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Sample records for long-term cellular responses

  1. A novel model for studies of blood-mediated long-term responses to cellular transplants

    PubMed Central

    Lindblom, Susanne; Hong, Jaan; Nilsson, Bo; Korsgren, Olle; Ronquist, Gunnar

    2015-01-01

    Aims Interaction between blood and bio-surfaces is important in many medical fields. With the aim of studying blood-mediated reactions to cellular transplants, we developed a whole-blood model for incubation of small volumes for up to 48 h. Methods Heparinized polyvinyl chloride tubing was cut in suitable lengths and sealed to create small bags. Multiple bags, with fresh venous blood, were incubated attached to a rotating wheel at 37°C. Physiological variables in blood were monitored: glucose, blood gases, mono- and divalent cations and chloride ions, osmolality, coagulation (platelet consumption, thrombin-antithrombin complexes (TAT)), and complement activation (C3a and SC5b-9), haemolysis, and leukocyte viability. Results Basic glucose consumption was high. Glucose depletion resulted in successive elevation of extracellular potassium, while sodium and calcium ions decreased due to inhibition of energy-requiring ion pumps. Addition of glucose improved ion balance but led to metabolic acidosis. To maintain a balanced physiological environment beyond 6 h, glucose and sodium hydrogen carbonate were added regularly based on analyses of glucose, pH, ions, and osmotic pressure. With these additives haemolysis was prevented for up to 72 h and leukocyte viability better preserved. Despite using non-heparinized blood, coagulation and complement activation were lower during long-term incubations compared with addition of thromboplastin and collagen. Conclusion A novel whole-blood model for studies of blood-mediated responses to a cellular transplant is presented allowing extended observations for up to 48 h and highlights the importance of stringent evaluations and adjustment of physiological conditions. PMID:25322825

  2. 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.

  3. 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. PMID:27117858

  4. 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

  5. 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

  6. Cellular responses of microcolonial rock fungi to long-term desiccation and subsequent rehydration

    PubMed Central

    Gorbushina, A.A.; Kotlova, E.R.; Sherstneva, O.A.

    2008-01-01

    Melanised rock-inhabiting fungi are astonishingly resistant to environmental stresses. Also known as micro-colonial fungi (MCF), they are ubiquitous and even colonise bare rocks in deserts. To survive in nutrient poor and extremely stressful conditions, MCF have reduced morphogenetic complexity to a minimum, and rely on a broad spectrum of stress protection mechanisms. Although visual signs of carotenoid presence are masked by heavily melanised black cell-walls, we were able to isolate and characterise a variety of carotenoids (ß-carotene, ζ-carotene, phytoene, torularhodin and torulene) in the rock-inhabiting, relatively fast-growing strain A95. The desiccation/rehydration stress response was used to measure the ability of A95 to adapt to slow or fast changes in external conditions. Revival of MCF after prolonged desiccation and rehydration was documented by biochemical (analyses of lipids and protective pigments), cultivation, and microscopic methods. Survival of MCF is enhanced when desiccation is rapid and mycostasis is instant rather than following prolonged periods of low metabolic activity. PMID:19287531

  7. 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.

  8. Assessment of cellular responses after short- and long-term exposure to silver nanoparticles in human neuroblastoma (SH-SY5Y) and astrocytoma (D384) cells.

    PubMed

    Coccini, Teresa; Manzo, Luigi; Bellotti, Vittorio; De Simone, Uliana

    2014-01-01

    Silver nanoparticle (AgNP, 20 nm) neurotoxicity was evaluated by an integrated in vitro testing protocol employing human cerebral (SH-SY5Y and D384) cell lines. Cellular response after short-term (4-48 h, 1-100 μ g/ml) and prolonged exposure (up to 10 days, 0.5-50 μ g/ml) to AgNP was assessed by MTT, calcein-AM/PI, clonogenic tests. Pulmonary A549 cells were employed for data comparison along with silver nitrate as metal ionic form. Short-term data: (i) AgNP produced dose- and time-dependent mitochondrial metabolism changes and cell membrane damage (effects starting at 25 μ g/ml after 4 h: EC50s were 40.7 ± 2.0 and 49.5 ± 2.1 μ g/ml for SH-SY5Y and D384, respectively). A549 were less vulnerable; (ii) AgNP doses of ≤ 18 μ g/ml were noncytotoxic; (iii) AgNO3 induced more pronounced effects compared to AgNP on cerebral cells. Long-term data: (i) low AgNP doses (≤ 1 μ g/ml) compromised proliferative capacity of all cell types (cell sensibility: SHSY5Y > A549 > D384). Colony number decrease in SH-SY5Y and D384 was 50% and 25%, respectively, at 1 μ g/ml, and lower dose (0.5 μ g/ml) was significantly effective towards SH-SY5Y and pulmonary cells; (ii) cell proliferation activity was more affected by AgNO3 than AgNPs. In summary, AgNP-induced cytotoxic effects after short-term and prolonged exposure (even at low doses) were evidenced regardless of cell model types. PMID:24693232

  9. Assessment of Cellular Responses after Short- and Long-Term Exposure to Silver Nanoparticles in Human Neuroblastoma (SH-SY5Y) and Astrocytoma (D384) Cells

    PubMed Central

    Manzo, Luigi; Bellotti, Vittorio

    2014-01-01

    Silver nanoparticle (AgNP, 20 nm) neurotoxicity was evaluated by an integrated in vitro testing protocol employing human cerebral (SH-SY5Y and D384) cell lines. Cellular response after short-term (4–48 h, 1–100 μg/ml) and prolonged exposure (up to 10 days, 0.5–50 μg/ml) to AgNP was assessed by MTT, calcein-AM/PI, clonogenic tests. Pulmonary A549 cells were employed for data comparison along with silver nitrate as metal ionic form. Short-term data: (i) AgNP produced dose- and time-dependent mitochondrial metabolism changes and cell membrane damage (effects starting at 25 μg/ml after 4 h: EC50s were 40.7 ± 2.0 and 49.5 ± 2.1 μg/ml for SH-SY5Y and D384, respectively). A549 were less vulnerable; (ii) AgNP doses of ≤ 18 μg/ml were noncytotoxic; (iii) AgNO3 induced more pronounced effects compared to AgNP on cerebral cells. Long-term data: (i) low AgNP doses (≤1 μg/ml) compromised proliferative capacity of all cell types (cell sensibility: SHSY5Y > A549 > D384). Colony number decrease in SH-SY5Y and D384 was 50% and 25%, respectively, at 1 μg/ml, and lower dose (0.5 μg/ml) was significantly effective towards SH-SY5Y and pulmonary cells; (ii) cell proliferation activity was more affected by AgNO3 than AgNPs. In summary, AgNP-induced cytotoxic effects after short-term and prolonged exposure (even at low doses) were evidenced regardless of cell model types. PMID:24693232

  10. 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

  11. 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...

  12. 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

  13. Long-term effect of PROLI/NO on cellular proliferation and phenotype after arterial injury.

    PubMed

    Bahnson, Edward S M; Vavra, Ashley K; Flynn, Megan E; Vercammen, Janet M; Jiang, Qun; Schwartz, Amanda R; Kibbe, Melina R

    2016-01-01

    Vascular interventions are associated with high failure rates from restenosis secondary to negative remodeling and neointimal hyperplasia. Periadventitial delivery of nitric oxide (NO) inhibits neointimal hyperplasia, preserving lumen patency. With the development of new localized delivery vehicles, NO-based therapies remain a promising therapeutic avenue for the prevention of restenosis. While the time course of events during neointimal development has been well established, a full characterization of the impact of NO donors on the cells that comprise the arterial wall has not been performed. Thus, the aim of our study was to perform a detailed assessment of proliferation, cellularity, inflammation, and phenotypic cellular modulation in injured arteries treated with the short-lived NO donor, PROLI/NO. PROLI/NO provided durable inhibition of neointimal hyperplasia for 6 months after arterial injury. PROLI/NO inhibited proliferation and cellularity in the media and intima at all of the time points studied. However, PROLI/NO caused an increase in adventitial proliferation at 2 weeks, resulting in increased cellularity at 2 and 8 weeks compared to injury alone. PROLI/NO promoted local protein S-nitrosation and increased local tyrosine nitration, without measurable systemic effects. PROLI/NO predominantly inhibited contractile smooth muscle cells in the intima and media, and had little to no effect on vascular smooth muscle cells or myofibroblasts in the adventitia. Finally, PROLI/NO caused a delayed and decreased leukocyte infiltration response after injury. Our results show that a short-lived NO donor exerts durable effects on proliferation, phenotype modulation, and inflammation that result in long-term inhibition of neointimal hyperplasia. PMID:26627935

  14. 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

  15. Synthetic amyloid-beta oligomers impair long-term memory independently of cellular prion protein.

    PubMed

    Balducci, Claudia; Beeg, Marten; Stravalaci, Matteo; Bastone, Antonio; Sclip, Alessandra; Biasini, Emiliano; Tapella, Laura; Colombo, Laura; Manzoni, Claudia; Borsello, Tiziana; Chiesa, Roberto; Gobbi, Marco; Salmona, Mario; Forloni, Gianluigi

    2010-02-01

    Inability to form new memories is an early clinical sign of Alzheimer's disease (AD). There is ample evidence that the amyloid-beta (Abeta) peptide plays a key role in the pathogenesis of this disorder. Soluble, bio-derived oligomers of Abeta are proposed as the key mediators of synaptic and cognitive dysfunction, but more tractable models of Abeta-mediated cognitive impairment are needed. Here we report that, in mice, acute intracerebroventricular injections of synthetic Abeta(1-42) oligomers impaired consolidation of the long-term recognition memory, whereas mature Abeta(1-42) fibrils and freshly dissolved peptide did not. The deficit induced by oligomers was reversible and was prevented by an anti-Abeta antibody. It has been suggested that the cellular prion protein (PrP(C)) mediates the impairment of synaptic plasticity induced by Abeta. We confirmed that Abeta(1-42) oligomers interact with PrP(C), with nanomolar affinity. However, PrP-expressing and PrP knock-out mice were equally susceptible to this impairment. These data suggest that Abeta(1-42) oligomers are responsible for cognitive impairment in AD and that PrP(C) is not required. PMID:20133875

  16. Synthetic amyloid-β oligomers impair long-term memory independently of cellular prion protein

    PubMed Central

    Balducci, Claudia; Beeg, Marten; Stravalaci, Matteo; Bastone, Antonio; Sclip, Alessandra; Biasini, Emiliano; Tapella, Laura; Colombo, Laura; Manzoni, Claudia; Borsello, Tiziana; Chiesa, Roberto; Gobbi, Marco; Salmona, Mario; Forloni, Gianluigi

    2010-01-01

    Inability to form new memories is an early clinical sign of Alzheimer’s disease (AD). There is ample evidence that the amyloid-β (Aβ) peptide plays a key role in the pathogenesis of this disorder. Soluble, bio-derived oligomers of Aβ are proposed as the key mediators of synaptic and cognitive dysfunction, but more tractable models of Aβ−mediated cognitive impairment are needed. Here we report that, in mice, acute intracerebroventricular injections of synthetic Aβ1–42 oligomers impaired consolidation of the long-term recognition memory, whereas mature Aβ1–42 fibrils and freshly dissolved peptide did not. The deficit induced by oligomers was reversible and was prevented by an anti-Aβ antibody. It has been suggested that the cellular prion protein (PrPC) mediates the impairment of synaptic plasticity induced by Aβ. We confirmed that Aβ1–42 oligomers interact with PrPC, with nanomolar affinity. However, PrP-expressing and PrP knock-out mice were equally susceptible to this impairment. These data suggest that Aβ1–42 oligomers are responsible for cognitive impairment in AD and that PrPC is not required. PMID:20133875

  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. PMID:22084531

  18. The costs of long-term care: distribution and responsibility.

    PubMed

    Wallack, S S; Cohen, M A

    1988-01-01

    Long-term care costs will result in financial hardship for millions of elderly Americans and their families. The growing number of elderly people has focused public attention on the catastrophic problem of coverage for long-term care. Social insurance is unlikely to emerge as a solution in the USA. One reason is that the expected total cost is viewed as an unmanageable burden by both Federal and State governments. To others, it is the uncertainty surrounding the projected costs. This paper reports on the results of a double-decrement life-table analysis, based on a national survey of the elderly taken in early 1977 and one year later, that estimated the distribution and total lifetime nursing-home costs of the elderly. Combining the probability of nursing-home entry and length of stay, a 65-year-old faces a 43% chance of entering a nursing home and spending about +11,000 (1980 dollars). The distribution of lifetime costs is however very skewed with 13% of the elderly consuming 90% of the resources. Thus, while the costs of nursing-home care can be catastrophic for an individual, spread across a group they are not unmanageable. Given the distribution of income and assets among the elderly, a sizeable proportion could readily afford the necessary premiums of different emerging insurance and delivery programmes. Alternative private and public models of long-term care must be evaluated in terms of the goals of a finance and delivery system for long-term care. PMID:3129256

  19. 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

  20. Long term responses with cetuximab therapy in glioblastoma multiforme.

    PubMed

    Belda-Iniesta, Cristóbal; Carpeño, Javier de Castro; Saenz, Enrique Casado; Gutiérrez, Manuel; Perona, Rosario; Barón, Manuel González

    2006-08-01

    Glioblastoma multiforme (GBM) is responsible for most of the deaths associated with primary brain tumors. Standard treatment includes maximal surgical resection followed by chemotherapy and concomitant radiotherapy. Most patients, however, recur shortly after treatment. Second line treatment has little efficacy and the majority of patients die soon from the disease. Recent advances in molecular biology have implicated the epidermal growth factor receptor (EGFR) signaling pathways in the progression and resistance to standard therapies for GBM. This has prompted the evaluation of EGFR tyrosine- kinase inhibitors with encouraging results. Cetuximab is a monoclonal antibody targeted against the extra cellular domain of the EGFR with activity against different tumor types, either alone or in combination with chemotherapy and/or radiation therapy. Here we describe three patients with recurrent, heavily pretreated, EGFR expressing GBM who responded to treatment with single agent cetuximab. PMID:16929166

  1. Providing long term care for sex offenders: liabilities and responsibilities.

    PubMed

    Corson, Tyler Rogers; Nadash, Pamela

    2013-11-01

    The high risk for recidivism among sex offenders who need long term care (LTC) raises serious issues when they are cared for alongside frail, vulnerable adults. LTC providers must balance offenders' right to access care with other residents' right to be free from abuse and must assess and manage the risks associated with admitting offenders. This article identifies sources of legal liability that derive from sex offender management and discusses the need for the LTC community to develop reasonable, balanced guidance on how best to mitigate the risks associated with sex offenders, protect the rights of all residents, and reduce provider liabilities. PMID:24094899

  2. Long-term response-stimulus associations can influence distractor-response bindings

    PubMed Central

    Moeller, Birte; Frings, Christian

    2014-01-01

    Strong associations between target stimuli and responses usually facilitate fast and effortless reactions. The present study investigated whether long-term associations between distractor stimuli and responses modulate behavior. In particular, distractor stimuli can affect behavior due to distractor-based stimulus-response retrieval, a phenomenon called distractor-response binding: An ignored stimulus becomes temporarily associated with a response and retrieves it at stimulus repetition. In a flanker task, participants ignored left and right pointing arrows and responded to a target letter either with left and right (strongly associated) responses or with upper and lower (weakly associated) responses. Binding effects were modulated in dependence of the long-term association strength between distractors and responses. If the association was strong (arrows pointing left and right with left and right responses), binding effects emerged but only in case of compatible responses. If the long-term association between distractors and responses was weak (arrows pointing left and right with upper and lower responses), binding was weaker and not modulated by compatibility. In contrast, sequential compatibility effects were not modulated by association strength between distractor and response. The results indicate that existing long-term associations between stimuli responses may modulate the impact of an ignored stimulus on action control. PMID:25157302

  3. [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

  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. Sugarcane yield and morphological responses to long-term flooding.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Sugarcane in south Florida is often subjected to flooding in the summer months or following hurricanes. While there has been considerable research on the response of sugarcane cultivars to high water tables, there is a lack of information on cultivar morphological adaptation and yield response to l...

  6. Long term rest from grazing: a response to Jones & Carter

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Jones and Carter (this issue) in a response to Davies et al. (2014) misrepresent the original article and other articles, develop arguments not supported by scientific literature, and ignore literature counter to their opinion. Most peculiar, Jones and Carter incorrectly state that Davies et al. co...

  7. Morphological responses of sugarcane to long-term flooding

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Sugarcane (Saccharum spp.) in south Florida is often subjected to flooding due to intense summer rainfall or tropical storm events. While there has been considerable research on the response of sugarcane cultivars to high water tables, there is a lack of information on cultivar morphological adapta...

  8. Probing cellular processes by long-term live imaging--historic problems and current solutions.

    PubMed

    Coutu, Daniel L; Schroeder, Timm

    2013-09-01

    Living organisms, tissues, cells and molecules are highly dynamic. The importance of their continuous and long-term observation has been recognized for over a century but has been limited by technological hurdles. Improvements in imaging technologies, genetics, protein engineering and data analysis have more recently allowed us to answer long-standing questions in biology using quantitative continuous long-term imaging. This requires a multidisciplinary collaboration between scientists of various backgrounds: biologists asking relevant questions, imaging specialists and engineers developing hardware, and informaticians and mathematicians developing software for data acquisition, analysis and computational modeling. Despite recent improvements, there are still obstacles to be addressed before this technology can achieve its full potential. This Commentary aims at providing an overview of currently available technologies for quantitative continuous long-term single-cell imaging, their limitations and what is required to bring this field to the next level. We provide an historical perspective on the development of this technology and discuss key issues in time-lapse imaging: keeping cells alive, using labels, reporters and biosensors, and hardware and software requirements. We highlight crucial and often non-obvious problems for researchers venturing into the field and hope to inspire experts in the field and from related disciplines to contribute to future solutions. PMID:23943879

  9. AIE-Active Tetraphenylethylene Cross-Linked N-Isopropylacrylamide Polymer: A Long-Term Fluorescent Cellular Tracker.

    PubMed

    Ma, Hengchang; Qi, Chunxuan; Cheng, Chao; Yang, Zengming; Cao, Haiying; Yang, Zhiwang; Tong, Jinhui; Yao, Xiaoqiang; Lei, Ziqiang

    2016-04-01

    There is a great demand to understand cell transplantation, migration, division, fusion, and lysis. Correspondingly, illuminant object-labeled bioprobes have been employed as long-term cellular tracers, which could provide valuable insights into detecting these biological processes. In this work, we designed and synthesized a fluorescent polymer, which was comprised of hydrophilic N-isopropylacrylamide polymers as matrix and a hydrophobic tetraphenylethene (TPE) unit as AIE-active cross-linkers (DDBV). It was found that when the feed molar ratio of N-isopropylacrylamides to cross-linkers was 22:1, the produced polymers demonstrated the desirable LCST at 37.5 °C. And also, the temperature sensitivity of polymers could induce phase transfer within a narrow window (32-38 °C). Meanwhile, phase transfer was able to lead the florescent response. And thus, we concluded that two responses occur when one stimulus is input. Therefore, the new cross-linker of DDBV rendered a new performance from PNIPAm and a new chance to create new materials. Moreover, the resulted polymers demonstrated very good biocompatibility with living A549 human lung adenocarcinoma cells and L929 mouse fibroblast cells, respectively. Both of these cells retained very active viabilities in the concentration range of 7.8-125 μL/mg of polymers. Notably, P[(NIPAm)22-(DDBV)1] (P6) could be readily internalized by living cells with a noninvasive manner. The cellular staining by the fluorescent polymer is so indelible that it enables cell tracing for at least 10 passages. PMID:26966832

  10. 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

  11. Cultural responsiveness in long-term-care case management: moving beyond competence.

    PubMed

    Werkmeister-Rozas, Lisa; Klein, Waldo C

    2009-01-01

    Case mangers must deal with the ever-changing makeup of their client population as well as those who provide managed services to these clients. There is great ethnocultural diversity in the elder population, and statistics contend that it will only increase with time. Similarly, the majority of long-term-care providers have been consistently female and of color. Providing culturally competent services becomes more complex when long-term-care providers and clients possess different identities, countries of origins, and social statuses. This article examines a framework that addresses the complex, multidimensional and bidirectional process that occurs between providers and consumers of any cultural makeup called cultural responsiveness. PMID:19353981

  12. 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...

  13. Molecular and physiological responses to long-term sublethal ammonia exposure in Atlantic salmon (Salmo salar)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective of this study was to determine the underlying physiological and molecular responses to long-term sublethal ammonia exposure in Atlantic salmon (Salmo salar) parr. Previous studies have pre- dominately focused on mechanisms during acute, short-term exposure. For that purpose Atlantic s...

  14. 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...

  15. 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…

  16. Morphometric analysis of cellular and vascular changes in gingival connective tissue in long-term insulin-dependent diabetes.

    PubMed

    Seppälä, B; Sorsa, T; Ainamo, J

    1997-12-01

    This study examined cellular and vascular changes in gingival connective tissue samples by stereologic point-counting procedures and interactive digital analyzing systems in long-term insulin-dependent diabetes mellitus patients. Gingival connective tissue capillaries representing a clinically healthy sulcus with no evidence of periodontal disease at the site of biopsy were studied in 29 patients with diabetes. Based upon their long-term medical records, 19 were identified as having poorly controlled (PIDD) and 10 as controlled insulin-dependent diabetes mellitus (CIDD). Ten nondiabetic, age- and gender-matched individuals served as controls. Thirty-nine biopsies were processed for light microscopy, and the blood vessel area was analyzed using an interactive digital analyzing system; 9 gingival biopsies, 5 diabetic and 4 controls, were processed for morphometric electron microscopic analysis. For each individual, site-specific recordings were made for the plaque index, bleeding index, probing depth, loss of attachment, and radiographic loss of interproximal alveolar bone. No evident signs of periodontitis occurred at the biopsy sites. For each PIDD patient, respective volumetric and numeric densities of cellular components including fibroblasts, neutrophilic granulocytes, monocyte/macrophages, mast cells, lymphocytes, blast cells, and plasma cells were recorded in the inflamed connective tissue (ICT). Non-cellular components such as collagen fibers and blood vessels were also recorded. PIDD patients had elevated plasma cell levels relative to controls and they appeared also to have a decreased collagen fiber density. In addition, fibroblasts occupied less volume in the ICT of PIDD patients than in controls. PIDD patients had the largest mean area of cross-section of the blood vessels, but this difference was not statistically significant (P > or = 0.211; t-test). No specific characteristics of ICT or vascular changes were detectable in adult well-controlled long-term

  17. Efficient creation of cellular micropatterns with long-term stability and their geometric effects on cell behavior.

    PubMed

    Huang, Ning-Ping; Yu, Hai; Wang, Yan-Yan; Shi, Jun-Cai; Mao, Xi

    2011-12-01

    Cellular micropatterning with bio-adhesive and nonadhesive areas has attracted increasing interest for the precise design of cell-to-surface attachment in cell biology studies, tissue engineering, cell-based biosensors, biological assays, and drug development and screening. In this paper we describe a simple and efficient method to create a two-dimensional stable cellular microenvironment, which is based on (1) forming a protein-resistant oligo(ethylene glycol) methyl ether methacrylate polymer layer on the substrates via surface-initiated atom transfer radical polymerization; (2) placing a defined photomask on the substrate and exposing the substrate to ultraviolet light; and (3) immersing the patterned surface in a fibronectin solution to form cell-adhesive protein patterns in a cell-resistant background. The resulting surfaces are tailored into cell-adhesive and cell-resistant regions. Three different types of cells (NIH-3T3, PC12, bone marrow-derived mesenchymal stem cells) are seeded on such patterned surfaces to form cellular patterns. The geometric effects on cell behavior are investigated. The long-term stability is tested by NIH-3T3 fibroblasts and mesenchymal stem cells and excellent retention of cellular patterns is observed. The strategy illustrated here offers an efficient way to create a stable, patterned cellular microenvironment, and could be employed in tissue engineering to study the effect of micropatterns on the proliferation and differentiation of cells, and in particular mesenchymal stem cells. PMID:22239806

  18. Long Term Immune Responses to Pandemic Influenza A/H1N1 Infection in Solid Organ Transplant Recipients

    PubMed Central

    Baluch, Aliyah; Humar, Atul; Egli, Adrian; Gubbay, Jonathan; Lisboa, Luiz; Wilson, Leticia; Kumar, Deepali

    2011-01-01

    In solid organ transplant (SOT) recipients it is unknown if natural infection with influenza confers protection from re-infection with the same strain during the next influenza season. The purpose of this study was to determine if infection with pandemic influenza A/H1N1 (pH1N1) resulted in a long-term immunologic response. Transplant recipients with microbiologically proven pH1N1 infection in 2009/2010 underwent humoral and cell-mediated immunity (CMI) testing for pH1N1 just prior to the next influenza season. Concurrent testing for A/Brisbane/59/2007 was done to rule-out cross-reacting antibody. We enrolled 22 adult transplant patients after pH1N1 infection. Follow up testing was done at a median of 7.4 months (range 5.8–15.4) after infection. After excluding those with cross-reactive antibody, 7/19 (36.8%) patients were seroprotected. Detectable pH1N1-specific CD4+ and CD8+ interferon-γ producing T-cells were found in 11/22 (50%) and 8/22 (36.4%) patients respectively. Humoral immunity had a significant correlation with a CD4 response. This is the first study in transplant patients to evaluate long-term humoral and cellular response after natural influenza infection. We show that a substantial proportion of SOT recipients with previous pH1N1 infection lack long-term humoral and cellular immune responses to pH1N1. These patients most likely are at risk for re-infection. PMID:22194870

  19. Cellular and molecular mechanisms in the long-term action of antidepressants.

    PubMed Central

    Racagni, Giorgio; Popoli, Maurizio

    2008-01-01

    The hypotheses on the pathophysiology of depression /mood disorders and on antidepressant mechanisms have greatly changed in recent years. The classical monoamine hypothesis was revealed to be simplistic, in that it could not explain the temporal delay in the therapeutic action of antidepressants. Converging lines of evidence have shown that adaptive changes in the several mechanisms of neuroplasticity are likely to be the cellular and molecular correlates of therapeutic effect. In this article, several mechanisms of neuroplasticity are analyzed in relation to the mechanism of antidepressants, ranging from changes in gene expression (including neurotrophic mechanisms), to synaptic transmission and plasticity, and neurogenesis. We propose that the current version of the hypothesis of antidepressant mechanism simply be called the “hypothesis of neuroplasticity. ” In the final section, we also briefly review the main current novel strategies in the pharmacology of depression and the new putative targets for antidepressants, with particular emphasis on nonmonoaminergic mechanisms. PMID:19170396

  20. Increasing the coverage area through relay node deployment in long term evolution advanced cellular networks

    NASA Astrophysics Data System (ADS)

    Aldhaibani, Jaafar A.; Ahmad, R. B.; Yahya, A.; Azeez, Suzan A.

    2015-05-01

    Wireless multi-hop relay networks have become very important technologies in mobile communications. These networks ensure high throughput and coverage extension with a low cost. The poor capacity at cell edges is not enough to meet with growing demand of high capacity and throughput irrespective of user's placement in the cellular network. In this paper we propose optimal placement of relay node that provides maximum achievable rate at users and enhances the throughput and coverage at cell edge region. The proposed scheme is based on the outage probability at users and taken on account the interference between nodes. Numerical analyses along with simulation results indicated there are an improvement in capacity for users at the cell edge is 40% increment from all cell capacity.

  1. 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

  2. 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. PMID:26473638

  3. 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

  4. Long-Term Effects of Acid Rain: Response and Recovery of a Forest Ecosystem

    NASA Astrophysics Data System (ADS)

    Likens, G. E.; Driscoll, C. T.; Buso, D. C.

    1996-04-01

    Long-term data from the Hubbard Brook Experimental Forest, New Hampshire, suggest that although changes in stream pH have been relatively small, large quantities of calcium and magnesium have been lost from the soil complex and exported by drainage water because of inputs of acid rain and declines in atmospheric deposition of base cations. As a result, the recovery of soil and streamwater chemistry in response to any decreases in acid deposition will be delayed significantly.

  5. 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

  6. Evaluating long-term cellular effects of the arsenic species thio-DMA(V): qPCR-based gene expression as screening tool.

    PubMed

    Ebert, Franziska; Thomann, Marlies; Witt, Barbara; Müller, Sandra M; Meyer, Sören; Weber, Till; Christmann, Markus; Schwerdtle, Tanja

    2016-09-01

    Thio-dimethylarsinic acid (thio-DMA(V)) is a human urinary metabolite of the class 1 human carcinogen inorganic arsenic as well as of arsenosugars. Thio-DMA(V) exerts strong cellular toxicity, whereas its toxic modes of action are not fully understood. For the first time, this study characterises the impact of a long-term (21days) in vitro incubation of thio-DMA(V) on the expression of selected genes related to cell death, stress response, epigenetics and DNA repair. The observed upregulation of DNMT1 might be a cellular compensation to counterregulate the in a very recent study observed massive global DNA hypomethylation after chronic thio-DMA(V) incubation. Moreover, our data suggest that chronic exposure towards subcytotoxic, pico- to nanomolar concentrations of thio-DMA(V) causes a stress response in human urothelial cells. The upregulation of genes encoding for proteins of DNA repair (Apex1, Lig1, XRCC1, DDB2, XPG, ATR) as well as damage response (GADD45A, GADD45G, Trp53) indicate a potential genotoxic risk emanating from thio-DMA(V) after long-term incubation. PMID:27320638

  7. 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

  8. Characterizing long-term hydrologic-response and sediment-transport for the R-5 catchment.

    PubMed

    Heppner, Christopher S; Loague, Keith

    2008-01-01

    Recently there have been several calls to establish long-term data collection networks to monitor near-surface hydrologic response and landscape evolution. The focus of this paper is a long-term dataset from the International Hydrologic Decade (1965-1974). The small upland catchment, known as R-5, located near Chickasha, Olahoma, has been the subject of considerable attention within the event-based hydrologic modeling community for more than 30 yr. Here, for the first time, 8 yr of continuous near-surface hydrologic-response and sediment-transport data are analyzed to show trends in the catchment's long-term behavior. The datasets include precipitation, temperature, solar radiation, soil-water content, infiltration, water discharge, and sediment discharge. Potential and actual evapotranspiration rates were estimated and used to calculate an average annual water balance for the catchment. Findings include, for example, that rainfall intensity rarely exceeds the threshold for Horton-type runoff, soil-water content is both spatially and temporally variable, and the water and sediment discharge rates are positively correlated. The R-5 data provide a unique opportunity to test (and refine) process-based models of continuous hydrologic response and sediment transport at the catchment scale for applications in the emerging fields of hydroecology and hydrogeomorphology. PMID:18948471

  9. Durable long-term responses in patients with myelodysplastic syndromes treated with lenalidomide.

    PubMed

    Kurtin, Sandra E; List, Alan F

    2009-06-01

    Lenalidomide has proven efficacy and safety and has been shown to reduce transfusion requirements and reverse cytogenetic abnormalities in lower-risk myelodysplastic syndromes (MDS). However, long-term follow-up data have not yet been reported. Here, we describe 6 patients with International Prognostic Scoring System low- or intermediate-1-risk MDS who began lenalidomide therapy between April 2002 and June 2003 as part of the MDS-001 study and who have maintained long-term therapy. Five of these patients had an ongoing requirement for red blood cell transfusions despite previous treatment with recombinant erythropoietin. One patient began lenalidomide therapy because of progressive and symptomatic anemia. To date, all patients maintained long-term transfusion independence (over 4.5 years) while receiving oral lenalidomide therapy, including 5 patients who remain on therapy. Sustained erythroid response was reported despite persistence of the deletion 5q [del(5q)] abnormality in 3 of the 4 patients with del(5q) at study entry. Side effects were largely predictable and manageable. The favorable outcomes presented here show that lenalidomide can induce durable erythroid responses with sustained transfusion independence that can exceed 6 years in patients with lower-risk MDS. PMID:19525184

  10. 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.

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

    PubMed Central

    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

  12. 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.

  13. 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

  14. 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

  15. Long-Term Arthralgia after Mayaro Virus Infection Correlates with Sustained Pro-inflammatory Cytokine Response

    PubMed Central

    Santiago, Felix W.; Halsey, Eric S.; Siles, Crystyan; Vilcarromero, Stalin; Guevara, Carolina; Silvas, Jesus A.; Ramal, Cesar; Ampuero, Julia S.; Aguilar, Patricia V.

