Brain-controlled muscle stimulation for the restoration of motor function

PubMed Central

Ethier, Christian; Miller, Lee E

2014-01-01

Loss of the ability to move, as a consequence of spinal cord injury or neuromuscular disorder, has devastating consequences for the paralyzed individual, and great economic consequences for society. Functional Electrical Stimulation (FES) offers one means to restore some mobility to these individuals, improving not only their autonomy, but potentially their general health and well-being as well. FES uses electrical stimulation to cause the paralyzed muscles to contract. Existing clinical systems require the stimulation to be preprogrammed, with the patient typically using residual voluntary movement of another body part to trigger and control the patterned stimulation. The rapid development of neural interfacing in the past decade offers the promise of dramatically improved control for these patients, potentially allowing continuous control of FES through signals recorded from motor cortex, as the patient attempts to control the paralyzed body part. While application of these ‘Brain Machine Interfaces’ (BMIs) has undergone dramatic development for control of computer cursors and even robotic limbs, their use as an interface for FES has been much more limited. In this review, we consider both FES and BMI technologies and discuss the prospect for combining the two to provide important new options for paralyzed individuals. PMID:25447224

Invited Review: The Myosins: Exploration of the Development of Our Current Understanding of These Mutations in the Motor

PubMed Central

Moore, Jeffrey R.; Leinwand, Leslie; Warshaw, David M.

2013-01-01

Hypertrophic (HCM) and dilated (DCM) cardiomyopathies are inherited diseases with a high incidence of death due to electrical abnormalities or outflow tract obstruction. In many of the families afflicted with either disease, causative mutations have been identified in various sarcomeric proteins. In this review, we focus on mutations in the cardiac muscle molecular motor, myosin and its associated light chains. Despite the >300 identified mutations there is still no clear understanding of how these mutations within the same myosin molecule can lead to the dramatically different clinical phenotypes associated with HCM and DCM. Localizing mutations within myosin’s molecular structure provides insight into the potential consequence of these perturbations to key functional domains of the motor. Review of biochemical and biophysical data that characterize the functional capacities of these mutant myosins suggests that mutant myosins with enhanced contractility lead to HCM while those displaying reduced contractility lead to DCM. With gain and loss of function potentially being the primary consequence of a specific mutation, how these functional changes trigger the hypertrophic response and lead to the distinct HCM and DCM phenotypes will be the future investigative challenge. PMID:22821910

The Consequences of Perpetrating Psychological Aggression in Dating Relationships: A Descriptive Investigation

PubMed Central

Shorey, Ryan C.; Temple, Jeff R.; Febres, Jeniimarie; Brasfield, Hope; Sherman, Amanda E.; Stuart, Gregory L.

2012-01-01

Psychological aggression is the most prevalent form of aggression in dating relationships, with women perpetrating as much, if not more, psychological aggression than men. Researchers have advocated for an examination of the consequences that follow psychological aggression for the perpetrator, in hopes that this will lead to innovative intervention programs aimed at ameliorating dating violence. The current study investigated the self-reported consequences of having perpetrated psychological aggression against a dating partner among female college students in a current dating relationship (N = 115). Participants endorsed numerous consequences as having followed their perpetration of psychological aggression, including both punishing and potentially reinforcing consequences. Furthermore, findings indicated that for some perpetrators, psychological aggression may function as a method of emotion regulation. Implications of these findings for future research and intervention are discussed. PMID:22550148

An automated system for evaluation of the potential functionome: MAPLE version 2.1.0

PubMed Central

Takami, Hideto; Taniguchi, Takeaki; Arai, Wataru; Takemoto, Kazuhiro; Moriya, Yuki; Goto, Susumu

2016-01-01

Metabolic and physiological potential evaluator (MAPLE) is an automatic system that can perform a series of steps used in the evaluation of potential comprehensive functions (functionome) harboured in the genome and metagenome. MAPLE first assigns KEGG Orthology (KO) to the query gene, maps the KO-assigned genes to the Kyoto Encyclopedia of Genes and Genomes (KEGG) functional modules, and then calculates the module completion ratio (MCR) of each functional module to characterize the potential functionome in the user’s own genomic and metagenomic data. In this study, we added two more useful functions to calculate module abundance and Q-value, which indicate the functional abundance and statistical significance of the MCR results, respectively, to the new version of MAPLE for more detailed comparative genomic and metagenomic analyses. Consequently, MAPLE version 2.1.0 reported significant differences in the potential functionome, functional abundance, and diversity of contributors to each function among four metagenomic datasets generated by the global ocean sampling expedition, one of the most popular environmental samples to use with this system. MAPLE version 2.1.0 is now available through the web interface (http://www.genome.jp/tools/maple/) 17 June 2016, date last accessed. PMID:27374611

Fundamentals of translational neuroscience in toxicologic pathology: optimizing the value of animal data for human risk assessment.

PubMed

Morrison, James P; Sharma, Alok K; Rao, Deepa; Pardo, Ingrid D; Garman, Robert H; Kaufmann, Wolfgang; Bolon, Brad

2015-01-01

A half-day Society of Toxicologic Pathology continuing education course on "Fundamentals of Translational Neuroscience in Toxicologic Pathology" presented some current major issues faced when extrapolating animal data regarding potential neurological consequences to assess potential human outcomes. Two talks reviewed functional-structural correlates in rodent and nonrodent mammalian brains needed to predict behavioral consequences of morphologic changes in discrete neural cell populations. The third lecture described practical steps for ensuring that specimens from rodent developmental neurotoxicity tests will be processed correctly to produce highly homologous sections. The fourth talk detailed demographic factors (e.g., species, strain, sex, and age); physiological traits (body composition, brain circulation, pharmacokinetic/pharmacodynamic patterns, etc.); and husbandry influences (e.g., group housing) known to alter the effects of neuroactive agents. The last presentation discussed the appearance, unknown functional effects, and potential relevance to humans of polyethylene glycol (PEG)-associated vacuoles within the choroid plexus epithelium of animals. Speakers provided real-world examples of challenges with data extrapolation among species or with study design considerations that may impact the interpretability of results. Translational neuroscience will be bolstered in the future as less invasive and/or more quantitative techniques are devised for linking overt functional deficits to subtle anatomic and chemical lesions. © 2014 by The Author(s).

[Risk of long-lasting negative cognitive consequences after electroconvulsive therapy].

PubMed

Svendsen, Anne Marie; Miskowiak, Kamilla; Vinberg, Maj

2013-10-28

This case study describes a patient who had a unipolar depression and experienced long-lasting cognitive problems after electroconvulsive therapy (ECT). Neuropsychological testing revealed lower scores on measures of learning, memory and sustained attention. These results stress the importance of informing patients who have ECT of the potential cognitive consequences of this treatment as it may influence the patients' functional capabilities. Prospective studies are needed since we do not have sufficient knowledge regarding the 3-5% of these patients who experience sustained cognitive problems.

EMBRYONIC VASCULAR DISRUPTION ADVERSE OUTCOMES: LINKING HIGH THROUGHPUT SIGNALING SIGNATURES WITH FUNCTIONAL CONSEQUENCES

EPA Science Inventory

Embryonic vascular disruption is an important adverse outcome pathway (AOP) given the knowledge that chemical disruption of early cardiovascular system development leads to broad prenatal defects. High throughput screening (HTS) assays provide potential building blocks for AOP d...

Potential impact of global climate change on benthic deep-sea microbes.

PubMed

Danovaro, Roberto; Corinaldesi, Cinzia; Dell'Anno, Antonio; Rastelli, Eugenio

2017-12-15

Benthic deep-sea environments are the largest ecosystem on Earth, covering ∼65% of the Earth surface. Microbes inhabiting this huge biome at all water depths represent the most abundant biological components and a relevant portion of the biomass of the biosphere, and play a crucial role in global biogeochemical cycles. Increasing evidence suggests that global climate changes are affecting also deep-sea ecosystems, both directly (causing shifts in bottom-water temperature, oxygen concentration and pH) and indirectly (through changes in surface oceans' productivity and in the consequent export of organic matter to the seafloor). However, the responses of the benthic deep-sea biota to such shifts remain largely unknown. This applies particularly to deep-sea microbes, which include bacteria, archaea, microeukaryotes and their viruses. Understanding the potential impacts of global change on the benthic deep-sea microbial assemblages and the consequences on the functioning of the ocean interior is a priority to better forecast the potential consequences at global scale. Here we explore the potential changes in the benthic deep-sea microbiology expected in the coming decades using case studies on specific systems used as test models. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Consequence of Winning: Interdisciplinary Analysis for Deontological Perspectives of Moral Function and the Interaction with Motivation in Division I College Athletes

ERIC Educational Resources Information Center

Orr, Brandon

2013-01-01

This is a pilot study of a proposed model for examining the main and interactionist effects of achievement goal orientations on moral function and the role of perceived ability as a potential moderator in sport morality levels through cluster analysis procedures. One hundred and three elite (103) athletes participating in Division I wrestling…

Paradoxical roles of dual oxidases in cancer biology.

