowering and fly activity periods during these years. If snowmelt continues to advance, temporal overlap between syrphids and their floral resources is therefore likely to increase. This case study shows that the phenology of interacting taxa may respond differently to climate cues, but that this does not necessarily lead to phenological

  12. miR-155 Drives Metabolic Reprogramming of ER+ Breast Cancer Cells Following Long-Term Estrogen Deprivation and Predicts Clinical Response to Aromatase Inhibitors.

    PubMed

    Bacci, Marina; Giannoni, Elisa; Fearns, Antony; Ribas, Ricardo; Gao, Qiong; Taddei, Maria Letizia; Pintus, Gianfranco; Dowsett, Mitch; Isacke, Clare M; Martin, Lesley-Ann; Chiarugi, Paola; Morandi, Andrea

    2016-03-15

    Aromatase inhibitors (AI) have become the first-line endocrine treatment of choice for postmenopausal estrogen receptor-positive (ER(+)) breast cancer patients, but resistance remains a major challenge. Metabolic reprogramming is a hallmark of cancer and may contribute to drug resistance. Here, we investigated the link between altered breast cancer metabolism and AI resistance using AI-resistant and sensitive breast cancer cells, patient tumor samples, and AI-sensitive human xenografts. We found that long-term estrogen deprivation (LTED), a model of AI resistance, was associated with increased glycolysis dependency. Targeting the glycolysis-priming enzyme hexokinase-2 (HK2) in combination with the AI, letrozole, synergistically reduced cell viability in AI-sensitive models. Conversely, MCF7-LTED cells, which displayed a high degree of metabolic plasticity, switched to oxidative phosphorylation when glycolysis was impaired. This effect was ER dependent as breast cancer cells with undetectable levels of ER failed to exhibit metabolic plasticity. MCF7-LTED cells were also more motile than their parental counterparts and assumed amoeboid-like invasive abilities upon glycolysis inhibition with 2-deoxyglucose (2-DG). Mechanistic investigations further revealed an important role for miR-155 in metabolic reprogramming. Suppression of miR-155 resulted in sensitization of MCF7-LTED cells to metformin treatment and impairment of 2-DG-induced motility. Notably, high baseline miR-155 expression correlated with poor response to AI therapy in a cohort of ER(+) breast cancers treated with neoadjuvant anastrozole. These findings suggest that miR-155 represents a biomarker potentially capable of identifying the subset of breast cancers most likely to adapt to and relapse on AI therapy. PMID:26795347

  13. Brief embryonic cadmium exposure induces a stress response and cell death in the developing olfactory system followed by long-term olfactory deficits in juvenile zebrafish

    SciTech Connect

    Blechinger, Scott R.; Kusch, Robin C.; Haugo, Kristine; Matz, Carlyn; Chivers, Douglas P.; Krone, Patrick H.

    2007-10-01

    The toxic effects of cadmium and other metals have been well established. A primary target of these metals is known to be the olfactory system, and fish exposed to a number of different waterborne metals display deficiencies in olfaction. Importantly, exposure over embryonic/larval development periods can cause deficits in chemosensory function in juvenile fish, but the specific cell types affected are unknown. We have previously characterized a transgenic zebrafish strain expressing the green fluorescent protein (eGFP) gene linked to the hsp70 gene promoter, and shown it to be a useful tool for examining cell-specific toxicity in living embryos and larvae. Here we show that the hsp70/eGFP transgene is strongly and specifically upregulated within the olfactory sensory neurons (OSNs) of transgenic zebrafish larvae following a brief 3-h exposure to water-borne cadmium. This molecular response was closely correlated to an endpoint for tissue damage within the olfactory placode, namely cell death. Furthermore, cadmium-induced olfactory cytotoxicity in zebrafish larvae gives rise to more permanent effects. Juvenile zebrafish briefly exposed to cadmium during early larval development display deficits in olfactory-dependent predator avoidance behaviors 4-6 weeks after a return to clean water. Lateral line neuromasts of exposed zebrafish larvae also activate both the endogenous hsp70 gene and the hsp70/eGFP transgene. The data reveal that even a very brief exposure period that gives rise to cell death within the developing olfactory placode results in long-term deficits in olfaction, and that hsp70/eGFP may serve as an effective indicator of sublethal cadmium exposure in sensory cells.