    2015-01-01

    Mayaro virus (MAYV), an alphavirus similar to chikungunya virus (CHIKV), causes an acute debilitating disease which results in the development of long-term arthralgia in more than 50% of infected individuals. Currently, the immune response and its role in the development of MAYV-induced persistent arthralgia remain unknown. In this study, we evaluated the immune response of individuals with confirmed MAYV infection in a one-year longitudinal study carried out in Loreto, Peru. We report that MAYV infection elicits robust immune responses that result in the development of a strong neutralizing antibody response and the secretion of pro-inflammatory immune mediators. The composition of these inflammatory mediators, in some cases, differed to those previously observed for CHIKV. Key mediators such as IL-13, IL-7 and VEGF were strongly induced following MAYV infection and were significantly increased in subjects that eventually developed persistent arthralgia. Although a strong neutralizing antibody response was observed in all subjects, it was not sufficient to prevent the long-term outcomes of MAYV infection. This study provides initial immunologic insight that may eventually contribute to prognostic tools and therapeutic treatments against this emerging pathogen. PMID:26496497

  16. Long-Term Arthralgia after Mayaro Virus Infection Correlates with Sustained Pro-inflammatory Cytokine Response.

    PubMed

    Santiago, Felix W; Halsey, Eric S; Siles, Crystyan; Vilcarromero, Stalin; Guevara, Carolina; Silvas, Jesus A; Ramal, Cesar; Ampuero, Julia S; Aguilar, Patricia V

    2015-01-01

    Mayaro virus (MAYV), an alphavirus similar to chikungunya virus (CHIKV), causes an acute debilitating disease which results in the development of long-term arthralgia in more than 50% of infected individuals. Currently, the immune response and its role in the development of MAYV-induced persistent arthralgia remain unknown. In this study, we evaluated the immune response of individuals with confirmed MAYV infection in a one-year longitudinal study carried out in Loreto, Peru. We report that MAYV infection elicits robust immune responses that result in the development of a strong neutralizing antibody response and the secretion of pro-inflammatory immune mediators. The composition of these inflammatory mediators, in some cases, differed to those previously observed for CHIKV. Key mediators such as IL-13, IL-7 and VEGF were strongly induced following MAYV infection and were significantly increased in subjects that eventually developed persistent arthralgia. Although a strong neutralizing antibody response was observed in all subjects, it was not sufficient to prevent the long-term outcomes of MAYV infection. This study provides initial immunologic insight that may eventually contribute to prognostic tools and therapeutic treatments against this emerging pathogen. PMID:26496497

  17. 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

  18. 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. PMID:26278659

  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. Achieving high quality long-term care for elderly people: consumers' wishes and providers' responsibilities.

    PubMed

    Morse, R; Jenkinson, D

    1995-01-01

    The organisation of long-term care for older people has major implications for all hospital and community health services. However, even health professionals have a poor understanding of the structure and purpose of long-term care and national professional bodies are still not giving enough attention to the issues involved. In the wider context, care of disabled older people has received little public debate in the UK despite the ethical, social, and financial issues involved and despite the recent major organisational changes in the health service. The past ten years have seen a huge expansion in private residential and nursing homes with a concomitant fall in NHS long-stay beds. Currently, approximately 500,000 elderly people in the UK are living in some form of long-stay care facility, and many other elderly people with multiple disabilities are being supported at home and should also be included under the umbrella of long-term care. Ensuring appropriate, equitable, and high-quality care is a responsibility not only for health and social services but also for society as a whole. This conference, organised jointly by the Royal College of Physicians, the British Geriatrics Society, and Age Concern England, with support from the Department of Health, was a much-needed and welcomed initiative. Over 200 delegates attended, consisting of doctors (geriatricians, psychiatrists, general practitioners), nurses (public and private sector), social services representatives, Department of Health representatives, managers of nursing homes, and members of charities such as Age Concern and the Relatives Association. PMID:7658422

  1. Predictors of Response Rates to a Long Term Follow-Up Mail out Survey

    PubMed Central

    Koloski, Natasha A.; Jones, Michael; Eslick, Guy; Talley, Nicholas J.

    2013-01-01

    Objective Very little is known about predictors of response rates to long-term follow-up mail-out surveys, including whether the timing of an incentive affects response rates. We aimed to determine whether the timing of the incentive affects response rates and what baseline demographic and psychological factors predict response rates to a 12 year follow-up survey. Study design and setting: Participants were 450 randomly selected people from the Penrith population, Australia who had previously participated in a mail-out survey 12 years earlier. By random allocation, 150 people received no incentive, 150 received a lottery ticket inducement with the follow-up survey and 150 received a lottery ticket inducement on the return of a completed survey. Results The overall response rate for the study was 63%. There were no significant differences in terms of response rates between the no incentive (58.8%;95%CI 49.8%,67.3%), incentive with survey (65.1%;95%CI 56.2%,73.3%) and promised incentive (65.3%;95%CI 56.1%,73.7%) groups. Independent predictors of responding to the 12 year survey were being older (OR=1.02, 95%CI 1.01,1.05,P=0.001) and being less neurotic as reported on the first survey 12 years earlier (OR=0.92, 95%CI 0.86,0.98, P=0.010). Conclusions Psychological factors may play a role in determining who responds to long-term follow-up surveys although timing of incentives does not. PMID:24223902

  2. 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.

  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. 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

  5. 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

  6. Hybrid alginate-polyester bimodal network hydrogel for tissue engineering--Influence of structured water on long-term cellular growth.

    PubMed

    Finosh, G T; Jayabalan, M; Vandana, S; Raghu, K G

    2015-11-01

    The development of biodegradable scaffolds (which promote cell-binding, proliferation, long-term cell viability and required biomechanical stability) for cardiac tissue engineering is a challenge. In this study, biosynthetic amphiphilic hybrid hydrogels were prepared using a graft comacromer of natural polysaccharide alginate and synthetic polyester polypropylene fumarate (PPF). Monomodal network hydrogel (HPAS-NO) and bimodal network hydrogel (HPAS-AA) were prepared. Between the two hydrogels, HPAS-AA hydrogel excels over the HPAS-NO hydrogel. HPAS-AA hydrogel is mechanically more stable in the culture medium and undergoes gradual degradation in vitro in PBS (phosphate buffered saline). HPAS-AA contains nano-porous structure and acquires structured water (non-freezing-bound water) (53.457%) along with free water (11.773%). It absorbs more plasma proteins and prevents platelet adsorption and hemolysis when contacted with blood. HPAS-AA hydrogel is cytocompatible and promote 3D cell growth (≈ 70%) of L929 fibroblast even after 18 days and H9C2 cardiomyoblasts. The enhanced and long-term cellular growth of HPAS-AA hydrogel is attributed to the cell responsive features of structured water. HPAS-AA hydrogel can be a better candidate for cardiac tissue engineering applications. PMID:25843368

  7. 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.

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

    SciTech Connect

    Not Available

    1993-11-01

    Twenty-nine comments from the US Nuclear Regulatory Commission and six from the Grand Junction Project Office for the long-term surveillance plan for the Collins Ranch Disposal Site, Lakeview, Oregon are documented along with their corresponding responses.

  9. Comment and response document for the long-term surveillance plan for the Shiprock, New Mexico, disposal site

    SciTech Connect

    Not Available

    1994-09-01

    This document contains comments and responses regarding the long-term surveillance plan for the Shiprock, New Mexico uranium mine tailings disposal site. Discrepencies and errors within the plan document are noted and corrections are recorded.

  10. Comment and response document for the long-term surveillance plan for the Bodo Canyon Disposal Site, Durango. Colorado

    SciTech Connect

    1996-07-01

    This document contains comments made by the US Nuclear Regulatory Commission upon their review of the Long-Term Surveillance Plan for the Bodo Canyon Disposal Site, Durango, Colorado. Responses to the comments are also included in the document.

  11. Insect immune system maintains long-term resident bacteria through a local response.

    PubMed

    Login, Frédéric H; Heddi, Abdelaziz

    2013-02-01

    Long-term associations between bacteria and animals are widely represented in nature and play an important role in animal adaptation and evolution. In insects thriving on nutritionally unbalanced diets, intracellular symbiotic bacteria (endosymbionts) complement the host nutrients with amino acids and vitamins and interfere with host physiology and reproduction. Endosymbionts permanently infect host cells, called bacteriocytes, which express an adapted local immune response that permits symbiont maintenance and control. Among the immune players in bacteriocytes, the coleoptericin A (ColA) antimicrobial peptide of the cereal weevil, Sitophilus zeamais, was recently found to specifically trigger endosymbionts and to inhibit their cytokinesis, thereby limiting bacterial cell division and dispersion throughout the insect tissues. This review focuses on the biological and evolutionary features of Sitophilus symbiosis, and discusses the possible interactions of ColA with weevil endosymbiont proteins and pathways. PMID:22771302

  12. Long term ionization response of several BiCMOS VLSIC technologies

    SciTech Connect

    Pease, R.L. ); Combs, W.; Clark, S. )

    1992-06-01

    BiCMOS is emerging as a strong competitor to CMOS for gate arrays and memories because of its performance advantages for the same feature size. In this paper, the authors examine the long term ionization response of five BiCMOS technologies by characterizing test structures which emphasize the various failure modes of CMOS and bipolar. The primary failure modes are found to be associated with the recessed field oxide isolation; edge leakage in the n channel MOSFETs and buried layer to buried layer leakage in the bipolar. The ionization failure thresholds for worst case bias were in the range of 5-20 Krad(Si) for both failure modes in all five technologies.

  13. Bioresorbable scaffolds: focus on vascular response and long-term safety.

    PubMed

    Scalone, G; Brugaletta, S; Gomez, O; Otsuki, S; Sabate, M

    2015-03-01

    Bioresorbable vascular scaffolds (BVS) are considered the fourth revolution in Interventional Cardiology, thus promising to address some of the pending issues with current-generation drug eluting stents (DES). Notably, most of the potential advantages of BVS over other current devices are due to a peculiar vascular response, called "vascular restoration therapy". The emerging data from real-world expanded use registries suggest that BVS use is feasible in a wide variety of patients (from low- to high- risk), and lesions (from simplex to complex). However, few safety concerns with currently available BVS have arised from initial experiences all over the word. Data from ongoing large-scale randomized controlled trials will be able to demonstrate whether BVS improve patient early and long-term outcomes compared to best-in-class DES. PMID:25373397

  14. The relation between the genetic architecture of quantitative traits and long-term genetic response.

    PubMed

    Abdollahi-Arpanahi, Rostam; Pakdel, Abbas; Nejati-Javaremi, Ardeshir; Shahrbabak, Mohammad Moradi; Ghafouri-Kesbi, Farhad

    2014-08-01

    The genetic architecture of a quantitative trait refers to the number of genetic variants, allele frequencies, and effect sizes of variants that affect a trait and their mode of gene action. This study was conducted to investigate the effect of four shapes of allelic frequency distributions (constant, uniform, L-shaped and U-shaped) and different number of trait-affecting loci (50, 100, 200, 500) on allelic frequency changes, long term genetic response, and maintaining genetic variance. To this end, a population of 440 individuals composed of 40 males and 400 females as well as a genome of 200 cM consisting of two chromosomes and with a mutation rate of 2.5 × 10(-5) per locus was simulated. Selection of superior animals was done using best linear unbiased prediction (BLUP) with assumption of infinitesimal model. Selection intensity was constant over 30 generations of selection. The highest genetic progress obtained when the allelic frequency had L-shaped distribution and number of trait-affecting loci was high (500). Although quantitative genetic theories predict the extinction of genetic variance due to artificial selection in long time, our results showed that under L- and U-shapped allelic frequency distributions, the additive genetic variance is persistent after 30 generations of selection. Further, presence or absence of selection limit can be an indication of low (<50) or high (>100) number of trait-affecting loci, respectively. It was concluded that the genetic architecture of complex traits is an important subject which should be considered in studies concerning long-term response to selection. PMID:24671636

  15. 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

  16. 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

  17. 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

  18. 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

  19. Response to methotrexate predicts long-term patient-related outcomes in rheumatoid arthritis.

    PubMed

    Krause, Dietmar; Gabriel, Bernadette; Herborn, Gertraud; Braun, Juergen; Rau, Rolf

    2016-05-01

    This study was conducted to investigate the predictive value of the initial response to methotrexate (MTX) on long-term patient-related outcomes (PROs) in rheumatoid arthritis (RA). All RA patients starting MTX treatment between 1980 and 1987 in our department were enrolled in a prospective observational study. After an average of 18 years, patient-related outcomes were assessed in three dimensions according to the International Classification of Functioning, Disability and Health (ICF). Statistical analyses employed multivariable models with baseline values for age, gender, disease duration, rheumatoid factor positivity, disease activity, response to MTX after 1 year and continuous use of MTX as covariates. The 271 patients enrolled had a mean disease duration of 8.5 years, a mean number of swollen joints of 18 (out of 32), and a mean erythrocyte sedimentation rate of 55 mm/h. After 18 years, PRO was available in 89 patients (33 %). A clinical improvement of at least 20 % 1 year after the initiation of MTX was associated with a favourable outcome in all three dimensions of the ICF, independent of continuation of MTX (p < 0.05). The initial response to MTX is an independent predictor of PRO in RA as assessed after an average of 18 years. PMID:26920753

  20. 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.

  1. 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

  2. Early Prediction of Long-Term Response to Cabergoline in Patients with Macroprolactinomas

    PubMed Central

    Lee, Youngki; Ku, Cheol Ryong; Kim, Eui-Hyun; Lee, Eun Jig; Kim, Sun Ho

    2014-01-01

    Background Cabergoline is typically effective for treating prolactinomas; however, some patients display cabergoline resistance, and the early characteristics of these patients remain unclear. We analyzed early indicators predicting long-term response to cabergoline. Methods We retrospectively reviewed the cases of 44 patients with macroprolactinomas who received cabergoline as first-line treatment; the patients were followed for a median of 16 months. The influence of various clinical parameters on outcomes was evaluated. Results Forty patients (90.9%) were treated medically and displayed tumor volume reduction (TVR) of 74.7%, a prolactin normalization (NP) rate of 81.8%, and a complete response (CR; TVR >50% with NP, without surgery) rate of 70.5%. Most patients (93.1%) with TVR ≥25% and NP at 3 months eventually achieved CR, whereas only 50% of patients with TVR ≥25% without NP and no patients with TVR <25% achieved CR. TVR at 3 months was strongly correlated with final TVR (R=0.785). Patients with large macroadenomas exhibited a low NP rate at 3 months, but eventually achieved TVR and NP rates similar to those of patients with smaller tumors. Surgery independently reduced the final dose of cabergoline (β=-1.181 mg/week), and two of four patients who underwent surgery were able to discontinue cabergoline. Conclusion Determining cabergoline response using TVR and NP 3 months after treatment is useful for predicting later outcomes. However, further cabergoline administration should be considered for patients with TVR >25% at 3 months without NP, particularly those with huge prolactinomas, because a delayed response may be achieved. As surgery can reduce the cabergoline dose necessary for successful disease control, it should be considered for cabergoline-resistant patients. PMID:25309786

  3. Adjuvant-specific regulation of long-term antibody responses by ZBTB20

    PubMed Central

    Wang, Yinan

    2014-01-01

    The duration of antibody production by long-lived plasma cells varies with the type of immunization, but the basis for these differences is unknown. We demonstrate that plasma cells formed in response to the same immunogen engage distinct survival programs depending on the adjuvant. After alum-adjuvanted immunization, antigen-specific bone marrow plasma cells deficient in the transcription factor ZBTB20 failed to accumulate over time, leading to a progressive loss of antibody production relative to wild-type controls. Fetal liver reconstitution experiments demonstrated that the requirement for ZBTB20 was B cell intrinsic. No defects were observed in germinal center numbers, affinity maturation, or plasma cell formation or proliferation in ZBTB20-deficient chimeras. However, ZBTB20-deficient plasma cells expressed reduced levels of MCL1 relative to wild-type controls, and transgenic expression of BCL2 increased serum antibody titers. These data indicate a role for ZBTB20 in promoting survival in plasma cells. Strikingly, adjuvants that activate TLR2 and TLR4 restored long-term antibody production in ZBTB20-deficient chimeras through the induction of compensatory survival programs in plasma cells. Thus, distinct lifespans are imprinted in plasma cells as they are formed, depending on the primary activation conditions. The durability of vaccines may accordingly be improved through the selection of appropriate adjuvants. PMID:24711582

  4. 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

  5. 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

  6. Cerebral Artery Alpha-1 AR Subtypes: High Altitude Long-Term Acclimatization Responses

    PubMed Central

    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. PMID:25393740

  7. Long-term functional duration of immune responses to HCV NS3/4A induced by DNA vaccination

    PubMed Central

    Ahlén, G; Holmström, F; Gibbs, A; Alheim, M; Frelin, L

    2014-01-01

    We have investigated the ability of hepatitis C virus non-structural (NS) 3/4A-DNA-based vaccines to activate long-term cell-mediated immune responses in mice. Wild-type and synthetic codon optimized (co) NS3/4A DNA vaccines have previously been shown to be immunogenic in mice, rabbits and humans, although we have very poor knowledge about the longevity of the immune responses primed. We therefore analyzed the functionality of primed NS3/4A-specific immune responses in BALB/c (H-2d) and/or C57BL/6J (H-2b) mice 1, 2, 3, 4, 6, 12 and 16 months after the last immunization. Mice were immunized one, two, three or four times using gene gun delivery to the skin or by intramuscular administration. Immunological responses after immunization were monitored by protection against in vivo challenge of NS3/4A-expressing syngeneic tumor cells. In addition, functionality of the NS3/4A-specific T cells was analyzed by a standard cytotoxicity assay. First, we identified a new unique murine H-2d-restricted NS3/4A cytotoxic T lymphocyte (CTL) epitope, which enabled us to study the epitope-specific immune responses. Our results show that the coNS3/4A vaccine was highly immunogenic by determination of interferon-γ/tumor necrosis factor-α production and lytic cytotoxic T cells, which could efficiently inhibit in vivo tumor growth. Importantly, we showed that one to four monthly immunizations protected mice from tumor development when challenged up to 16 months after the last immunization. When determining the functionality of NS3/4A-specific T cells in vitro, we showed detectable lytic activity up to 12 months after the last immunization. Thus, NS3/4A-based DNA vaccines activate potent cellular immune responses that are present and function in both BALB/c and C57BL/6J mice up to 12–16 months after the last immunization. The induction of long-term immunity after NS3/4A DNA immunization has not been shown previously and supports the use of NS3/4A in hepatitis C virus

  8. Long-term functional duration of immune responses to HCV NS3/4A induced by DNA vaccination.

    PubMed

    Ahlén, G; Holmström, F; Gibbs, A; Alheim, M; Frelin, L

    2014-08-01

    We have investigated the ability of hepatitis C virus non-structural (NS) 3/4A-DNA-based vaccines to activate long-term cell-mediated immune responses in mice. Wild-type and synthetic codon optimized (co) NS3/4A DNA vaccines have previously been shown to be immunogenic in mice, rabbits and humans, although we have very poor knowledge about the longevity of the immune responses primed. We therefore analyzed the functionality of primed NS3/4A-specific immune responses in BALB/c (H-2(d)) and/or C57BL/6J (H-2(b)) mice 1, 2, 3, 4, 6, 12 and 16 months after the last immunization. Mice were immunized one, two, three or four times using gene gun delivery to the skin or by intramuscular administration. Immunological responses after immunization were monitored by protection against in vivo challenge of NS3/4A-expressing syngeneic tumor cells. In addition, functionality of the NS3/4A-specific T cells was analyzed by a standard cytotoxicity assay. First, we identified a new unique murine H-2(d)-restricted NS3/4A cytotoxic T lymphocyte (CTL) epitope, which enabled us to study the epitope-specific immune responses. Our results show that the coNS3/4A vaccine was highly immunogenic by determination of interferon-γ/tumor necrosis factor-α production and lytic cytotoxic T cells, which could efficiently inhibit in vivo tumor growth. Importantly, we showed that one to four monthly immunizations protected mice from tumor development when challenged up to 16 months after the last immunization. When determining the functionality of NS3/4A-specific T cells in vitro, we showed detectable lytic activity up to 12 months after the last immunization. Thus, NS3/4A-based DNA vaccines activate potent cellular immune responses that are present and function in both BALB/c and C57BL/6J mice up to 12-16 months after the last immunization. The induction of long-term immunity after NS3/4A DNA immunization has not been shown previously and supports the use of NS3/4A in hepatitis C virus vaccine

  9. 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

  10. 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

  11. 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.

  12. 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

  13. 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 ...

  14. 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...

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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

  1. 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...

  2. 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 ...

  3. 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...

  4. Treatment response and long-term dentofacial adaptations to maxillary expansion and protraction.

    PubMed

    Ngan, P W; Hagg, U; Yiu, C; Wei, S H

    1997-12-01

    The purpose of this article is to summarize the short-term and long-term results of the authors' clinical prospective study on the treatment of Class III malocclusion using the protraction facemask. An attempt is made to answer questions pertaining to this treatment modality. Twenty patients with skeletal Class III malocclusion were treated consecutively with maxillary expansion and a protraction facemask. A positive overjet was obtained in all cases after 6 to 9 months of treatment. These changes were contributed to by a forward movement of the maxilla, backward and downward rotation of the mandible, proclination of the maxillary incisors, and retroclination of the mandibular incisors. The molar relationship was overcorrected to Class I or Class II dental arch relationship. The overbite was reduced with a significant increase in lower facial height. The treatment was found to be stable 2 years after removal of the appliances. At the end of the 4-year observation period, 15 of the 20 patients maintained a positive overjet or an end-to-end incisal relationship. Patients who reverted back to a negative overjet were found to have excess horizontal mandibular growth that was not compensated by proclination of the maxillary incisors. A review of the literature showed that maxillary expansion in conjunction with protraction produced greater forward movement of the maxilla. Maxillary protraction with a 30 degrees forward and downward force applied at the canine region produced an acceptable clinical response. The reciprocal force from maxillary protraction transmitted to the temporomandibular joint did not increase masticatory muscle pain or activity. Significant soft tissue profile change can be expected with maxillary protraction including straightening of the facial profile and better lip competence and posture. However, one should anticipate individual variations in treatment response and subsequent growth changes. Treatment with the protraction facemask is most

  5. 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.

  6. 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.

  7. 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…

  8. 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.

  9. Non-linear ecosystem response to long-term changes in precipitation and nitrogen availability in a desert grassland

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Our objective was to assess ecosystem responses to long-term changes in precipitation and nitrogen availability in the Northern Chihuahuan Desert (NM, USA), using rainfall manipulations (80% reduced PPT, ambient, 80% increased) and fertilization additions (with and without ammonium nitrate) for five...

  10. Long-term Terrestrial Carbon and Water Cycle Responses to Projected Climate Change Beyond 2100

    NASA Astrophysics Data System (ADS)

    Hoffman, F. M.; Randerson, J. T.; Fu, W.; Lindsay, K. T.; Munoz, E.; Mahowald, N. M.; Bonan, G. B.

    2014-12-01

    Understanding the long-term responses of ecosystems to climate change is important for quantifying the strength of carbon-climate feedbacks and informing carbon management and energy policies. Using simulations from the Community Earth System Model version 1.0 (CESM1-BGC), we quantified the effects of increasing atmospheric CO2 and the resulting increases in temperature and changes in precipitation from 1850 to 2300 on terrestrial ecosystems. We analyzed the evolution of the global carbon and water cycles in four sets of Historical (1850-2005), Representative Concentration Pathway 8.5 (2006-2100), and Extended Concentration Pathway 8.5 (2101-2300) simulations with active land and ocean biogeochemical cycles. In the first set of simulations, the increasing atmospheric CO2 and other greenhouse gases and aerosols were radiatively coupled. In the second set, the CO2 was radiatively uncoupled; while in the third, CO2 and the other atmospheric forcing agents were radiatively uncoupled. The fourth set was radiatively coupled, but the ocean and land biogeochemistry experienced only the pre-industrial CO2 forcing. We found that carbon-climate feedbacks intensify as a consequence of weakening CO2 uptake by oceans and the terrestrial biosphere through the end of the 23rd century. We also investigated the effects of changing water availability on land uptake and biosphere productivity, and found an increase in terrestrial water storage globally as a result of intensification of the water cycle. Water cycle changes were driven by the balance between increasing temperatures, changing precipitation, melting snow and ice, thawing permafrost, and increasing leaf area and water use efficiency. Regional changes in precipitation and runoff were not consistent within latitude zones, resulting in differential effects on ecosystem productivity and fire frequency, particularly in the tropics. While tropical and mid-latitude productivity increases largely slowed or became negative at or

  11. Long-Term Care and Health Information Technology: Opportunities and Responsibilities for Long-Term and Post-Acute Care Providers

    PubMed Central

    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

  12. 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

  13. 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

  14. 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. PMID:26385695

  15. Brief, pre-retrieval stress differentially influences long-term memory depending on sex and corticosteroid response.

    PubMed

    Zoladz, Phillip R; Kalchik, Andrea E; Hoffman, Mackenzie M; Aufdenkampe, Rachael L; Burke, Hanna M; Woelke, Sarah A; Pisansky, Julia M; Talbot, Jeffery N

    2014-03-01

    Previous work has indicated that stress generally impairs memory retrieval. However, little research has addressed discrepancies that exist in this line of work and the factors that could explain why stress can exert differential effects on retrieval processes. Therefore, we examined the influence of brief, pre-retrieval stress that was administered immediately before testing on long-term memory in males and females. Participants learned a list of 42 words varying in emotional valence and arousal. Following the learning phase, participants were given an immediate free recall test. Twenty-four hours later, participants submerged their non-dominant hand in a bath of ice cold (Stress) or warm (No Stress) water for 3 min. Immediately following this manipulation, participants' memory for the word list was assessed via free recall and recognition tests. We observed no group differences on short-term memory. However, male participants who showed a robust cortisol response to the stress exhibited enhanced long-term recognition memory, while male participants who demonstrated a blunted cortisol response to the stress exhibited impaired long-term recall and recognition memory. These findings suggest that the effects of brief, pre-retrieval stress on long-term memory are sex-specific and mediated by corticosteroid mechanisms. PMID:24509087

  16. 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.

  17. 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

  18. Responsiveness and accountability in long-term care: strategies for policy development and empowerment.

    PubMed

    Wells, L M

    1990-01-01

    This paper presents a model for engaging planners, service providers and consumers in a collaborative process of improving quality of life in long-term care facilities, discussing the implications of this approach for standards of care and policy development. This empowerment model was refined and tested in a large system of skilled-nursing-care facilities using a matched-pair comparison group design. The rationale, theory base and the relationship of the empowerment model to current concepts of health promotion are shown. Subsequent follow-up indicated examples of the impact of the model on broader aspects of public policy. PMID:2123737

  19. Label-free proteomic analysis of PBMCs reveals gender differences in response to long-term antiretroviral therapy of HIV.

    PubMed

    Zhang, Lu; Wang, Zhuoran; Chen, Yulong; Zhang, Chi; Xie, Shiping; Cui, Yinglin; Wang, Zhao

    2015-08-01

    The association of gender with the treatment outcome during long-term antiretroviral therapy (ART) in human immunodeficiency virus (HIV)-infected patients has been controversial. Here, we performed a comparative proteomic analysis of peripheral blood mononuclear cells (PBMC) by using a label-free shotgun method with nano-LC-MS/MS to investigate the gender differences in responses to long-term ART. This analysis enrolled 30 HIV-infected patients (16 males and 14 females), as well as 20 healthy adults (10 males and 10 females) as control. Quantitative real-time RT-PCR and immunoblotting were used to validate the results of proteomic approach. A total of 53 proteins showing differential expression (± 1.5 fold, p < 0.05) were identified in HIV-infected patients versus healthy adults. Of these proteins, 22 proteins showed identical regulation patterns in both men and women, while 31 proteins were gender-specific (21 men-specific and 10 women-specific proteins). Bioinformatics analysis indicated that long-term ART causes up-regulation of apoptosis, oxidative phosphorylation and mitochondrial dysfunction while down-regulation of oxidative stress and immune system process in men compared to women. These findings point to a concept that gender has a significant influence on the outcomes of ART at protein level and women present a potential favorable immunological pattern and recovery during long-term ART. PMID:26045010

  20. 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.

  1. 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

  2. Stress and glucocorticoid receptor-dependent mechanisms in long-term memory: from adaptive responses to psychopathologies

    PubMed Central

    Finsterwald, Charles; Alberini, Cristina M.

    2013-01-01

    A proper response against stressors is critical for survival. In mammals, the stress response is primarily mediated by secretion of glucocorticoids via the hypothalamic-pituitaryadrenocortical (HPA) axis and release of catecholamines through adrenergic neurotransmission. Activation of these pathways results in a quick physical response to the stress and, in adaptive conditions, mediates long-term changes in the brain that lead to the formation of long-term memories of the experience. These long-term memories are an essential adaptive mechanism that allows an animal to effectively face similar demands again. Indeed, a moderate stress level has a strong positive effect on memory and cognition, as a single arousing or moderately stressful event can be remembered for up to a lifetime. Conversely, exposure to extreme, traumatic, or chronic stress can have the opposite effect and cause memory loss, cognitive impairments, and stress-related psychopathologies such as anxiety disorders, depression and post-traumatic stress disorder (PTSD). While more effort has been devoted to the understanding of the effects of the negative effects of chronic stress, much less has been done thus far on the identification of the mechanisms engaged in the brain when stress promotes long-term memory formation. Understanding these mechanisms will provide critical information for use in ameliorating memory processes in both normal and pathological conditions. Here, we will review the role of glucocorticoids and glucocorticoid receptors (GRs) in memory formation and modulation. Furthermore, we will discuss recent findings on the molecular cascade of events underlying the effect of GR activation in adaptive levels of stress that leads to strong, long-lasting memories. Our recent data indicate that the positive effects of GR activation on memory consolidation critically engage the brain-derived neurotrophic factor (BDNF) pathway. We propose and will discuss the hypothesis that stress promotes the

  3. Stress and glucocorticoid receptor-dependent mechanisms in long-term memory: from adaptive responses to psychopathologies.

    PubMed

    Finsterwald, Charles; Alberini, Cristina M

    2014-07-01

    A proper response against stressors is critical for survival. In mammals, the stress response is primarily mediated by secretion of glucocorticoids via the hypothalamic-pituitary-adrenocortical (HPA) axis and release of catecholamines through adrenergic neurotransmission. Activation of these pathways results in a quick physical response to the stress and, in adaptive conditions, mediates long-term changes in the brain that lead to the formation of long-term memories of the experience. These long-term memories are an essential adaptive mechanism that allows an animal to effectively face similar demands again. Indeed, a moderate stress level has a strong positive effect on memory and cognition, as a single arousing or moderately stressful event can be remembered for up to a lifetime. Conversely, exposure to extreme, traumatic, or chronic stress can have the opposite effect and cause memory loss, cognitive impairments, and stress-related psychopathologies such as anxiety disorders, depression and post-traumatic stress disorder (PTSD). While more effort has been devoted to the understanding of the negative effects of chronic stress, much less has been done thus far on the identification of the mechanisms engaged in the brain when stress promotes long-term memory formation. Understanding these mechanisms will provide critical information for use in ameliorating memory processes in both normal and pathological conditions. Here, we will review the role of glucocorticoids and glucocorticoid receptors (GRs) in memory formation and modulation. Furthermore, we will discuss recent findings on the molecular cascade of events underlying the effect of GR activation in adaptive levels of stress that leads to strong, long-lasting memories. Our recent data indicate that the positive effects of GR activation on memory consolidation critically engage the brain-derived neurotrophic factor (BDNF) pathway. We propose and will discuss the hypothesis that stress promotes the formation of

  4. Early Life Arsenic Exposure and Acute and Long-term Responses to Influenza A Infection in Mice

    PubMed Central

    Foong, Rachel E.; Sly, Peter D.; Larcombe, Alexander N.; Zosky, Graeme R.

    2013-01-01

    Background: Arsenic is a significant global environmental health problem. Exposure to arsenic in early life has been shown to increase the rate of respiratory infections during infancy, reduce childhood lung function, and increase the rates of bronchiectasis in early adulthood. Objective: We aimed to determine if early life exposure to arsenic exacerbates the response to early life influenza infection in mice. Methods: C57BL/6 mice were exposed to arsenic in utero and throughout postnatal life. At 1 week of age, a subgroup of mice were infected with influenza A. We then assessed the acute and long-term effects of arsenic exposure on viral clearance, inflammation, lung structure, and lung function. Results: Early life arsenic exposure reduced the clearance of and exacerbated the inflammatory response to influenza A, and resulted in acute and long-term changes in lung mechanics and airway structure. Conclusions: Increased susceptibility to respiratory infections combined with exaggerated inflammatory responses throughout early life may contribute to the development of bronchiectasis in arsenic-exposed populations. Citation: Ramsey KA, Foong RE, Sly PD, Larcombe AN, Zosky GR. 2013. Early life arsenic exposure and acute and long-term responses to influenza A infection in mice. Environ Health Perspect 121:1187–1193; http://dx.doi.org/10.1289/ehp.1306748 PMID:23968752

  5. 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.