PubMed

Little, Andrew C; Sulovari, Arvis; Danyal, Karamatullah; Heppner, David E; Seward, David J; van der Vliet, Albert

2017-09-01

Dysregulated oxidative metabolism is a well-recognized aspect of cancer biology, and many therapeutic strategies are based on targeting cancers by altering cellular redox pathways. The NADPH oxidases (NOXes) present an important enzymatic source of biological oxidants, and the expression and activation of several NOX isoforms are frequently dysregulated in many cancers. Cell-based studies have demonstrated a role for several NOX isozymes in controlling cell proliferation and/or cell migration, further supporting a potential contributing role for NOX in promoting cancer. While various NOX isoforms are often upregulated in cancers, paradoxical recent findings indicate that dual oxidases (DUOXes), normally prominently expressed in epithelial lineages, are frequently suppressed in epithelial-derived cancers by epigenetic mechanisms, although the functional relevance of such DUOX silencing has remained unclear. This review will briefly summarize our current understanding regarding the importance of reactive oxygen species (ROS) and NOXes in cancer biology, and focus on recent observations indicating the unique and seemingly opposing roles of DUOX enzymes in cancer biology. We will discuss current knowledge regarding the functional properties of DUOX, and recent studies highlighting mechanistic consequences of DUOX1 loss in lung cancer, and its consequences for tumor invasiveness and current anticancer therapy. Finally, we will also discuss potentially unique roles for the DUOX maturation factors. Overall, a better understanding of mechanisms that regulate DUOX and the functional consequences of DUOX silencing in cancer may offer valuable new diagnostic insights and novel therapeutic opportunities. Copyright © 2017 Elsevier Inc. All rights reserved.

An automated system for evaluation of the potential functionome: MAPLE version 2.1.0.

PubMed

Takami, Hideto; Taniguchi, Takeaki; Arai, Wataru; Takemoto, Kazuhiro; Moriya, Yuki; Goto, Susumu

2016-07-03

Metabolic and physiological potential evaluator (MAPLE) is an automatic system that can perform a series of steps used in the evaluation of potential comprehensive functions (functionome) harboured in the genome and metagenome. MAPLE first assigns KEGG Orthology (KO) to the query gene, maps the KO-assigned genes to the Kyoto Encyclopedia of Genes and Genomes (KEGG) functional modules, and then calculates the module completion ratio (MCR) of each functional module to characterize the potential functionome in the user's own genomic and metagenomic data. In this study, we added two more useful functions to calculate module abundance and Q-value, which indicate the functional abundance and statistical significance of the MCR results, respectively, to the new version of MAPLE for more detailed comparative genomic and metagenomic analyses. Consequently, MAPLE version 2.1.0 reported significant differences in the potential functionome, functional abundance, and diversity of contributors to each function among four metagenomic datasets generated by the global ocean sampling expedition, one of the most popular environmental samples to use with this system. MAPLE version 2.1.0 is now available through the web interface (http://www.genome.jp/tools/maple/) 17 June 2016, date last accessed. © The Author 2016. Published by Oxford University Press on behalf of Kazusa DNA Research Institute.

Shifts in diversity and function of lake bacterial communities upon glacier retreat.

PubMed

Peter, Hannes; Sommaruga, Ruben

2016-07-01

Global climate change is causing a wastage of glaciers and threatening biodiversity in glacier-fed ecosystems. The high turbidity typically found in those ecosystems, which is caused by inorganic particles and result of the erosive activity of glaciers is a key environmental factor influencing temperature and light availability, as well as other factors in the water column. Once these lakes loose hydrological connectivity to glaciers and turn clear, the accompanying environmental changes could represent a potential bottleneck for the established local diversity with yet unknown functional consequences. Here, we study three lakes situated along a turbidity gradient as well as one clear unconnected lake and evaluate seasonal changes in their bacterial community composition and diversity. Further, we assess potential consequences for community functioning. Glacier runoff represented a diverse source community for the lakes and several taxa were able to colonize downstream turbid habitats, although they were not found in the clear lake. Operational taxonomic unit-based alpha diversity and phylogenetic diversity decreased along the turbidity gradient, but metabolic functional diversity was negatively related to turbidity. No evidence for multifunctional redundancy, which may allow communities to maintain functioning upon alterations in diversity, was found. Our study gives a first view on how glacier-fed lake bacterial communities are affected by the melting of glaciers and indicates that diversity and community composition significantly change when hydrological connectivity to the glacier is lost and lakes turn clear.

Alpine soil carbon is vulnerable to rapid microbial decomposition under climate cooling.

PubMed

Wu, Linwei; Yang, Yunfeng; Wang, Shiping; Yue, Haowei; Lin, Qiaoyan; Hu, Yigang; He, Zhili; Van Nostrand, Joy D; Hale, Lauren; Li, Xiangzhen; Gilbert, Jack A; Zhou, Jizhong

2017-09-01

As climate cooling is increasingly regarded as important natural variability of long-term global warming trends, there is a resurging interest in understanding its impact on biodiversity and ecosystem functioning. Here, we report a soil transplant experiment from lower to higher elevations in a Tibetan alpine grassland to simulate the impact of cooling on ecosystem community structure and function. Three years of cooling resulted in reduced plant productivity and microbial functional potential (for example, carbon respiration and nutrient cycling). Microbial genetic markers associated with chemically recalcitrant carbon decomposition remained unchanged despite a decrease in genes associated with chemically labile carbon decomposition. As a consequence, cooling-associated changes correlated with a decrease in soil organic carbon (SOC). Extrapolation of these results suggests that for every 1 °C decrease in annual average air temperature, 0.1 Pg (0.3%) of SOC would be lost from the Tibetan plateau. These results demonstrate that microbial feedbacks to cooling have the potential to differentially impact chemically labile and recalcitrant carbon turnover, which could lead to strong, adverse consequences on soil C storage. Our findings are alarming, considering the frequency of short-term cooling and its scale to disrupt ecosystems and biogeochemical cycling.

Brain and Retinal Pericytes: Origin, Function and Role

PubMed Central

Trost, Andrea; Lange, Simona; Schroedl, Falk; Bruckner, Daniela; Motloch, Karolina A.; Bogner, Barbara; Kaser-Eichberger, Alexandra; Strohmaier, Clemens; Runge, Christian; Aigner, Ludwig; Rivera, Francisco J.; Reitsamer, Herbert A.

2016-01-01

Pericytes are specialized mural cells located at the abluminal surface of capillary blood vessels, embedded within the basement membrane. In the vascular network these multifunctional cells fulfil diverse functions, which are indispensable for proper homoeostasis. They serve as microvascular stabilizers, are potential regulators of microvascular blood flow and have a central role in angiogenesis, as they for example regulate endothelial cell proliferation. Furthermore, pericytes, as part of the neurovascular unit, are a major component of the blood-retina/brain barrier. CNS pericytes are a heterogenic cell population derived from mesodermal and neuro-ectodermal germ layers acting as modulators of stromal and niche environmental properties. In addition, they display multipotent differentiation potential making them an intriguing target for regenerative therapies. Pericyte-deficiencies can be cause or consequence of many kinds of diseases. In diabetes, for instance, pericyte-loss is a severe pathological process in diabetic retinopathy (DR) with detrimental consequences for eye sight in millions of patients. In this review, we provide an overview of our current understanding of CNS pericyte origin and function, with a special focus on the retina in the healthy and diseased. Finally, we highlight the role of pericytes in de- and regenerative processes. PMID:26869887

Increasing the applicability of density functional theory. IV. Consequences of ionization-potential improved exchange-correlation potentials.