  14. Evaluation of the Long-Term Anti-Human Papillomavirus 6 (HPV6), 11, 16, and 18 Immune Responses Generated by the Quadrivalent HPV Vaccine

    PubMed Central

    Saah, Alfred; Munk, Christian; Tryggvadottir, Laufey; Enerly, Espen; Hortlund, Maria; Sigurdardottir, Lara G.; Vuocolo, Scott; Kjaer, Susanne K.; Dillner, Joakim

    2015-01-01

    This quadrivalent human papillomavirus (qHPV) (HPV6, -11, -16, and -18) vaccine long-term follow-up (LTFU) study is an ongoing extension of a pivotal clinical study (FUTURE II) taking place in the Nordic region. The LTFU study was designed to evaluate the effectiveness, immunogenicity, and safety of the qHPV vaccine (Gardasil) for at least 10 years following completion of the base study. The current report presents immunogenicity data from testing samples of the year 5 LTFU visit (approximately 9 years after vaccination). FUTURE II vaccination arm subjects, who consented to being followed in the LTFU, donated serum at regular intervals and in 2012. Anti-HPV6, -11, -16, and -18 antibodies were detected by the competitive Luminex immunoassay (cLIA), and in addition, serum samples from 2012 were analyzed by the total IgG Luminex immunoassay (LIA) (n = 1,598). cLIA geometric mean titers (GMTs) remained between 70% and 93% of their month 48 value depending on HPV type. For all HPV types, the lower bound of the 95% confidence interval (CI) for the year 9 GMTs remained above the serostatus cutoff value. The proportion of subjects who remained seropositive based on the IgG LIA was higher than the proportion based on cLIA, especially for anti-HPV18. As expected, the anti-HPV serum IgG and cLIA responses were strongly correlated for all HPV types. Anti-HPV GMTs and the proportion of vaccinated individuals who are seropositive remain high for up to 9 years of follow-up after vaccination. PMID:26084514

  15. Response of intertidal macrobenthic communities to long term human induced changes in the Eo estuary (Asturias, Spain): implications for environmental management.

    PubMed

    de Paz, L; Neto, J M; Marques, J C; Laborda, A J

    2008-08-01

    Long term macrobenthos data together with physical habitat parameters were analysed to investigate spatial and temporal changes at an estuary under different anthropogenic pressures, mainly increasing shellfish farming. The aim was to assess the possible impacts of these pressures on the macrobenthic communities by comparing a period before and after changes in these pressures. Benthic samples were seasonally collected in 1990 (before major anthropogenic changes), 2000 and 2005 at the same sampling stations located on three different habitats in the Eo estuary (Northern Spanish coast). Multivariate and univariate methods were used to assess spatial variability of benthic assemblages and to compare community changes over time. Data from 1990 was assumed as the reference situation to appraise the subsequent impacts. We observed a significant spatial variability of the benthic assemblages in the system as a function of habitat heterogeneity in relation to sediment composition, presence/absence and density of seagrasses, and hydrodynamic regime. Changes were detected in the community composition at all sites during this 15 year period. The extent of changes was related to initial community conditions, rather than the intensity of the pressure. The results suggest that the responses of the benthic communities to human induced perturbations occurring in the system are largely dependent on its intrinsic buffer capacity, and that these communities have been able to cope with an increasing environmental stress (organic enrichment). In conclusion, to keep shellfish farming at a sustainable level without undesirable impacts, the disturbance intensity must be kept below the system carrying capacity. This will allow natural communities to cope with pressures and thus avoid further deterioration in ecological quality.

  16. Response to long-term growth hormone therapy in patients affected by RASopathies and growth hormone deficiency: Patterns of growth, puberty and final height data.