  6. GPS observations of seasonal crustal deformation and long-term land subsidence in response to water storage changes in California

    NASA Astrophysics Data System (ADS)

    Anderson, K. J.; De Linage, C.; Famiglietti, J. S.

    2011-12-01

    Observations of vertical land surface height from Scripps Orbit and Permanent Array Center (SOPAC) GPS stations throughout California and the Western United States reveal significant seasonal and long-term land surface responses to water storage changes. Long-term land surface subsidence in the Central Valley is due to aquifer compaction resulting from ongoing groundwater depletion. Seasonal motion of the land surface due to elastic crustal loading provides insight about seasonal surface water loads such as snow water equivalent, soil moisture, and reservoir storage. This research explores the relationship between water storage changes observed by GRACE and Snotel and the land surface responses observed by GPS, and the potential for new applications of GPS for monitoring various components of water storage.

  7. [Dermatology - the key to ensure a good long term clinical response].

    PubMed

    Sahil, Maral; Boehncke, Wolf-Henning

    2016-01-13

    After efficacy and safety have been used for many years to evaluate therapies and treatment success in medicine, patient reported outcomes are now increasingly being incorported in this process. This trend acknowledges that patient adherence is a prerequisit for the good long-term outcome of a treatment. In the field of dermatology, namely for psoriasis, current guidelines already recommend to base clinical decision-making on a combination of objective as well as patient-reported outcomes. These parameters provide the basis for the concept of happy drug survival, building on the belief that a good quality of life reflects meaningful treatment success from the patient's point of view, motivating him to carry on with the therapy. PMID:26946698

  8. [Emotional response to long-term unemployment. A study in Lillesand].

    PubMed

    Ytterdahl, T

    1997-02-28

    Unemployment threatens the economic welfare of the family. It can affect self-respect and social status and remove the supportive network of the workplace. This cross-sectional survey from 1993-94 in a Norwegian community with 8,500 inhabitants describes emotional reactions to loss of job and the effects of unemployment on the lives of 148 long-term unemployed in Lillesand. A large majority were not mentally prepared for losing their job. Most reacted with defensive feelings, and a quarter experienced negative reactions from their social circle to their losing their job. Even if new extra leisure time was used for more social contact with friends and family, and more exercise and outdoor activity, satisfaction with life was reduced by being out of work. Women and the older unemployed seemed to adapt better to the new situation. The coping mechanisms of young men seemed much more limited. PMID:9102978

  9. 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. PMID:23701388

  10. 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

  11. Short- and long-term physiological responses of grapevine leaves to UV-B radiation.

    PubMed

    Martínez-Lüscher, J; Morales, F; Delrot, S; Sánchez-Díaz, M; Gomés, E; Aguirreolea, J; Pascual, I

    2013-12-01

    The present study aimed at evaluating the short- and long-term effects of UV-B radiation on leaves of grapevine Vitis vinifera (cv. Tempranillo). Grapevine fruit-bearing cuttings were exposed to two doses of supplemental biologically effective UV-B radiation (UV-BBE) under glasshouse-controlled conditions: 5.98 and 9.66kJm(-2)d(-1). The treatments were applied either for 20d (from mid-veraison to ripeness) or 75d (from fruit set to ripeness). A 0kJm(-2)d(-1) UV-B treatment was included as control. The main effects of UV-B were observed after the short-term exposure (20d) to 9.66kJm(-2)d(-1). Significant decreases in net photosynthesis, stomatal conductance, sub-stomatal CO2 concentration, the actual photosystem II (PSII) efficiency, total soluble proteins and de-epoxidation state of the VAZ cycle were observed, whereas the activities of several antioxidant enzymes increased significantly. UV-B did not markedly affect dark respiration, photorespiration, the maximum potential PSII efficiency (Fv/Fm), non-photochemical quenching (NPQ), as well as the intrinsic PSII efficiency. However, after 75d of exposure to 5.98and 9.66kJm(-2)d(-1) UV-B most photosynthetic and biochemical variables were unaffected and there were no sign of oxidative damage in leaves. The results suggest a high long-term acclimation capacity of grapevine to high UV-B levels, associated with a high accumulation of UV-B absorbing compounds in leaves, whereas plants seemed to be tolerant to moderate doses of UV-B. PMID:24157214

  12. 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

  13. 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

  14. 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

  15. Histochemical responses of human soleus muscle fibers to long-term bedrest with or without countermeasures.

    PubMed

    Ohira, Y; Yoshinaga, T; Nonaka, I; Ohara, M; Yoshioka, T; Yamashita-Goto, K; Izumi, R; Yasukawa, K; Sekiguchi, C; Shenkman, B S; Kozzlovskaya, I B

    2000-02-01

    Effects of 2- or 4-month bedrest in -6 degrees head-down tilt position with or without countermeasures on the histochemical properties of fiber phenotype and cross-sectional area (CSA) were studied in human soleus. The CSAs in slow fibers decreased approximately 32% during 4-month bedrest. This reduction was normalized after 1-month recovery. Although the reduction of percent slow fibers was not significant statistically, the percent intermediate fibers was significantly elevated 4 months after bedrest. Such shift in fiber type was not normalized following 1-month recovery. Effects of wearing an anti-g Penguin suit which has a modest, but continuous resistance at the knee and ankle (Penguin-1) or with knee resistance without loading on the ankle (Penguin-2) for 10 consecutive hours daily were also investigated during approximately 2 months of bedrest. The subjects performed knee extension and flexion for the last 15 min of each hour while in a supine position in bed. Bedrest-induced fiber atrophy was prevented in the Penguin-1 group but not the Penguin-2 group. Transformation of fiber type was not prevented in either Penguin suit group. It is suggested that long-term bedrest causes an atrophy and a shift of fiber phenotype toward fast-twitch type in human soleus. Data also indicated that loading on the muscle is an effective countermeasure for prevention of fiber atrophy but not fiber-type transformation. PMID:10866696

  16. Funding Long-Term Care in Canada: Who Is Responsible for What?

    PubMed

    Deber, Raisa B; Laporte, Audrey

    2016-01-01

    As Adams and Vanin (2016) have noted, different ways of funding long-term care (LTC) have different implications. Because health is not just healthcare, and LTC is not homogeneous, determining the appropriate public-private mix is complex. We suggest that how issues are framed helps influence policy choices, including who should pay for what, and how things should be financed. In addition, the distribution of expenditures for some services can be highly skewed, affecting the extent to which average cost data are useful in extrapolating their costs. We note that health expenditures fall into multiple categories, each presenting different policy issues. For example, framing LTC as health, as basic costs associated with living or as forced savings (like pensions) affects which funding approaches might be used, and the extent to which changes in the population distribution will affect cost structures. Underlying these discussions are questions of solidarity, and how much we believe that we are our brother's - or grandmother's - keeper. PMID:27230717

  17. Long-term anisotropic mechanical response of surgical meshes used to repair abdominal wall defects.

    PubMed

    Hernández-Gascón, B; Peña, E; Pascual, G; Rodríguez, M; Bellón, J M; Calvo, B

    2012-01-01

    Routine hernia repair surgery involves the implant of synthetic mesh. However, this type of procedure may give rise to pain and bowel incarceration and strangulation, causing considerable patient disability. The purpose of this study was to compare the long-term behaviour of three commercial meshes used to repair the partially herniated abdomen in New Zealand White rabbits: the heavyweight (HW) mesh, Surgipro(®) and lightweight (LW) mesh, Optilene(®), both made of polypropylene (PP), and a mediumweight (MW) mesh, Infinit(®), made of polytetrafluoroethylene (PTFE). The implanted meshes were mechanical and histological assessed at 14, 90 and 180 days post-implant. This behaviour was compared to the anisotropic mechanical behaviour of the unrepaired abdominal wall in control non-operated rabbits. Both uniaxial mechanical tests conducted in craneo-caudal and perpendicular directions and histological findings revealed substantial collagen growth over the repaired hernial defects causing stiffness in the repair zone, and thus a change in the original properties of the meshes. The mechanical behaviour of the healthy tissue in the craneo-caudal direction was not reproduced by any of the implanted meshes after 14 days or 90 days of implant, whereas in the perpendicular direction, SUR and OPT achieved similar behaviour. From a mechanical standpoint, the anisotropic PP-lightweight meshes may be considered a good choice in the long run, which correlates with the structure of the regenerated tissue. PMID:22100101

  18. Long-term, non-local coastline responses to local shoreline stabilization

    NASA Astrophysics Data System (ADS)

    Ells, Kenneth; Murray, A. Brad

    2012-10-01

    The future of large-scale coastline evolution will be strongly coupled to human manipulations designed to prevent erosion. We explore the consequences of this coupling using a numerical model for large-scale coastline evolution to compare the long-term, non-local effects of two generalized classes of shoreline stabilization: 1) beach nourishment (the addition of dredged sand to an eroding beach), and 2) hard-structures (e.g., seawalls, groynes, etc.) which fix the position of the shoreline without adding sand. In centurial model experiments where localized stabilization is maintained in the context of changing climate forcing, both forms of stabilization are found to significantly alter patterns of erosion and accretion at distances up to tens of kilometers. On a cuspate-cape coastline similar to the North and South Carolina coast, USA, with stabilization applied to the eroding updrift flank of a single cape, perturbations to coastline evolution are qualitatively similar within ˜20 km for each stabilization scenario, though they differ in magnitude both updrift and downdrift of the stabilized shoreline. The “human” signal in coastline change can extend as far as a neighboring cape (approximately 100 km away), but these long-range effects differ for each scenario. Nourishment resulted in seaward growth of the stabilized cape, increasing the extent that it blocked sediment flux in downdrift regions of the coast through wave shadowing. When stabilized with a hard structure the cape's initial position remain fixed, decreasing wave shadowing.

  19. 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. PMID:21845166

  20. 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

  1. 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

  2. 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

  3. Long-term outcomes in patients initially responsive to selective laser trabeculoplasty

    PubMed Central

    Patel, Varun; El Hawy, Eman; Waisbourd, Michael; Zangalli, Camila; Shapiro, Daniel M.; Gupta, Lalita; Hsieh, Michael; Kasprenski, Abigail; Katz, L. Jay; Spaeth, George L.

    2015-01-01

    AIM To determine the long-term effects of selective laser trabeculoplasty (SLT) on intraocular pressure (IOP) and the number of medications used up to 5y following treatment in glaucoma patients receiving maximally tolerated medical therapy (MTMT). METHODS The Wills Eye Hospital Glaucoma Research Center retrospectively reviewed the charts of glaucoma patients who underwent SLT after receiving MTMT. Eyes that did not achieve their target pressure within 3mo following SLT were excluded from the study. Changes in mean IOP and number of glaucoma medications used were analyzed at 1, 3, and 5y following SLT. RESULTS Seventy-five eyes of 67 patients were included in the study. Fifteen eyes that received SLT failed to achieve their target pressure within 3mo and were excluded from the study. The average follow-up time was 37.4mo (±14.4). Mean IOP was significantly reduced 1y after treatment (P=0.005). It was also reduced 3, 5y after treatment without reaching statistical significance (P=0.20 and P=0.072, respectively). There was a significant decrease in mean number of medications used 1, 3, 5y after treatment (P<0.001, P<0.001, and P=0.039, respectively). In the span of 5y, 2 eyes (2.7%) underwent repeat SLT, 7 eyes (9.3%) underwent glaucoma surgery and an additional 3 eyes (4.0%) underwent both. CONCLUSION SLT significantly reduced the number of glaucoma medications used 5y following treatment in glaucoma patients receiving MTMT. SLT may delay operating-room surgery. PMID:26558209

  4. Impact of a Student Response System on Short- and Long-Term Learning in a Drug Literature Evaluation Course

    PubMed Central

    Liu, Flora C.; Gettig, Jacob P.

    2010-01-01

    Objective To evaluate the effectiveness of a student response system on short- and long-term learning in a required second-year pharmacy course. Method Student volunteers enrolled in the course Drug Literature Evaluation were blinded and randomized to 1 of 2 groups. Group 1 attended a lecture in which the instructor used a student response system. Group 2 attended the same lecture by the same instructor an hour later, but no student response system was used. A 16-point unannounced quiz on the lecture material was administered to both groups at the end of class. Approximately 1 month later, both groups were given another unannounced quiz on the same material to test long-term student learning. Results One hundred seventy-nine (92.3%) students participated in both quizzes. Students who attended the class in which the student response system was used scored an average 1 point higher on quiz 1 than students who were assigned to the control group (10.7 vs. 9.7; p = 0.02). No significant difference was seen between the quiz 2 scores of the 2 groups (9.5 vs. 9.5; p = 0.99). Conclusions The use of a student response system can positively impact students' short-term learning; however, that positive effect did not appear to last over time. Faculty members may want to consider the use of student response systems to enhance student learning in large lecture classes. PMID:20221357

  5. The long-term effects of prenatal nicotine exposure on response inhibition: an fMRI study of young adults.

    PubMed

    Longo, Carmelinda A; Fried, Peter A; Cameron, Ian; Smith, Andra M

    2013-01-01

    The long-term effects of prenatal nicotine exposure on response inhibition were investigated in young adults using functional magnetic resonance imaging (fMRI). Participants were members of the Ottawa Prenatal Prospective Study, a longitudinal study that collected a unique body of information on participants from infancy to young adulthood, which allowed for the measurement of an unprecedented number of potentially confounding drug exposure variables including: prenatal marijuana and alcohol exposure and current marijuana, nicotine and alcohol use. Twelve young adults with prenatal nicotine exposure and 13 non-exposed controls performed a Go/No-Go task while fMRI blood oxygen level-dependent responses were examined. Despite similar task performance, participants prenatally exposed to nicotine demonstrated significantly greater activity in several regions of the brain that typically subserve response inhibition including the inferior frontal gyrus, the inferior parietal lobe, the thalamus and the basal ganglia. In addition, prenatally exposed participants showed greater activity in relatively large posterior regions of the cerebellum. These results suggest that prenatal nicotine exposure leads to altered neural functioning during response inhibition that continues into adulthood. This alteration is compensated for by recruitment of greater neural resources within regions of the brain that subserve response inhibition and the recruitment of additional brain regions to successfully perform the task. Response inhibition is an important executive functioning skill and impairments can impede functioning in much of everyday life. Thus, awareness of the continued long-term neural physiological effects of prenatal nicotine exposure is critical. PMID:23743331

  6. Cellular Stress Responses and Monitored Cellular Activities.

    PubMed

    Sawa, Teiji; Naito, Yoshifumi; Kato, Hideya; Amaya, Fumimasa

    2016-08-01

    To survive, organisms require mechanisms that enable them to sense changes in the outside environment, introduce necessary responses, and resist unfavorable distortion. Consequently, through evolutionary adaptation, cells have become equipped with the apparatus required to monitor their fundamental intracellular processes and the mechanisms needed to try to offset malfunction without receiving any direct signals from the outside environment. It has been shown recently that eukaryotic cells are equipped with a special mechanism that monitors their fundamental cellular functions and that some pathogenic proteobacteria can override this monitoring mechanism to cause harm. The monitored cellular activities involved in the stressed intracellular response have been researched extensively in Caenorhabditis elegans, where discovery of an association between key mitochondrial activities and innate immune responses was named "cellular associated detoxification and defenses (cSADD)." This cellular surveillance pathway (cSADD) oversees core cellular activities such as mitochondrial respiration and protein transport into mitochondria, detects xenobiotics and invading pathogens, and activates the endocrine pathways controlling behavior, detoxification, and immunity. The cSADD pathway is probably associated with cellular responses to stress in human inflammatory diseases. In the critical care field, the pathogenesis of lethal inflammatory syndromes (e.g., respiratory distress syndromes and sepsis) involves the disturbance of mitochondrial respiration leading to cell death. Up-to-date knowledge about monitored cellular activities and cSADD, especially focusing on mitochondrial involvement, can probably help fill a knowledge gap regarding the pathogenesis of lethal inflammatory syndromes in the critical care field. PMID:26954943

  7. 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

  8. 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

  9. Experimentally Simulating Paternity Uncertainty: Immediate and Long-Term Responses of Male and Female Reed Warblers Acrocephalus scirpaceus

    PubMed Central

    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. Effect of long-term salinity on cellular antioxidants, compatible solute and fatty acid profile of Sweet Annie (Artemisia annua L.).

    PubMed

    Qureshi, M Irfan; Abdin, Malik Zainul; Ahmad, Javed; Iqbal, Muhammad

    2013-11-01

    Impact of long-term salinity and subsequent oxidative stress was studied on cellular antioxidants, proline accumulation and lipid profile of Artemisia annua L. (Sweet Annie or Qinghao) which yields artemisinin (Qinghaosu), effective against cerebral malaria-causing strains of Plasmodium falciparum. Under salinity (0.0-160 mM NaCl), in A. annua, proline accumulation, contents of ascorbate and glutathione and activities of superoxide dismutase (SOD), ascorbate peroxidase (APX), glutathione reductase (GR) and catalase (CAT) increased, but the contents of reduced forms of glutathione (GSH) and ascorbate declined. The fatty-acid profiling revealed a major salinity-induced shift towards long-chain and mono-saturated fatty acids. Myristic acid (14:0), palmitoleic acid (16:1), linoleic acid (18:2) and erucic acid (22:1) increased by 141%, 186%, 34% and 908%, respectively, in comparison with the control. Contents of oleic acid (18:1), linolenic acid (18:3), arachidonic acid (22:0) and lignoceric acid (24:0) decreased by 50%, 17%, 44% and 78%, respectively. Thus, in A. annua, salinity declines ascorbate and GSH contents. However, increased levels of proline and total glutathione (GSH+GSSG), and activities of antioxidant enzymes might provide a certain level of tolerance. Modification in fatty-acid composition might be a membrane adaptation to long-term salinity and oxidative stress. PMID:23871298

  11. A Guide to Implementing Response to Intervention in Long-Term Residential Juvenile Justice Schools

    ERIC Educational Resources Information Center

    McDaniel, Sara; Heil, Kristen M.; Houchins, David E.; Duchaine, Ellen L.

    2011-01-01

    Since the passage of the Individuals with Disabilities Education Improvement Act (2004), public schools have been permitted to use a response to intervention model to address academic and social problems of students and identify students with disabilities. As the collective educational community tackles implementation of response to intervention…

  12. 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

  13. 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. PMID:24072549

  14. 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

  15. 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

  16. 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.

  17. 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.

  18. Virological Response and Muscular Adverse Events during Long-Term Clevudine Therapy in Chronic Hepatitis B Patients

    PubMed Central

    Kim, Byung Kook; Ko, Soon Young; Kwon, So Young; Park, Eugene; Kim, Jeong Han; Choe, Won Hyeok; Lee, Chang Hong

    2013-01-01

    Background Recently, several reports issued clevudine induced myopathy in the long term use. Objectives The aim of this study was to investigate antiviral effects and adverse events of clevudine monotherapy in patients with chronic hepatitis B (CHB). Patients and Methods The subjects were 110 treatment-naïve CHB patients. They were treated with 30 mg clevudine/day for more than six months. Virological and biochemical tests, including that for serum creatine kinase (CK), were monitored at baseline and at 3-month intervals during treatment period. Results In HBeAg-positive patients, the cumulative rates of virological response were 74.0 %, 68.5 %, and 67.3 % after one, two, and three years of clevudine treatment, respectively. Cumulative rates of HBeAg loss or seroconversion were 17.8 %, 30 %, and 31.5 % after one, two and, three years of clevudine treatment, respectively. In HBeAg-negative patients, the cumulative rates of virological response were 97.3 %, 100 %, and 94.6 %, respectively. Virological breakthrough occurred in 27 patients. The rtM204I mutation in HBV polymerase was predominantly detected. Muscular adverse events were observed in 15 patients. All patients with myopathy recovered after the cessation of clevudine monotherapy. Fluctuations in CK level during the clevudine treatment period were frequently observed irrespective of development of myopathy. Multiple episodes of CK elevation were significantly related to the development of myopathy. Conclusions Long-term clevudine monotherapy is effective for suppression of serum HBV DNA level and normalization of serum alanine amino transaminase levels, but associated with occurrence of rtM204I mutation. Clevudine-induced muscular adverse events are not uncommon, although they are totally reversible after cessation of the treatment. Muscular adverse events and serum CK level should be carefully monitored during long-term treatment with clevudine. PMID:23805155

  19. Characterizing the therapeutic response to deep brain stimulation for treatment-resistant depression: a single center long-term perspective

    PubMed Central

    Crowell, Andrea L.; Garlow, Steven J.; Riva-Posse, Patricio; Mayberg, Helen S.

    2015-01-01

    The number of depressed patients treated with deep brain stimulation (DBS) is relatively small. However, experience with this intervention now spans more than 10 years at some centers, with study subjects typically monitored closely. Here we describe one center’s evolving impressions regarding optimal patient selection for DBS of the subcallosal cingulate (SCC) as well as observations of short- and long-term patterns in antidepressant response and mood reactivity. A consistent time course of therapeutic response with distinct behavioral phases is observed. Early phases are characterized by changes in mood reactivity and a transient and predictable worsening in self ratings prior to stabilization of response. It is hypothesized that this characteristic recovery curve reflects the timeline of neuroplasticity in response to DBS. Further investigation of these emerging predictable psychiatric, biological, and psychosocial patterns will both improve treatment optimization and enhance understanding and recognition of meaningful DBS antidepressant effects. PMID:26124710

  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. Evidence from Individual Inference for High-Dimensional Coexistence: Long-Term Experiments on Recruitment Response

    PubMed Central

    Clark, James S.; Soltoff, Benjamin D.; Powell, Amanda S.; Read, Quentin D.

    2012-01-01

    Background For competing species to coexist, individuals must compete more with others of the same species than with those of other species. Ecologists search for tradeoffs in how species might partition the environment. The negative correlations among competing species that would be indicative of tradeoffs are rarely observed. A recent analysis showed that evidence for partitioning the environment is available when responses are disaggregated to the individual scale, in terms of the covariance structure of responses to environmental variation. That study did not relate that variation to the variables to which individuals were responding. To understand how this pattern of variation is related to niche variables, we analyzed responses to canopy gaps, long viewed as a key variable responsible for species coexistence. Methodology/Principal Findings A longitudinal intervention analysis of individual responses to experimental canopy gaps with 12 yr of pre-treatment and 8 yr post-treatment responses showed that species-level responses are positively correlated – species that grow fast on average in the understory also grow fast on average in response to gap formation. In other words, there is no tradeoff. However, the joint distribution of individual responses to understory and gap showed a negative correlation – species having individuals that respond most to gaps when previously growing slowly also have individuals that respond least to gaps when previously growing rapidly (e.g., Morus rubra), and vice versa (e.g., Quercus prinus). Conclusions/Significance Because competition occurs at the individual scale, not the species scale, aggregated species-level parameters and correlations hide the species-level differences needed for coexistence. By disaggregating models to the scale at which the interaction occurs we show that individual variation provides insight for species differences. PMID:22393349

  2. 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.

  3. 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

  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. PMID:27017604

  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. PMID:27151883

  6. Responses of Nannochloropsis oceanica IMET1 to Long-Term Nitrogen Starvation and Recovery1[C][W][OA

    PubMed Central

    Dong, Hong-Po; Williams, Ernest; Wang, Da-zhi; Xie, Zhang-Xian; Hsia, Ru-ching; Jenck, Alizée; Halden, Rolf; Li, Jing; Chen, Feng; Place, Allen R.

    2013-01-01

    The Nannochloropsis genus contains oleaginous microalgae that have served as model systems for developing renewable biodiesel. Recent genomic and transcriptomic studies on Nannochloropsis species have provided insights into the regulation of lipid production in response to nitrogen stress. Previous studies have focused on the responses of Nannochloropsis species to short-term nitrogen stress, but the effect of long-term nitrogen deprivation remains largely unknown. In this study, physiological and proteomic approaches were combined to understand the mechanisms by which Nannochloropsis oceanica IMET1 is able to endure long-term nitrate deprivation and its ability to recover homeostasis when nitrogen is amended. Changes of the proteome during chronic nitrogen starvation espoused the physiological changes observed, and there was a general trend toward recycling nitrogen and storage of lipids. This was evidenced by a global down-regulation of protein expression, a retained expression of proteins involved in glycolysis and the synthesis of fatty acids, as well as an up-regulation of enzymes used in nitrogen scavenging and protein turnover. Also, lipid accumulation and autophagy of plastids may play a key role in maintaining cell vitality. Following the addition of nitrogen, there were proteomic changes and metabolic changes observed within 24 h, which resulted in a return of the culture to steady state within 4 d. These results demonstrate the ability of N. oceanica IMET1 to recover from long periods of nitrate deprivation without apparent detriment to the culture and provide proteomic markers for genetic modification. PMID:23637339

  7. 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

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

    PubMed Central

    Sun, Yue; Zhou, Liping; Fang, Lingdong; Su, Yong; Zhu, Weiyun

    2015-01-01

    Intake of raw potato starch (RPS) has been associated with various intestinal health benefits, but knowledge of its mechanism in a long-term is limited. The aim of this study was to investigate the effects of long-term intake of RPS on microbial composition, genes expression profiles in the colon of pigs. Thirty-six Duroc × Landrace × Large White growing barrows were randomly allocated to corn starch (CS) and RPS groups with a randomized block design. Each group consisted of six replicates (pens), with three pigs per pen. Pigs in the CS group were offered a corn/soybean-based diet, while pigs in the RPS group were put on a diet in which 230 g/kg (growing period) or 280 g/kg (finishing period) purified CS was replaced with purified RPS during a 100-day trial. Real-time PCR assay showed that RPS significantly decreased the number of total bacteria in the colonic digesta. MiSeq sequencing of the V3-V4 region of the 16S rRNA genes showed that RPS significantly decreased the relative abundance of Clostridium, Treponema, Oscillospira, Phascolarctobacterium, RC9 gut group, and S24-7-related operational taxonomic units (OTUs), and increased the relative abundance of Turicibacter, Blautia, Ruminococcus, Coprococcus, Marvinbryantia, and Ruminococcus bromii-related OTUs in colonic digesta and mucosa. Analysis of the colonic transcriptome profiles revealed that the RPS diet changed the colonic expression profile of the host genes mainly involved in immune response pathways. RPS significantly increased proinflammartory cytokine IL-1β gene expression and suppressed genes involved in lysosome. Our findings suggest that long-term intake of high resistant starch (RS) diet may result in both positive and negative roles in gut health. PMID:26379652

  9. Larval viability and serological response in horses with long term Trichinella infection.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In this study, 35 horses were infected with 1000, 5000, or 10,000 T. spiralis muscle larvae and the course of infection was followed for 1 year. Larval burdens in selected muscles, the condition and infectivity of larvae in tissue, and the serological response of infected horses were assessed. The ...

  10. 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 ...

  11. 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…

  12. Long-Term Clinical Responses of Neoadjuvant Dendritic Cell Infusions and Radiation in Soft Tissue Sarcoma

    PubMed Central

    Raj, Shailaja; Bui, Marilyn M.; Springett, Gregory; Conley, Anthony; Lavilla-Alonso, Sergio; Zhao, Xiuhua; Chen, Dungsa; Haysek, Randy; Gonzalez, Ricardo; Letson, G. Douglas; Finkelstein, Steven Eric; Chiappori, Alberto A.; Gabrilovitch, Dmitry I.; Antonia, Scott J.

    2015-01-01

    Purpose. Patients with large >5 cm, high-grade resectable soft tissue sarcomas (STS) have the highest risk of distant metastases. Previously we have shown that dendritic cell (DC) based vaccines show consistent immune responses. Methods. This was a Phase I single institution study of neoadjuvant radiation with DC injections on 18 newly diagnosed high-risk STS patients. Neoadjuvant treatment consisted of 50 Gy of external beam radiation (EBRT), given in 25 fractions delivered five days/week, combined with four intratumoral injections of DCs followed by complete resection. The primary endpoint was to establish the immunological response to neoadjuvant therapy and obtain data on its clinical safety and outcomes. Results. There were no unexpected toxicities or serious adverse events. Twelve out of 18 (67%) patients were alive, of which an encouraging 11/18 (61%) were alive with no systemic recurrence over a period of 2–8 years. Favorable immunological responses correlated with clinical responses in some cases. Conclusions. This study provides clinical support to using dendritic cell injections along with radiation in sarcomas, which when used optimally in combination can help clinical outcomes in soft tissue sarcoma. Study registration number is NCT00365872. PMID:26880867

  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. 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.

  15. An unusual response with long term survival using erlotinib in NSCLC lung with brain metastases.

    PubMed

    Rastogi, Madhup; Nanda, Sambit Swarup; Prakash, Chandra; Kulshreshtha, Dinkar

    2016-01-01

    We present a case of a middle-aged woman with adenocarcinoma of the lung and metastatic brain lesions. In view of her poor general condition and poor compliance to first-line chemotherapy, the patient was kept on tablet erlotinib after whole brain radiotherapy. This novel treatment resulted in a dramatic response with radiological regression in both the primary lung lesion and metastatic intracranial lesions translating in unexpected and ongoing 24-month survival. PMID:26729829

  16. 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

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

    PubMed Central

    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

  18. 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 ...

  19. Changes in Innate and Permissive Immune Responses after HBV Transgenic Mouse Vaccination and lLong-Term-siRNA Treatment

    PubMed Central

    Fang, Ying; Ma, Heng-Hao; Xu, Man-Chun; Zhang, Hong-Bin; Zhang, Wei-Yun; Zhao, Ya-Gang; Sun, Da-Yong; Hu, Wen-Kui; Liu, Jian

    2013-01-01

    Background Currently, no licensed therapy can thoroughly eradicate hepatitis B virus (HBV) from the body, including interferon α and inhibitors of HBV reverse-transcription. Small interfering RNA (siRNA) seem to be a promising tool for treating HBV, but had no effect on the pre-existing HBV covalently closed circular DNA. Because it is very difficult to thoroughly eradicate HBV with unique siRNAs, upgrading the immune response is the best method for fighting HBV infection. Here, we aim to explore the immune response of transgenic mice to HBV vaccination after long-term treatment with siRNAs and develop a therapeutic approach that combines siRNAs with immunopotentiators. Methodology/Principal Findings To explore the response of transgenic mice to hepatitis B vaccine, innate and acquired immunity were detected after long-term treatment with siRNAs and vaccination. Antiviral cytokines and level of anti-hepatitis B surface antigen antibody (HBsAg-Ab) were measured after three injections of hepatitis B vaccine. Results Functional analyses indicated that toll-like receptor-mediated innate immune responses were reinforced, and antiviral cytokines were significantly increased, especially in the pSilencer4.1/HBV groups. Analysis of CD80+/CD86+ dendritic cells in the mouse liver indicated that dendritic cell antigen presentation was strengthened. Furthermore, the siRNA-treated transgenic mice could produce detectable HBsAg-Ab after vaccination, especially in the CpG oligonucleotide vaccine group. Conclusions/Significance For the first time, our studies demonstrate that siRNAs with CpG HBV vaccine could strengthen the immune response and break the immune tolerance status of transgenic mice to HBV. Thus, siRNAs and HBV vaccine could provide a sharp double-edged sword against chronic HBV infection. PMID:23472088

  20. Lack of stress responses to long-term effects of corticosterone in Caps2 knockout mice.

    PubMed

    Mishima, Yuriko; Shinoda, Yo; Sadakata, Tetsushi; Kojima, Masami; Wakana, Shigeharu; Furuichi, Teiichi

    2015-01-01

    Chronic stress is associated with anxiety and depressive disorders, and can cause weight gain. Ca(2+)-dependent activator protein for secretion 2 (CAPS2) is involved in insulin release. Caps2 knockout (KO) mice exhibit decreased body weight, reduced glucose-induced insulin release, and abnormal psychiatric behaviors. We chronically administered the stress hormone corticosterone (CORT), which induces anxiety/depressive-like behavior and normally increases plasma insulin levels, via the drinking water for 10 weeks, and we examined the stress response in KO mice. Chronic CORT exposure inhibited stress-induced serum CORT elevation in wild-type (WT) mice, but not in KO mice. Poor weight gain in CORT-treated animals was observed until week 6 in WT mice, but persisted for the entire duration of the experiment in KO mice, although there is no difference in drug*genotype interaction. Among KO mice, food consumption was unchanged, while water consumption was higher, over the duration of the experiment in CORT-treated animals, compared with untreated animals. Moreover, serum insulin and leptin levels were increased in CORT-treated WT mice, but not in KO mice. Lastly, both WT and KO mice displayed anxiety/depressive-like behavior after CORT administration. These results suggest that Caps2 KO mice have altered endocrine responses to CORT administration, while maintaining CORT-induced anxiety/depressive-like behavior. PMID:25754523

  1. 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.

  2. Long-Term Dose Response of Trabecular Bone in Mice to Proton Radiation

    PubMed Central

    Bandstra, Eric R.; Pecaut, Michael J.; Anderson, Erica R.; Willey, Jeffrey S.; De Carlo, Francesco; Stock, Stuart R.; Gridley, Daila S.; Nelson, Gregory A.; Levine, Howard G.; Bateman, Ted A.