PubMed

Verma, Prakash; Bartlett, Rodney J

2014-05-14

This paper's objective is to create a "consistent" mean-field based Kohn-Sham (KS) density functional theory (DFT) meaning the functional should not only provide good total energy properties, but also the corresponding KS eigenvalues should be accurate approximations to the vertical ionization potentials (VIPs) of the molecule, as the latter condition attests to the viability of the exchange-correlation potential (VXC). None of the prominently used DFT approaches show these properties: the optimized effective potential VXC based ab initio dft does. A local, range-separated hybrid potential cam-QTP-00 is introduced as the basis for a "consistent" KS DFT approach. The computed VIPs as the negative of KS eigenvalue have a mean absolute error of 0.8 eV for an extensive set of molecule's electron ionizations, including the core. Barrier heights, equilibrium geometries, and magnetic properties obtained from the potential are in good agreement with experiment. A similar accuracy with less computational efforts can be achieved by using a non-variational global hybrid variant of the QTP-00 approach.

TERRORIST PROTECTION PLANNING USING A RELATIVE RISK REDUCTION APPROACH, SESSION VIII: TECHNOLOGY FORUM FOCUS GROUPS.

DOE Office of Scientific and Technical Information (OSTI.GOV)

INDUSI,J.P.

2003-06-16

Since the events of 9/11, there have been considerable concerns and associated efforts to prevent or respond to acts of terrorism. Very often we hear calls to reduce the threat from or correct vulnerabilities to various terrorist acts. Others fall victim to anxiety over potential scenarios with the gravest of consequences involving hundreds of thousands of casualties. The problem is complicated by the fact that planners have limited, albeit in some cases significant, resources and less than perfect intelligence on potential terrorist plans. However, valuable resources must be used prudently to reduce the overall risk to the nation. A systematicmore » approach to this process of asset allocation is to reduce the overall risk and not just an individual element of risk such as vulnerabilities. Hence, we define risk as a function of three variables: the threat (the likelihood and scenario of the terrorist act), the vulnerability (the vulnerability of potential targets to the threat), and the consequences (health and safety, economic, etc.) resulting from a successful terrorist scenario. Both the vulnerability and consequences from a postulated adversary scenario can be reasonably well estimated. However, the threat likelihood and scenarios are much more difficult to estimate. A possible path forward is to develop scenarios for each potential target in question using experts from many disciplines. This should yield a finite but large number of target-scenario pairs. The vulnerabilities and consequences for each are estimated and then ranked relative to one another. The resulting relative risk ranking will have targets near the top of the ranking for which the threat is estimated to be more likely, the vulnerability greatest, and the consequences the most grave. In the absence of perfect intelligence, this may be the best we can do.« less

Integrated pathway-based approach identifies association between genomic regions at CTCF and CACNB2 and schizophrenia.

PubMed

Juraeva, Dilafruz; Haenisch, Britta; Zapatka, Marc; Frank, Josef; Witt, Stephanie H; Mühleisen, Thomas W; Treutlein, Jens; Strohmaier, Jana; Meier, Sandra; Degenhardt, Franziska; Giegling, Ina; Ripke, Stephan; Leber, Markus; Lange, Christoph; Schulze, Thomas G; Mössner, Rainald; Nenadic, Igor; Sauer, Heinrich; Rujescu, Dan; Maier, Wolfgang; Børglum, Anders; Ophoff, Roel; Cichon, Sven; Nöthen, Markus M; Rietschel, Marcella; Mattheisen, Manuel; Brors, Benedikt

2014-06-01

In the present study, an integrated hierarchical approach was applied to: (1) identify pathways associated with susceptibility to schizophrenia; (2) detect genes that may be potentially affected in these pathways since they contain an associated polymorphism; and (3) annotate the functional consequences of such single-nucleotide polymorphisms (SNPs) in the affected genes or their regulatory regions. The Global Test was applied to detect schizophrenia-associated pathways using discovery and replication datasets comprising 5,040 and 5,082 individuals of European ancestry, respectively. Information concerning functional gene-sets was retrieved from the Kyoto Encyclopedia of Genes and Genomes, Gene Ontology, and the Molecular Signatures Database. Fourteen of the gene-sets or pathways identified in the discovery dataset were confirmed in the replication dataset. These include functional processes involved in transcriptional regulation and gene expression, synapse organization, cell adhesion, and apoptosis. For two genes, i.e. CTCF and CACNB2, evidence for association with schizophrenia was available (at the gene-level) in both the discovery study and published data from the Psychiatric Genomics Consortium schizophrenia study. Furthermore, these genes mapped to four of the 14 presently identified pathways. Several of the SNPs assigned to CTCF and CACNB2 have potential functional consequences, and a gene in close proximity to CACNB2, i.e. ARL5B, was identified as a potential gene of interest. Application of the present hierarchical approach thus allowed: (1) identification of novel biological gene-sets or pathways with potential involvement in the etiology of schizophrenia, as well as replication of these findings in an independent cohort; (2) detection of genes of interest for future follow-up studies; and (3) the highlighting of novel genes in previously reported candidate regions for schizophrenia.

Neurobiology of Decision Making in Depressed Adolescents: A Functional Magnetic Resonance Imaging Study

ERIC Educational Resources Information Center

Shad, Mujeeb U.; Bidesi, Anup P.; Chen, Li-Ann; Ernst, Monique; Rao, Uma

2011-01-01

Objective: Despite evidence that impaired reward- and risk-related behavior during adolescence can have potentially serious short- and long-term consequences, few studies have investigated the impact of depression on reward-related selection in adolescents. This study examined the relationship between reward-related behavior and prefrontal…

Is U.S. climatic diversity well represented within the existing federal protection network?

Treesearch

Enric Batllori; Carol Miller; Marc-Andre Parisien; Sean A. Parks; Max A. Moritz

2014-01-01

Establishing protection networks to ensure that biodiversity and associated ecosystem services persist under changing environments is a major challenge for conservation planning. The potential consequences of altered climates for the structure and function of ecosystems necessitates new and complementary approaches be incorporated into traditional conservation plans....

Physics Meets Biology (LBNL Summer Lecture Series)

ScienceCinema

Chu, Steven

2018-05-09

Summer Lecture Series 2006: If scientists could take advantage of the awesomely complex and beautiful functioning of biology's natural molecular machines, their potential for application in many disciplines would be incalculable. Nobel Laureate and Director of the Lawrence Berkeley National Laboratory Steve Chu explores Possible solutions to global warming and its consequences.

PATHOPHYSIOLOGICAL CONSEQUENCES OF TAT-HKII PEPTIDE ADMINISTRATION ARE INDEPENDENT OF IMPAIRED VASCULAR FUNCTION AND ENSUING ISCHEMIA

PubMed Central

Nederlof, Rianne; Xie, Chaoqin; Eerbeek, Otto; Koeman, Anneke; Milstein, Dan MJ; Hollmann, Markus W; Mik, Egbert G; Warley, Alice; Southworth, Richard; Akar, Fadi G.; Zuurbier, Coert J

2013-01-01

Rationale We have shown that partial dissociation of HKII from mitochondria in the intact heart using low dose (200 nM) TAT-HKII prevents the cardioprotective effects of ischemic preconditioning (IPC) whereas high-dose (10 μM) TAT-HKII administration results in rapid myocardial dysfunction, mitochondrial depolarization and disintegration. In this issue of Circulation Research, Pasdois et al argue that the deleterious effects of TAT-HKII administration on cardiac function are likely due to vasoconstriction and ensuing ischemia. Objective To investigate whether altered vascular function and ensuing ischemia recapitulate the deleterious effects of TAT-HKII in intact myocardium. Methods and Results Using a variety of complementary techniques, including mitochondrial membrane potential (ΔΨm) imaging, high-resolution optical action potential (AP) mapping, analysis of lactate production, NADH epifluorescence, lactate dehydrogenase (LDH) release, and electron microscopy, we provide direct evidence that refutes the notion that acute myocardial dysfunction by high-dose TAT-HKII peptide administration is a consequence of impaired vascular function. Moreover, we demonstrate that low-dose TAT-HKII treatment, which abrogates the protective effects of IPC, is not associated with ischemia or ischemic-injury. Conclusions Our findings challenge the notion that the effects of TAT-HKII are attributable to impaired vascular function and ensuing ischemia; thereby, lending further credence to the role of mitochondria bound HKII as a critical regulator of cardiac function, ischemia-reperfusion (IR) injury, and cardioprotection by IPC. PMID:23329797

Youth unemployment and functional somatic symptoms in adulthood: results from the Northern Swedish cohort.