    PubMed

    Tamburrino, Federica; Gibertoni, Dino; Rossi, Cesare; Scarano, Emanuela; Perri, Annamaria; Montanari, Francesca; Fantini, Maria Pia; Pession, Andrea; Tartaglia, Marco; Mazzanti, Laura

    2015-11-01

    RASopathies are developmental disorders caused by heterozygous germline mutations in genes encoding proteins in the RAS-MAPK signaling pathway. Reduced growth is a common feature. Several studies generated data on growth, final height (FH), and height velocity (HV) after growth hormone (GH) treatment in patients with these disorders, particularly in Noonan syndrome, the most common RASopathy. These studies, however, refer to heterogeneous cohorts in terms of molecular information, GH status, age at start and length of therapy, and GH dosage. This work reports growth data in 88 patients affected by RASopathies with molecularly confirmed diagnosis, together with statistics on body proportions, pubertal pattern, and FH in 33, including 16 treated with GH therapy for proven GH deficiency. Thirty-three patients showed GH deficiency after pharmacological tests, and were GH-treated for an average period of 6.8 ± 4.8 years. Before starting therapy, HV was -2.6 ± 1.3 SDS, and mean basal IGF1 levels were -2.0 ± 1.1 SDS. Long-term GH therapy, starting early during childhood, resulted in a positive height response compared with untreated patients (1.3 SDS in terms of height-gain), normalizing FH for Ranke standards but not for general population and Target Height. Pubertal timing negatively affected pubertal growth spurt and FH, with IGF1 standardized score increased from -2.43 to -0.27 SDS. During GH treatment, no significant change in bone age velocity, body proportions, or cardiovascular function was observed.

  17. Cellular immune response experiment MA-031

    NASA Technical Reports Server (NTRS)

    Criswell, B. S.

    1976-01-01

    Significant changes in phytohemagglutinin (PHA) lymphocytic responsiveness occurred in the cellular immune response of three astronauts during the 9 day flight of the Apollo Soyuz Test Project. Parameters studied were white blood cell concentrations, lymphocyte numbers, B- and T-lymphocyte distributions in peripheral blood, and lymphocyte responsiveness to PHA, pokeweed mitogen, Concanavalin A, and influenza virus antigen.

  18. Professionalism in Long-Term Care Settings

    ERIC Educational Resources Information Center

    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…

  19. Long-Term Quiescent Fibroblast Cells Transit into Senescence

    PubMed Central

    Marthandan, Shiva; Priebe, Steffen; Hemmerich, Peter; Klement, Karolin; Diekmann, Stephan

    2014-01-01

    Cellular senescence is described to be a consequence of telomere erosion during the replicative life span of primary human cells. Quiescence should therefore not contribute to cellular aging but rather extend lifespan. Here we tested this hypothesis and demonstrate that cultured long-term quiescent human fibroblasts transit into senescence due to similar cellular mechanisms with similar dynamics and with a similar maximum life span as proliferating controls, even under physiological oxygen conditions. Both, long-term quiescent and senescent fibroblasts almost completely fail to undergo apoptosis. The transition of long-term quiescent fibroblasts into senescence is also independent of HES1 which protects short-term quiescent cells from becoming senescent. Most significantly, DNA damage accumulates during senescence as well as during long-term quiescence at physiological oxygen levels. We suggest that telomere-independent, potentially maintenance driven gradual induction of cellular senescence during quiescence is a counterbalance to tumor development. PMID:25531649

  20. CECILIA, a versatile research tool for cellular responses to gravity.

    PubMed

    Braucker, Richard; Machemer, Hans

    2002-01-01

    We describe a centrifuge designed and constructed according to current demands for a versatile instrument in cellular gravitational research, in particular protists (ciliates, flagellates). The instrument (called CECILIA, centrifuge for ciliates) is suited for videomonitoring, videorecording, and quantitative evaluation of data from large numbers of swimming cells in a ground-based laboratory or in a drop tower/drop shaft under microgravity conditions. The horizontal rotating platform holds up to six 8mm-camcorders and six chambers holding the experimental cells. Under hypergravity conditions (up to 15 g) chambers can be rotated about 2 axes to adjust the swimming space at right angles or parallel to the resulting gravity vector. Evaluations of cellular responses to central acceleration-- in the presence of gravitational 1 g--are used for extrapolation of cellular behaviour under hypogravity conditions. CECILIA is operated and monitored by computer using a custom-made software. Times and slopes of rising and decreasing acceleration, values and and quality of steady acceleration are supervised online. CECILIA can serve as an on-ground research instrument for precursor investigations of the behaviour of ciliates and flagellates under microgravity conditions such as long-term experiments in the International Space Station.