    2015-01-01

    Astronauts on exploratory missions will experience a complex environment, including microgravity and radiation. While the deleterious effects of unloading on bone are well established, fewer studies have focused on the effects of radiation. We previously demonstrated that 2 Gy of ionizing radiation has deleterious effects on trabecular bone in mice 4 months after exposure. The present study investigated the skeletal response after total doses of proton radiation that astronauts may be exposed to during a solar particle event. We exposed mice to 0.5, 1 or 2 Gy of whole-body proton radiation and killed them humanely 117 days later. Tibiae and femora were analyzed using microcomputed tomography, mechanical testing, mineral composition and quantitative histomorphometry. Relative to control mice, mice exposed to 2 Gy had significant differences in trabecular bone volume fraction (−20%), trabecular separation (+11%), and trabecular volumetric bone mineral density (−19%). Exposure to 1 Gy radiation induced a nonsignificant trend in trabecular bone volume fraction (−13%), while exposure to 0.5 Gy resulted in no differences. No response was detected in cortical bone. Further analysis of the 1-Gy mice using synchrotron microCT revealed a significantly lower trabecular bone volume fraction (−13%) than in control mice. Trabecular bone loss 4 months after exposure to 1 Gy highlights the importance of further examination of how space radiation affects bone. PMID:18494551

  3. 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

  4. 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

  5. An exposure-response method for assessing the long term health effects of the bhopal gas disaster.

    PubMed

    Dhara, V R; Kriebel, D

    1993-12-01

    Approximately 200,000 persons were exposed to methyl isocyanate in the Bhopal Gas leak in Bhopal, India. 4037 deaths have resulted and 30 per cent of the population are estimated to be suffering from long-term health effects. Though inflammatory damage to the eyes and lungs is the main cause of morbidity, other systems are also reported to be affected. For a disaster of this magnitude, there is a relative paucity of medical information. Very little information has been published on the late recovery period, a phase in which the detection of chronic and long-term effects is vital. Early cross-sectional studies suffer from a number of defects in study design, including validity and precision of exposure and outcome variables, selection of study and control groups, etc. By using exposure concentrations derived from Singh's analytic dispersion model, this paper outlines a strategy for doing community epidemiology in Bhopal using exposure strata for sampling. Pulmonary dose can be estimated from exposure concentration, duration and activity during exposure. For respiratory end-points, a sample size of 100/stratum will ensure study power of 90 per cent. Using multiple linear regression, data from the study can be used to build a model for prediction of lung function parameters. Exposure-stratified sampling techniques may provide valid estimates of exposure-response without including the total exposed community. PMID:20958771

  6. 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.

  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. Water relations, gas exchange, and nutrient response to a long term constant water deficit.

    PubMed

    Berry, W L; Goldstein, G; Dreschel, T W; Wheeler, R M; Sager, J C; Knott, W M

    1992-06-01

    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 m-2 s-1 and a decrease in total apparent hydraulic conductance from 47 to 12 micromoles s-1 MPa-1. 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 facilitates

  9. 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

  10. 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

  11. Changes in soil bacterial communities and diversity in response to long-term silver exposure.

    PubMed

    Vasileiadis, Sotirios; Puglisi, Edoardo; Trevisan, Marco; Scheckel, Kirk G; Langdon, Kate A; McLaughlin, Mike J; Lombi, Enzo; Donner, Erica

    2015-10-01

    Silver-induced selective pressure is becoming increasingly important due to the growing use of silver (Ag) as an antimicrobial agent in biomedical and commercial products. With demonstrated links between environmental resistomes and clinical pathogens, it is important to identify microbial profiles related to silver tolerance/resistance. We investigated the effects of ionic Ag stress on soil bacterial communities and identified resistant/persistent bacterial populations. Silver treatments of 50-400 mg Ag kg(-1) soil were established in five soils. Chemical lability measurements using diffusive gradients in thin-film devices confirmed that significant (albeit decreasing) labile Ag concentrations were present throughout the 9-month incubation period. Synchrotron X-ray absorption near edge structure spectroscopy demonstrated that this decreasing lability was due to changes in the Ag speciation to less soluble forms such as Ag(0) and Ag2S. Real-time PCR and Illumina MiSeq screening of 16S rRNA bacterial genes showed β-diversity changes, increasing α-diversity in response to Ag pressure, and immediate and significant reductions in 16S rRNA gene counts with varying degrees of recovery. These effects were more strongly influenced by exposure time than by Ag dose at these rates. Ag-selected dominant OTUs principally resided in known persister taxa (mainly Gram positive), including metal-tolerant bacteria and slow-growing Mycobacteria. PMID:26391377

  12. 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.

  13. Role of movement in long-term basal ganglia changes: implications for abnormal motor responses

    PubMed Central

    Simola, Nicola; Morelli, Micaela; Frazzitta, Giuseppe; Frau, Lucia

    2013-01-01

    Abnormal involuntary movements (AIMs) and dyskinesias elicited by drugs that stimulate dopamine receptors in the basal ganglia are a major issue in the management of Parkinson’s disease (PD). Preclinical studies in dopamine-denervated animals have contributed to the modeling of these abnormal movements, but the precise neurochemical and functional mechanisms underlying these untoward effects are still elusive. It has recently been suggested that the performance of movement may itself promote the later emergence of drug-induced motor complications, by favoring the generation of aberrant motor memories in the dopamine-denervated basal ganglia. Our recent results from hemiparkinsonian rats subjected to the priming model of dopaminergic stimulation are in agreement with this. These results demonstrate that early performance of movement is crucial for the manifestation of sensitized rotational behavior, indicative of an abnormal motor response, and neurochemical modifications in selected striatal neurons following a dopaminergic challenge. Building on this evidence, this paper discusses the possible role of movement performance in drug-induced motor complications, with a look at the implications for PD management. PMID:24167489

  14. Long-term change in storm hydrographs in response to peatland vegetation change

    NASA Astrophysics Data System (ADS)

    Grayson, R.; Holden, J.; Rose, R.

    2010-08-01

    SummaryThe runoff from blanket peatland catchments tends to be dominated by flashy stormflows. However, it is not known whether changes in vegetation cover influence the nature of stormflow hydrographs from blanket peatlands. This is important since degraded peatlands are of concern to restoration bodies who seek to understand the wider impacts of restoration investment on ecosystem services. This paper tests the hypothesis that peak flows are significantly higher and lag times shorter at the catchment scale when blanket peat vegetation cover is reduced. Storm hydrograph data from the 1950s to the present day are analysed from a blanket peat catchment in northern England. The proportion of the catchment that was vegetated appears to have declined between the early 1950s and mid 1970s and then increased again to the present day. The changes in the proportion of bare peat over the catchment are coincident with changes in storm hydrographs. Hydrographs were significantly peakier with higher peaks per unit of rainfall (0.40 m 3 mm -1 compared with 0.27 m 3 mm -1) and narrower hydrograph shapes during the more eroded periods in the catchment and less so as the site has revegetated. Mean peak storm discharge was also significantly higher during the most eroded period. Thus, for the first time we have found evidence in a blanket peat headwater catchment that vegetation cover influences river flow response to rainfall.

  15. A mechanical auxiliary ventricle. Histologic responses to long-term, intermittent pumping in calves.

    PubMed

    Kantrowitz, A; Freed, P S; Zhou, Y; Mandell, G; DeDecker, P; Riddle, J; Wilson, D; Mullaney, T P

    1995-01-01

    The mechanical auxiliary ventricle (MAV) is an avalvular, inseries left ventricular assist device (LVAD) comprised of a 60 cc Biomer blood pump implanted in the descending thoracic aorta, a percutaneous access device (PAD), and an external pneumatic drive. In four calves the MAV was implanted and activated intermittently for 192, 249, 423, and 785 days, respectively; no anticoagulants were administered. When the animals were killed, the implants were retrieved, and autopsies, including gross, light microscopic, scanning electron microscopy (SEM), and transmission electron microscopy (TEM) examinations, were performed. The MAV was securely attached to the aorta in every animal. A thin, even smooth, pseudoneointimal layer (PNI) contiguous with the aorta at the level of the suture line covered the MAV's blood-contacting surface. Areas of calcification beneath the PNI, expected in growing animals with implanted pumping devices, were noted. At autopsy there was no evidence of thrombosis or infection in the regions of the blood pump or the PAD. These findings confirm the calves' benign histologic response to the MAV, and together with the results of hematologic and biochemiccal studies, and bench tests of system components being reported elsewhere, indicate the system's readiness for limited clinical investigation in selected patients with chronic congestive failure. PMID:8573821

  16. 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

  17. Passive microfluidic chamber for long-term imaging of axon guidance in response to soluble gradients.

    PubMed

    Taylor, A M; Menon, S; Gupton, S L

    2015-07-01

    Understanding how axons are guided to target locations within the brain is of fundamental importance for neuroscience, and is a widely studied area of research. Biologists have an unmet need for reliable and easily accessible methods that generate stable, soluble molecular gradients for the investigation of axon guidance. Here we developed a microfluidic device with contiguous media-filled compartments that uses gravity-driven flow to generate a stable and highly reproducible gradient within a viewing compartment only accessible to axons. This device uses high-resistance microgrooves to both direct the growth of axons into an isolated region and to generate a stable gradient within the fluidically isolated axon viewing compartment for over 22 h. Establishing a stable gradient relies on a simple and quick pipetting procedure with no external pump or tubing. Since the axons extend into the axonal compartment through aligned microgrooves, the analysis of turning is simplified. Further, the multiple microgrooves in parallel alignment serve to increase sample sizes, improving statistical analyses. We used this method to examine growth cone turning in response to the secreted axon guidance cue netrin-1. We report the novel finding that growth cones of embryonic mouse cortical axons exhibited attractive turning in the lower concentrations of netrin-1, but were repulsed when exposed to higher concentrations. We also performed immunocytochemistry in growth cones exposed to a netrin-1 gradient within the axon viewing compartment and show that netrin receptors associated with both attraction and repulsion, DCC and UNC5H, localized to these growth cones. Together, we developed an accessible gradient chamber for higher throughput axon guidance studies and demonstrated its capabilities. PMID:26000554

  18. 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. PMID:24165925

  19. 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

  20. 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.

  1. 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

  2. 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

  3. Short-term versus long-term responses to drought stress: coupling manipulation experiments with gradient studies

    NASA Astrophysics Data System (ADS)

    Martin, Nicolas; Misson, Laurent

    2010-05-01

    Water availability is the main factor shaping plants form and function in Mediterranean ecosystems. Understanding the mechanisms that drive plants productivity in drought conditions is crucial in a climate change context. So far, functional relationships between drought stress and leaf physiology has mostly been studied in short term experiments unable to address the potential acclimation in leaf function and the link between short term responses and long term acclimation. Here we hypothesize that the functional relationships between drought and leaf physiology can change under the temporal scale at witch drought is applied. Hence, we measured leaf physiological parameters (gs, gm, Amax, Vcmax Jmax) implicated in the limitation of carbon assimilation on Holm Oak leaves using a design combining 2 contrasting field experiments: (1) a rainfall exclusion experiment simulating a spring extreme drought in order to study short term processes, (2) a natural rainfall gradient (650 mm to 1150 mm) made of 3 plots in order to study long term acclimation. For each experiment we related leaf physiological parameters and their respective limitation to carbon assimilation with predawn leaf water potential as a surrogate of drought stress. Results showed that functional relationships relating gs, Vcmax and Jmax to leaf water potential changed in the total rainfall exclusion, probably because of a strong effect of spring drought on phenology. In addition, trees in the wet plot of the rainfall gradient showed a stronger stomatal conductance decline relative to leaf water potential than trees in the dry plot. We interpret these changes as a result of structural modification at canopy level in the rainfall gradient related to changes in leaf area index (LAI), hydraulic adjustment or fine root/LAI ratio. As a consequence, stomatal limitation of carbon assimilation was stronger in the wet plot than in the dry plot, while total limitation was lower in the dry plot. Water conservation in

  4. 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.

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

    PubMed

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

    1996-01-01

    When higher plants are exposed to elevated levels of CO2 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 plants bases are altered in a species specific manner. The most common pattern in C3 plants is an enhanced rate of whole plant photosynthesis in a well irradiated canopy. Nevertheless, in some herbaceous species prolonged exposure to high CO2 results in remobilization of nitrogenous reserves (i.e., leaf protein degradation) and reduced rates of mature leaf photosynthesis when assayed at ambient CO2 and O2 levels. Both short- and long-term exposures to those CO2 levels (i.e., 100 to 2,000 microliter l-1) which modify photosynthesis and export, also modify both endogenous ethylene gas (C2H4) release, and substrate, 1-aminocyclopropane-1-carboxylic acid (ACC), saturated C2H4 release rates from irradiated leaves. Photosynthetically active canopy leaves contribute most of the C2H4 released from the canopy. Prolonged growth at high CO2 results in a persistent increase in the rate of endogenous C2H4 release from leaves which can, only in part, be attributed to the increase of the endogenous pools of C2H4 pathway intermediates (e.g., methionine, M-ACC, and ACC). The capacity for increasing the rate of C2H4 release in response to short-term exposures to varying CO2 levels does not decline after prolonged growth at high CO2. When leaves, whole plants, and model canopies of tomato plants are exposed to exogenous C2H4 a reduction in the rate of photosynthesis can, in each case, be attributed to the classical effects of C2H4 on plant development and morphology. The effect of C2H4 on CO2 gas exchange of plant canopies is shown to be dependent on the canopy leaf area index. PMID:11538799

  6. 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.

  7. 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.

  8. 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

  9. Corticosterone stress response shows long-term repeatability and links to personality in free-living Nazca boobies.

    PubMed

    Grace, Jacquelyn K; Anderson, David J

    2014-11-01

    The concept of "coping styles", or consistently different responses to stressors, is of broad interest in behavioral ecology and biomedicine. Two critical predictions of this concept are individual consistency of neurophysiological and behavioral responses (relative to population variability) and a negative relationship between aggression/proactivity and hypothalamic-pituitary-adrenal axis reactivity. Recent studies failed to provide strong support for these predictions, especially outside of strictly controlled conditions, and long-term measures to test the first prediction are rare. Here, we demonstrate individual repeatability across 2-3years of maximum circulating corticosterone concentration [CORT] and area under the [CORT] response curve (AUCI) during a standard capture-restraint test in wild, free-living adult Nazca boobies (Sula granti). We also show that the stress response predicts the personality traits aggression and anxiety in these birds (measured in the wild); however, the strength of these results was weak. Maximum [CORT] and AUCI showed higher repeatability between years than baseline [CORT]. After controlling breeding status, sex, mass, date sampled, and their interactions, baseline [CORT] was most closely related to personality traits, followed by AUCI, and then maximum [CORT]. The direction of these relationships depended on whether the testing context was social or non-social. [CORT] parameters had little to no relationship with cross-context plasticity in personality traits. Our results generally affirm two critical predictions of coping styles, but match the emerging trend that these relationships are weak in the wild, and may depend on testing context. PMID:25220912

  10. Galantamine treatment in Alzheimer’s disease: response and long-term outcome in a routine clinical setting

    PubMed Central

    Wallin, Åsa K; Wattmo, Carina; Minthon, Lennart

    2011-01-01

    Background: In the absence of long-term, placebo-controlled studies of cholinesterase inhibitors in Alzheimer’s disease (AD), analysis of the results of open-label trials becomes crucial. This study aimed to explore the three-year effects of galantamine treatment, as well as subgroups of response and adherence to treatment. Methods: Two hundred and eighty patients with a clinical diagnosis of AD were included in the prospective, open-label, multicenter Swedish Alzheimer Treatment Study, and received galantamine treatment. Efficacy measures included cognitive tests, ie, the Mini-Mental State Examination (MMSE) and Alzheimer’s Disease Assessment Scale Cognitive Subscale (ADAS-cog), functional rating (Instrumental Activities of Daily Living Scale [IADL]), and global rating. Assessments were carried out before treatment and every six months for a period of three years. K-means cluster analysis was used to identify response subgroups. Results: After three years of treatment, the mean change from baseline was 2.6 points in MMSE and 5.6 points in ADAS-cog scores. Globally, half of the patients improved or remained unchanged for two years. Cluster analysis identified two response clusters. Cluster 1 included patients with low ability in ADAS-cog and IADL scores at baseline. Even though the patients in cluster 1 were older and less educated, they responded better at six months compared with patients in cluster 2. Cluster 2 included patients with better ADAS-cog and IADL scores at baseline. Patients in cluster 2 had a higher frequency of the APOE ɛ4 allele, a slower pretreatment progression rate, and remained in the study longer than those in cluster 1. Three-year completers (n = 129, 46%) received higher doses of galantamine compared with dropouts. Conclusion: AD patients who received long-term galantamine treatment were cognitively and globally stabilized. Subgroup response analysis identified a better short-term response in older patients with lower cognitive and

  11. Loose-coupling a cellular automaton model and GIS: long-term urban growth prediction for San Francisco and Washington/Baltimore

    USGS Publications Warehouse

    Clarke, K.C.; Gaydos, L.J.

    1998-01-01

    Prior research developed a cellular automaton model, that was calibrated by using historical digital maps of urban areas and can be used to predict the future extent of an urban area. The model has now been applied to two rapidly growing, but remarkably different urban areas: the San Francisco Bay region in California and the Washington/Baltimore corridor in the Eastern United States. This paper presents the calibration and prediction results for both regions, reviews their data requirements, compares the differences in the initial configurations and control parameters for the model in the two settings, and discusses the role of GIS in the applications. The model has generated some long term predictions that appear useful for urban planning and are consistent with results from other models and observations of growth. Although the GIS was only loosely coupled with the model, the model's provision of future urban patterns as data layers for GIS description and analysis is an important outcome of this type of calculation.

  12. 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

  13. 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

  14. 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

  15. 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

  16. Long-term anti-FVIII antibody response in Bethesda-negative haemophilia A patients receiving continuous replacement therapy.

    PubMed

    Klintman, Jenny; Hillarp, Andreas; Berntorp, Erik; Astermark, Jan

    2013-11-01

    It has previously been shown that patients with haemophilia A may develop non-neutralizing anti-factor VIII (FVIII) antibodies (NNA) that escape detection by the Bethesda assay, but are detected using immune-based assays. We and others found NNAs to be directed not only towards non-functional parts of the protein, but towards all regions of the FVIII protein. We also showed a heterogeneous antibody response towards different FVIII products. However, the clinical relevance and the natural history of NNA remain unclear. Therefore, we followed a cohort of unrelated subjects with haemophilia A for 4 years with the goal of exploring the long-term development of NNA using an enzyme-linked immunosorbent assay (ELISA). Ten of 78 subjects (12·8%) exhibited an immune response that was transient and heterogeneous, and none of the subjects developed an FVIII inhibitor. The result of the ELISA was examined in relation to clinical variables and no significant associations between a positive ELISA and age, F8 mutation, port-à-cath implantation and HCV infection were shown. Interestingly, patients with NNA had significantly fewer bleeding episodes (P = 0·048) compared with NNA-negative subjects. The results indicate that the immune response to FVIII products within an individual may vary over time. However, the clinical impact of NNA remains unclear. PMID:24032553

  17. 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

  18. 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.

  19. 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

  20. 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

  1. 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. PMID:23980249

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

    PubMed Central

    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. PMID:25009784

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

    PubMed Central

    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

    2016-01-01

    ABSTRACT 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.

  4. 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

  5. Which care? Whose responsibility? And why family? A Confucian account of long-term care for the elderly.

    PubMed

    Fan, Ruiping

    2007-01-01

    Across the world, socio-economic forces are shifting the locus of long-term care from the family to institutional settings, producing significant moral, not just financial costs. This essay explores these costs and the distortions in the role of the family they involve. These reflections offer grounds for critically questioning the extent to which moral concerns regarding long-term care in Hong Kong and in mainland China are the same as those voiced in the United States, although family resemblances surely exist. Chinese moral values such as virtue and filial piety embedded in a Confucian moral and social context cannot be recast without distortion in terms of modern Western European notions. The essay concludes that the Confucian resources must be taken seriously in order to develop an authentic Chinese bioethics of long-term care and a defensible approach to long-term care policy for contemporary society in general and Chinese society in particular. PMID:17924274

  6. Difference in tumor incidence and other tissue responses to polyetherurethanes and polydimethylsiloxane in long-term subcutaneous implantation into rats.

    PubMed

    Nakamura, A; Kawasaki, Y; Takada, K; Aida, Y; Kurokama, Y; Kojima, S; Shintani, H; Matsui, M; Nohmi, T; Matsuoka, A

    1992-05-01

    The long-term (1- and 2-year) adverse tissue responses including tumor formation by subcutaneous implantation of polyurethanes (PUs) and silicone (Sil) films into rats were compared. The weight-averaged molecular weights (Mw) of the PUs prepared from 4,4'-diphenylmethanediisocyanate, poly(tetramethyleneglycol) of Mn = 1000 and 1,4-butanediol are 220,000 (U-4), 124,000 (U-6), and 55,600 (U-8). The 50:50 mixed film of U-6 and silicone (U-6/sil) was prepared by roll-mixing of the noncured silicone and the U-6 solution followed by evaporation of the solvent and heat-curing at 70 degrees C. The tissue responses around implants were classified into four groups as follows: (A) tumor, (B) atypical cell proliferation accompanied by preneoplastic changes, (C) cell proliferation without preneoplastic changes, (D) no obvious responses. In both implantation periods, the PUs gave higher incidents of the adverse responses including tumor formation in comparison to Sil. No significant molecular weight-dependent trend was found in a 1-year study using U-4, 6, and 8. Significant PU-dose-dependent trends were found in a 2-year study: the total active incidence (A+B+C), U-6(22/29) greater than U-6/sil(11/29) greater than sil(7/28); tumor incidence (A), U-6(11/29) greater than U-6/sil(2/29) = sil(2/28). No detectable amounts of 4,4'-methylenedianiline (MDA) were found in the PUs. The methanol extracts from the PUs were negative in the mutagenicity tests. These indicate no relationship between the tumor formation by the PU films and the mutagenicities of the chemicals (mainly oligomers) leached from the PUs. PMID:1512283

  7. 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.

  8. 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.

  9. 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.

  10. 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

  11. 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

  12. 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

  13. 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

  14. Metabolomic and transcriptomic responses induced in the livers of pigs by the long-term intake of resistant starch.

    PubMed

    Sun, Y; Yu, K; Zhou, L; Fang, L; Su, Y; Zhu, W

    2016-03-01

    The present study investigated metabolomic and transcriptomic responses in the livers of pigs to evaluate the effects of resistant starch on the body's metabolism at the extraintestinal level. Thirty-six Duroc× Landrace × Large White growing barrows (70 d of age) were randomly allocated to either the corn starch (CS) group or the raw potato starch (RPS) group with a randomized complete block design; each group consisted of 6 replicates (pens), with 3 pigs per pen. Pigs in the CS group were offered a corn-soybean-based diet, whereas pigs in the RPS group were put on a diet in which 230 (growing) or 280 g/kg (finishing) purified CS was replaced with purified RPS during a 100-d trial. The livers of pigs were collected for metabolome and gene expression analysis. Gas chromatography-mass spectrometry analysis showed that compared with the CS diet, the RPS diet decreased ( < 0.05) cholesterol and palmitic acid as well as increased ( < 0.05) 3-hydroxybutyric acid, which indicated the reduction of adipose weight and fatty acid biosynthesis and the elevation of fatty acid β-oxidation. In addition, 2-ketoglutaric acid and glucose-6-phosphate were increased (< 0.05) although pyruvic acid was decreased ( < 0.05) in the RPS group, indicating the upregulated capacity of glucose phosphorylation and glycolysis. Microarray analysis showed that the mRNA expression of (), (), and () were downregulated ( < 0.05) whereas (), (), and () were upregulated ( < 0.05) in the RPS diet, indicating a decrease in fatty acid intake and synthesis and an increase in fatty acid oxidation and glycerophospholipid synthesis. The results demonstrated that the long-term consumption of RPS could modulate hepatic lipid metabolism by decreasing fatty acid synthesis as well as increasing lipid oxidation and glycerophospholipid synthesis. PMID:27065270

  15. 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

  16. 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

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

    NASA Astrophysics Data System (ADS)

    Jones, J. A.; Creed, I. F.; Spargo, A.; Buttle, J. M.; Adams, M.; Beall, F. D.; Booth, E.; Campbell, J. L.; Clow, D. W.; Elder, K.; Ford, C. R.; Grimm, N. B.; Ramlal, P.; Saha, A.; Sebestyen, S. D.; Spittlehouse, D.; Sterling, S. M.; Williams, M. W.; Winkler, R. D.; Yao, H.

    2013-12-01

    Climate warming is projected to affect forest catchment water yields, but effects may vary among biomes. We hypothesized that catchments where water yields have varied relatively little in response to climate warming would be more resilient to warming effects than other types of catchments are. To test this hypothesis, we examined the variability in historical catchment water yields at long-term experimental watershed sites across Canada and the United States. Using the theoretical framework of the Budyko curve, which estimates catchment evaporation as a function of catchment dryness, we calculated the effects of climate warming on the annual partitioning of precipitation (P) into evapotranspiration (ET) and water yield. Deviation was defined as a catchment's change in actual ET divided by P (AET/P) coincident with a shift from a cool to warm period. Elasticity was defined as the ratio of inter-annual variation in potential ET divided by P (PET/P, the dryness index) to inter-annual variation in actual ET divided by P (AET/P, the evaporative index). Deviation in water yields was related to elasticity. Alpine sites showed greatest sensitivity to climate warming with any warming leading to increased water yields. Conifer sites included catchments with lowest elasticity and had stable to higher water yields, deciduous sites included catchments with intermediate elasticity and had stable to lower water yields, and mixed forests included catchments with highest elasticity and had stable water yields. For all forest types, there was a tendency for elasticity to converge to 1.0 with forest age. Both forest type and age were determinants of elasticity, which leads to resilience of catchment water yields to climate warming.

  18. 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

  19. Total water storage dynamics in response to climate variability and extremes: Inference from long-term terrestrial gravity measurement

    NASA Astrophysics Data System (ADS)

    Creutzfeldt, Benjamin; Ferré, Ty; Troch, Peter; Merz, Bruno; Wziontek, Hartmut; Güntner, Andreas

    2012-04-01

    Terrestrial water storage is a basic element of the hydrological cycle and a key state variable for land surface-atmosphere interaction. However, measuring water storage in a comprehensive way for different storage compartments and beyond the point scale is a challenge. In this study, we explore a 10-year time series of total water storage changes derived from high-precision superconducting gravimeter observations in a headwater catchment in Southern Germany. In combination with hydro-meteorological data, we examine the relationship between gravity-derived water storage changes, climate, and river discharge. Distinct seasonal water storage dynamics observed by the gravimeter are strongly related to the meteorological forcing, in particular evapotranspiration. Intra-annual water storage variations demonstrate that the simplifying assumption of water storage averaging to zero at the annual scale is not valid for this catchment. At the event-scale, gravimeters provide a measure of the available subsurface water storage capacity, which can be useful for runoff prediction. During the Central European drought in 2003, the gravimeter data show a strong depletion of water storage and a long-term recovery that extended over a period of several years. In comparison to point measurements or different environmental indices, our findings suggest that depth-integrated gravimeter measurements give a more complete picture of the dynamics of a hydrologic system in response to climate variability and extremes. In view of the considerable costs of gravimeters concerning the infrastructure and measurements, we suggest the strategic deployment of gravimeters at selected sites of hydro-meteorological monitoring networks.

  20. 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

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

    PubMed

    Zugmaier, Gerhard; 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

    2015-12-10

    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

  2. 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

  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. 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…

  5. Acute and long-term transcriptional responses in sulfur mustard-exposed SKH-1 hairless mouse skin.

    PubMed

    Vallet, V; Poyot, T; Cléry-Barraud, C; Coulon, D; Sentenac, C; Peinnequin, A; Boudry, I

    2012-03-01

    Sulfur mustard (HD) ranks among the alkylating chemical warfare agents. Skin contact with HD produces an inflammatory response that evolves into separation at the epidermal-dermal junction conducting to blistering and epidermis necrosis. Up to now, current treatment strategies of HD burns have solely consisted in symptomatic management of skin damage. Therapeutic efficacy studies are still being conducted; classically using appropriate animal skin toxicity models. In order to substantiate the use of SKH-1 hairless mouse as an appropriate model for HD-induced skin lesions, we investigate the time-dependent quantitative gene expression of various selected transcripts associated to the dorsal skin exposure to HD saturated vapors. Using quantitative real time polymerase chain reaction (RT-qPCR), the expression of interleukins (IL-1β and IL-6), tumor necrosis factor (TNF)-α, macrophage inflammatory proteins (MIP)-2α (also called Cxcl2) and MIP-1αR (also called Ccr1), matrix metalloproteases (MMP-9 and MMP-2), laminin γ2 monomer (Lamc2) and keratin (K)1 was determined up to 21 days after HD challenge in order to allow enough time for wound repair to begin. Specific transcript RT-qPCR analysis demonstrated that IL-6, IL-1β, Ccr1, Cxcl2 mRNA levels increased as early as 6 h in HD-exposed skins and remained up-regulated over a 14-day period. Topical application of HD also significantly up-regulated MMP-9, TNF-α, and Lamc2 expression at specific time points. In contrast, MMP-2 mRNA levels remained unaffected by HD over the time-period considered, whereas that long-term study revealed that K1 mRNA level significantly increased only 21 days after HD challenge. Our study hereby provides first-hand evidence to substantiate a long period variation expression in the inflammatory cytokine, MMPs and structural components following cutaneous HD exposure in hairless mouse SKH-1. Our data credit the use of SKH-1 for investigating mechanisms of HD-induced skin toxicity and for

  6. 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

  7. 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.

  8. 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

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

    NASA Astrophysics Data System (ADS)

    Lauer, Matthew; Aswani, Shankar

    2010-05-01

    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.

  10. Indigenous knowledge and long-term ecological change: detection, interpretation, and responses to changing ecological conditions in Pacific Island communities.

    PubMed

    Lauer, Matthew; Aswani, Shankar

    2010-05-01

    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

  11. 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

  12. 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

  13. 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. PMID:10353091

  14. Trace gas and vegetation feedback responses of Alaskan tussock tundra to long-term snow depth manipulations

    NASA Astrophysics Data System (ADS)

    Ebbs, L. M.; Taneva, L.; Sullivan, P.; Welker, J. M.

    2009-12-01

    Changes in the precipitation and temperature regimes in Northern Alaska are manifesting themselves through shifts in sea ice, vegetation traits, animal migration timing and hydrologic dynamics. Changes in precipitation and soil temperature result in changes in plant mineral nutrition, soil nutrient availability, trace gas exchanges and differential nutrient acquisition strategies by arctic plants. In this study, we report on the extent to which long-term increases in snow depth, along with reductions in snow depth alter the magnitudes and pattern of CO2 exchange, soil properties and vegetation traits. A doubling of snow depth (from ~0.5 to ~1.0m) results in a delay of the growing season by ~ 2 weeks, however, by peak season, the rates of CO2 exchange are 50% higher in areas which had experienced deeper snow depth levels. To the contrary, long-term reductions in snow depth results in accelerated rates of plant phenology, however CO2 exchange rates at peak season are 30% less than those areas under ambient snow cover in the preceding winter. Reduced snow depth areas had the coldest winter soil temperatures while the deeper areas had the warmest winter soil temperatures, which may partially explain the summer CO2 fluxes indirectly via different rates of winter N mineralization and differences in leaf N properties. Our results indicate that shifting fall, winter and spring when snow is the primary form of precipitation, may have profound effects on tussock tundra systems.

  15. Response of a three dimensional bioelectrochemical denitrification system to the long-term presence of graphene oxide.

    PubMed

    Chen, Dan; Wang, Xufeng; Yang, Kai; Wang, Hongyu

    2016-08-01

    In this study, a three dimensional bioelectrochemical denitrification system (3D-BEDS) was operated under long-term graphene oxide (GO) condition to treat high nitrate polluted water. When GO concentration increased from 0 to 100mgL(-1), nitrate removal efficiency slightly decreased from 99.52% to 94.81%. However, when GO concentration was further increased to 150mgL(-1), the denitrification efficiency dramatically decreased to 74.95%. Increasing GO concentration in this BEDS resulted in decreased community richness, and the abundances of the dominant bacterial communities presented obvious shift. The abundances of denitrifying genes napA, nirS, and nirK showed no obvious changes with GO concentration lower than 50mgL(-1). However, the abundances of the three genes decreased when GO concentration was further increased to higher than 100mgL(-1). The increased lactate dehydrogenase (LDH) release and reactive oxygen species (ROS) production demonstrated that long-term presence of GO caused chronic impacts onto microorganisms in this BEDS. PMID:27115747

  16. Long-Term Persistence of Donor Alveolar Macrophages in Human Lung Transplant Recipients That Influences Donor-Specific Immune Responses.