PubMed

Brydsten, Anna; Hammarström, Anne; Strandh, Mattias; Johansson, Klara

2015-10-01

Little is known about the possible long-term health consequences of youth unemployment. Research indicates that unemployment may lead to socioeconomic downward mobility and mental health problems, but we still lack knowledge of the long-term health consequences of youth unemployment. This article examines the potential long-term association between youth unemployment and functional somatic symptoms in adulthood. The 'Northern Swedish cohort' was used with data from five data collections, from 1981 (age 16) until 2007 (age 42). Youth unemployment was measured as months in unemployment between age 16 and 21, and health outcome as functional somatic symptoms (an index of 10 items of self-reported symptoms). Linear regression was used to analyse the relationship between months in youth unemployment and functional somatic symptoms at age 21 and age 42, stratified for women and men and adjusted for potential confounders, such as time spent in education at age 21 and later unemployment between age 21 and 42. Youth unemployment was significantly related to functional somatic symptoms at age 21 for men after controlling for confounders, but not for women. Among men, the association remained for functional somatic symptoms at age 42, after controlling for confounders. Adolescence seems to be a sensitive period during which unemployment could have remaining health effects in adulthood, at least for men, though assumptions of causality are tentative and more research is needed. © The Author 2015. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.

Classes of exact Einstein Maxwell solutions

NASA Astrophysics Data System (ADS)

Komathiraj, K.; Maharaj, S. D.

2007-12-01

We find new classes of exact solutions to the Einstein Maxwell system of equations for a charged sphere with a particular choice of the electric field intensity and one of the gravitational potentials. The condition of pressure isotropy is reduced to a linear, second order differential equation which can be solved in general. Consequently we can find exact solutions to the Einstein Maxwell field equations corresponding to a static spherically symmetric gravitational potential in terms of hypergeometric functions. It is possible to find exact solutions which can be written explicitly in terms of elementary functions, namely polynomials and product of polynomials and algebraic functions. Uncharged solutions are regainable with our choice of electric field intensity; in particular we generate the Einstein universe for particular parameter values.

The Impact of Organismal Innovation on Functional and Ecological Diversification.

PubMed

Wainwright, Peter C; Price, Samantha A

2016-09-01

Innovations in organismal functional morphology are thought to be a major force in shaping evolutionary patterns, with the potential to drive adaptive radiation and influence the evolutionary prospects for lineages. But the evolutionary consequences of innovation are diverse and usually do not result in adaptive radiation. What factors shape the macroevolutionary impact of innovations? We assert that little is known in general about the macroevolutionary outcomes associated with functional innovations and we discuss a framework for studying biological innovations in an evolutionary context. Innovations are novel functional mechanisms that enhance organismal performance. The ubiquity of trade-offs in functional systems means that enhanced performance on one axis often occurs at the expense of performance on another axis, such that many innovations result in an exchange of performance capabilities, rather than an expansion. Innovations may open up new resources for exploitation but their consequences for functional and ecological diversification depend heavily on the adaptive landscape around these novel resources. As an example of a broader program that we imagine, we survey five feeding innovations in labrid fishes, an exceptionally successful and ecologically diverse group of reef fishes, and explore their impact on the rate of evolution of jaw functional morphology. All of the innovations provide performance enhancements and result in changes in patterns of resource use, but most are not associated with subsequent functional diversification or substantial ecological diversification. Because selection acts on a specific performance enhancement and not on the evolutionary potential of an innovation, the enhancement of diversity may be highly serendipitous. The macroevolutionary potential of innovations depends critically on the interaction between the performance enhancement and the ecological opportunity that is exposed. © The Author 2016. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email: journals.permissions@oup.com.

So what really is user experience? An experimental study of user needs and emotional responses as underlying constructs.

PubMed

Jung, Tirza; Kaß, Christina; Schramm, Thomas; Zapf, Dieter

2017-12-01

This driving simulator study extended knowledge on user experience using a strategy to mitigate distraction resulting from the use of in-vehicle information systems (IVISs). It examined the impact of system restrictions on users' needs, emotions and consequences of users' experience in terms of psychological reactance. In a repeated measures design, we asked 53 participants to perform secondary tasks with an IVIS while driving. Three versions of the system varied with respect to the number of operable functionalities. The more functionalities that were disabled while driving, the more negatively users rated the systems. Multilevel regression analyses of at least n = 155 data points revealed that drivers' need fulfilment predicted their emotions. Reactance depended on users' need fulfilment and emotions. Experienced autonomy mediated the relation between functional limitations and reactance. When developing interactive systems, one should focus on needs and be aware of potential unwanted consequences such as psychological reactance. Practitioner Summary: This driving simulator study highlights the importance of considering need fulfilment and users' emotions when developing an interactive system that provides high user experience. System restrictions could have negative consequences as users might show psychological reactance.

Exact Time-Dependent Exchange-Correlation Potential in Electron Scattering Processes

NASA Astrophysics Data System (ADS)

Suzuki, Yasumitsu; Lacombe, Lionel; Watanabe, Kazuyuki; Maitra, Neepa T.

2017-12-01

We identify peak and valley structures in the exact exchange-correlation potential of time-dependent density functional theory that are crucial for time-resolved electron scattering in a model one-dimensional system. These structures are completely missed by adiabatic approximations that, consequently, significantly underestimate the scattering probability. A recently proposed nonadiabatic approximation is shown to correctly capture the approach of the electron to the target when the initial Kohn-Sham state is chosen judiciously, and it is more accurate than standard adiabatic functionals but ultimately fails to accurately capture reflection. These results may explain the underestimation of scattering probabilities in some recent studies on molecules and surfaces.

Tricuspid Valve Dysfunction Following Pacemaker or Cardioverter-Defibrillator Implantation.

PubMed

Chang, James D; Manning, Warren J; Ebrille, Elisa; Zimetbaum, Peter J

2017-05-09

The potential for cardiac implantable electronic device leads to interfere with tricuspid valve (TV) function has gained increasing recognition as having hemodynamic and clinical consequences associated with incremental morbidity and death. The diagnosis and treatment of lead-related (as distinct from functional) tricuspid regurgitation pose unique challenges. Because of pitfalls in routine diagnostic imaging, a high level of clinical suspicion must be maintained to avoid overlooking the possibility that worsening heart failure is a consequence of mechanical interference with TV leaflet mobility or coaptation and is amenable to lead extraction or valve repair or replacement. The future of cardiac implantable electronic devices includes pacing and perhaps defibrillation without a lead traversing the TV. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Influence of hypoxia on excitation and GABAergic inhibition in mature and developing rat neocortex.

PubMed

Luhmann, H J; Kral, T; Heinemann, U

1993-01-01

To analyze the functional consequences of hypoxia on the efficacy of intracortical inhibitory mechanisms mediated by gamma-aminobutyric acid (GABA), extra- and intracellular recordings were obtained from rat primary somatosensory cortex in vitro. Hypoxia, induced by transient N2 aeration, caused a decrease in stimulus-evoked inhibitory postsynaptic potentials (IPSPs), followed by a pronounced anoxic depolarization. Upon reoxygenation, the fast (f-) and long-latency (l-) IPSP showed a positive shift in the reversal potential by 24.4 and 14.9 mV, respectively. The peak conductance of the f- and l-IPSP was reversibly reduced in the postanoxic period by 72% and 94%, respectively. Extracellular field potential recordings and application of a paired-pulse inhibition protocol confirmed the enhanced sensitivity of inhibitory synaptic transmission for transient oxygen deprivation. Intracellular recordings from morphologically or electrophysiologically identified interneurons did not reveal any enhanced susceptibility for hypoxia as compared to pyramidal cells, suggesting that inhibitory neurons are not selectively impaired in their functional properties. Intracellularly recorded spontaneous IPSPs were transiently augmented in the postanoxic period, indicating that presynaptic GABA release was not suppressed. Developmental studies in adult (older than postnatal day 28), juvenile (P14-18), and young (P5-8) neocortical slices revealed a prominent functional resistance of immature tissue for hypoxia. In comparison with adult cortex, the hypoxia-induced reduction in excitatory and inhibitory synaptic transmission was significantly smaller in immature cortex. Our data indicate a hypoxia-induced distinct reduction of postsynaptic GABAergic mechanisms, leading to the manifestation of intracortical hyperexcitability as a possible functional consequence.

Local classifiers for evoked potentials recorded from behaving rats.

PubMed

Jakuczun, Wit; Kublik, Ewa; Wójcik, Daniel K; Wróbel, Andrzej

2005-01-01

Dynamic states of the brain determine the way information is processed in local neural networks. We have applied classical conditioning paradigm in order to study whether habituated and aroused states can be differentiated in single barrel column of rat's somatosensory cortex by means of analysis of field potentials evoked by stimulation of a single vibrissa. A new method using local classifiers is presented which allows for reliable and meaningful classification of single evoked potentials which might be consequently attributed to different functional states of the cortical column.