  1. Making the Pack the Hero, Tobacco Industry Response to Marketing Restrictions in the UK: Findings from a Long-Term Audit

    ERIC Educational Resources Information Center

    Moodie, Crawford; Hastings, Gerard B.

    2011-01-01

    The Tobacco Advertising and Promotion Act (TAPA), introduced between 2003 and 2005 in the UK, prohibits all tobacco advertising, promotion and sponsorship. Packaging, however, is not covered in the Act. Two strands of a long-term audit (trade press review and panel of smokers) are examined to monitor change in tobacco packaging from January 2002…

  2. Effects of postimplantation systemic inflammatory response on long-term clinical outcomes after endovascular aneurysm repair of an abdominal aortic aneurysm

    PubMed Central

    Kwon, Hyunwook; Ko, Gi-Young; Kim, Min-Ju; Han, Youngjin; Noh, Minsu; Kwon, Tae-Won; Cho, Yong-Pil

    2016-01-01

    Abstract The aim of this study was to determine the association between postimplantation syndrome (PIS) and long-term clinical outcomes after elective endovascular aneurysm repair (EVAR) of an abdominal aortic aneurysm. In this single-center, observational cohort study, a total of 204 consecutive patients undergoing EVAR were included. Primary outcome was long-term mortality from any cause; secondary outcomes included long-term mortality, systemic or implant-related complications, and secondary therapeutic procedures. The diagnosis of PIS was established in 64 patients (31.4%). PIS patients were more likely to receive woven polyester endografts and have a longer postoperative hospital stay and lower incidence of type II endoleaks. In multivariate analysis, PIS was significantly associated with a decreased risk of developing type II endoleaks (P = 0.044). During follow-up period of 44 months, clinical outcomes showed no significant differences in mortality (P = 0.876), systemic (P = 0.668), or implant-related complications (P = 0.847), although rates of secondary therapeutic procedure were significantly higher in non-PIS patients (P = 0.037). The groups had similar rates of overall survival (P = 0.761) and other clinical outcomes (P = 0.562). Patients with and without PIS had similar long-term overall survival rates and other clinical outcomes. PIS was beneficial in preventing type II endoleaks during postoperative period. PMID:27512875

  3. Response to Nadler's Commentary on Arch and Craske's (2011) "Addressing Relapse in Cognitive Behavioral Therapy for Panic Disorder: Methods for Optimizing Long-Term Treatment Outcomes"

    ERIC Educational Resources Information Center

    Arch, Joanna J.; Craske, Michelle G.

    2012-01-01

    Nadler (this issue), in his commentary of our article, "Addressing Relapse in Cognitive Behavioral Therapy for Panic Disorder: Methods for Optimizing Long-Term Treatment Outcomes" (Arch & Craske, 2011), argues that we misrepresent the role of panic attacks within learning theory and overlook cognitive treatment targets. He presents several case…

  4. Effects of postimplantation systemic inflammatory response on long-term clinical outcomes after endovascular aneurysm repair of an abdominal aortic aneurysm.

    PubMed

    Kwon, Hyunwook; Ko, Gi-Young; Kim, Min-Ju; Han, Youngjin; Noh, Minsu; Kwon, Tae-Won; Cho, Yong-Pil

    2016-08-01

    The aim of this study was to determine the association between postimplantation syndrome (PIS) and long-term clinical outcomes after elective endovascular aneurysm repair (EVAR) of an abdominal aortic aneurysm.In this single-center, observational cohort study, a total of 204 consecutive patients undergoing EVAR were included. Primary outcome was long-term mortality from any cause; secondary outcomes included long-term mortality, systemic or implant-related complications, and secondary therapeutic procedures.The diagnosis of PIS was established in 64 patients (31.4%). PIS patients were more likely to receive woven polyester endografts and have a longer postoperative hospital stay and lower incidence of type II endoleaks. In multivariate analysis, PIS was significantly associated with a decreased risk of developing type II endoleaks (P = 0.044). During follow-up period of 44 months, clinical outcomes showed no significant differences in mortality (P = 0.876), systemic (P = 0.668), or implant-related complications (P = 0.847), although rates of secondary therapeutic procedure were significantly higher in non-PIS patients (P = 0.037). The groups had similar rates of overall survival (P = 0.761) and other clinical outcomes (P = 0.562).Patients with and without PIS had similar long-term overall survival rates and other clinical outcomes. PIS was beneficial in preventing type II endoleaks during postoperative period. PMID:27512875