    PubMed

    Nayak, D K; Zhou, F; Xu, M; Huang, J; Tsuji, M; Hachem, R; Mohanakumar, T

    2016-08-01

    Steady-state alveolar macrophages (AMs) are long-lived lung-resident macrophages with sentinel function. Evidence suggests that AM precursors originate during embryogenesis and populate lungs without replenishment by circulating leukocytes. However, their presence and persistence are unclear following human lung transplantation (LTx). Our goal was to examine donor AM longevity and evaluate whether AMs of recipient origin seed the transplanted lungs. Origin of AMs was accessed using donor-recipient HLA mismatches. We demonstrate that 94-100% of AMs present in bronchoalveolar lavage (BAL) were donor derived and, importantly, AMs of recipient origin were not detected. Further, analysis of BAL cells up to 3.5 years post-LTx revealed that the majority of AMs (>87%) was donor derived. Elicitation of de novo donor-specific antibody (DSA) is a major post-LTx complication and a risk factor for development of chronic rejection. The donor AMs responded to anti-HLA framework antibody (Ab) with secretion of inflammatory cytokines. Further, in an experimental murine model, we demonstrate that adoptive transfer of allogeneic AMs stimulated humoral and cellular immune responses to alloantigen and lung-associated self-antigens and led to bronchiolar obstruction. Therefore, donor-derived AMs play an essential role in the DSA-induced inflammatory cascade leading to obliterative airway disease of the transplanted lungs. PMID:27062199

  17. 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

  18. 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

  19. 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

  20. 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

  1. Experimental Traumatic Brain Injury Results in Long-Term Recovery of Functional Responsiveness in Sensory Cortex but Persisting Structural Changes and Sensorimotor, Cognitive, and Emotional Deficits.

    PubMed

    Johnstone, Victoria P A; Wright, David K; Wong, Kendrew; O'Brien, Terence J; Rajan, Ramesh; Shultz, Sandy R

    2015-09-01

    Traumatic brain injury (TBI) is a leading cause of death worldwide. In recent studies, we have shown that experimental TBI caused an immediate (24-h post) suppression of neuronal processing, especially in supragranular cortical layers. We now examine the long-term effects of experimental TBI on the sensory cortex and how these changes may contribute to a range of TBI morbidities. Adult male Sprague-Dawley rats received either a moderate lateral fluid percussion injury (n=14) or a sham surgery (n=12) and 12 weeks of recovery before behavioral assessment, magnetic resonance imaging, and electrophysiological recordings from the barrel cortex. TBI rats demonstrated sensorimotor deficits, cognitive impairments, and anxiety-like behavior, and this was associated with significant atrophy of the barrel cortex and other brain structures. Extracellular recordings from ipsilateral barrel cortex revealed normal neuronal responsiveness and diffusion tensor MRI showed increased fractional anisotropy, axial diffusivity, and tract density within this region. These findings suggest that long-term recovery of neuronal responsiveness is owing to structural reorganization within this region. Therefore, it is likely that long-term structural and functional changes within sensory cortex post-TBI may allow for recovery of neuronal responsiveness, but that this recovery does not remediate all behavioral deficits. PMID:25739059

  2. Long-term opioid blockade and hedonic response: preliminary data from two open-label extension studies with extended-release naltrexone.

    PubMed

    O'Brien, Charles P; Gastfriend, David R; Forman, Robert F; Schweizer, Edward; Pettinati, Helen M

    2011-01-01

    The emergence of extended-release naltrexone (XR-NTX) raises the opportunity to explore the role of endorphin blockade on hedonic response during long-term alcohol dependence treatment. A hedonic survey was administered to 74 alcohol dependent patients treated for an average of 3.5 years with nearly continuous month-long intramuscular XR-NTX. The paper-and-pencil, one-time survey asked patients about the degree of pleasure they experienced in the past 90 days with drinking alcohol, sex, exercise and other daily activities. The data revealed lower pleasure ratings for alcohol than for sex, exercise and 10 other common activities. Mean responses to drinking alcohol and gambling were significantly lower than to listening to music, sex, reading, being with friends, eating good food, eating spicy food, and playing video/card games. This effect was independent of XR-NTX dose or duration. Although this exploratory study lacked baseline data, a comparison group or control for the impact of patient discontinuation, the data indicate the feasibility of examining long-term hedonic response in recovery. The differential hedonic ratings suggest that, in patients who persist with long-term continuous therapy, XR-NTX may selectively inhibit the pleasure associated with drinking alcohol, compared to a variety of other activities.  PMID:21314752

  3. Long-term Opioid Blockade and Hedonic Response: Preliminary Data from Two Open-Label Extension Studies with Extended-Release Naltrexone

    PubMed Central

    O’Brien, Charles P.; Gastfriend, David R.; Forman, Robert F.; Schweizer, Edward; Pettinati, Helen M.

    2013-01-01

    The emergence of extended-release naltrexone (XR-NTX) raises the opportunity to explore the role of endorphin blockade on hedonic response during long-term alcohol dependence treatment. A hedonic survey was administered to 74 alcohol dependent patients treated for an average of 3.5 years with nearly continuous month-long intramuscular XR-NTX. The paper-and-pencil, one-time survey asked patients about the degree of pleasure they experience in the past 90 days with drinking alcohol, sex, exercise and other daily activities. The data revealed lower pleasure ratings for alcohol than for sex, exercise and 10 other common activities. Mean responses to drinking alcohol and gambling were significantly lower than to listening to music, sex, reading, being with friends, eating good food, eating spicy food and playing video/card games. This effect was independent of XR-NTX dose or duration. Although this exploratory study lacked baseline data, a comparison group or control for the impact of patient discontinuation, the data indicate the feasibility of examining long-term hedonic response in recovery. The differential hedonic ratings suggest that, in patients who persist with long-term continuous therapy, XR-NTX may selectively inhibit the pleasure associated with drinking alcohol, compared to a variety of other activities. PMID:21314752

  4. 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

  5. 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

  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. PMID:26782026

  7. Change in vascular smooth muscle response to 5-HT due to short- or long-term endothelial denudation of the bovine digital vein.

    PubMed

    Punzi, Simona; Belloli, Chiara; Gogny, Marc; Desfontis, Jean-Claude; Mallem, Mohamed Y

    2016-01-01

    Several chronic progressive vascular diseases, such as laminitis, show vasocontractile dysfunction that might evolve into reperfusion injury and/or vessel structural remodelling, which may be traced back to aberrant endothelial function. In the present study, the vasomotor responses of bovine digital veins (BDVs) to 5-hydroxytryptamine (5-HT) were investigated in blood vessels, with and without endothelium present, and in samples deprived of endothelium before or after overnight incubation in tissue culture medium, to evaluate the effects of short- and long-term endothelial damage on vascular smooth muscle (VSM) reactivity. No significant effects were observed in the blood vessels tested immediately after the removal of endothelium. In contrast, a significant increase in VSM reactivity to 5-HT was seen in vessels incubated without endothelium. This long-term change in smooth muscle reactivity was prevented by exposure to the nitric oxide (NO) donor nitroprusside (P < 0.01), suggesting that the long-term lack of inhibitory control exerted by endothelium-derived NO is involved in increased VSM reactivity. The RhoA/ROCK pathway inhibitor fasudil reduced VSM hyper-contractility to ~65% (P < 0.001), the superoxide dismutase-mimetic tempol normalised the vascular response and the non-selective COX-inhibitor indomethacin exerted a moderate inhibitory effect (P < 0.05). Thus, over-activation of the RhoA/ROCK pathway and production of reactive oxygen species could account for VSM hyper-reactivity, triggered by long-term endothelium-deprivation in BDVs, suggesting that these biochemical mechanisms are potential targets for controlling the progressive vasocontractile dysfunction of digital veins in animals affected with laminitis. PMID:26670334

  8. 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.

  9. Long-term preservation of antibody-dependent cellular cytotoxicity (ADCC) of natural killer cells amplified in vitro from the peripheral blood of breast cancer patients after chemotherapy.

    PubMed

    Clémenceau, Béatrice; Gallot, Géraldine; Vivien, Régine; Gaschet, Joëlle; Campone, Mario; Vié, Henri

    2006-01-01

    Twenty percent of breast cancer adenocarcinomas overexpress the oncogene c-erb-2 that is recognized by the humanized anti-Her2/neu monoclonal antibody Herceptin. Results from clinical studies suggest that antibody-dependent cellular cytotoxicity (ADCC) is involved in the clinical response of Herceptin-treated patients. The purpose of the current study was to evaluate the possibility of amplifying in vitro the CD3-/CD16+ natural killer (NK) cell subset that mediates ADCC from breast cancer patients after chemotherapy. Peripheral blood mononuclear cells from six breast cancer patients taken 2 months after chemotherapy completion were co-cultured with an autologous irradiated Epstein-Barr virus-transformed B-lymphoblastoid cell line (LCL) in the presence of interleukin-2 (IL-2) for 4-6 weeks. These LCL + IL2 activated cultures (ACs) were tested for ADCC potential, and their CD3/CD16 NK proportion was quantified. Among the ACs, the proportion of CD3-/CD16+ NK cells increased up to 64% over the first 2 weeks of culture and the ACs continued to expand for 1 month thereafter. Control and patient ACs displayed ADCC activity (tested in the presence of Rituximab against the autologous LCL to take into account any possible effect of inhibitory NK receptors) as well as against the MCF-7(Her2/neu) breast cancer cell line in the presence of Herceptin. This ADCC activity was maintained during the entire culture period. In conclusion, chemotherapy in breast cancer patients does not obviate the possibility of amplifying in vitro the NK cell subset that mediates ADCC. Consequently, adoptive transfer of lymphocytes mediating ADCC can be considered using this protocol to test its benefit in patients under Herceptin treatment. PMID:16365600

  10. 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

  11. 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.

  12. Response of ammonia-oxidizing archaea and bacteria to long-term industrial effluent-polluted soils, Gujarat, Western India.

    PubMed

    Subrahmanyam, Gangavarapu; Shen, Ju-Pei; Liu, Yu-Rong; Archana, Gattupalli; He, Ji-Zheng

    2014-07-01

    Soil nitrifiers have been showing an important role in assessing environmental pollution as sensitive biomarkers. In this study, the abundance and diversity of ammonia-oxidizing archaea (AOA) and ammonia-oxidizing bacteria (AOB) were investigated in long-term industrial waste effluent (IWE) polluted soils. Three different IWE polluted soils characterized as uncontaminated (R1), moderately contaminated (R2), and highly contaminated (R3) were collected in triplicate along Mahi River basin, Gujarat, Western India. Quantitative numbers of ammonia monooxygenase α-subunit (amoA) genes as well as 16S rRNA genes indicated apparent deleterious effect of IWE on abundance of soil AOA, AOB, bacteria, and archaeal populations. Relatively, AOB was more abundant than AOA in the highly contaminated soil R3, while predominance of AOA was noticed in uncontaminated (R1) and moderately contaminated (R2) soils. Soil potential nitrification rate (PNR) significantly (P < 0.05) decreased in polluted soils R2 and R3. Reduced diversity accompanied by apparent community shifts of both AOB and AOA populations was detected in R2 and R3 soils. AOB were dominated with Nitrosospira-like sequences, whereas AOA were dominated by Thaumarchaeal "group 1.1b (Nitrososphaera clusters)." We suggest that the significant reduction in abundance and diversity AOA and AOB could serve as relevant bioindicators for soil quality monitoring of polluted sites. These results could be further useful for better understanding of AOB and AOA communities in polluted soils. PMID:24554021

  13. 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

  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. 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

  16. 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.

  17. 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

  18. 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

  19. Early changes in biochemical markers of bone turnover predict the long-term response to alendronate therapy in representative elderly women: a randomized clinical trial.

    PubMed

    Greenspan, S L; Parker, R A; Ferguson, L; Rosen, H N; Maitland-Ramsey, L; Karpf, D B

    1998-09-01

    Although the antiresorptive agent alendronate has been shown to increase bone mineral density (BMD) at the hip and spine and decrease the incidence of osteoporotic fractures in older women, few data are available regarding early prediction of long-term response to therapy, particularly with regard to increases in hip BMD. Examining short-term changes in biochemical markers incorporates physiologic response with therapeutic compliance and should provide useful prognostic information for patients. The objective of this study was to examine whether early changes in biochemical markers of bone turnover predict long-term changes in hip BMD in elderly women. The study was a double-blind, placebo-controlled, randomized clinical trial which took place in a community-based academic hospital. One hundred and twenty community-dwelling, ambulatory women 65 years of age and older participated in the study. Intervention consisted of alendronate versus placebo for 2.5 years. All patients received appropriate calcium and vitamin D supplementation. The principal outcome measures included BMD of the hip (total hip, femoral neck, trochanter, and intertrochanter), spine (posteroanterior [PA] and lateral), total body, and radius. Biochemical markers of bone resorption included urinary N-telopeptide cross-linked collagen type I and free deoxypyridinoline; markers of bone formation included serum osteocalcin and bone-specific alkaline phosphatase. Long-term alendronate therapy was associated with increased BMD at the total hip (4.0%), femoral neck (3.1%), trochanter (5.5%), intertrochanter (3.8%), PA spine (7.8%), lateral spine (10.6%), total body (2.2%), and one-third distal radius (1.3%) in elderly women (all p < 0.01). In the placebo group, bone density increased 1.9-2.1% at the spine (p < 0.05) and remained stable at all other sites. At 6 months, there were significant decreases in all markers of bone turnover (-10% to -53%, p < 0.01) in women on alendronate. The changes in urinary

  20. 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.

  1. 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. PMID:25504893

  2. 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

  3. 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.

  4. 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

  5. Simulation of the long term radiometric responses of the Terra MODIS and EO-1 ALI using Hyperion spectral responses over Railroad Valley Playa in Nevada (RVPN)

    NASA Astrophysics Data System (ADS)

    Choi, Taeyoung; Xiong, Xiaoxiong J.; Angal, Amit; Chander, Gyanesh

    2010-10-01

    The Earth Observing-1 (EO-1) Hyperion instrument provides 220 spectral bands with wavelengths between 400 and 2500 nm at 30 m spatial resolution, which covers a 7.5 km by 100 km area on the ground. The EO-1 spacecraft has another multispectral sensor called the Advanced Land Imager (ALI), which has 10 spectral bands with wavelengths between 400 and 2350 nm at 30 m spatial resolution. The Moderate Resolution Imaging Spectroradiometer (MODIS) sensor onboard the Terra spacecraft was launched in Dec., 1999, and flies approximately 30 minutes behind EO-1. Nearsimultaneous observations from Terra MODIS, EO-1 ALI and Hyperion over a well characterized Railroad Valley Playa in Nevada (RVPN) target are chosen for this study. A uniform region of interest (ROI) within the playa within latitudes and longitudes of 38.48 and -115.71 to 38.53 and -115.66 was chosen for this analysis. A representation of the ground spectra during every near-simultaneous acquisition of MODIS and ALI is obtained using EO-1 Hyperion data. Using the EO-1 Hyperion derived top-of-atmosphere (TOA) reflectance profile along with the ALI and MODIS relative spectral responses (RSR), simulated reflectance for the matching band pairs is calculated. The Hyperion simulated TOA reflectance results are compared to the measured TOA reflectance trends of ALI and MODIS. The long-term measured versus simulated reflectance results are used to examine the relationships and calibration differences between the ALI and MODIS sensors.

  6. 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. PMID:24115504

  7. Prostate stem cell antigen vaccination induces a long-term protective immune response against prostate cancer in the absence of autoimmunity.

    PubMed

    Garcia-Hernandez, Maria de la Luz; Gray, Andrew; Hubby, Bolyn; Klinger, Otto J; Kast, W Martin

    2008-02-01

    Prostate stem cell antigen (PSCA) is an attractive antigen to target using therapeutic vaccines because of its overexpression in prostate cancer, especially in metastatic tissues, and its limited expression in other organs. Our studies offer the first evidence that a PSCA-based vaccine can induce long-term protection against prostate cancer development in prostate cancer-prone transgenic adenocarcinoma mouse prostate (TRAMP) mice. Eight-week-old TRAMP mice displaying prostate intraepithelial neoplasia were vaccinated with a heterologous prime/boost strategy consisting of gene gun-delivered PSCA-cDNA followed by Venezuelan equine encephalitis virus replicons encoding PSCA. Our results show the induction of an immune response against a newly defined PSCA epitope that is mediated primarily by CD8 T cells. The prostates of PSCA-vaccinated mice were infiltrated by CD4-positive, CD8-positive, CD11b-positive, and CD11c-positive cells. Vaccination induced MHC class I expression and cytokine production [IFN-gamma, tumor necrosis factor-alpha, interleukin 2 (IL-2), IL-4, and IL-5] within prostate tumors. This tumor microenvironment correlated with low Gleason scores and weak PSCA staining on tumor cells present in hyperplastic zones and in areas that contained focal and well-differentiated adenocarcinomas. PSCA-vaccinated TRAMP mice had a 90% survival rate at 12 months of age. In contrast, all control mice had succumbed to prostate cancer or had heavy tumor loads. Crucially, this long-term protective immune response was not associated with any measurable induction of autoimmunity. The possibility of inducing long-term protection against prostate cancer by vaccination at the earliest signs of its development has the potential to cause a dramatic paradigm shift in the treatment of this disease. PMID:18245488

  8. 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

  9. Is long-term virological response related to CCR5 Δ32 deletion in HIV-1-infected patients started on highly active antiretroviral therapy?

    PubMed Central

    Laurichesse, Jean-Jacques; Taieb, Audrey; Capoulade-Metay, Corinne; Katlama, Christine; Villes, Virginie; Drobacheff-Thiebaud, Marie-Christine; Raffi, François; Chêne, Genevieve; Theodorou, Ioannis; Leport, Catherine

    2010-01-01

    Objective To examine whether CCR5 Δ32 deletion is associated with long-term response to combination antiretroviral treatment (cART) in HIV-1 infected patients. Methods The genetic sub-study of ANRS CO8 APROCO-COPILOTE cohort included 609 patients who started a protease inhibitor-containing cART in 1997–99. Patients were considered to have a sustained virological response if all plasma HIV-RNA measurements between month 4 and years 3–5 were <500 copies/ml, allowing for a single blip. Virological response was compared between patients heterozygous for CCR5 Δ32 (Δ32/wt) and wild-type patients (wt/wt) from month 4 to year 3 and month 4 to year 5. Logistic regression analysis was used to adjust for baseline demographical data, HIV-RNA, CD4 cell counts, antiretroviral naive status, time spent on antiretroviral therapy at year 3 and 5 and adherence to treatment (month 4 to year 3 and 5). Results Sustained virological response was better in Δ32/wt than in wt/wt patients: 66% versus 52% up to year 3 (p=0.02), nearly significant after adjustment to potential cofounders (p=0.07). Δ32/wt patients had a better virological response, up to year 5, 48% versus 35% (p=0.01), and remained significantly better, after adjustment, associated with a better virological response up to 5 years post initiation of cART (p=0.04). There was no association with CD4 response. Conclusion Δ32/wt deletion is associated with a beneficial virological response to cART on the long-term. Whether this association can be a direct effect of Δ32/wt deletion remains questionable and needs confirmation in other observational studies. PMID:20050936

  10. 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.

  11. 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

  12. 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

  13. Long-Term Antibody and Immune Memory Response Induced by Pulmonary Delivery of the Influenza Iscomatrix Vaccine

    PubMed Central

    Vujanic, Ana; Snibson, Kenneth J.; Wee, Janet L. K.; Edwards, Stirling J.; Pearse, Martin J.; Scheerlinck, Jean-Pierre Y.

    2012-01-01

    Pulmonary delivery of an influenza Iscomatrix adjuvant vaccine induces a strong systemic and mucosal antibody response. Since an influenza vaccine needs to induce immunological memory that lasts at least 1 year for utility in humans, we examined the longevity of the immune response induced by such a pulmonary vaccination, with and without antigen challenge. Sheep were vaccinated in the deep lung with an influenza Iscomatrix vaccine, and serum and lung antibody levels were quantified for up to 1 year. The immune memory response to these vaccinations was determined following antigen challenge via lung delivery of influenza antigen at 6 months and 1 year postvaccination. Pulmonary vaccination of sheep with the influenza Iscomatrix vaccine induced antigen-specific antibodies in both sera and lungs that were detectable until 6 months postimmunization. Importantly, a memory recall response following antigenic challenge was detected at 12 months post-lung vaccination, including the induction of functional antibodies with hemagglutination inhibition activity. Pulmonary delivery of an influenza Iscomatrix vaccine induces a long-lived influenza virus-specific antibody and memory response of suitable length for annual vaccination against influenza. PMID:22072721

  14. Long-term channel block is required to inhibit cellular transformation by human ether-à-go-go-related gene (hERG1) potassium channels.

    PubMed

    Pier, David M; Shehatou, George S G; Giblett, Susan; Pullar, Christine E; Trezise, Derek J; Pritchard, Catrin A; Challiss, R A John; Mitcheson, John S

    2014-08-01

    Both human ether-à-go-go-related gene (hERG1) and the closely related human ether-à-go-go (hEAG1) channel are aberrantly expressed in a large proportion of human cancers. In the present study, we demonstrate that transfection of hERG1 into mouse fibroblasts is sufficient to induce many features characteristic of malignant transformation. An important finding of this work is that this transformation could be reversed by chronic incubation (for 2-3 weeks) with the hERG channel blocker dofetilide (100 nM), whereas more acute applications (for 1-2 days) were ineffective. The hERG1 expression resulted in a profound loss of cell contact inhibition, multiple layers of overgrowing cells, and high saturation densities. Cells also changed from fibroblast-like to a more spindle-shaped morphology, which was associated with a smaller cell size, a dramatic increase in cell polarization, a reduction in the number of actin stress fibers, and less punctate labeling of focal adhesions. Analysis of single-cell migration and scratch-wound closure clearly demonstrated that hERG1-expressing cells migrated more rapidly than vector-transfected control cells. In contrast to previous studies on hEAG1, there were no increases in rates of proliferation, or loss of growth factor dependency; however, hERG1-expressing cells were capable of substrate-independent growth. Allogeneic transplantation of hERG1-expressing cells into nude mice resulted in an increased incidence of tumors. In contrast to hEAG1, the mechanism of cellular transformation is dependent on ion conduction. Trafficking-deficient and conduction-deficient hERG1 mutants also prevented cellular transformation. These results provide evidence that hERG1 expression is sufficient to induce cellular transformation by a mechanism distinct from hEAG1. The most important conclusion of this study is that selective hERG1 channel blockers have therapeutic potential in the treatment of hERG1-expressing cancers. PMID:24830940

  15. 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

  16. 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. PMID:21800171

  17. Eradication of liver-implanted tumors by Semliki Forest virus expressing IL-12 requires efficient long-term immune responses.

    PubMed

    Quetglas, Jose I; Rodriguez-Madoz, Juan R; Bezunartea, Jaione; Ruiz-Guillen, Marta; Casales, Erkuden; Medina-Echeverz, Jose; Prieto, Jesus; Berraondo, Pedro; Hervas-Stubbs, Sandra; Smerdou, Cristian

    2013-03-15

    Semliki Forest virus vectors expressing IL-12 (SFV-IL-12) were shown to induce potent antitumor responses against s.c. MC38 colon adenocarcinomas in immunocompetent mice. However, when MC38 tumors were implanted in liver, where colon tumors usually metastasize, SFV-IL-12 efficacy was significantly reduced. We reasoned that characterization of immune responses against intrahepatic tumors in responder and nonresponder animals could provide useful information for designing more potent antitumor strategies. Remarkably, SFV-IL-12 induced a high percentage of circulating tumor-specific CD8 T cells in all treated animals. Depletion studies showed that these cells were essential for SFV-IL-12 antitumor activity. However, in comparison with nonresponders, tumor-specific cells from responder mice acquired an effector-like phenotype significantly earlier, were recruited more efficiently to the liver, and, importantly, persisted for a longer period of time. All treated mice had high levels of functional specific CD8 T cells at 8 d posttreatment reflected by both in vivo killing and IFN-γ-production assays, but responder animals showed a more avid and persistent IFN-γ response. Interestingly, differences in immune responses between responders and nonresponders seemed to correlate with the immune status of the animals before treatment and were not due to the treatment itself. Mice that rejected tumors were protected against tumor rechallenge, indicating that sustained memory responses are required for an efficacious therapy. Interestingly, tumor-specific CD8 T cells of responder animals showed upregulation of IL-15Rα expression compared with nonresponders. These results suggest that SFV-IL-12 therapy could benefit from the use of strategies that could either upregulate IL-15Rα expression or activate this receptor. PMID:23401594

  18. 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.

  19. Aqueous exposure to Aroclor 1254 modulates the mitogenic response of Atlantic salmon anterior kidney T-cells: indications of short- and long-term immunomodulation.

    PubMed

    Iwanowicz, Luke R; Lerner, Darren T; Blazer, Vicki S; McCormick, Stephen D

    2005-05-15

    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 microgL-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 microgL-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 microgL-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 microgL-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 microgL-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. PMID:15848250

  20. 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

  1. Long-term effects of chronic cocaine exposure throughout adolescence on anxiety and stress responsivity in a Wistar rat model.

    PubMed

    Alves, C J; Magalhães, A; Melo, P; de Sousa, L; Tavares, M A; Monteiro, P R R; Summavielle, T

    2014-09-26

    Adolescents display increased vulnerability to engage in drug experimentation. This is often considered a risk factor for later drug abuse. In this scenario, the permanent effects of cocaine exposure during adolescence on anxiety levels and stress responsivity, which may result in behavioral phenotypes prone to addiction, are now starting to be unveiled. Thus, the purpose of the present study was to evaluate the long-lasting effects of chronic cocaine administration during adolescence, on anxiety-like behavior and on stress response. Adolescent male Wistar rats were daily administered 45-mg cocaine/kg of body weight in three equal intraperitoneal doses with 1-h interval, from postnatal day (PND) 35 to 50. The effects of cocaine administration on anxiety levels, assessed in the Elevated Plus Maze (EPM), and on social stress response, assessed in the resident-intruder paradigm (R/I), were evaluated 10 days after withdrawal, when rats were reaching the adulthood. The underlying dopaminergic activity, and the corticosterone and testosterone levels were determined. Our results showed that cocaine induced long-lasting alterations in the hypothalamus-pituitary-adrenals (HPA) axis function and in testosterone levels. Such alterations resulted in significant and enduring changes in behavioral responses to environmental challenges, such as the EPM and R/I, including the evaluation of potential threats that may lead to high-risk behavior and low-benefit choices. This was further supported by an altered dopaminergic function in the amygdala and hippocampus. The present findings provide new insights into how the use of cocaine during adolescent development may modulate emotional behavior later in life. Compromised ability to recognize and deal with potential threats is an important risk factor to perpetuate compulsive drug seeking and relapse susceptibility. PMID:25047999

  2. 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

  3. 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

  4. A Case of Long-Term Seronegative Human Immunodeficiency Virus (HIV) Infection: The Importance of the Humoral Response to HIV

    PubMed Central

    Siemieniuk, Reed A. C.; van der Meer, Frank; van Marle, Guido; Gill, M. John

    2016-01-01

    Background. Seronegative human immunodeficiency virus (HIV) infections are exceedingly rare but might inform HIV-host physiology. Methods. We investigate the cause and consequences of a patient infected with HIV who did not mount a humoral response to HIV for 4 years. Results. The patient was confirmed HIV-uninfected by nucleic acid testing 4 months before rapidly progressing to acquired immune deficiency syndrome. The patient's humoral deficit was specific to HIV: he mounted robust humoral responses to all challenge vaccines including influenza A(H1N1)pdm09 and all T cell-dependent and -independent serotypes in the 23-valent pneumococcal polysaccharide vaccine. The virus had similar gp120 antigenicity to HIV-positive control serum as NL4-3 and YU2 prototype strains. Two human leukocyte antigen alleles associated with rapid progression were identified (B*08 and B*35), and a cytotoxic T-lymphocyte epitope site variant was noted: E277K. Viral decay (t1/2 ≈ 39 weeks) suggested that relatively long-lived cells were the source of ongoing viremia. Human immunodeficiency virus viremia was not suppressed until after the patient developed a humoral immune response, despite therapeutic antiretroviral levels. No resistance was detected by virtual phenotyping of virus obtained from serum or from gastrointestinal biopsies despite considerable antiretroviral selection pressure. Conclusions. Ineffective antibody production may be associated with a subgroup of extremely rapid HIV progressors. Although antiretroviral therapy may be sufficient to slow propagation of infection, it appears to be ineffective for HIV viral clearance in the absence of a humoral response. PMID:26858962

  5. 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.

  6. 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

  7. 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

  8. 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. PMID:25415976

  9. UDP-glucose pyrophosphorylase Ugp1 is involved in oxidative stress response and long-term survival during stationary phase in Saccharomyces cerevisiae.

    PubMed

    Yi, Dae-Gwan; Huh, Won-Ki

    2015-11-27

    Ugp1, UDP-glucose pyrophosphorylase, plays an important role in carbohydrate metabolism because it provides UDP-glucose that is a pivotal metabolite in several metabolic pathways in Saccharomyces cerevisiae. In this study, we show that a considerable reduction of glycogen and trehalose content in ugp1 knockdown cells is rescued by complementing the expression of Ugp1, indicating that Ugp1 is required for the production of storage carbohydrates. Because of the specific function of trehalose as a stress protectant, Ugp1 expression contributed to oxidative stress response and long-term cell survival during stationary phase. Furthermore, the modulation of Ugp1 level readjusted glycogen and trehalose accumulation in the protein kinase A (PKA)-related gene mutants. The PKA-dependent phenotypes of oxidative stress resistance and long-term cell survival were also alleviated via adjustment of Ugp1 level. Collectively, our data suggest that the regulation of UPG1 influences several PKA-dependent processes by adjusting the levels of various carbohydrates. PMID:26498530

  10. 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

  11. Response of benthic foraminifera to ocean acidification in their natural sediment environment: a long-term culturing experiment

    NASA Astrophysics Data System (ADS)

    Haynert, K.; Schönfeld, J.; Schiebel, R.; Wilson, B.; Thomsen, J.

    2013-06-01

    Calcifying foraminifera are expected to be endangered by ocean acidification, However, the response of a complete community kept in natural sediment and over multiple generations under controlled laboratory conditions has not been constrained to date. During six month incubation, foraminiferal assemblages were treated with pCO2 enriched seawater of 430, 907, 1865 and 3247 μatm pCO2. The fauna was dominated by Ammonia aomoriensis and Elphidium species, whereas agglutinated species were rare. After 6 months incubation, pore water alkalinity was much higher in comparison to the overlying seawater. Consequently, the saturation state of Ωcalc was much higher in the sediment than in the water column in all pCO2 treatments and remained close to saturation. As a result, the life cycle of living assemblages was largely unaffected by the tested pCO2 treatments. Growth rates, reproduction and mortality, and therefore population densities and size-frequency distribution of Ammonia aomoriensis varied markedly during the experimental period. Growth rates varied between 25 and 50 μm per month, which corresponds to an addition of 1 or 2 new chambers per month. According to the size-frequency distribution, foraminifera start reproduction at a diameter of 250 μm. Mortality of large foraminifera was recognized, commencing at a test size of 285 μm at a pCO2 ranging from 430 to 1865 μatm, and of 258 μm at 3247 μatm. The total organic content of living Ammonia aomoriensis has been determined to be 4.3% of dry weight. Living individuals had a calcium carbonate production rate of 0.47 g m-2 yr-1, whereas dead empty tests accumulated at a rate of 0.27 g m-2 a-1. Although Ωcalc was close to 1, some empty tests of Ammonia aomoriensis showed dissolution features at the end of incubation. In contrast, tests of the subdominant species, Elphidium incertum, stayed intact. This species specific response could be explained by differences in the elemental test composition, in particular the

  12. Laser Doppler monitoring of alterations of blood-flow parameters in fish embryos in response to light irradiation: study of long-term and short-term reactions

    NASA Astrophysics Data System (ADS)

    Savchenko, Natalia B.; Priezzhev, Alexander V.; Revutsky, Pavel V.; Levenko, Borislav A.

    1997-05-01

    In this paper new experimental results on monitoring of alterations of blood flow parameters in growing fish embryos under laser and non-laser light irradiation are discussed. The measurements were performed by means of laser Doppler technique with high temporal and spatial resolution. Two parameters of blood flows were mostly measured: average velocity and frequency of velocity pulsations. These parameters were shown to be an adequate characteristics of nonstationary blood flows in fishes. The problem of noninvasivity of such experiments is discussed. For this purpose absorption spectra of fish embryos were measured. The quantitative response of blood flows to irradiation at different light wavelengths was recorded. Different species of fishes were used to compare the responses. Different effects were recorded which depend upon the doze and the wavelength of irradiation, and upon the stage of the embryo development at which the irradiation had taken place. Among those effects long-term and short-term reactions can be distinguished.