Behavioral function effects on intervention acceptability and effectiveness for self-injurious behavior.

PubMed

Hastings, Richard P; Boulton, Holly V N; Monzani, Louisa C; Tombs, Anna K H

2004-01-01

A variety of variables have been found to augment perceived social validity of behavioral interventions. In the present study, potential effects of behavioral function were evaluated. Sixty students inexperienced in work with people with mental retardation, and 60 experienced staff watched one of two carefully matched acted videos depicting self-injury maintained by attention or escape from task demands. Participants were also told whether the self-injury depicted typically led to mild or severe consequences for the person filmed. Participants rated six interventions in terms of their acceptability and effectiveness for the behavior depicted. A hierarchy of acceptability was replicated: reinforcement-based procedures were rated as more acceptable and effective. There were also effects of behavior severity and rater experience. However, few effects of behavioral function were found. Potential implications of staff undifferentiated attitudes towards functional treatments are discussed.

The Functional Impact of Alternative Splicing in Cancer.

PubMed

Climente-González, Héctor; Porta-Pardo, Eduard; Godzik, Adam; Eyras, Eduardo

2017-08-29

Alternative splicing changes are frequently observed in cancer and are starting to be recognized as important signatures for tumor progression and therapy. However, their functional impact and relevance to tumorigenesis remain mostly unknown. We carried out a systematic analysis to characterize the potential functional consequences of alternative splicing changes in thousands of tumor samples. This analysis revealed that a subset of alternative splicing changes affect protein domain families that are frequently mutated in tumors and potentially disrupt protein-protein interactions in cancer-related pathways. Moreover, there was a negative correlation between the number of these alternative splicing changes in a sample and the number of somatic mutations in drivers. We propose that a subset of the alternative splicing changes observed in tumors may represent independent oncogenic processes that could be relevant to explain the functional transformations in cancer, and some of them could potentially be considered alternative splicing drivers (AS drivers). Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Methamphetamine Exposure, Iron Deficiency, and Implications for Cognitive-Communicative Function: A Case Study

ERIC Educational Resources Information Center

Goldberg, Lynette R.; Heiss, Cynthia J.; White, Letitia; Kaf, Wafaa A.; Becker, Alan; Schindler, Jessica B.; Dion, Nancy; Oswalt, Jill

2010-01-01

Methamphetamine (meth) exposure during fetal development has the potential to adversely affect the development of multiple organ systems. An interdisciplinary case study of a 4-year 11-month-old child born to a mother addicted to meth revealed significant cognitive and communicative delays. Possible meth-related consequences for these delays…

Changes in Production and Nutrient Cycling across a Wetness Gradient within a Floodplain Forest

Treesearch

Robin G. Clawson; B. Graeme Lockaby; Bob Rummer

2001-01-01

Floodplain forest ecosystems are highly valuable to society because of their potential for water quality improvement and vegetation productivity, among many other functions. Previous studies have indicated that hydrology influences productivity but that the relationship between hydroperiod and productivity is a complex one. Consequently, we compared multiple indexes of...

Using Social Media to Facilitate Knowledge Transfer in Complex Engineering Environments: A Primer for Educators

ERIC Educational Resources Information Center

Murphy, Glen; Salomone, Sonia

2013-01-01

While highly cohesive groups are potentially advantageous they are also often correlated with the emergence of knowledge and information silos based around those same functional or occupational clusters. Consequently, an essential challenge for engineering organisations wishing to overcome informational silos is to implement mechanisms that…

Aquatic ecosystems in a changing climate

USGS Publications Warehouse

Inamdar, Shreeram; Shanley, James B.; McDowell, William H.

2017-01-01

Extreme climate events (ECEs) such as tropical storms and hurricanes, thunderstorms, heat waves, droughts, ice storms, and snow storms have increased and are projected to further increase in intensity and frequency across the world. These events are expected to have significant consequences for aquatic ecosystems with the potential for large changes in ecosystem processes, responses, and functions.

Educational Malpractice: Can the Judiciary Remedy the Growing Problem of Functional Illiteracy?

ERIC Educational Resources Information Center

Klein, Alice J.

1979-01-01

Investigates the viability of a negligence action for inadequate public school education. Explores the problems inherent in proving each element of negligence, the available defense, and the potential consequences for plaintiffs, defendants, and educational policy-making that would flow from judicial recognition of a cause of action. Journal…

A landscape based, systems dynamic model for assessing impacts of urban development on water quality for sustainable seagrass growth in Tampa Bay, Florida

EPA Science Inventory

We present an integrated assessment model to predict potential unintended consequences of urban development on the sustainability of seagrasses and preservation of ecosystem services, such as catchable fish, in Tampa Bay. Ecosystem services are those ecological functions and pro...

Feeling Closer to the Future Self and Doing Better: Temporal Psychological Mechanisms Underlying Academic Performance

ERIC Educational Resources Information Center

Adelman, Robert Mark; Herrmann, Sarah D.; Bodford, Jessica E.; Barbour, Joseph E.; Graudejus, Oliver; Okun, Morris A.; Kwan, Virginia S. Y.

2017-01-01

This research examined the function of future self-continuity and its potential downstream consequences for academic performance through relations with other temporal psychological factors and self-control. We also addressed the influence of cultural factors by testing whether these relations differed by college generation status. Undergraduate…

Functional characterization of cytochrome P450-derived epoxyeicosatrienoic acids in adipogenesis and obesity

PubMed Central

Zha, Weibin; Edin, Matthew L.; Vendrov, Kimberly C.; Schuck, Robert N.; Lih, Fred B.; Jat, Jawahar Lal; Bradbury, J. Alyce; DeGraff, Laura M.; Hua, Kunjie; Tomer, Kenneth B.; Falck, John R.; Zeldin, Darryl C.; Lee, Craig R.

2014-01-01

Adipogenesis plays a critical role in the initiation and progression of obesity. Although cytochrome P450 (CYP)-derived epoxyeicosatrienoic acids (EETs) have emerged as a potential therapeutic target for cardiometabolic disease, the functional contribution of EETs to adipogenesis and the pathogenesis of obesity remain poorly understood. Our studies demonstrated that induction of adipogenesis in differentiated 3T3-L1 cells (in vitro) and obesity-associated adipose expansion in high-fat diet (HFD)-fed mice (in vivo) significantly dysregulate the CYP epoxygenase pathway and evoke a marked suppression of adipose-derived EET levels. Subsequent in vitro experiments demonstrated that exogenous EET analog administration elicits potent anti-adipogenic effects via inhibition of the early phase of adipogenesis. Furthermore, EET analog administration to mice significantly mitigated HFD-induced weight gain, adipose tissue expansion, pro-adipogenic gene expression, and glucose intolerance. Collectively, these findings suggest that suppression of EET bioavailability in adipose tissue is a key pathological consequence of obesity, and strategies that promote the protective effects of EETs in adipose tissue offer enormous therapeutic potential for obesity and its downstream pathological consequences. PMID:25114171

Impaired Tuning of Neural Ensembles and the Pathophysiology of Schizophrenia: A Translational and Computational Neuroscience Perspective.

PubMed

Krystal, John H; Anticevic, Alan; Yang, Genevieve J; Dragoi, George; Driesen, Naomi R; Wang, Xiao-Jing; Murray, John D

2017-05-15

The functional optimization of neural ensembles is central to human higher cognitive functions. When the functions through which neural activity is tuned fail to develop or break down, symptoms and cognitive impairments arise. This review considers ways in which disturbances in the balance of excitation and inhibition might develop and be expressed in cortical networks in association with schizophrenia. This presentation is framed within a developmental perspective that begins with disturbances in glutamate synaptic development in utero. It considers developmental correlates and consequences, including compensatory mechanisms that increase intrinsic excitability or reduce inhibitory tone. It also considers the possibility that these homeostatic increases in excitability have potential negative functional and structural consequences. These negative functional consequences of disinhibition may include reduced working memory-related cortical activity associated with the downslope of the "inverted-U" input-output curve, impaired spatial tuning of neural activity and impaired sparse coding of information, and deficits in the temporal tuning of neural activity and its implication for neural codes. The review concludes by considering the functional significance of noisy activity for neural network function. The presentation draws on computational neuroscience and pharmacologic and genetic studies in animals and humans, particularly those involving N-methyl-D-aspartate glutamate receptor antagonists, to illustrate principles of network regulation that give rise to features of neural dysfunction associated with schizophrenia. While this presentation focuses on schizophrenia, the general principles outlined in the review may have broad implications for considering disturbances in the regulation of neural ensembles in psychiatric disorders. Published by Elsevier Inc.