  5. Long-term sensory stimulation therapy improves hand function and restores cortical responsiveness in patients with chronic cerebral lesions. Three single case studies

    PubMed Central

    Kattenstroth, Jan-Christoph; Kalisch, Tobias; Peters, Sören; Tegenthoff, Martin; Dinse, Hubert R.

    2012-01-01

    Rehabilitation of sensorimotor impairment resulting from cerebral lesion (CL) utilizes task specific training and massed practice to drive reorganization and sensorimotor improvement due to induction of neuroplasticity mechanisms. Loss of sensory abilities often complicates recovery, and thus the individual's ability to use the affected body part for functional tasks. Therefore, the development of additional and alternative approaches that supplement, enhance, or even replace conventional training procedures would be advantageous. Repetitive sensory stimulation protocols (rSS) have been shown to evoke sensorimotor improvements of the affected limb in patients with chronic stroke. However, the possible impact of long-term rSS on sensorimotor performance of patients with CL, where the incident dated back many years remains unclear. The particular advantage of rSS is its passive nature, which does not require active participation of the subjects. Therefore, rSS can be applied in parallel to other occupations, making the intervention easier to implement and more acceptable to the individual. Here we report the effects of applying rSS for 8, 36, and 76 weeks to the paretic hand of three long-term patients with different types of CL. Different behavioral tests were used to assess sensory and/or sensorimotor performance of the upper extremities prior, after, and during the intervention. In one patient, the impact of long-term rSS on restoration of cortical activation was investigated by recording somatosensory evoked potentials (SEP). After long-term rSS all three patients showed considerable improvements of their sensory and motor abilities. In addition, almost normal evoked potentials could be recorded after rSS in one patient. Our data show that long-term rSS applied to patients with chronic CL can improve tactile and sensorimotor functions, which, however, developed in some cases only after many weeks of stimulation, and continued to further improve on a time scale of

  6. Long-term sensory stimulation therapy improves hand function and restores cortical responsiveness in patients with chronic cerebral lesions. Three single case studies.

    PubMed

    Kattenstroth, Jan-Christoph; Kalisch, Tobias; Peters, Sören; Tegenthoff, Martin; Dinse, Hubert R

    2012-01-01

    Rehabilitation of sensorimotor impairment resulting from cerebral lesion (CL) utilizes task specific training and massed practice to drive reorganization and sensorimotor improvement due to induction of neuroplasticity mechanisms. Loss of sensory abilities often complicates recovery, and thus the individual's ability to use the affected body part for functional tasks. Therefore, the development of additional and alternative approaches that supplement, enhance, or even replace conventional training procedures would be advantageous. Repetitive sensory stimulation protocols (rSS) have been shown to evoke sensorimotor improvements of the affected limb in patients with chronic stroke. However, the possible impact of long-term rSS on sensorimotor performance of patients with CL, where the incident dated back many years remains unclear. The particular advantage of rSS is its passive nature, which does not require active participation of the subjects. Therefore, rSS can be applied in parallel to other occupations, making the intervention easier to implement and more acceptable to the individual. Here we report the effects of applying rSS for 8, 36, and 76 weeks to the paretic hand of three long-term patients with different types of CL. Different behavioral tests were used to assess sensory and/or sensorimotor performance of the upper extremities prior, after, and during the intervention. In one patient, the impact of long-term rSS on restoration of cortical activation was investigated by recording somatosensory evoked potentials (SEP). After long-term rSS all three patients showed considerable improvements of their sensory and motor abilities. In addition, almost normal evoked potentials could be recorded after rSS in one patient. Our data show that long-term rSS applied to patients with chronic CL can improve tactile and sensorimotor functions, which, however, developed in some cases only after many weeks of stimulation, and continued to further improve on a time scale of