  13. 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.

  14. Complete response and long-term survival of leptomeningeal carcinomatosis from breast cancer with maintenance endocrine therapy.

    PubMed

    Almajed, Muneera Majed; Esfahani, Khashayar; Pelmus, Manuela; Panasci, Lawrence

    2016-01-01

    Leptomeningeal carcinomatosis carries a poor prognosis in breast cancer. Treatment modalities are geared towards tumour molecular characteristics, as well as symptoms and patient performance status. It has previously been postulated that endocrine treatments used for the treatment of metastatic breast cancer do cross the blood-brain barrier and can achieve antineoplastic effects in the central nervous system. We report a case of metastatic breast cancer in a 65-year-old woman who developed leptomeningeal carcinomatosis. She was initially treated with intrathecal methotrexate, which was stopped due to toxicity, followed by maintenance endocrine therapy. She achieved a sustained complete radiological and cerebrospinal fluid cytological response for over 9 years. She eventually passed away of ischaemic bowel unrelated to her cancer. PMID:27256996

  15. A Long-Term Study of Science Literacy and Attitudes Towards Science: Comparing Survey Responses of Undergraduates to Scientists

    NASA Astrophysics Data System (ADS)

    Buxner, Sanlyn; Impey, C.; Tijerino, K.; Antonellis, J.; Collaboration of Astronomy Teaching Scholars CATS

    2012-01-01

    Drawing from a database of over 10,000 undergraduate student responses to a science literacy survey, derived from policy driven projects (e.g. NSF Science Indicators), we have explored the change in students’ understandings and beliefs about science and technology from 1989 to 2011. Our analysis has revealed little change in students’ science literacy scores over twenty-two years. In addition, student demographic variables, including major and number of science courses completed, predicts less than 10% of the variance in students’ overall science literacy scores. Recently, we have analyzed students’ responses to four open-ended questions and compared their ideas to those of scientists asked the same questions. A word count analysis showed that when describing what it means to study something scientifically, students used the words "hypothesis", "study", "method", "test", and "experiment” the most. Surprisingly, scientists used the same words the most when answering the same question on a similar survey. In contrast, other words that scientists considered to be important in describing how to study something scientifically such as "creativity” and "imagination” were mentioned by only eleven students across the twenty-two years. Overall, there is evidence that non-science major students are able to describe science using many of the words we consider to be important in science although not in the same way as scientists. We describe implications of assessing student science literacy and learning what our students know about specific topics in science. This material is based in part upon work supported by the National Science Foundation under Grant No. 0715517, a CCLI Phase III Grant for the Collaboration of Astronomy Teaching Scholars (CATS). Any opinions, findings, and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the National Science Foundation.

  16. Local Seismicity Recorded by ChilePEPPER: Implications for Dynamic Accretionary Prism Response and Long-term Prism Evolution

    NASA Astrophysics Data System (ADS)

    de Moor, A.; Trehu, A. M.; Tryon, M. D.

    2015-12-01

    To investigate the dynamic response of the outer accretionary wedge updip from the patch of greatest slip during the Mw8.8 2010 Maule earthquake, 10 Ocean Bottom Seismometers (OBS) were deployed from May 2012 to March 2013 in a small array with an inter-instrument spacing of ~12 km . Nine instruments were recovered, with 4 recording data on 3 intermediate-band 3-component seismometers and a differential pressure gauge and 5 recording data from absolute pressure gauges. [note: All instruments were also equipped with a fluid flow meter sensitive to flow rates as low as 0.0001 cm/yr in or out of the sediments. However, no flow signal was detected.] Here we present hypocenters for 569 local events that have S-P times less than 17 seconds (i.e. within ~125 km of the array) using hand-picked arrival times and a 1D velocity model derived from a 2D seismic refraction profile through the region (Moscoso et al 2011, EPSL). We analyze the distribution of seismicity in the context of published slip models, ChilePEPPER high-resolution seismic reflection data, critical taper analysis done by Cubas et al 2013 (EPSL), and offshore gravity data. The data show distinct segmentation within the outer prism. The northern section of the study area is characterized by a lack of seismicity, accretion of nearly all incoming sediment and a prism at critical taper. In contrast, abundant seismicity, significant sediment underthrusting at the deformation front and a prism below critical taper angle characterize the southern part of the study area. Both coseismic slip and post-rupture local seismicity can be related to density anomalies within the upper plate as revealed by free air gravity data corrected for the effects of bathymetry and the subducting plate. [ChilePEPPER - Project Evaluating Prism Post-Earthquake Response

  17. Cardiac-like flow generator for long-term imaging of endothelial cell responses to circulatory pulsatile flow at microscale.

    PubMed

    Chen, Huaying; Cornwell, James; Zhang, Han; Lim, Tse; Resurreccion, Rena; Port, Timothy; Rosengarten, Gary; Nordon, Robert E

    2013-08-01

    In vitro models of circulatory hemodynamics are required to mimic the microcirculation for study of endothelial cell responses to pulsatile shear stress by live cell imaging. This study reports the design, fabrication and characterisation of a microfluidic device that generates cardiac-like flow in a continuous culture system with a circulatory volume of only 2-3 μL. The device mimics a single chamber heart, with the following cardiac phases: (1) closure of the ventricle inlet valve, (2) contraction of the ventricle (systole) followed by opening of the outlet valve and (3) relaxation of the ventricle (diastole) with opening of the inlet valve whilst the outlet valve remains closed. Periodic valve states and ventricular contractions were actuated by microprocessor controlled pneumatics. The time-dependent velocity-field was characterised by micro-particle image velocimetry (μ-PIV). μ-PIV observations were used to help tune electronic timing of valve states and ventricular contractions for synthesis of an arterial pulse waveform to study the effect of pulsatile shear stress on bovine artery endothelial cells (BAECs). BAECs elongated and aligned with the direction of shear stress after 48 h of exposure to a pulsatile waveform with a maximum shear stress of 0.42 Pa. The threshold for BAECs alignment and elongation under steady (non-pulsatile) flow reported by Kadohama et al. (2006) is 0.7-1.4 Pa. These cells respond to transient shear stress because the time average shear stress of the pulse waveform to generate this morphological response was only 0.09 Pa, well below the steady flow threshold. The microfluidic pulse generator can simulate circulatory hemodynamics for live cell imaging of shear-induced signalling pathways. PMID:23727941

  18. 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

  19. 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

  20. 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

  1. 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

  2. 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

  3. Response of benthic foraminifera to ocean acidification in their natural sediment environment: a long-term culturing experiment

    NASA Astrophysics Data System (ADS)

    Haynert, K.; Schönfeld, J.; Schiebel, R.; Wilson, B.; Thomsen, J.

    2014-03-01

    Calcifying foraminifera are expected to be endangered by ocean acidification; however, the response of a complete community kept in natural sediment and over multiple generations under controlled laboratory conditions has not been constrained to date. During 6 months of incubation, foraminiferal assemblages were kept and treated in natural sediment with pCO2-enriched seawater of 430, 907, 1865 and 3247 μatm pCO2. The fauna was dominated by Ammonia aomoriensis and Elphidium species, whereas agglutinated species were rare. After 6 months of incubation, pore water alkalinity was much higher in comparison to the overlying seawater. Consequently, the saturation state of Ωcalc was much higher in the sediment than in the water column in nearly all pCO2 treatments and remained close to saturation. As a result, the life cycle (population density, growth and reproduction) of living assemblages varied markedly during the experimental period, but was largely unaffected by the pCO2 treatments applied. According to the size-frequency distribution, we conclude that foraminifera start reproduction at a diameter of 250 μm. Mortality of living Ammonia aomoriensis was unaffected, whereas size of large and dead tests decreased with elevated pCO2 from 285 μm (pCO2 from 430 to 1865 μatm) to 258 μm (pCO2 3247 μatm). The total organic content of living Ammonia aomoriensis has been determined to be 4.3% of CaCO3 weight. Living individuals had a calcium carbonate production rate of 0.47 g m-2 a-1, whereas dead empty tests accumulated a rate of 0.27 g m-2 a-1. Although Ωcalc was close to 1, approximately 30% of the empty tests of Ammonia aomoriensis showed dissolution features at high pCO2 of 3247 μatm during the last 2 months of incubation. In contrast, tests of the subdominant species, Elphidium incertum, stayed intact. Our results emphasize that the sensitivity to ocean acidification of the endobenthic foraminifera Ammonia aomoriensis in their natural sediment habitat is much

  4. Microbial lipid and amino sugar responses to long-term simulated global environmental changes in a California annual grassland

    PubMed Central

    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

  5. 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

  6. 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

  7. 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.

  8. Mediterranean fluvial response to long-term Quaternary climate change: Improving chronologies by coupling OSL and U-series techniques

    NASA Astrophysics Data System (ADS)

    Candy, Ian; Pope, Richard

    2010-05-01

    Many studies have attempted to understand the relationship between Late Quaternary climate change and Mediterranean river activity over the last 200,000 years (Macklin et al., 2002). The long-terrace records associated with most large river systems and the thick aggradation of fan sediments associated with smaller catchments in southern Europe and north Africa make the Mediterranean an ideal region to test this relationship. Such studies have been further enhanced by recent improvements in optically stimulated luminescence (OSL) and U-series dating techniques which are widely applicable in this region. Despite the fact that combining these two techniques provides the best potential method for constructing high precision chronologies this has rarely been done. In this paper we discuss the problems and advantages of producing "coupled" chronologies with reference to examples from southern Spain and Crete. In both of these examples the use of U-series and OSL dating has allowed the age of terrace aggradation and terrace abandonment (incision) to be constrained, consequently our understanding of fluvial "response" is greatly improved. The paper concludes by discussing further problems in terms of constructing fluvial chronologies which need to be considered and the problems of understanding the climate history of the region in which the catchment is found. Macklin, M.G., Fuller, I.C., Lewin, J., Maas, G.S., Passmore, D.G., Rose, J., Woodward, J.C., Black, S., Hamlin, R.H.B., Rowan, J.S., 2002. Correlation of fluvial sequences in the Mediterranean basin over the last 200 ka and their relationship to climate change. Quaternary Science Reviews, 21, 1633 - 1641.

  9. 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.

  10. Long-term testing

    NASA Astrophysics Data System (ADS)

    Ferber, M.; Graves, G. A., Jr.

    Land-based gas turbines are significantly different from automotive gas turbines in that they are designed to operate for 50,000 h or greater (compared to 5,000-10,000 h). The primary goal of this research is to determine the long-term survivability of ceramic materials for industrial gas turbine applications. Research activities in this program focus on the evaluation of the static tensile creep and stress rupture (SR) behavior of three commercially available structural ceramics which have been identified by the gas turbine manufacturers as leading candidates for use in industrial gas turbines. For each material investigated, a minimum of three temperatures and four stresses will be used to establish the stress and temperature sensitivities of the creep and SR behavior. Because existing data for many candidate structural ceramics are limited to testing times less than 2,000 h, this program will focus on extending these data to times on the order of 10,000 h, which represents the lower limit of operating time anticipated for ceramic blades and vanes in gas turbine engines. A secondary goal of the program will be to investigate the possibility of enhancing life prediction estimates by combining interrupted tensile SR tests and tensile dynamic fatigue tests in which tensile strength is measured as a function of stressing rate. The third goal of this program will be to investigate the effects of water vapor upon the SR behavior of the three structural ceramics chosen for the static tensile studies by measuring the flexural strength as a function of stressing rate at three temperatures.

  11. Long-term testing

    SciTech Connect

    Ferber, M.; Graves, G.A. Jr.

    1994-12-31

    Land-based gas turbines are significantly different from automotive gas turbines in that they are designed to operate for 50,000 h or greater (compared to 5,000--10,000 h). The primary goal of this research is to determine the long-term survivability of ceramic materials for industrial gas turbine applications. Research activities in this program focus on the evaluation of the static tensile creep and stress rupture (SR) behavior of three commercially available structural ceramics which have been identified by the gas turbine manufacturers as leading candidates for use in industrial gas turbines. For each material investigated, a minimum of three temperatures and four stresses will be used to establish the stress and temperature sensitivities of the creep and SR behavior. Because existing data for many candidate structural ceramics are limited to testing times less than 2,000 h, this program will focus on extending these data to times on the order of 10,000 h, which represents the lower limit of operating time anticipated for ceramic blades and vanes in gas turbine engines. A secondary goal of the program will be to investigate the possibility of enhancing life prediction estimates by combining interrupted tensile SR tests and tensile dynamic fatigue tests in which tensile strength is measured as a function of stressing rate. The third goal of this program will be to investigate the effects of water vapor upon the SR behavior of the three structural ceramics chosen for the static tensile studies by measuring the flexural strength as a function of stressing rate at three temperatures.

  12. 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

  13. 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

  14. 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

  15. 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. PMID:26324464

  16. 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. PMID:22000270

  17. 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

  18. 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

  19. 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

  20. 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

  1. 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

  2. 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.

  3. 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

  4. 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

  5. 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

  6. 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

  7. Metabolic disorders and adipose tissue insulin responsiveness in neonatally STZ-induced diabetic rats are improved by long-term melatonin treatment.

    PubMed

    de Oliveira, Ariclécio C; Andreotti, Sandra; Farias, Talita da S M; Torres-Leal, Francisco L; de Proença, André R G; Campaña, Amanda B; de Souza, Arnaldo H; Sertié, Rogério A L; Carpinelli, Angelo R; Cipolla-Neto, José; Lima, Fábio B

    2012-05-01

    Diabetes mellitus is a product of low insulin sensibility and pancreatic β-cell insufficiency. Rats with streptozotocin-induced diabetes during the neonatal period by the fifth day of age develop the classic diabetic picture of hyperglycemia, hypoinsulinemia, polyuria, and polydipsia aggravated by insulin resistance in adulthood. In this study, we investigated whether the effect of long-term treatment with melatonin can improve insulin resistance and other metabolic disorders in these animals. At the fourth week of age, diabetic animals started an 8-wk treatment with melatonin (1 mg/kg body weight) in the drinking water at night. Animals were then killing, and the sc, epididymal (EP), and retroperitoneal (RP) fat pads were excised, weighed, and processed for adipocyte isolation for morphometric analysis as well as for measuring glucose uptake, oxidation, and incorporation of glucose into lipids. Blood samples were collected for biochemical assays. Melatonin treatment reduced hyperglycemia, polydipsia, and polyphagia as well as improved insulin resistance as demonstrated by constant glucose disappearance rate and homeostasis model of assessment-insulin resistance. However, melatonin treatment was unable to recover body weight deficiency, fat mass, and adipocyte size of diabetic animals. Adiponectin and fructosamine levels were completely recovered by melatonin, whereas neither plasma insulin level nor insulin secretion capacity was improved in diabetic animals. Furthermore, melatonin caused a marked delay in the sexual development, leaving genital structures smaller than those of nontreated diabetic animals. Melatonin treatment improved the responsiveness of adipocytes to insulin in diabetic animals measured by tests of glucose uptake (sc, EP, and RP), glucose oxidation, and incorporation of glucose into lipids (EP and RP), an effect that seems partially related to an increased expression of insulin receptor substrate 1, acetyl-coenzyme A carboxylase and fatty acid

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. Optimal pathological response indicated better long-term outcome among patients with stage IB2 to IIB cervical cancer submitted to neoadjuvant chemotherapy.

    PubMed

    Huang, Kecheng; Sun, Haiying; Chen, Zhilan; Li, Xiong; Wang, ShaoShuai; Zhao, Xiaolin; Tang, Fangxu; Jia, Yao; Hu, Ting; Du, Xiaofang; Wang, Haoran; Lu, Zhiyong; Huang, Jia; Gui, Juan; Wang, Xiaoli; Zhou, Shasha; Wang, Lin; Zhang, Jincheng; Guo, Lili; Yang, Ru; Shen, Jian; Zhang, Qinghua; Li, Shuang; Wang, Shixuan

    2016-01-01

    The role of pathological response in long-term outcome is still unclear in cervical cancer patients treated with neoadjuvant chemotherapy (NACT) in China. This study aimed to investigate the effect of optimal pathologic response (OPR) on survival in the patients treated with NACT and radical hysterectomy. First, 853 patients with stage IB2-IIB cervical cancer were included in a retrospective analysis; a Cox proportional hazards model was used to investigate the relationship between pathological response and disease-free survival (DFS). In the retrospective database, 64 (7.5%) patients were found to have achieved an OPR (residual disease <3 mm stromal invasion); in the multivariate Cox model, the risk of death was much greater in the non-OPR group than in the OPR group (HR, 2.61; 95%CI, 1.06 to 6.45; P = 0.037). Next, the role of OPR was also evaluated in a prospective cohort of 603 patients with cervical cancer. In the prospective cohort, 56 (9.3%) patients were found to have achieved an OPR; the log-rank tests showed that the risk of recurrence was higher in the non-OPR patients than in the OPR group (P = 0.05). After combined analysis, OPR in cervical cancer was found to be an independent prognostic factor for DFS. PMID:27325186

  18. Optimal pathological response indicated better long-term outcome among patients with stage IB2 to IIB cervical cancer submitted to neoadjuvant chemotherapy

    PubMed Central

    Huang, Kecheng; Sun, Haiying; Chen, Zhilan; Li, Xiong; Wang, ShaoShuai; Zhao, Xiaolin; Tang, Fangxu; Jia, Yao; Hu, Ting; Du, Xiaofang; Wang, Haoran; Lu, Zhiyong; Huang, Jia; Gui, Juan; Wang, Xiaoli; Zhou, Shasha; Wang, Lin; Zhang, Jincheng; Guo, Lili; Yang, Ru; Shen, Jian; Zhang, Qinghua; Li, Shuang; Wang, Shixuan

    2016-01-01

    The role of pathological response in long-term outcome is still unclear in cervical cancer patients treated with neoadjuvant chemotherapy (NACT) in China. This study aimed to investigate the effect of optimal pathologic response (OPR) on survival in the patients treated with NACT and radical hysterectomy. First, 853 patients with stage IB2-IIB cervical cancer were included in a retrospective analysis; a Cox proportional hazards model was used to investigate the relationship between pathological response and disease-free survival (DFS). In the retrospective database, 64 (7.5%) patients were found to have achieved an OPR (residual disease <3 mm stromal invasion); in the multivariate Cox model, the risk of death was much greater in the non-OPR group than in the OPR group (HR, 2.61; 95%CI, 1.06 to 6.45; P = 0.037). Next, the role of OPR was also evaluated in a prospective cohort of 603 patients with cervical cancer. In the prospective cohort, 56 (9.3%) patients were found to have achieved an OPR; the log-rank tests showed that the risk of recurrence was higher in the non-OPR patients than in the OPR group (P = 0.05). After combined analysis, OPR in cervical cancer was found to be an independent prognostic factor for DFS. PMID:27325186

  19. 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

  20. 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

  1. Long-term memory of visually cued fear conditioning: roles of the neuronal nitric oxide synthase gene and cyclic AMP response element-binding protein.

    PubMed

    Kelley, J B; Anderson, K L; Altmann, S L; Itzhak, Y

    2011-02-01

    Nitric oxide (NO) produced by neuronal nitric oxide synthase (nNOS) has a role in late-phase long-term potentiation (LTP) and long-term memory (LTM) formation. Our recent studies implicated NO signaling in contextual and auditory cued fear conditioning. The present study investigated the role of NO signaling in visually cued fear conditioning. First, visually cued fear conditioning was investigated in wild-type (WT) and nNOS knockout (KO) mice. Second, the effects of pharmacological modulators of NO signaling on the acquisition of visually cued fear conditioning were investigated. Third, plasma levels of corticosterone were measured to determine a relationship between physiological and behavioral responses to fear conditioning. Fourth, levels of extracellular signal-related kinase (ERK1/2) and cyclic AMP response element binding protein (CREB) phosphorylation, downstream of NO signaling, were determined in the amygdala as potential correlates of fear learning. Mice underwent single or multiple (4) spaced trainings that consisted of a visual cue (blinking light) paired with footshock. WT mice acquired cued and contextual LTM following single and multiple trainings. nNOS KO mice acquired neither cued nor contextual LTM following a single training; however, multiple trainings improved contextual but not cued LTM. The selective nNOS inhibitor S-methyl-thiocitrulline (SMTC) impaired cued and contextual LTM in WT mice. The NO donor molsidomine recovered contextual LTM but had no effect on cued LTM in nNOS KO mice. Re-exposure to the visual cue 24 h posttraining elicited freezing response and a marked increase in plasma corticosterone levels in WT but not nNOS KO mice. The expression of CREB phosphorylation (Ser-133) was significantly higher in naive nNOS KO mice than in WT counterparts, and pharmacological modulators of NO had significant effects on levels of CREB phosphorylation and expression. These findings suggest that visual cue-dependent LTM is impaired in nNOS KO

  2. 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

  3. 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.

  4. 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

  5. Sensitization of dorsal horn neurons in a two-compartment cell culture model: wind-up and long-term potentiation-like responses.

    PubMed

    Vikman, K S; Kristensson, K; Hill, R H

    2001-10-01

    One of the main characteristics of central sensitization associated with postinjury pain and chronic pain is increased excitability of the dorsal horn neurons in the spinal cord. Two electrophysiological features associated with the origin and modulation of central sensitization are wind-up of action potential frequency and long-term potentiation (LTP), which have been demonstrated previously in the intact dorsal horn. Here we present evidence for electrically evoked sensitization of dorsal horn neurons in a two-compartment cell culture system of rat dorsal root ganglia (DRGs) and dorsal horn neurons. Whole-cell recordings of dorsal horn neurons showed that repetitive low-frequency stimulation of DRG axons induced a frequency-dependent cumulative depolarization of the membrane potential with a concomitant increase in action potential frequency in a subset of neurons (41%). The characteristics presented here for dissociated cells are in accordance with those ascribed to classical wind-up in the intact dorsal horn. In addition, tetanic stimulation of DRG axons resulted in a significant increase in the number of action potentials in response to test stimuli in 42% of the cells tested. This prolonged potentiation of neuronal excitability in the dorsal horn lasted throughout the recording period (>1 hr) and tended to be voltage dependent in an LTP-like manner. To our knowledge, this is the first time that wind-up and LTP-like responses are reported for dorsal horn neurons in cell culture. PMID:11567080

  6. 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

  7. 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. PMID:25011109

  8. Adenylyl cyclase subtype 1 is essential for late-phase long term potentiation and spatial propagation of synaptic responses in the anterior cingulate cortex of adult mice.

    PubMed

    Chen, Tao; O'Den, Gerile; Song, Qian; Koga, Kohei; Zhang, Ming-Ming; Zhuo, Min

    2014-01-01

    Long-term potentiation (LTP) is a key cellular mechanism for pathological pain in the central nervous system. LTP contains at least two different phases: early-phase LTP (E-LTP) and late-phase LTP (L-LTP). Among several major cortical areas, the anterior cingulate cortex (ACC) is a critical brain region for pain perception and its related emotional changes. Periphery tissue or nerve injuries cause LTP of excitatory synaptic transmission in the ACC. Our previous studies have demonstrated that genetic deletion of calcium-stimulated adenylyl cyclase 1 (AC1) or pharmacological application of a selective AC1 inhibitor NB001 blocked E-LTP in the ACC. However, the effect of AC1 on L-LTP, which requires new protein synthesis and is important for the process of chronic pain, has not been investigated. Here we tested the effects of NB001 on the ACC L-LTP and found that bath application of NB001 (0.1 μM) totally blocked the induction of L-LTP and recruitment of cortical circuitry without affecting basal excitatory transmission. In contrast, gabapentin, a widely used analgesic drug for neuropathic pain, did not block the induction of L-LTP and circuitry recruitment even at a high concentration (100 μM). Gabapentin non-selectively decreased basal synaptic transmission. Our results provide strong evidence that the selective AC1 inhibitor NB001 can be used to inhibit pain-related cortical L-LTP without affecting basal synaptic transmission. It also provides basic mechanisms for possible side effects of gabapentin in the central nervous system and its ineffectiveness in some patients with neuropathic pain. PMID:25304256

  9. 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

  10. 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. PMID:25378217

  11. 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

  12. The Tumour Response to Induction Chemotherapy has Prognostic Value for Long-Term Survival Outcomes after Intensity-Modulated Radiation Therapy in Nasopharyngeal Carcinoma

    PubMed Central

    Peng, Hao; Chen, Lei; Zhang, Yuan; Li, Wen-Fei; Mao, Yan-Ping; Liu, Xu; Zhang, Fan; Guo, Rui; Liu, Li-Zhi; Tian, Li; Lin, Ai-Hua; Sun, Ying; Ma, Jun

    2016-01-01

    The prognostic value of the tumour response to induction chemotherapy (IC) for long-term survival outcomes after intensity-modulated radiation therapy in nasopharyngeal carcinoma (NPC) remains unknown. We retrospectively reviewed 1811 consecutive patients with newly diagnosed NPC treated using IMRT, and 399 eligible patients with pre- and post-induction chemotherapy magnetic resonance images were recruited. The clinicopathological features of patients with different tumour responses were compared using the Chi-square test or Fisher’s exact test. Prognostic value was assessed using a multivariate Cox proportional hazards model. After IC, 101/399 (25.3%) patients had a complete tumour response overall (CR), 262 (65.7%) had a partial response (PR) and 36 (9.0%) had stable disease (SD). The 4-year disease-free survival (DFS), overall survival (OS), distant metastasis-free survival (DMFS) and locoregional relapse-free survival (LRRFS) rates for CR vs. PR vs. SD were 90.0% vs. 79.0% vs. 58.2% (CR vs. PR: P1 = 0.007; CR vs. SD: P2 < 0.001; PR vs. SD: P3 = 0.004), 95.7% vs. 88.7% vs. 70.2% (P1 = 0.017, P2 < 0.001, P3 = 0.005), 92.0% vs. 87.4% vs. 74.3% (P1 = 0.162, P2 = 0.005, P3 = 0.029) and 95.9% vs. 88.8% vs. 81.8% (P1 = 0.024, P2 = 0.006, P3 = 0.268), respectively. Multivariate analysis identified that the tumour response to IC was an independent prognostic factor for DFS, OS and LRRFS. PMID:27099096

  13. 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.

  14. 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

  15. 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

  16. 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.

  17. [Long-term pattern of diatom community structure changes in response to multiple environmental stressors at Datun Lake, Southeast Yunnan, China].

    PubMed

    Tao, Jian-shuang; Chen, Guang-jie; Chen, Xiao-lin; Liu, Yuan-yuan; Lu, Hui-bin; Hu, Kui

    2015-08-01

    Subtropical plateau lakes in Southeast Yunnan are known to have experienced multiple environmental stressors (lake pollution, eutrophication, land reclamation and droughts) during the past decades. Here, we applied multi-proxy analyses (i.e., diatom, grain size, C and N isotopic and chronology) of lake sediments, aiming to track the history of lake environment change and the characteristics of diatom community responses in Datun Lake for the past century. The results proved that the sedimentary diatom community records showed significant changes with the replacement of Fragilaria construens by Achnanthes minutissima. Combining with multiple-proxy records (i.e., isotopic data) and modern monitoring records, the ordination analyses and variation partitioning further suggested that industrial pollution and eutrophication were the major driving factors that led to the long-term shift of diatom community. In addition, the grain size results and meteorological data revealed that the reductions in hydrodynamic and water exchange intensity associated with damming and the occurrence of extreme droughts, thus led to the corresponding diatom community change. PMID:26685618

  18. Metabolite Profiling of Diverse Rice Germplasm and Identification of Conserved Metabolic Markers of Rice Roots in Response to Long-Term Mild Salinity Stress.

    PubMed

    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

  19. Effect of lipid and fatty acid composition of phospholipid vesicles on long-term stability and their response to Staphylococcus aureus and Pseudomonas aeruginosa supernatants.

    PubMed

    Marshall, Serena E; Hong, Sung-Ha; Thet, N T; Jenkins, A Toby A

    2013-06-11

    Phospholipid vesicles have been the focus of attention as potential vehicles for drug delivery, as they are biomimetic, easy to produce, and contain an aqueous compartment which can be used to carry hydrophilic material, such as drugs or dyes. Lipid vesicles used for this purpose present a particular challenge, as they are not especially stable and can rapidly break down and release their contents away from the target area, especially at physiological temperatures/environments. This study aims to investigate optimum methods for vesicle stabilization where the vesicles are employed as part of a system or technology that signals the presence of pathogenic bacteria via the effect of secreted cytolytic virulence factors on a sensor interface. A number of approaches have been investigated and are presented here as a systematic study of the long-term (14 day) stability at 37 °C, and at various pHs. The response of vesicles, both in suspension and within hydrogels, to Staphylococcus aureus (RN 4282) and Pseudomonas aeruginosa (PAO1) whole bacteria, and supernatants from overnight cultures of both (containing secreted proteins but free of cells), was measured via a sensitive encapsulated carboxyfluorescein release assay. The results showed that lipid chain length, cholesterol concentration, and stabilization via photopolymer stable components were critical in achieving stability. Finally, dispersion of the optimum vesicle formulation in hydrogel matrixes was investigated, culminating in the in vivo demonstration of a simple prototype wound dressing. PMID:23668367

  20. 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. PMID:23832975

  1. 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

  2. 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

  3. 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. PMID:20557146

  4. 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 ...

  5. 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 ...

  6. 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. PMID:24199690

  7. Carbon-nutrient interactions in response to CO/sub 2/ enrichment: physiological and long-term perspectives. [Quercus alba L

    SciTech Connect

    Norby, R.J.; Pastor, J.; Melillo, J.M.

    1985-01-01

    The responses of forest trees to atmospheric CO/sub 2/ enrichment will depend in part on carbon-nutrient linkages. Insights into the possible long-term ecological consequences of CO/sub 2/ enrichment can be gained from studying physiological responses in short-term experiments. One-year-old white oak (Quercus alba L.) seedlings were grown in an unfertilized forest soil for 40 weeks in controlled-environment chambers with ambient (362 ..mu..L.L/sup -1/) or elevated (690 ..mu..L.L/sup -1/) CO/sub 2/. Seedling dry weight was 85% greater in the elevated CO/sub 2/ environment, despite a severe nitrogen deficiency in all seedlings. The increase in growth occurred without a concomitant increase in nitrogen uptake, indicating an increase in nitrogen-use efficiency in elevated CO/sub 2/. The weight of new buds was greater in elevated CO/sub 2/, suggesting that shoot growth in the next year would have been enhanced relative to that of seedlings in ambient CO/sub 2/. However, there was a lower amount of translocatable nitrogen in perennial woody tissue in elevated CO/sub 2/; thus, further increases in nitrogen-use efficiency may not be possible. The leaves that abscised from seedlings in elevated CO/sub 2/ contained higher amounts of soluble sugars and tannin and a lower amount of lignin compared with amounts in abscised leaves in ambient CO/sub 2/. Based on lignin to N and lignin to P ratios, the rates of litter decomposition might not be greatly affected by CO/sub 2/ enrichment, but the total amount of nitrogen returned to soil would be lower in elevated CO/sub 2/.

  8. 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

  9. 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

  10. 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

  11. Long-term exposure to low-concentrations of Cr(VI) induce DNA damage and disrupt the transcriptional response to benzo[a]pyrene

    PubMed Central

    Ovesen, Jerald L.; Fan, Yunxia; Chen, Jing; Medvedovic, Mario; Xia, Ying; Puga, Alvaro

    2014-01-01

    Living organisms are exposed on a daily basis to widespread mixtures of toxic compounds. Mixtures pose a major problem in the assessment of health effects because they often generate substance-specific effects that cannot be attributed to a single mechanism. Two compounds often found together in the environment are the heavy metal chromium and the polycyclic aromatic hydrocarbon benzo[a]pyrene (B[a]P). We have examined how long-term exposure to a low concentration of Cr(VI) affects the transcriptional response to B[a]P, a second toxicant with an unrelated mechanism of action. Growth of mouse hepatoma cells for 20 passages in medium with 0.1 or 0.5 μM Cr(VI) increases DNA damage and apoptosis while decreasing clonogenic ability. Treated cells also show transcriptome changes indicative of increased expression of DNA damage response and repair genes. In them, B[a]P activates cancer progression pathways, unlike in cells never exposed to Cr(VI), where B[a]P activates mostly xenobiotic metabolism pathways. Cells grown in Cr(VI) for 20 passages and then cultured for an additional 5 passages in the absence of Cr(VI) recover from some but not all the chromium effects. They show B[a]P-dependent transcriptome changes strongly weighted towards xenobiotic metabolism, similar to those in B[a]P-treated cells that had no previous Cr(VI) exposure, but retain a high level of Cr(VI)-induced DNA damage and silence the expression of DNA damage and cancer progression genes. We conclude that the combined effect of these two toxicants appears to be neither synergistic nor additive, generating a toxic/adaptive condition that cannot be predicted from the effect of each toxicant alone. PMID:24374135

  12. Long-term response to first-line trabectedin in an elderly female patient with a metastatic leiomyosarcoma unfit for anthracycline.