Shifts in diversity and function of lake bacterial communities upon glacier retreat

PubMed Central

Peter, Hannes; Sommaruga, Ruben

2016-01-01

Global climate change is causing a wastage of glaciers and threatening biodiversity in glacier-fed ecosystems. The high turbidity typically found in those ecosystems, which is caused by inorganic particles and result of the erosive activity of glaciers is a key environmental factor influencing temperature and light availability, as well as other factors in the water column. Once these lakes loose hydrological connectivity to glaciers and turn clear, the accompanying environmental changes could represent a potential bottleneck for the established local diversity with yet unknown functional consequences. Here, we study three lakes situated along a turbidity gradient as well as one clear unconnected lake and evaluate seasonal changes in their bacterial community composition and diversity. Further, we assess potential consequences for community functioning. Glacier runoff represented a diverse source community for the lakes and several taxa were able to colonize downstream turbid habitats, although they were not found in the clear lake. Operational taxonomic unit-based alpha diversity and phylogenetic diversity decreased along the turbidity gradient, but metabolic functional diversity was negatively related to turbidity. No evidence for multifunctional redundancy, which may allow communities to maintain functioning upon alterations in diversity, was found. Our study gives a first view on how glacier-fed lake bacterial communities are affected by the melting of glaciers and indicates that diversity and community composition significantly change when hydrological connectivity to the glacier is lost and lakes turn clear. PMID:26771929

Integration of social dimension in an index oriented methodology for consequence analysis of natural hazards: application to the Upper Guil Catchment (Southern French Alps)

NASA Astrophysics Data System (ADS)

Carlier, Benoit; Puissant, Anne; Dujarric, Constance

2017-04-01

Vulnerability assessment together with hazard exposure is generally accepted as the two main steps of risk analysis. If quantitative methods to estimate hazard exposure are now well-defined, it is not the case regarding vulnerability assessment. Vulnerability is a complex concept involving a variety of disciplines from physical and socio-economic sciences (i.e. engineering, economics, social and health sciences etc.). Currently, two opposite trends exist: the 'physical' approach in which vulnerability is analysed as potential impacts (i.e. structural and functional) on the elements at risk (building, network, land cover); and the 'social' approach in which vulnerability is a combination of socio-economic variables determining people's ability to anticipate before a catastrophic event, to react during it, and to recover after it. For a complete analysis of vulnerability it is essential to combine these two approaches but in reality few works exists. The objective of this research is to improve the Potential Damage Index (PDI), detailed in Puissant el al. (2013), originally developed to assess physical injury, structural and functional consequences of landslide hazard, by including socio-economic characteristics of population information. Data from the French Census data (INSEE, 2012) and a survey on risk perception (100 questionnaires obtained between 2014 and 2015/16) were used to propose an overall index taking into account the three main phases of risk management: preparedness, crisis management and recovery. This new index called Global Potential Damage Index (GPDI) is applied on the Upper Guil Catchment to assess potential torrential floods hazard in the context of the French funded project SAMCO (Society Adaptation for coping with Mountain risks in a global change Context). Results of the PDI are compared with the GPDI and show significant differences. GPDI scores mapping are lower than PDI scores indicating that resilient population may qualify results obtained for physical consequences. In GPDI the social and institutional component is expressed by a unique value applied for the overall stakes of a same community. Consequently, socio-economics differences between Upper Guil catchments communities are highlighted and make results easily understandable for local manager.

Pathophysiological consequences of VEGF-induced vascular permeability

NASA Astrophysics Data System (ADS)

Weis, Sara M.; Cheresh, David A.

2005-09-01

Although vascular endothelial growth factor (VEGF) induces angiogenesis, it also disrupts vascular barrier function in diseased tissues. Accordingly, VEGF expression in cancer and ischaemic disease has unexpected pathophysiological consequences. By uncoupling endothelial cell-cell junctions VEGF causes vascular permeability and oedema, resulting in extensive injury to ischaemic tissues after stroke or myocardial infarction. In cancer, VEGF-mediated disruption of the vascular barrier may potentiate tumour cell extravasation, leading to widespread metastatic disease. Therefore, by blocking the vascular permeability promoting effects of VEGF it may be feasible to reduce tissue injury after ischaemic disease and minimize the invasive properties of circulating tumour cells.

Linking Prenatal Maternal Adversity to Developmental Outcomes in Infants: The Role of Epigenetic Pathways

PubMed Central

Monk, Catherine; Spicer, Julie; Champagne, Frances A.

2013-01-01

Prenatal exposure to maternal stress, anxiety, and depression can have lasting effects on infant development with consequences for risk of psychopathology. Though the impact of prenatal maternal distress has been well documented, the potential mechanisms through which maternal psychosocial variables shape development have yet to be fully elucidated. Advances in molecular biology have highlighted the role of epigenetic mechanisms in regulating gene activity, neurobiology, and behavior and the potential role of environmentally-induced epigenetic variation in linking early life exposures to long-term biobehavioral outcomes. In this review, we discuss evidence illustrating the association between maternal prenatal distress and both fetal and infant developmental trajectories and the potential role of epigenetic mechanisms in mediating these effects. Postnatal experiences may have a critical moderating influence on prenatal effects, and here we review findings illustrating prenatal-postnatal interplay and the developmental and epigenetic consequences of postnatal mother-infant interactions. The in utero environment is regulated by placental function and there is emerging evidence that the placenta is highly susceptible to maternal distress and a target of epigenetic dysregulation. Integrating studies of prenatal exposures, placental function, and postnatal maternal care with the exploration of epigenetic mechanisms may provide novel insights into the pathophysiology induced by maternal distress. PMID:23062303

Unintended consequences of Helicobacter pylori infection in children in developing countries

PubMed Central

Queiroz, Dulciene MM; Rocha, Andreia MC; Crabtree, Jean E

2013-01-01

Helicobacter pylori infection is predominantly acquired early in life. The prevalence of the infection in childhood is low in developed countries, whereas in developing countries most children are infected by 10 y of age. In poor resource settings, where malnutrition, parasitic/enteropathogen and H. pylori infection co-exist in young children, H. pylori might have potentially more diverse clinical outcomes. This paper reviews the impact of childhood H. pylori infection in developing countries that should now be the urgent focus of future research. The extra-gastric manifestations in early H. pylori infection in infants in poor resource settings might be a consequence of the infection associated initial hypochlorhydria. The potential role of H. pylori infection on iron deficiency, growth impairment, diarrheal disease, malabsorption and cognitive function is discussed in this review. PMID:23988829

From Toxins Targeting Ligand Gated Ion Channels to Therapeutic Molecules

PubMed Central

Nasiripourdori, Adak; Taly, Valérie; Grutter, Thomas; Taly, Antoine

2011-01-01

Ligand-gated ion channels (LGIC) play a central role in inter-cellular communication. This key function has two consequences: (i) these receptor channels are major targets for drug discovery because of their potential involvement in numerous human brain diseases; (ii) they are often found to be the target of plant and animal toxins. Together this makes toxin/receptor interactions important to drug discovery projects. Therefore, toxins acting on LGIC are presented and their current/potential therapeutic uses highlighted. PMID:22069709

Nuclear risk analysis of the Ulysses mission

NASA Astrophysics Data System (ADS)

Bartram, Bart W.; Vaughan, Frank R.; Englehart, Richard W., Dr.

1991-01-01

The use of a radioisotope thermoelectric generator fueled with plutonium-238 dioxide on the Space Shuttle-launched Ulysses mission implies some level of risk due to potential accidents. This paper describes the method used to quantify risks in the Ulysses mission Final Safety Analysis Report prepared for the U.S. Department of Energy. The starting point for the analysis described herein is following input of source term probability distributions from the General Electric Company. A Monte Carlo technique is used to develop probability distributions of radiological consequences for a range of accident scenarios thoughout the mission. Factors affecting radiological consequences are identified, the probability distribution of the effect of each factor determined, and the functional relationship among all the factors established. The probability distributions of all the factor effects are then combined using a Monte Carlo technique. The results of the analysis are presented in terms of complementary cumulative distribution functions (CCDF) by mission sub-phase, phase, and the overall mission. The CCDFs show the total probability that consequences (calculated health effects) would be equal to or greater than a given value.