    PubMed

    Maruzzo, Marco; Brunello, Antonella; Diminutto, Alberto; Rastrelli, Marco; Basso, Umberto

    2016-03-01

    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/m 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

  13. [Responses of Soil and Plant 15N Natural Abundance to Long-term N Addition in an N-Saturated Pinus massoniana Forest in Southwest China].

    PubMed

    Liu, Wen-jing; Kang, Rong-hua; Zhang, Ting; Zhu, Jing; Duan, Lei

    2015-08-01

    Increasing N deposition in China will possibly cause N saturation of forest ecosystem, further resulting in a series of serious environmental problems. In order to explore the response of forest ecosystem to N deposition in China, and further evaluate and predict the N status of ecosystem, the 15N natural abundance (delta 15N) of soil and plants was measured in a typical Masson pine (Pinus massoniana) forest in southwest China to examine the potential use of delta 15N enrichment factor (epsilon(p/s)) as an effective indicator of N status. Long-term high N addition could significantly increase delta 15N of soil and plants, which was suggested by an on-going N fertilizing experiment with NH4NO3 or NaNO3 for 7 years. Meanwhile, delta 15N of soil and plants under NH, deposition was significantly higher than that under NO- deposition, suggesting different responses of ecosystem to different N-forms of deposition. The "N enrichment factor (epsilon(p/s)) had positive correlations with N deposition, N nitrification, and N leaching in the soil water. Linear correlation between "N enrichment factor and N deposition was found for all Masson pine forests investigated in this and previous studies in China, demonstrating that 15N enrichment factor could be used as an indicator of N status. The NH3 emission control should also be carried out accompanying with NOx emission control in the future, because NH4- deposition had significantly greater impact on the forest ecosystem than NO3- deposition with the same equivalence. PMID:26592030

  14. 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. PMID:22335184

  15. 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

  16. Cellular Host Responses to Gliomas

    PubMed Central

    Barish, Michael E.; Garcia, Elizabeth; Metz, Marianne Z.; Myers, Sarah M.; Gutova, Margarita; Frank, Richard T.; Miletic, Hrvoje; Kendall, Stephen E.; Glackin, Carlotta A.; Bjerkvig, Rolf; Aboody, Karen S.

    2012-01-01

    Background Glioblastoma multiforme (GBM) is the most aggressive type of malignant primary brain tumors in adults. Molecular and genetic analysis has advanced our understanding of glioma biology, however mapping the cellular composition of the tumor microenvironment is crucial for understanding the pathology of this dreaded brain cancer. In this study we identified major cell populations attracted by glioma using orthotopic rodent models of human glioma xenografts. Marker-specific, anatomical and morphological analyses revealed a robust influx of host cells into the main tumor bed and tumor satellites. Methodology/Principal Findings Human glioma cell lines and glioma spheroid orthotopic implants were used in rodents. In both models, the xenografts recruited large numbers of host nestin-expressing cells, which formed a ‘network’ with glioma. The host nestin-expressing cells appeared to originate in the subventricular zone ipsilateral to the tumor, and were clearly distinguishable from pericytes that expressed smooth muscle actin. These distinct cell populations established close physical contact in a ‘pair-wise’ manner and migrated together to the deeper layers of tumor satellites and gave rise to tumor vasculature. The GBM biopsy xenografts displayed two different phenotypes: (a) low-generation tumors (first in vivo passage in rats) were highly invasive and non-angiogenic, and host nestin-positive cells that infiltrated into these tumors displayed astrocytic or elongated bipolar morphology; (b) high-generation xenografts (fifth passage) had pronounced cellularity, were angiogenic with ‘glomerulus-like’ microvascular proliferations that contained host nestin-positive cells. Stromal cell-derived factor-1 and its receptor CXCR4 were highly expressed in and around glioma xenografts, suggesting their role in glioma progression and invasion. Conclusions/Significance Our data demonstrate a robust migration of nestin-expressing host cells to glioma, which

  17. Stapedectomy - long-term report.

    PubMed

    Shea, J J

    1982-01-01

    The long-term results with large fenestra stapedectomy with vein graft and Teflon piston are compared with results with the small fenestra stapedectomy with teflon piston directly into the vestibule. There were 1,943 operations in the former group and 2,155 in the latter when compared in 1970. One hundred consecutive patients from the beginning of each group with follow-up to present were compared. Results were generally the same with no great change in 15 and 20 years as compared to those at 5 years. The complication of perilymph fistula was caused by creating an opening in the footplate much larger than the prosthesis and was eliminated by interposing a living oval window seal if the opening was much larger than the prosthesis and a flap of lining membrane from the promontory when it was not. Other factors that influence a good result are discussed, including the type and the diameter of the piston used, the type of living oval window seal and the method of attachment to the incus. The small fenestra operation was found to be superior to the large, not only for the hearing gain achieved, but the case of performance and the freedom from complications due to migration of the prosthesis and/or the oval window seal. At present we have done about all that can be done for the conductive components. What remains is the sensorineural component which our studies indicate may be due to an autoimmune response. PMID:6897157

  18. [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

  19. 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

  20. 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.

  1. 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. PMID:26227443

  2. 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

  3. Lipid peroxidation and apoptotic response in rat brain areas induced by long-term administration of nandrolone: the mutual crosstalk between ROS and NF-kB.

    PubMed

    Turillazzi, Emanuela; Neri, Margherita; Cerretani, Daniela; Cantatore, Santina; Frati, Paola; Moltoni, Laura; Busardò, Francesco Paolo; Pomara, Cristoforo; Riezzo, Irene; Fineschi, Vittorio

    2016-04-01

    The aim of this study was to evaluate the played by oxidative stress in the apoptotic response in different brain areas of rats chronically treated with supra-physiological doses of nandrolone decanoate (ND). Immunohistochemical study and Western blot analysis were performed to evaluate cells' apoptosis and to measure the effects of expression of specific mediators, such as NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells), Bcl-2 (B-cell lymphoma 2), SMAC/DIABLO (second mitochondria-derived activator of caspases/direct IAP-binding protein with low PI) and VMAT2 (vesicular monoamine transporter 2) on apoptosis. The results of the present study indicate that a long-term administration of ND promotes oxidative injury in rat brain specific areas. A link between oxidative stress and NF-κB signalling pathways is supported by our results. In addition to high levels of oxidative stress, we consistently observed a strong immunopositivity to NF-κB. It has been argued that one of the pathways leading to the activation of NF-κB could be under reactive oxygen species (ROS)-mediated control. In fact, growing evidence suggests that although in limited doses, endogenous ROS may play an activating role in NF-κB signalling, while above a certain threshold, they may negatively impact upon this signalling. However, a mutual crosstalk between ROS and NF-κB exists and recent studies have shown that ROS activity is subject to negative feedback regulation by NF-κB, and that this negative regulation of ROS is the means through which NF-κB counters programmed cells. PMID:26828721

  4. Therapeutic administration of IL-15 superagonist complex ALT-803 leads to long-term survival and durable antitumor immune response in a murine glioblastoma model.

    PubMed

    Mathios, Dimitrios; Park, Chul-Kee; Marcus, Warren D; Alter, Sarah; Rhode, Peter R; Jeng, Emily K; Wong, Hing C; Pardoll, Drew M; Lim, Michael

    2016-01-01

    Glioblastoma is the most aggressive primary central nervous system malignancy with a poor prognosis in patients. Despite the need for better treatments against glioblastoma, very little progress has been made in discovering new therapies that exhibit superior survival benefit than the standard of care. Immunotherapy has been shown to be a promising treatment modality that could help improve clinical outcomes of glioblastoma patients by assisting the immune system to overcome the immunosuppressive tumor environment. Interleukin-15 (IL-15), a cytokine shown to activate several effector components of the immune system, may serve as an excellent immunotherapeutic candidate for the treatment of glioblastoma. Thus, we evaluated the efficacy of an IL-15 superagonist complex (IL-15N72D:IL-15RαSu-Fc; also known as ALT-803) in a murine GL261-luc glioblastoma model. We show that ALT-803, as a single treatment as well as in combination with anti-PD-1 antibody or stereotactic radiosurgery, exhibits a robust antitumor immune response resulting in a prolonged survival including complete remission in tumor bearing mice. In addition, ALT-803 treatment results in long-term immune memory against glioblastoma tumor rechallenge. Flow cytometric analysis of tumor infiltrating immune cells shows that ALT-803 leads to increased percentage of CD8+-cell infiltration, but not the NK cells, and IFN-γ production into the tumor microenvironment. Cell depletion studies, in accordance with the flow cytometric results, show that the ALT-803 therapeutic effect is dependent on CD4+ and CD8+ cells. These results provide a rationale for evaluating the therapeutic activity of ALT-803 against glioblastoma in the clinical setting. PMID:26174883

  5. Long-term immunologic and virologic responses on raltegravir-containing regimens among ART-experienced participants in the HIV Outpatient Study

    PubMed Central

    Buchacz, Kate; Wiegand, Ryan; Armon, Carl; Chmiel, Joan S.; Wood, Kathleen; Brooks, John T.; Palella, Frank J.

    2015-01-01

    Objectives Raltegravir (RAL)-containing antiretroviral therapy (ART) produced better immunologic and virologic responses than optimized background ART in clinical trials of heavily ART-experienced patients, but few data exist on long-term outcomes in routine HIV care. Methods We studied ART-experienced HIV outpatient study (HOPS) participants seen at 10 US HIV-specialty clinics during 2007–2011. We identified patients who started (baseline date) either continuous ≥30 days of RAL-containing or RAL-sparing ART, and used propensity score (PS) matching methods to account for baseline clinical and demographic differences. We used Kaplan–Meier methods and log-rank tests for the matched subsets to evaluate probability of death, achieving HIV RNA <50 copies/ml, and CD4 cell count (CD4) increase of ≥50 cells mm−3 during follow-up. Results Among 784 RAL-exposed and 1062 RAL-unexposed patients, 472 from each group were matched by PS. At baseline, the 472 RAL-exposed patients (mean nadir CD4, 205 cells mm−3; mean baseline CD4, 460 cells mm−3; HIV RNA <50 copies ml−1 in 61%; mean years on prescribed ART, 7.5) were similar to RAL unexposed. During a mean follow-up of over 3 years, mortality rates and immunologic and virologic trajectories did not differ between the two groups. Among patients with detectable baseline HIV RNA levels, 76% of RAL-exposed and 63% of RAL-unexposed achieved HIV RNA <50 copies ml−1 (P=0.51); 69 and 58%, respectively, achieved a CD4 increase ≥50 cells mm−3 (P=0.70). Discussion In our large cohort of US ART-experienced patients with a wide spectrum of clinical history, similar outcomes were observed when prescribed RAL containing versus other contemporary ART. PMID:26126549

  6. Evaluation of the Long-Term Anti-Human Papillomavirus 6 (HPV6), 11, 16, and 18 Immune Responses Generated by the Quadrivalent HPV Vaccine.

    PubMed

    Nygård, Mari; Saah, Alfred; Munk, Christian; Tryggvadottir, Laufey; Enerly, Espen; Hortlund, Maria; Sigurdardottir, Lara G; Vuocolo, Scott; Kjaer, Susanne K; Dillner, Joakim

    2015-08-01

    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

  7. 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

  8. Long-Term Coffee Consumption and Risk of Cardiovascular Disease: A Systematic Review and a Dose-Response Meta-Analysis of Prospective Cohort Studies

    PubMed Central

    Ding, Ming; Bhupathiraju, Shilpa N; Satija, Ambika; van Dam, Rob M; Hu, Frank B

    2013-01-01

    Background Considerable controversy exists regarding the association between coffee consumption and cardiovascular disease (CVD) risk. A meta-analysis was performed to assess the dose-response relationship of long-term coffee consumption with CVD risk. Methods and Results Pubmed and EMBASE were searched for prospective cohort studies of the relationship between coffee consumption and CVD risk, which included coronary heart disease, stroke, heart failure, and CVD mortality. Thirty-six studies were included with 1,279,804 participants and 36,352 CVD cases. A non-linear relationship of coffee consumption with CVD risk was identified (P for heterogeneity = 0.09, P for trend < 0.001, P for non-linearity < 0.001). Compared with the lowest category of coffee consumption (median: 0 cups/d), the relative risk of CVD was 0.95 (95% CI, 0.87 to 1.03) for the highest (median: 5 cups/d) category, 0.85 (0.80 to 0.90) for the second highest (median: 3.5 cups/d), and 0.89 (0.84 to 0.94) for the third highest category (median: 1.5 cups/d). Looking at separate outcomes, coffee consumption was non-linearly associated with both CHD (P for heterogeneity = 0.001, P for trend < 0.001, P for non-linearity < 0.001) and stroke risks (P for heterogeneity = 0.07, P for trend < 0.001, P for non-linearity< 0.001) (P for trend differences > 0.05). Conclusions A non-linear association between coffee consumption with CVD risk was observed in this meta-analysis. Moderate coffee consumption was inversely significantly associated with CVD risk, with the lowest CVD risk at 3 to 5 cups/d, and heavy coffee consumption was not associated with elevated CVD risk. PMID:24201300

  9. 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.

  10. 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

  11. 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…

  12. Could the long term cover change of three Mediterranean shrubs be explained by their photosynthetic responses to drought in a rainfall exclusion experiment ?

    NASA Astrophysics Data System (ADS)

    Liberati, Dario; De Dato, Giovanbattista; Guidolotti, Gabriele; De Angelis, Paolo

    2013-04-01

    In the Mediterranean climates water stress is considered to be the main environmental factor limiting plant growth. In front of water limitations plants have developed a wide diversity of adaptation mechanism, and co-occurring species often display different physiological, functional, and life history strategies. In the contest of a rainfall exclusion experiment (project INCREASE), the present work is aimed to assess if the seasonal response of photosynthesis to the water stress (based on gas exchange data collected during 2010) can explain the long term change in the cover degree (assessed by seven pin point survey carried out from 2001 to 2012) of the three main species present in the Italian experimental site, Cistus monspeliensis L. (Cistaceae), Dorycnium pentaphyllum Scop. (Fabaceae) and Helichrysum italicum subsp. microphyllum (Willd.) Nyman (Asteraceae) From 2001 to 2012, in the untreated plots, the cover degree increased in C. monspeliensis (+ 0.34% per year), did not show any significant trend in D. pentaphyllum and decreased in H. italicum (- 1.54% per year). In the same period the rainfall exclusion system has worked during Spring and Autumn, mainly reducing the soil water content of the drought plots in Autumn: this treatment did not affect the cover trend of D. pentaphyllum and H. italicum, whereas C. monspeliensis displayed in the drought plots an opposite dynamic (- 1.23% per year) compared to the natural conditions. During 2010 all monitored species reached the maximum photosynthesis rates in spring, with a depression during summer drought and a recovery after the first Autumn rainfalls. The recovery of the spring rates was almost complete in C. monspeliensis and D. pentaphyllum, while in H. italicum did not exceed the 30% of the spring value. The rainfall exclusion reduced the photosynthesis rates in C. monspeliensis and H. italicum in Autumn. In the control plots the opposite cover trend observed in C. monspeliensis and H.italicum could be

  13. 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

  14. 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…

  15. Long-term soil microbial community and enzyme activity responses to an integrated cropping-livestock system in a semi-arid region

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study is part of a larger long-term project to develop and evaluate integrated crop and livestock systems in order to reduce dependence on underground water sources by optimizing cotton (Gossypium hirsutum) production in the Texas High Plains of U.S. Microbial communities and activities were e...

  16. 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…

  17. 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

  18. Short and Long-Term Physiological Responses of Male and Female Rats to Two Dietary Levels of Pre-Gelatinized Maca (Lepidium Peruvianum Chacon)

    PubMed Central

    Meissner, H. O.; Kedzia, B.; Mrozikiewicz, P. M.; Mscisz, A.

    2006-01-01

    Objective: The aim of this study is to identify physiological responses of male and female rats to either a short- or long-term administration of two doses of Maca (Lepidium peruvianum) and observe relationships which may exist between groups of hormones and effects mediated by them. Design: The effect of pre-gelatinized (extruded) organic Maca powder (Maca-GO) was studied on Sprague-Dowley male and female rats (1:1 ratio) receiving two dietary levels of Maca-GO (0.75 g/kg and 7.5 g/kg body weight) and assessed against control during 28 and 90 day laboratory trials on 30 and 60 rats respectively. Blood morphology, biochemistry (hormones, lipids and minerals) and histology of internal organs were determined. Homogenates of skeletal muscles and bones of rats were also analyzed. Results: Maca-GO has low toxicity (LD=7.5 g/kg) and appears to be safe for short-term and extended use as dietary supplement or as a component of functional dietary and therapeutic preparations. There were different responses of male and female rats to different levels of Maca-GO administered during a short- and a longer-term periodl. When administered at higher dose for extended period of time (90 days), Maca-GO acted as a toner of hormonal processes in adult female rats at increased progesterone and a steady estradiol level, without affecting levels of blood FSH, LH and TSH. Conclusions: Obtained results justify further clinical research on use of Maca-GO in sportsmen, physically-active people of both sexes and peri-menopausal women to clarify mechanisms underlaying physiological mode of action of Maca-GO validaet in clinical study on humans. Substantial decrease in blood cortisol levels in a short- and longer-term trial and simultaneous tendency to lower blood ACTH, may indicate antidepressive effect of Maca-GO, which together with reduction in body weight, lowering triglycerides in blood plasma and increasing calcium and phosphorus deposition in bone and muscle tissues is worthy

  19. Previous exercise training increases levels of PPAR-α in long-term post-myocardial infarction in rats, which is correlated with better inflammatory response

    PubMed Central

    Santos, Marília Harumi Higuchi; de Lourdes Higuchi, Maria; Tucci, Paulo J F; Garavelo, Shérrira M; Reis, Márcia M; Antonio, Ednei L; Serra, Andrey J; Maranhão, Raul Cavalcante

    2016-01-01

    OBJECTIVE: Exercise is a protective factor for cardiovascular morbidity and mortality, with unclear mechanisms. Changing the myocardial metabolism causes harmful consequences for heart function and exercise contributes to metabolic adjustment modulation. Peroxisome proliferator-activated receptors (PPARs) are also myocardium metabolism regulators capable of decreasing the inflammatory response. We hypothesized that PPAR-α is involved in the beneficial effects of previous exercise on myocardial infarction (MI) and cardiac function, changing the expression of metabolic and inflammatory response regulators and reducing myocardial apoptosis, which partially explains the better outcome. METHODS AND RESULTS: Exercised rats engaged in swimming sessions for 60 min/day, 5 days/week, for 8 weeks. Both the exercised rats and sedentary rats were randomized to MI surgery and followed for 1 week (EI1 or SI1) or 4 weeks (EI4 or SI4) of healing or to sham groups. Echocardiography was employed to detect left ventricular function and the infarct size. Additionally, the TUNEL technique was used to assess apoptosis and immunohistochemistry was used to quantitatively analyze the PPAR-α, TNF-α and NF-κB antigens in the infarcted and non-infarcted myocardium. MI-related mortality was higher in SI4 than in EI4 (25% vs 12%), without a difference in MI size. SI4 exhibited a lower shortening fraction than EI4 did (24% vs 35%) and a higher apoptosis/area rate (3.97±0.61 vs 1.90±1.82) in infarcted areas (both p=0.001). Immunohistochemistry also revealed higher TNF-α levels in SI1 than in EI1 (9.59 vs 4.09, p<0.001) in infarcted areas. In non-infarcted areas, EI4 showed higher levels of TNF-α and positive correlations between PPAR-α and NF-κB (r=0.75, p=0.02), in contrast to SI4 (r=0.05, p=0.87). CONCLUSION: Previously exercised animals had better long-term ventricular function post-MI, in addition to lower levels of local inflammatory markers and less myocardial apoptosis, which

  20. Uncertainty functions of modelled soil organic carbon changes in response to crop management derived from a French long term experiments dataset

    NASA Astrophysics Data System (ADS)

    Dimassi, Bassem; Guenet, Bertrand; Mary, Bruno; Trochard, Robert; Bouthier, Alain; Duparque, Annie; Sagot, Stéphanie; Houot, Sabine; Morel, Christian; Martin, Manuel

    2016-04-01

    The land use, land-use change and forestry (LULUCF) activities and crop management (CM) in Europe could be an important carbon sink through soil organic carbon (SOC) sequestration. Recently, the (EU decision 529/2013) requires European Union's member states to assess modalities to include greenhouse gas (GHG) emissions and removals resulting from activities relating to LULUCF and CM into the Union's (GHG) emissions reduction commitment and their national inventories reports (NIR). Tier 1, the commonly used method to estimate emissions for NIR, provides a framework for measuring SOC stocks changes. However, estimations have high uncertainty, especially in response to crop management at regional and specific national contexts. Understanding and quantifying this uncertainty with accurate confidence interval is crucial for reliably reporting and support decision-making and policies that aims to mitigate greenhouse gases through soil C storage. Here, we used the Tier 3 method, consisting of process-based modelling, to address the issue of uncertainty quantification at national scale in France. Specifically, we used 20 Long-term croplands experiments (LTE) in France with more than 100 treatments taking into account different agricultural practices such as tillage, organic amendment, inorganic fertilization, cover crops, etc. These LTE were carefully selected because they are well characterized with periodic SOC stocks monitoring overtime and covered a wide range of pedo-climatic conditions. We applied linear mixed effect model to statistically model, as a function of soil, climate and cropping system characteristics, the uncertainty resulting from applying this Tier 3 approach. The model was fitted on the dataset yielded by comparing the simulated (with the Century model V 4.5) to the observed SOC changes on the LTE at hand. This mixed effect model will then be used to derive uncertainty related to the simulation of SOC stocks changes of the French Soil Monitoring

  1. Long-term feeding with Euglena gracilis cells modulates immune responses, oxidative balance and metabolic condition in Diplodon chilensis (Mollusca, Bivalvia, Hyriidae) exposed to living Escherichia coli.

    PubMed

    Bianchi, Virginia A; Castro, Juan M; Rocchetta, Iara; Nahabedian, Daniel E; Conforti, Visitación; Luquet, Carlos M

    2015-02-01

    We evaluated the modulating effect of long-term feeding with lyophilized Euglena gracilis cells on immune response, oxidative balance and metabolic condition of the freshwater mussel Diplodon chilensis. Mussels, previously fed with Scenedesmus vacuolatus (SV) or E. gracilis (EG) for 90 days, were challenged with an environmentally relevant concentration of Escherichia coli in water for 5 days, under feeding or starvation conditions. EG diet increased overall phagocytic activity and tissue hemocyte accumulation (gill and mantle), and favored hemocyte viability upon E. coli challenge. Tissular hemocyte accumulation, and humoral bacteriolytic activity and protein content were similarly stimulated by EG and E. coli, with no further effect when both stimuli were combined. Both, E. coli challenge and EG diet reduced gill bacteriolytic activity with respect to nonchallenged SV mussels, while no effect was observed in challenged EG mussels. Gill and digestive gland protein contents, along with digestive gland bacteriolytic activity were higher in EG than in SV mussels. Both SV and EG mussels showed increased gill mass upon E. coli challenge, while digestive gland mass was increased by bacterial challenge only in SV mussels. Bacterial challenge produced no effect on humoral reactive oxygen species levels of both groups. Total oxyradical scavenging capacity levels was reduced in challenged SV mussels but remained unaffected in EG ones. In general, EG diet decreased glutathione S-transferase and catalase activities in gill and digestive gland, compared with SV diet; but increased enzyme activity was evident in challenged mussels of both groups. Gill and digestive gland lipid peroxidation levels were higher in EG than in SV mussels but E. coli challenge had stronger effect on SV mussels. Adductor muscle RNA:DNA ratio was higher in EG mussels than in SV ones, and increased upon E. coli challenge in mussels of both groups. E. gracilis can be suggested as a nutritional and

  2. Evaluation of the long-term variability of seawater salinity and temperature in response to natural and anthropogenic stressors in the Arabian Gulf.

    PubMed

    Elhakeem, Abubaker; Elshorbagy, Walid

    2013-11-15

    Evaluating the long-term variability of the seawater salinity and temperature due to climate change is a limiting economical and operational factor in planning the design of new and expansion of existing desalination plants. This need is amplified in the Arabian Gulf due to the natural arid climate and anthropological stresses related to energy exploration and ongoing major developments. The lack of data in this region further adds additional dimension to the problem. The present work represents a systematic innovative approach to evaluate the anticipated long-term changes in the seawater salinity and temperature under the stresses of projected climate change and massive industrial effluents using statistical correlation and hydrodynamic simulation. The proposed approach employs the direct relation between the net freshwater losses (evaporation) entrenched with the investigated stressors and the mean sea salinity and sea temperature variation of an inverse estuary to formulate the statistical correlation and the hydrodynamic simulation conditions. PMID:24055462

  3. Long Term Illness and Wages

    ERIC Educational Resources Information Center

    Sandy, Robert; Elliott, Robert R.

    2005-01-01

    Long-term illness (LTI) is a more prevalent workplace risk than fatal accidents but there is virtually no evidence for compensating differentials for a broad measure of LTI. In 1990 almost 3.4 percent of the U.K. adult population suffered from a LTI caused solely by their working conditions. This paper provides the first estimates of compensating…

  4. Bacterial response to a continuous long-term exposure of silver nanoparticles at sub-ppm silver concentrations in a membrane bioreactor activated sludge system.

    PubMed

    Zhang, Chiqian; Liang, Zhihua; Hu, Zhiqiang

    2014-03-01

    Silver nanoparticles (nanosilver or AgNPs) have excellent antimicrobial properties. Because of their increasing use, there is a concern about the potential impact of AgNPs in wastewater treatment systems. This study investigated the long-term effects of AgNPs (continuous loading for more than 60 days) on membrane bioreactor (MBR) activated sludge performance. At the influent AgNP concentration of 0.10 mg Ag/L, there was no significant difference in effluent water quality or bacterial activities before and after AgNP exposure. Nitrifying bacterial community structure was relatively stable before and after the long-term AgNP loading. Both ammonia-oxidizing bacteria (AOB) Nitrosomonas spp. and Nitrosospira spp. were present while Nitrospira spp. was the dominant nitrite-oxidizing bacterial species throughout this study. Abundance of silver resistance gene silE in the MBR, however, increased by 50-fold 41 days after the AgNP exposure, and then decreased with continuous AgNP exposure. The long-term nanosilver exposure did not change the membrane fouling rate although extracellular polymeric substances (EPS) concentration increased significantly after nanosilver dosing. The results suggest that AgNPs at the influent concentrations of 0.10 mg/L and below have almost no impact on activated sludge wastewater treatment performance, as activated sludge can effectively reduce nanosilver toxicity by adsorbing or precipitating AgNPs and silver ions (Ag(+)) released from the dissolution of AgNPs. PMID:24210505

  5. Cellular responses to environmental DNA damage

    SciTech Connect

    Not Available

    1994-08-01

    This volume contains the proceedings of the conference entitled Cellular Responses to Environmental DNA Damage held in Banff,Alberta December 1--6, 1991. The conference addresses various aspects of DNA repair in sessions titled DNA repair; Basic Mechanisms; Lesions; Systems; Inducible Responses; Mutagenesis; Human Population Response Heterogeneity; Intragenomic DNA Repair Heterogeneity; DNA Repair Gene Cloning; Aging; Human Genetic Disease; and Carcinogenesis. Individual papers are represented as abstracts of about one page in length.

  6. Long-term data archiving

    SciTech Connect

    Moore, David Steven

    2009-01-01

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

  7. Unintentional Long-Term Esophageal Stenting due to a Complete Response in a Patient with Stage UICC IV Adenocarcinoma of the Gastroesophageal Junction.

    PubMed

    Paeschke, Anna; Bojarski, Christian; Küpferling, Susanne; Hucklenbroich, Thomas; Siegmund, Britta; Daum, Severin

    2016-01-01

    Endoscopic stent implantation is a common short-treatment option in palliative settings in patients with esophageal cancer. Advanced disease is associated with low survival rates; therefore, data on the long-term outcome are limited. So far, cases of long-term remission or even cure of metastasized adenocarcinoma of the gastroesophageal junction or stomach (AGS) have only been reported from Asia. A 51-year-old male patient primarily diagnosed with metastasized adenocarcinoma of the gastroesophageal junction (GEJ) [type I, cT3cN+cM1 (hep), CEA positive, UICC stage IV] received palliative esophageal stenting with a self-expandable metal stent. As disease progressed after four cycles with epirubicin, oxaliplatin, and capecitabin, treatment was changed to 5-FU and Irinotecan. The patient did not return after 5 cycles of FOLFIRI, but presented 4 years later with mild dysphagia. Endoscopy surprisingly revealed no relevant stenosis or stent migration. Repeated histological analyses of a residual mass at the GEJ did not detect malignancy. Since the initially diagnosed hepatic metastases were no longer detectable by computed tomography, cure from esophageal cancer was assumed. Dysphagia was ascribed to esophageal motility disorder by a narrowed esophageal lumen after long-term stenting. Thus, endoscopic stent implantation is an important method in palliative treatment of dysphagia related to AGS. New systemic treatment strategies like trastuzumab in Her2neu positive cases or new VEGF-inhibitors like ramucirumab will lead to more long-time survivors with AGS. In conclusion, future endoscopic treatment strategies in AGS represent a challenge for the development of new stent techniques in either extraction or programmed complete dissolution. PMID:27462189

  8. Unintentional Long-Term Esophageal Stenting due to a Complete Response in a Patient with Stage UICC IV Adenocarcinoma of the Gastroesophageal Junction

    PubMed Central

    Paeschke, Anna; Bojarski, Christian; Küpferling, Susanne; Hucklenbroich, Thomas; Siegmund, Britta; Daum, Severin

    2016-01-01

    Endoscopic stent implantation is a common short-treatment option in palliative settings in patients with esophageal cancer. Advanced disease is associated with low survival rates; therefore, data on the long-term outcome are limited. So far, cases of long-term remission or even cure of metastasized adenocarcinoma of the gastroesophageal junction or stomach (AGS) have only been reported from Asia. A 51-year-old male patient primarily diagnosed with metastasized adenocarcinoma of the gastroesophageal junction (GEJ) [type I, cT3cN+cM1 (hep), CEA positive, UICC stage IV] received palliative esophageal stenting with a self-expandable metal stent. As disease progressed after four cycles with epirubicin, oxaliplatin, and capecitabin, treatment was changed to 5-FU and Irinotecan. The patient did not return after 5 cycles of FOLFIRI, but presented 4 years later with mild dysphagia. Endoscopy surprisingly revealed no relevant stenosis or stent migration. Repeated histological analyses of a residual mass at the GEJ did not detect malignancy. Since the initially diagnosed hepatic metastases were no longer detectable by computed tomography, cure from esophageal cancer was assumed. Dysphagia was ascribed to esophageal motility disorder by a narrowed esophageal lumen after long-term stenting. Thus, endoscopic stent implantation is an important method in palliative treatment of dysphagia related to AGS. New systemic treatment strategies like trastuzumab in Her2neu positive cases or new VEGF-inhibitors like ramucirumab will lead to more long-time survivors with AGS. In conclusion, future endoscopic treatment strategies in AGS represent a challenge for the development of new stent techniques in either extraction or programmed complete dissolution. PMID:27462189

  9. Surface coal mine land reclamation using a dry flue gas desulfurization product: Short-term and long-term water responses.

    PubMed

    Chen, Liming; Stehouwer, Richard; Tong, Xiaogang; Kost, Dave; Bigham, Jerry M; Dick, Warren A

    2015-09-01

    Abandoned coal-mined lands are a worldwide concern due to their potential negative environmental impacts, including erosion and development of acid mine drainage. A field study investigated the use of a dry flue gas desulfurization product for reclamation of abandoned coal mined land in USA. Treatments included flue gas desulfurization product at a rate of 280 Mg ha(-1) (FGD), FGD at the same rate plus 112 Mg ha(-1) yard waste compost (FGD/C), and conventional reclamation that included 20 cm of re-soil material plus 157 Mg ha(-1) of agricultural limestone (SOIL). A grass-legume sward was planted after treatment applications. Chemical properties of surface runoff and tile water (collected from a depth of 1.2m below the ground surface) were measured over both short-term (1-4 yr) and long-term (14-20 yr) periods following reclamation. The pH of surface runoff water was increased from approximately 3, and then sustained at 7 or higher by all treatments for up to 20 yr, and the pH of tile flow water was also increased and sustained above 5 for 20 yr. Compared with SOIL, concentrations of Ca, S and B in surface runoff and tile flow water were generally increased by the treatments with FGD product in both short- and long-term measurements and concentrations of the trace elements were generally not statistically increased in surface runoff and tile flow water over the 20-yr period. However, concentrations of As, Ba, Cr and Hg were occasionally elevated. These results suggest the use of FGD product for remediating acidic surface coal mined sites can provide effective, long-term reclamation. PMID:26001939

  10. On the importance of coupled THM processes to predict the long-term response of a generic salt repository for high-level nuclear waste

    NASA Astrophysics Data System (ADS)

    Blanco Martin, L.; Rutqvist, J.; Birkholzer, J. T.

    2013-12-01

    Salt is a potential medium for the underground disposal of nuclear waste because it has several assets, in particular its ability to creep and heal fractures generated by excavation and its water and gas tightness in the undisturbed state. In this research, we focus on disposal of heat-generating nuclear waste (such as spent fuel) and we consider a generic salt repository with in-drift emplacement of waste packages and subsequent backfill of the drifts with run-of-mine crushed salt. As the natural salt creeps, the crushed salt backfill gets progressively compacted and an engineered barrier system is subsequently created. In order to evaluate the integrity of the natural and engineered barriers over the long-term, it is important to consider the coupled effects of the thermal, hydraulic and mechanical processes that take place. In particular, the results obtained so far show how the porosity reduction of the crushed salt affects the saturation and pore pressure evolution throughout the repository, both in time and space. Such compaction is induced by the stress and temperature regime within the natural salt. Also, transport properties of the host rock are modified not only by thermo-mechanically and hydraulically-induced damaged processes, but also by healing/sealing of existing fractures. In addition, the THM properties of the backfill evolve towards those of the natural salt during the compaction process. All these changes are based on dedicated laboratory experiments and on theoretical considerations [1-3]. Different scenarios are modeled and compared to evaluate the relevance of different processes from the perspective of effective nuclear waste repositories. The sensitivity of the results to some parameters, such as capillarity, is also addressed. The simulations are conducted using an updated version of the TOUGH2-FLAC3D simulator, which is based on a sequential explicit method to couple flow and geomechanics [4]. A new capability for large strains and creep

  11. A qualitative study of cancer survivors' responses to information on the long-term and late effects of pelvic radiotherapy 1-11 years post treatment.

    PubMed

    Boulton, M; Adams, E; Horne, A; Durrant, L; Rose, P; Watson, E

    2015-09-01

    As more patients survive cancer for longer term, the long-term and late effects of treatments become increasingly important issues for cancer survivors and providing information to enable survivors to recognise and manage them becomes an increasingly pressing challenge for health care professionals. The aim of this study was to explore the experiences of cancer survivors regarding information given on potential long-term and late effects of pelvic radiotherapy. Semi-structured interviews were conducted with 28 cancer survivors who had had radiotherapy to the pelvic area for a range of cancers 1-11 years previously. Participants were recruited using maximum variation sampling from a larger questionnaire survey of patients treated at one hospital. Interviews were recorded, transcribed and analysed using Framework. Participants recognised the value of information to reassure and to inform action but also its potentially undesirable effects to frighten or raise anxieties about future problems and its inherent limitations in meeting their wider needs. They identified the timing, amount of information and context in which it was given as of particular importance. Information based on personal experience was also valued. These findings highlight the importance of appropriate, individualised information during treatment, at hospital discharge and subsequently in primary care. PMID:26202602

  12. Final Technical Report: The Effects of Iron Complexing Ligands on the Long Term Ecosystem Response to Iron Enrichment of HNLC waters

    SciTech Connect

    Cochlan, William P.

    2008-06-13

    Substantial increases in the concentrations of the stronger of two Fe(III) complexing organic ligand classes measured during the mesoscale Fe enrichment studies IronEx II and SOIREE appeared to sharply curtailed Fe availability to diatoms and thus limited the efficiency of carbon sequestration to the deep. Detailed observations during IronEx II (equatorial Pacific Ocean) and SOIREE (Southern Ocean –Pacific sector) indicate that the diatoms began re-experiencing Fe stress even though dissolved Fe concentrations remained elevated in the patch. This surprising outcome likely is related to the observed increased concentrations of strong Fe(III)-complexing ligands in seawater. Preliminary findings from other studies indicate that diatoms may not readily obtain Fe from these chemical species whereas Fe bound by strong ligands appears to support growth of cyanobacteria and nanoflagellates. The difficulty in assessing the likelihood of these changes with in-situ mesoscale experiments is the extended monitoring period needed to capture the long-term trajectory of the carbon cycle. A more detailed understanding of Fe complexing ligand effects on long-term ecosystem structure and carbon cycling is essential to ascertain not only the effect of Fe enrichment on short-term carbon sequestration in the oceans, but also the potential effect of Fe enrichment in modifying ecosystem structure and trajectory.

  13. Final Activity Report: The Effects of Iron Complexing Ligands on the Long Term Ecosystem Response to Iron Enrichment of HNLC waters

    SciTech Connect

    Trick, Charles Gordon

    2013-07-30

    Substantial increases in the concentrations of the stronger of two Fe(III) complexing organic ligand classes measured during the mesoscale Fe enrichment studies IronEx II and SOIREE appeared to sharply curtailed Fe availability to diatoms and thus limited the efficiency of carbon sequestration to the deep. Detailed observations during IronEx II (equatorial Pacific Ocean) and SOIREE (Southern Ocean –Pacific sector) indicate that the diatoms began re-experiencing Fe stress even though dissolved Fe concentrations remained elevated in the patch. This surprising outcome likely is related to the observed increased concentrations of strong Fe(III)-complexing ligands in seawater. Preliminary findings from other studies indicate that diatoms may not readily obtain Fe from these chemical species whereas Fe bound by strong ligands appears to support growth of cyanobacteria and nanoflagellates. The difficulty in assessing the likelihood of these changes with in-situ mesoscale experiments is the extended monitoring period needed to capture the long-term trajectory of the carbon cycle. A more detailed understanding of Fe complexing ligand effects on long-term ecosystem structure and carbon cycling is essential to ascertain not only the effect of Fe enrichment on short-term carbon sequestration in the oceans, but also the potential effect of Fe enrichment in modifying ecosystem structure and trajectory.

  14. Phenobarbital induction of cytochromes P-450. High-level long-term responsiveness of primary rat hepatocyte cultures to drug induction, and glucocorticoid dependence of the phenobarbital response.

    PubMed Central

    Waxman, D J; Morrissey, J J; Naik, S; Jauregui, H O

    1990-01-01

    The induction of hepatic cytochromes P-450 by phenobarbital (PB) was studied in rat hepatocytes cultured for up to 5 weeks on Vitrogen-coated plates in serum-free modified Chee's medium then exposed to PB (0.75 mM) for an additional 4 days. Immunoblotting analysis indicated that P-450 forms PB4 (IIB1) and PB5 (IIB2) were induced dramatically (greater than 50-fold increase), up to levels nearly as high as those achieved in PB-induced rat liver in vivo. The newly synthesized cytochrome P-450 was enzymically active, as shown by the major induction of the P-450 PB4-dependent steroid 16 beta-hydroxylase and pentoxyresorufin O-dealkylase activities in the PB-induced hepatocyte microsomes (up to 90-fold increase). PB induction of these P-450s was markedly enhanced by the presence of dexamethasone (50 nM-1 microM), which alone was not an affective inducing agent, and was inhibited by greater than 90% by 10% fetal bovine serum. The PB response was also inhibited (greater than 85%) by growth hormone (250 ng/ml), indicating that this hormone probably acts directly on the hepatocyte when it antagonizes the induction of P-450 PB4 in intact rats. In untreated hepatocytes, P-450 RLM2 (IIA2), P-450 3 (IIA1) and NADPH P-450 reductase levels were substantially maintained in the cultures for 10-20 days. The latter two enzymes were also inducible by PB to an extent (3-4 fold elevation) that is comparable with that observed in the liver in vivo. Moreover, P-450c (IA1) and P-450 3 (IIA1) were highly inducible by 3-methylcholanthrene (5 microM; 48 h exposure) even after 3 weeks in culture. In contrast, the male-specific pituitary-regulated P-450 form 2c (IIC11) was rapidly lost upon culturing the hepatocytes, suggesting that supplementation of appropriate hormonal factors may be necessary for its expression. The present hepatocyte culture system exhibits a responsiveness to drug inducers that is qualitatively and quantitatively comparable with that observed in vivo, and should prove

  15. The relationship between interannual and long-term cloud feedbacks

    SciTech Connect

    Zhou, Chen; Zelinka, Mark D.; Dessler, Andrew E.; Klein, Stephen A.

    2015-12-11

    The analyses of Coupled Model Intercomparison Project phase 5 simulations suggest that climate models with more positive cloud feedback in response to interannual climate fluctuations also have more positive cloud feedback in response to long-term global warming. Ensemble mean vertical profiles of cloud change in response to interannual and long-term surface warming are similar, and the ensemble mean cloud feedback is positive on both timescales. However, the average long-term cloud feedback is smaller than the interannual cloud feedback, likely due to differences in surface warming pattern on the two timescales. Low cloud cover (LCC) change in response to interannual and long-term global surface warming is found to be well correlated across models and explains over half of the covariance between interannual and long-term cloud feedback. In conclusion, the intermodel correlation of LCC across timescales likely results from model-specific sensitivities of LCC to sea surface warming.

  16. Long-term efficacy and safety of certolizumab pegol in Japanese rheumatoid arthritis patients with an inadequate response to methotrexate: 52-week results from an open-label extension of the J-RAPID study

    PubMed Central

    Tanaka, Yoshiya; Yamamoto, Kazuhiko; Takeuchi, Tsutomu; Yamanaka, Hisashi; Ishiguro, Naoki; Eguchi, Katsumi; Watanabe, Akira; Origasa, Hideki; Shoji, Toshiharu; Miyasaka, Nobuyuki; Koike, Takao

    2014-01-01

    Abstract Objectives. To evaluate the long-term efficacy and safety of certolizumab pegol (CZP) plus methotrexate treatment and to assess the efficacy of two CZP maintenance dosing schedules in Japanese rheumatoid arthritis (RA) patients with an inadequate response to methotrexate. Methods. J-RAPID double-blind patients were entered into an open-label extension (OLE) study. Patients withdrawn due to lack of efficacy at 16 weeks and double-blind completers without a week-24 American College of Rheumatology (ACR) 20 response received CZP 200 mg every other week (Q2W) plus methotrexate. Double-blind completers with week-24 ACR20 responses were randomized to CZP 200 mg Q2W plus methotrexate or CZP 400 mg every 4 weeks plus methotrexate. Results. The ACR20/ACR50/ACR70 response rates of double-blind completers (n = 204) were 89.7%/67.2%/36.3% at OLE entry and 95.6%/84.8%/58.3% at 52 weeks, respectively. Other clinical, functional and radiographic outcomes were sustained with long-term CZP plus methotrexate. Long-term treatment with CZP was well-tolerated with no new unexpected adverse events observed. The efficacy and safety of CZP treatment were similar between the two dosing schedules. Conclusions. Continued CZP administration with methotrexate maintained efficacy over 52 weeks and was well-tolerated for Japanese RA patients. No obvious differences in clinical efficacy and safety were observed between the two dosing schedules, giving flexibility in maintenance administration schedules. PMID:24593170

  17. Observed and Potential Responses of Upland Tundra Ecosystems to a Changing Climate: Results from the Arctic Long-Term Ecological Research Project, North Slope, Alaska, USA

    NASA Astrophysics Data System (ADS)

    Bowden, W. B.

    2014-12-01

    The Arctic is one of the most rapidly changing biomes on earth. Research at the Toolik Field Station by the Arctic Long-Term Ecological Research project provides a perspective on changes that are impacting the upland tussock tundra region of the North Slope of Alaska, a region that is typical of ~15% of the arctic region. The arctic is responding to a combination of long-term, gradual changes (presses) and short-term, event-driven changes (pulses). The most important press, of course, is the persistent rise in average annual air temperature observed in most places (though not at Toolik). Associated with this increase in SAT is a well-documented increase in shallow permafrost temperature (which is observed around Toolik). Our long-term research shows that this trend will favor taller and more productive shrub and grass vegetation. Higher SAT translates to earlier spring breakup and later onset of winter. This change in seasonality is affecting interactions between shrub leaf-out, insect emergence, and bird nesting. Persistent and more frequent droughts are having important impacts on the ability of Arctic grayling - the top consumer is most upland tundra streams - to survive and has the potential to block their ability to migrate to essential overwintering lakes. The interaction between temperature (which is changing) and light (which is not) creates a "seasonal asynchrony" that may be increasing the loading of nutrients - notably nitrate - to upland tundra streams late in the season, with impacts that we do not fully understand yet. The upland tundra environment is also responding to an increasing frequency of pulses, most notably wildfires and the development of thermo-erosional failures (TEFs). Wildfires transfer large quantities of carbon and nitrogen directly to the atmosphere. TEFs may deliver large quantities of sediment and nutrients to streams and lakes. Currently these pulse disturbances seem to be having only limited, local impacts. However, as shallow

  18. Nitrogen fluxes in response to changing NOx emissions and deposition at EPA's Mid-Atlantic Long Term Monitoring (LTM) stream sites, 1990-2009

    NASA Astrophysics Data System (ADS)

    Funk, C.; Lynch, J. A.

    2012-12-01

    Surface water chemistry provides direct indicators of the potential effects of anthropogenic impacts, such as acid deposition and climate change, on the overall health of aquatic ecosystems. Long-term surface water monitoring networks provide a host of environmental data that can be used, in conjunction with other networks, to assess how water bodies respond to stressors and if they are potentially at risk (e.g., receiving pollutant deposition beyond its critical load). Two EPA-administered monitoring programs provide information on the effects of acidic deposition on headwater aquatic systems: the Temporally Integrated Monitoring of Ecosystems (TIME) program and Long Term Monitoring (LTM) program, designed to track the effectiveness of the 1990 Clean Air Act Amendments (CAAA) in reducing the acidity of surface waters in the Northeast and Mid-Atlantic. Here we compare trends in inorganic nitrogen emissions and deposition to streamwater nitrate (NO3-) concentration trends and NO3- export in headwater Mid-Atlantic streams. Annual NOx emissions from the fossil fuel based power sector, regulated under Title IV of the 1990 CAAA, decreased 67% from 6.7 million tones in 1990 to 2.0 million tones in 2009. Commensurate with decreased NOx emissions, there was a 31% reduction in total inorganic nitrogen deposition in the Mid-Atlantic region, from 8.7 kg N/ha to 6.0 kg N/yr. Over the same time period, surface water nitrate concentrations in headwater streams in the Northern Appalachian Plateau (n=9) and Central Appalachian mountains (n=66) improve (show a decreasing NO3- trend) at 30% and 50% of monitored sites, respectively. Despite these improvements, only 10% of monitored Appalachian streams show improvement in critical load status to no longer exceed the acid sensitivity threshold and experience adverse ecological effects. Information from long-term monitoring has shown that emission reductions have in improved environmental conditions and increased ecosystem protection

  19. Method and Apparatus for a Miniature Bioreactor System for Long-Term Cell Culture

    NASA Technical Reports Server (NTRS)

    Kleis, Stanley J. (Inventor); Geffert, Sandra K. (Inventor); Gonda, Steve R. (Inventor)

    2015-01-01

    A bioreactor and method that permits continuous and simultaneous short, moderate, or long term cell culturing of one or more cell types or tissue in a laminar flow configuration is disclosed, where the bioreactor supports at least two laminar flow zones, which are isolated by laminar flow without the need for physical barriers between the zones. The bioreactors of this invention are ideally suited for studying short, moderate and long term studies of cell cultures and the response of cell cultures to one or more stressors such as pharmaceuticals, hypoxia, pathogens, or any other stressor. The bioreactors of this invention are also ideally suited for short, moderate or long term cell culturing with periodic cell harvesting and/or medium processing for secreted cellular components.

  20. Long-term benthic responses to sustained disturbance by aggregate extraction in an area off the east coast of the United Kingdom

    NASA Astrophysics Data System (ADS)

    Barrio Froján, Christopher R. S.; Boyd, Siân E.; Cooper, Keith M.; Eggleton, Jacqueline D.; Ware, Suzanne

    2008-08-01

    The temporal variability of benthic assemblages inhabiting offshore gravel deposits in the North Sea is poorly known, as purpose-collected long-term data sets have until recently been non-existent. It has therefore proved difficult to understand the stability and resilience of these benthic ecosystems after disturbance caused by the extraction of aggregates on an industrial scale. The present investigation examines an 8-year time series of data collected in and around an active commercial aggregate extraction site off the east coast of the United Kingdom. Both physical and biological data sets suggest a distinct yet localised effect after sustained gravel extraction, with impacted sediments generally appearing more physically homogeneous and faunistically impoverished than undisturbed sediments. Although inter-annual variability of selected assemblage metrics was reduced in disturbed sediments, differences in some assemblage metrics became significant between years. Despite such observations, significant impacts to the benthos in any given year were not sustained for long. However, the magnitude of impact in almost every year would be enough to merit remedial intervention based on an existing model of measuring acceptable levels of disturbance as a result of organic enrichment. Caution must be exercised in making any such recommendations, especially as there are presently no models specifically designed to assess the degree of acceptable disturbance from aggregate extraction. This study not only highlights the importance of and need for long-term data sets in order to better understand the difference between natural and human-induced variability in benthic assemblages, but also emphasises the need to develop more relevant monitoring tools to better manage the activities of the marine aggregate extraction industry.

  1. PI3K signalling in GnRH actions on dispersed goldfish pituitary cells: relationship with PKC-mediated LH and GH release and regulation of long-term effects on secretion and total cellular hormone availability.

    PubMed

    Pemberton, Joshua G; Orr, Michael E; Stafford, James L; Chang, John P

    2014-09-01

    Goldfish pituitary cells are exposed to two GnRHs, salmon (s)GnRH and chicken (c)GnRH-II. Phosphoinositide 3-kinase (PI3K) and protein kinase C (PKC) both participate in acute sGnRH- and cGnRH-II-stimulated LH and GH release. Using goldfish pituitary cells, we examined the relationship between PI3K and PKC in acute LH and GH secretion, and PI3K involvement in chronic hormone release and total LH and GH availability. The PI3K inhibitor LY294002 did not affect PKC agonists-induced LH or GH release, and PKC agonists did not alter PI3K p85 phosphorylation, suggesting PKC activation is not upstream of PI3K in acute hormone release. In 2, 6, 12 and 24h treatments, LY294002 did not affect LH release but stimulated total LH availability at 6h. sGnRH stimulatory actions on LH release and total availability at 12 and 24h, and cGnRH-II effects on these parameters at 6h were inhibited by LY294002. LY294002 enhanced basal GH release at 2 and 6h, but reduced total GH at 12 and 24h. Increased GH release was seen following 6, 12 and 24h of sGnRH, and 2, 6 and 24h of cGnRH-II treatment but total GH availability was only elevated by 24h cGnRH-II treatment. Whereas LY294002 inhibited GH release responses to sGnRH at 12h and cGnRH-II at 6h, it attenuated cGnRH-II-elicited, but not sGnRH-induced, effects on total GH. These results indicate that PI3K differentially modulates long-term basal and GnRH-stimulated hormone release, and total hormone availability, in a time-, cell-type-, and GnRH isoform-selective manner. PMID:24681225

  2. Rapid Cellular Identification by Dynamic Electromechanical Response

    SciTech Connect

    Nikiforov, Maxim; Jesse, Stephen; Kalinin, Sergei V; Reukov, Vladimir V; Vertegel, Alexey; Thompson, Gary L

    2009-01-01

    Coupling between electrical and mechanical phenomena is ubiquitous in living systems. Here, we demonstrate rapid identification of cellular organisms using difference in electromechanical activity in a broad frequency range. Principal component analysis of the dynamic electromechanical response spectra bundled with neural network based recognition provides a robust identification algorithm based on their electromechanical signature, and allows unambiguous differentiation of model Micrococcus Lysodeikticus and Pseudomonas Fluorescens system. This methodology provides a universal pathway for biological identification obviating the need for well-defined analytical models of Scanning Probe Microscopy response.

  3. Usefulness of plasma renin activity in predicting haemodynamic and clinical responses and survival during long term converting enzyme inhibition in severe chronic heart failure. Experience in 100 consecutive patients.

    PubMed Central

    Packer, M; Medina, N; Yushak, M; Lee, W H

    1985-01-01

    The relation between plasma renin activity before treatment and the haemodynamic and clinical responses to converting enzyme inhibition was determined in 100 consecutive patients with severe chronic heart failure who were treated with captopril or enalapril. Initial doses of captopril produced significant increases in cardiac index and decreases in left ventricular filling pressure, mean arterial pressure, mean right atrial pressure, heart rate, and systemic vascular resistance that varied linearly with the pretreatment value for plasma renin activity. In contrast, there was no relation between the pretreatment activity and the magnitude of haemodynamic improvement after 1-3 months of treatment with the converting enzyme inhibitors, and, consequently, a similar proportion of patients with a high (greater than 6 ng/ml/h; greater than 4.62 mmol/l/h), intermediate (2-6 ng/ml/h; 1.54-4.62 mmol/l/h), and low (less than 2 ng/ml/h; less than 1.54 mmol/l/h) pretreatment value improved clinically during long term treatment (64%, 60%, and 64% respectively). Long term survival after one, two, and three years was similar in the three groups. Estimating the degree of activation of the renin-angiotensin system by measuring pretreatment plasma renin activity fails to predict the long term haemodynamic or clinical responses to converting enzyme inhibitors in patients with severe chronic heart failure, and thus appears to be of limited value in selecting those patients likely to benefit from treatment with these drugs. PMID:2994697

  4. Holocene sediment distribution on the inner continental shelf of northeastern South Carolina: implications for the regional sediment budget and long-term shoreline response

    USGS Publications Warehouse

    Denny, Jane F.; Schwab, William C.; Baldwin, Wayne E.; Barnhardt, Walter A.; Gayes, Paul T.; Morton, R.A.; Warner, John C.; Driscoll, Neal W.; Voulgaris, George

    2013-01-01

    High-resolution geophysical and sediment sampling surveys were conducted offshore of the Grand Strand, South Carolina to define the shallow geologic framework of the inner shelf. Results are used to identify and map Holocene sediment deposits, infer sediment transport pathways, and discuss implications for the regional coastal sediment budget. The thickest deposits of Holocene sediment observed on the inner shelf form shoal complexes composed of moderately sorted fine sand, which are primarily located offshore of modern tidal inlets. These shoal deposits contain ~67 M m3 of sediment, approximately 96% of Holocene sediment stored on the inner shelf. Due to the lack of any significant modern fluvial input of sand to the region, the Holocene deposits are likely derived from reworking of relict Pleistocene and older inner-shelf deposits during the Holocene marine transgression. The Holocene sediments are concentrated in the southern part of the study area, due to a combination of ancestral drainage patterns, a regional shift in sediment supply from the northeast to the southwest in the late Pleistocene, and proximity to modern inlet systems. Where sediment is limited, only small, low relief ridges have formed and Pleistocene and older deposits are exposed on the seafloor. The low-relief ridges are likely the result of a thin, mobile veneer of sediment being transported across an irregular, erosional surface formed during the last transgression. Sediment textural trends and seafloor morphology indicate a long-term net transport of sediment to the southwest. This is supported by oceanographic studies that suggest the long-term sediment transport direction is controlled by the frequency and intensity of storms that pass through the region, where low pressure systems yield net along-shore flow to the southwest and a weak onshore component. Current sediment budget estimates for the Grand Strand yield a deficit for the region. Volume calculations of Holocene deposits on the

  5. A Budyko analysis of long-term ecological research sites: evidence for resistance and resilience of water yield responses to climate variability

    NASA Astrophysics Data System (ADS)

    Creed, I. F.; Jones, J.; A Consortium of Scientists from Long Term Ecological Research Sites

    2011-12-01

    Analyses of long-term records at pristine small headwater catchments in the US and Canada indicate that climate change effects on hydrology depend strongly on ecosystem processes, including evaporation, transpiration, and water storage in soil, snow, ice, and groundwater. A Budyko analysis was used to explore the extent to which watersheds are using the maximum possible water for evapotranspiration (ET), given the measured precipitation (P), discharge (Q) and energy balance at each site. This analysis focused on small catchments (< 1,000 km2) that form the basis of US LTER, USFS-EF, and Canadian experimental catchment sites. The questions driving this analysis included: (1) How closely do average annual values of reference catchments fall to the Budyko curve, indicating that the vegetation water use at these sites is close to the maximum possible under these climate conditions; (2) To what extent do climatic variability, oscillations or change lead to year-to-year deviations from the Budyko curve indicating either a change in the water supply held in storage within the catchment and/or a change in the water use efficiency of vegetation under certain transient climate conditions; and (3) To what extent do legacies of historical or recent disturbances lead to year-to-year deviations from the Budyko curve indicating a disturbance legacy effect on vegetation water use. The distribution of catchments on the Budyko curve indicates that climate has a substantial influence on a catchment's hydrological, ecological, and physiological behavior. However, there were deviations from the theoretical Budyko curve - both in the annual average and among individual years. Catchments with small deviations were able to maintain steady-state P-Q relations and showed high resistance (low resilience) to changing climatic conditions. In contrast, catchments with large deviations were unable to maintain steady state P-Q relations and showed low resistance (high resilience) to changing

  6. Neurobiological problems in long-term deep space flights.

    PubMed

    Vazquez, M E

    1998-01-01

    Future missions in space may involve long-term travel beyond the magnetic field of the Earth, subjecting astronauts to radiation hazards posed by solar flares and galactic cosmic rays, altered gravitation fields and physiological stress. Thus, it is critical to determine if there will be any reversible or irreversible, detrimental neurological effects from this prolonged exposure to space. A question of particular importance focuses on the long-term effects of the space environment on the central nervous system (CNS) neuroplasticity, with the potential acute and/or delayed effects that such perturbations might entail. Although the short-term effects of microgravity on neural control were studied on previous low earth orbit missions, the late consequences of stress in space, microgravity and space radiation have not been addressed sufficiently at the molecular, cellular and tissue levels. The possibility that space flight factors can interact influencing the neuroplastic response in the CNS looms critical issue not only to understand the ontogeny of the CNS and its functional integrity, but also, ultimately the performance of astronauts in extended space forays. The purpose of this paper is to review the neurobiological modifications that occur in the CNS exposed to the space environment, and its potential consequences for extended deep space flight. PMID:11541395

  7. Long-term acclimatization of hydraulic properties, xylem conduit size, wall strength and cavitation resistance in Phaseolus vulgaris in response to different environmental effects.

    PubMed

    Holste, Ellen K; Jerke, Megan J; Matzner, Steven L

    2006-05-01

    Phaseolus vulgaris grown under various environmental conditions was used to assess long-term acclimatization of xylem structural characteristics and hydraulic properties. Conduit diameter tended to be reduced and 'wood' density (of 'woody' stems) increased under low moisture ('dry'), increased soil porosity ('porous soil') and low phosphorus ('low P') treatments. Dry and low P had the largest percentage of small vessels. Dry, low light ('shade') and porous soil treatments decreased P50 (50% loss in conductivity) by 0.15-0.25 MPa (greater cavitation resistance) compared with 'controls'. By contrast, low P increased P50 by 0.30 MPa (less cavitation resistance) compared with porous soil (the control for low P). Changes in cavitation resistance were independent of conduit diameter. By contrast, changes in cavitation resistance were correlated with wood density for the control, dry and porous soil treatments, but did not appear to be a function of wood density for the shade and low P treatments. In a separate experiment comparing control and porous soil plants, stem hydraulic conductivity (kh), specific conductivity (ks), leaf specific conductivity (LSC), total pot water loss, plant biomass and leaf area were all greater for control plants compared to porous soil plants. Porous soil plants, however, demonstrated higher midday stomatal conductance to water vapour (gs), apparently because they experienced proportionally less midday xylem cavitation. PMID:17087467

  8. Long-Term Starvation and Posterior Feeding Effects on Biochemical and Physiological Responses of Midgut Gland of Cherax quadricarinatus Juveniles (Parastacidae).

    PubMed

    Sacristán, Hernán Javier; Ansaldo, Martín; Franco-Tadic, Luis Marcelo; Fernández Gimenez, Analía Verónica; López Greco, Laura Susana

    2016-01-01

    We investigated the effect of long-term starvation and posterior feeding on energetic reserves, oxidative stress, digestive enzymes, and histology of C. quadricarinatus midgut gland. The crayfish (6.27 g) were randomly assigned to one of three feeding protocols: continuous feeding throughout 80 day, continuous starvation until 80 day, and continuous starvation throughout 50 day and then feeding for the following 30 days. Juveniles from each protocol were weighed, and sacrificed at day 15, 30, 50 or 80. The lipids, glycogen, reduced glutathione (GSH), soluble protein, lipid peroxidation (TBARS), protein oxidation (PO), catalase (CAT), lipase and proteinase activities, and histology were measured on midgut gland. Starved crayfish had a lower hepatosomatic index, number of molts, specific growth rate, lipids, glycogen, and GSH levels than fed animals at all assay times. The starvation did not affect the soluble protein, TBARS, PO levels and CAT. In starved juveniles the lipase activity decreased as starvation time increased, whereas proteinase activity decreased only at day 80. The histological analysis of the starved animals showed several signs of structural alterations. After 30 days of feeding, the starved-feeding animals exhibited a striking recovery of hepatosomatic index, number of molts, lipids and glycogen, GSH, lipase activity and midgut gland structure. PMID:27018793

  9. Acute and Long-Term Response of Dopamine Nigrostriatal Synapses to a Single Low Dose Episode of 3-Nitropropionic Acid-Mediated Chemical Hypoxia

    PubMed Central

    Crawford, Cynthia A.; Akopian, Garnik; Ring, Justin; Jakowec, Michael W.; Petzinger, Giselle M.; Andersen, Julie K.; Vittozzi-Wong, Philip; Wang, Kristie; Farley, Cristal M.; Charntikov, Sergios; Mitroi, Danut; Beal, M. Flint; Chow, Robert; Walsh, John P.

    2010-01-01

    The goal of the present investigation was to determine the persistence of striatal dopaminergic dysfunction after a mild chemically-induced hypoxic event in Fisher 344 rats. To this end, we gave a single injection of the mitochondrial complex II inhibitor 3-nitropropionic acid (3-NP; 16.5 mg/kg, i.p.) to 2 month old male F344 rats and measured various indices of striatal dopaminergic functioning and lipid peroxidation over a 3 month span. Separate groups of rats were used to measure rod walking, evoked dopamine (DA) release, DA content, MDA accumulation, DA receptor binding, and tyrosine hydroxylase activity. The results showed that 3-NP exposure reduced most measures of DA functioning including motoric ability, DA release, and D2 receptor densities for 1 to 3 months post drug administration. Interestingly, DA content was reduced 1 week after 3-NP exposure, but rose to 147% of control values 1 month after 3-NP treatment. MDA accumulation, a measure of lipid peroxidation activity, was increased 24 hr and 1 month after 3-NP treatment. 3-NP did not affect tyrosine hydroxylase activity, suggesting that alterations in DA functioning were not the result of nigrostriatal terminal loss. These data demonstrate that a brief mild hypoxic episode caused by 3-NP exposure has long-term detrimental effects on the functioning of the nigrostriatal DA system. PMID:20730800

  10. Does Maintenance CBT Contribute to Long-Term Treatment Response of Panic Disorder With or Without Agoraphobia? A Randomized Controlled Clinical Trial

    PubMed Central

    White, Kamila S.; Payne, Laura A.; Gorman, Jack M.; Shear, M. Katherine; Woods, Scott W.; Saksa, John R.; Barlow, David H.

    2012-01-01

    Objective To examine the possibility that maintenance cognitive behavior therapy (M–CBT) may improve the likelihood of sustained improvement and reduced relapse in a multi-site randomized controlled clinical trial of patients who met criteria for panic disorder with or without agoraphobia. Method Participants were all patients (N = 379) who first began an open trial of acute-phase CBT. Patients completing and responding to acute-phase treatment were randomized to receive either nine monthly sessions of M-CBT (n = 79) or assessment only (n = 78) and were then followed for an additional 12 months without treatment. Results M–CBT produced significantly lower relapse rates (5.2%) and reduced work and social impairment compared to the assessment only condition (18.4%) at a 21-month follow-up (MFU). Multivariate Cox proportional hazards models showed that residual symptoms of agoraphobia at the end of acute-phase treatment were independently predictive of time to relapse during 21-MFU (HR = 1.15, p < .01). Conclusions M–CBT aimed at reinforcing acute treatment gains to prevent relapse and offset disorder recurrence may improve long-term outcome in PD/A. PMID:23127290

  11. Long-Term Starvation and Posterior Feeding Effects on Biochemical and Physiological Responses of Midgut Gland of Cherax quadricarinatus Juveniles (Parastacidae)

    PubMed Central

    Sacristán, Hernán Javier; Ansaldo, Martín; Franco-Tadic, Luis Marcelo; Fernández Gimenez, Analía Verónica; López Greco, Laura Susana

    2016-01-01

    We investigated the effect of long-term