Convergence of the strong-potential-Born approximation in Z/sub less-than//Z/sub greater-than/

DOE Office of Scientific and Technical Information (OSTI.GOV)

McGuire, J.H.; Sil, N.C.

1986-01-01

Convergence of the strong-potential Born (SPB) approximation as a function of the charges of the projectile and target is studied numerically. Time-reversal invariance (or detailed balance) is satisfied at sufficiently high velocities even when the charges are asymmetric. This demonstarates that the SPB approximation converges to the correct result even when the charge of the ''weak'' potential, which is kept to first order, is larger than the charge of the ''strong'' potential, which is retained to all orders. Consequently, the SPB approximation is valid for systems of arbitrary charge symmetry (including symmetric systems) at sufficiently high velocities.

Young Women's Adolescent Experiences of Oral Sex: Relation of Age of Initiation to Sexual Motivation, Sexual Coercion, and Psychological Functioning

ERIC Educational Resources Information Center

Fava, Nicole M.; Bay-Cheng, Laina Y.

2012-01-01

Research examining oral sex during adolescence tends to investigate only potential negative consequences without considering its place in sexual development or distinctions between cunnilingus and fellatio. Using retrospective reports from 418 undergraduate women, we examined the relations among young women's ages of initiation of both cunnilingus…

A global index for mapping the exposure of water resources to wildfire

Treesearch

Francois-Nicolas Robinne; Carol Miller; Marc-Andre Parisien; Monica B. Emelko; Kevin D. Bladon; Uldis Silins; Mike Flannigan

2016-01-01

Wildfires are keystone components of natural disturbance regimes that maintain ecosystem structure and functions, such as the hydrological cycle, in many parts of the world. Consequently, critical surface freshwater resources can be exposed to post-fire effects disrupting their quantity, quality and regularity. Although well studied at the local scale, the potential...

The Relationship between Type of Bullying Experienced in Childhood and Psychosocial Functioning in Young Adulthood

ERIC Educational Resources Information Center

Heretick, Jennifer A.

2012-01-01

Bullying is well recognized as an experience with negative and potentially adverse consequences. Specifically, research has consistently shown that involvement in bullying has been linked to a wide range of psychosocial difficulties. There are three forms of bullying that have been identified in the literature: Overt bullying, relational bullying,…

Dual Standards of School Performance and Funding? Empirical Searches of School Funding Adequacy in Kentucky and Maine

ERIC Educational Resources Information Center

Lee, Jaekyung

2010-01-01

This study examines potential consequences of the discrepancies between national and state performance standards for school funding in Kentucky and Maine. Applying the successful schools observation method and cost function analysis method to integrated data-sets that match schools' eight-grade mathematics test performance measures to district…

Coordinate High-Frequency Pattern of Stimulation and Calcium Levels Control the Induction of LTP in Striatal Cholinergic Interneurons

ERIC Educational Resources Information Center

Bonsi, Paola; De Persis, Cristiano; Calabresi, Paolo; Bernardi, Giorgio; Pisani, Antonio

2004-01-01

Current evidence appoints a central role to cholinergic interneurons in modulating striatal function. Recently, a long-term potentiation (LTP) of synaptic transmission has been reported to occur in these neurons. The relationship between the pattern of cortico/thalamostriatal fibers stimulation, the consequent changes in the intracellular calcium…

Inappropriate trust in technology: implications for critical care nurses.

PubMed

Browne, Mike; Cook, Penny

2011-01-01

To explore evidence from the literature that critical care nurses may have inappropriate levels of trust in the technological equipment they use and the implications of this for patient safety. Nurses in intensive care units are required to observe the operation of an array of complex equipment. Failure of this equipment can have potentially fatal consequences for the patient. Research from other settings, such as the work of airline pilots, suggests that experienced operators of highly reliable automation may display inappropriately high levels of trust in the automation and this can lead to inadequate monitoring of the equipment by the operator. Inadequate monitoring means that the operator may fail to notice that the equipment is not functioning correctly which may have serious consequences. An initial search was made of a number of databases including Academic Search Premier, CINAHL, Pubmed and ScienceDirect. Extensive use was also made of citations found in articles uncovered by this initial search. Evidence suggests that there is potential for critical care nurses to display complacent attitudes. In addition, there are a number of reasons why the consequences of this complacency are not as visible as in other settings. If nurses are not aware of the potential and consequences of inappropriate trust, there is a real possibility that patients may suffer harm because of it. There is an urgent need for more research to identify direct evidence of complacency and its consequences. There is also a need for these issues to be highlighted in the training of intensive care nurses and there are implications for intensive care unit practice protocols and equipment manufacturers. © 2011 The Authors. Nursing in Critical Care © 2011 British Association of Critical Care Nurses.

New therapeutic approaches in the treatment of diabetic keratopathy: a review.

PubMed

Abdelkader, Hamdy; Patel, Dipika V; McGhee, Charles Nj; Alany, Raid G

2011-04-01

The cornea is densely innervated, and the integrity of these nerve fibres is critical in maintaining the refractive and protective functions of the cornea. Many ocular and systemic diseases can adversely affect corneal sensory nerves and consequently impair their function, with vision loss being the inevitable consequence of severe corneal neurotrophic ulceration. However, current standard treatments regimens are often ineffective. Over the past three decades, the role of growth factors in maintaining the normal structure and function of the cornea, and in corneal epithelial healing, has become increasingly evident. Many preclinical and clinical trials have shown that growth factors and cytokines can significantly enhance epithelialization (epithelial proliferation and migration) and consequently accelerate wound healing. More recently, local/topical administration of insulin, naltrexone (opioid antagonist) and nicergoline (ergoline derivatives) were found to improve, and significantly increase, the corneal wound healing rate. This report reviews the major attributes of these growth factors and therapeutic agents that may be used in ameliorating impaired corneal wound healing, and presents a perspective on the potential clinical use of these agents as a new generation of ophthalmic pharmaceuticals for the treatment of diabetic keratopathy. © 2011 The Authors. Clinical and Experimental Ophthalmology © 2011 Royal Australian and New Zealand College of Ophthalmologists.

Epigenetic dysregulation in cognitive disorders.

PubMed

Gräff, Johannes; Mansuy, Isabelle M

2009-07-01

Epigenetic mechanisms are not only essential for biological functions requiring stable molecular changes such as the establishment of cell identity and tissue formation, they also constitute dynamic intracellular processes for translating environmental stimuli into modifications in gene expression. Over the past decade it has become increasingly clear that both aspects of epigenetic mechanisms play a pivotal role in complex brain functions. Evidence from patients with neurodegenerative and neurodevelopmental disorders such as Alzheimer's disease and Rett syndrome indicated that epigenetic mechanisms and chromatin remodeling need to be tightly controlled for proper cognitive functions, and their dysregulation can have devastating consequences. However, because they are dynamic, epigenetic mechanisms are also potentially reversible and may provide powerful means for pharmacological intervention. This review outlines major cognitive disorders known to be associated with epigenetic dysregulation, and discusses the potential of 'epigenetic medicine' as a promising cure.

Oxidative Stress and Maxi Calcium-Activated Potassium (BK) Channels

PubMed Central

Hermann, Anton; Sitdikova, Guzel F.; Weiger, Thomas M.

2015-01-01

All cells contain ion channels in their outer (plasma) and inner (organelle) membranes. Ion channels, similar to other proteins, are targets of oxidative impact, which modulates ion fluxes across membranes. Subsequently, these ion currents affect electrical excitability, such as action potential discharge (in neurons, muscle, and receptor cells), alteration of the membrane resting potential, synaptic transmission, hormone secretion, muscle contraction or coordination of the cell cycle. In this chapter we summarize effects of oxidative stress and redox mechanisms on some ion channels, in particular on maxi calcium-activated potassium (BK) channels which play an outstanding role in a plethora of physiological and pathophysiological functions in almost all cells and tissues. We first elaborate on some general features of ion channel structure and function and then summarize effects of oxidative alterations of ion channels and their functional consequences. PMID:26287261

Non-localization of eigenfunctions for Sturm-Liouville operators and applications

NASA Astrophysics Data System (ADS)

Liard, Thibault; Lissy, Pierre; Privat, Yannick

2018-02-01

In this article, we investigate a non-localization property of the eigenfunctions of Sturm-Liouville operators Aa = -∂xx + a (ṡ) Id with Dirichlet boundary conditions, where a (ṡ) runs over the bounded nonnegative potential functions on the interval (0 , L) with L > 0. More precisely, we address the extremal spectral problem of minimizing the L2-norm of a function e (ṡ) on a measurable subset ω of (0 , L), where e (ṡ) runs over all eigenfunctions of Aa, at the same time with respect to all subsets ω having a prescribed measure and all L∞ potential functions a (ṡ) having a prescribed essentially upper bound. We provide some existence and qualitative properties of the minimizers, as well as precise lower and upper estimates on the optimal value. Several consequences in control and stabilization theory are then highlighted.

Dynamic modulation of innate immunity programming and memory.

PubMed

Yuan, Ruoxi; Li, Liwu

2016-01-01

Recent progress harkens back to the old theme of immune memory, except this time in the area of innate immunity, to which traditional paradigm only prescribes a rudimentary first-line defense function with no memory. However, both in vitro and in vivo studies reveal that innate leukocytes may adopt distinct activation states such as priming, tolerance, and exhaustion, depending upon the history of prior challenges. The dynamic programming and potential memory of innate leukocytes may have far-reaching consequences in health and disease. This review aims to provide some salient features of innate programing and memory, patho-physiological consequences, underlying mechanisms, and current pressing issues.

mRNA changes in nucleus accumbens related to methamphetamine addiction in mice

NASA Astrophysics Data System (ADS)

Zhu, Li; Li, Jiaqi; Dong, Nan; Guan, Fanglin; Liu, Yufeng; Ma, Dongliang; Goh, Eyleen L. K.; Chen, Teng

2016-11-01

Methamphetamine (METH) is a highly addictive psychostimulant that elicits aberrant changes in the expression of microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) in the nucleus accumbens of mice, indicating a potential role of METH in post-transcriptional regulations. To decipher the potential consequences of these post-transcriptional regulations in response to METH, we performed strand-specific RNA sequencing (ssRNA-Seq) to identify alterations in mRNA expression and their alternative splicing in the nucleus accumbens of mice following exposure to METH. METH-mediated changes in mRNAs were analyzed and correlated with previously reported changes in non-coding RNAs (miRNAs and lncRNAs) to determine the potential functions of these mRNA changes observed here and how non-coding RNAs are involved. A total of 2171 mRNAs were differentially expressed in response to METH with functions involved in synaptic plasticity, mitochondrial energy metabolism and immune response. 309 and 589 of these mRNAs are potential targets of miRNAs and lncRNAs respectively. In addition, METH treatment decreases mRNA alternative splicing, and there are 818 METH-specific events not observed in saline-treated mice. Our results suggest that METH-mediated addiction could be attributed by changes in miRNAs and lncRNAs and consequently, changes in mRNA alternative splicing and expression. In conclusion, our study reported a methamphetamine-modified nucleus accumbens transcriptome and provided non-coding RNA-mRNA interaction networks possibly involved in METH addiction.

[Functional meat products; development and evaluation of their health-promoting properties].

PubMed

Olmedilla-Alonso, Begoña; Jiménez-Colmenero, Francisco

2014-06-01

For a number of reasons, meat products are an exceptionally adequate means for introducing different bioactive compounds into the diet without modifying eating habits. In recent years, there has been a notable development of meat products designed as potentially functional foods. Within the framework of the functional food, this article provides a general view of the reasons that motivate and justify their formulation, with special emphasis on: a) aspects to be considered in their design in order to be able to make nutrition claims and statements concerning their health-promoting properties; b) the strategies employed to optimize the presence of functional ingredients, favoring the presence of beneficial bioactive compounds and limiting others with negative consequences for our health, and c) the procedures for demonstrating a relationship between the consumption of potentially functional meat products with beneficial effects on health and the way in which these studies are reflected in the literature. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

Increasing the applicability of density functional theory. V. X-ray absorption spectra with ionization potential corrected exchange and correlation potentials.

PubMed

Verma, Prakash; Bartlett, Rodney J

2016-07-21

Core excitation energies are computed with time-dependent density functional theory (TD-DFT) using the ionization energy corrected exchange and correlation potential QTP(0,0). QTP(0,0) provides C, N, and O K-edge spectra to about an electron volt. A mean absolute error (MAE) of 0.77 and a maximum error of 2.6 eV is observed for QTP(0,0) for many small molecules. TD-DFT based on QTP (0,0) is then used to describe the core-excitation spectra of the 22 amino acids. TD-DFT with conventional functionals greatly underestimates core excitation energies, largely due to the significant error in the Kohn-Sham occupied eigenvalues. To the contrary, the ionization energy corrected potential, QTP(0,0), provides excellent approximations (MAE of 0.53 eV) for core ionization energies as eigenvalues of the Kohn-Sham equations. As a consequence, core excitation energies are accurately described with QTP(0,0), as are the core ionization energies important in X-ray photoionization spectra or electron spectroscopy for chemical analysis.

Violence against teachers: prevalence and consequences.

PubMed

Wilson, Catherine M; Douglas, Kevin S; Lyon, David R

2011-08-01

Data collected from 731 teachers were used to examine the consequences of violence directed toward teachers while in the workplace. Analyses showed that the majority of respondents (n = 585, 80.0%) had experienced school-related violence—broadly defined—at one point in their careers. Serious violence (actual, attempted, or threatened physical violence) was less common, but still common enough to be of concern (n = 202, 27.6%). Violence predicted physical and emotional effects, as well as teaching-related functioning. In addition, a model with fear as a potential mediator revealed that both fear and violence were independently predictive of these negative outcomes. Finally, analyses showed that, in general, women reported higher levels of physical symptoms compared to men. We discuss the implications of violence against teachers in terms of personal consequences and the implications for mental health professionals working in an educational setting.

Discovery of naturally occurring ESR1 mutations in breast cancer cell lines modelling endocrine resistance.

PubMed

Martin, Lesley-Ann; Ribas, Ricardo; Simigdala, Nikiana; Schuster, Eugene; Pancholi, Sunil; Tenev, Tencho; Gellert, Pascal; Buluwela, Laki; Harrod, Alison; Thornhill, Allan; Nikitorowicz-Buniak, Joanna; Bhamra, Amandeep; Turgeon, Marc-Olivier; Poulogiannis, George; Gao, Qiong; Martins, Vera; Hills, Margaret; Garcia-Murillas, Isaac; Fribbens, Charlotte; Patani, Neill; Li, Zheqi; Sikora, Matthew J; Turner, Nicholas; Zwart, Wilbert; Oesterreich, Steffi; Carroll, Jason; Ali, Simak; Dowsett, Mitch

2017-11-30

Resistance to endocrine therapy remains a major clinical problem in breast cancer. Genetic studies highlight the potential role of estrogen receptor-α (ESR1) mutations, which show increased prevalence in the metastatic, endocrine-resistant setting. No naturally occurring ESR1 mutations have been reported in in vitro models of BC either before or after the acquisition of endocrine resistance making functional consequences difficult to study. We report the first discovery of naturally occurring ESR1 Y537C and ESR1 Y537S mutations in MCF7 and SUM44 ESR1-positive cell lines after acquisition of resistance to long-term-estrogen-deprivation (LTED) and subsequent resistance to fulvestrant (ICIR). Mutations were enriched with time, impacted on ESR1 binding to the genome and altered the ESR1 interactome. The results highlight the importance and functional consequence of these mutations and provide an important resource for studying endocrine resistance.

Insights about Striatal Circuit Function and Schizophrenia from a Mouse Model of D2 Receptor Upregulation

PubMed Central

Simpson, Eleanor H.; Kellendonk, Christoph

2016-01-01

The dopamine hypothesis of schizophrenia is supported by a large number of imaging studies that have identified an increase in dopamine binding at the D2 receptor selectively in the striatum. Here we review a decade of work using a regionally restricted and temporally regulated transgenic mouse model to investigate the behavioral, molecular, electrophysiological, and anatomical consequences of selective D2 receptor upregulation in the striatum. These studies have identified new and potentially important biomarkers at the circuit and molecular level that can now be explored in patients with schizophrenia. They provide an example of how animal models and their detailed level of neurobiological analysis allow a deepening of our understanding of the relationship between neuronal circuit function and symptoms of schizophrenia, and as a consequence generate new hypotheses that are testable in patients. PMID:27720388

Toxic Effects of Mercury on the Cardiovascular and Central Nervous Systems

PubMed Central

Fernandes Azevedo, Bruna; Barros Furieri, Lorena; Peçanha, Franck Maciel; Wiggers, Giulia Alessandra; Frizera Vassallo, Paula; Ronacher Simões, Maylla; Fiorim, Jonaina; Rossi de Batista, Priscila; Fioresi, Mirian; Rossoni, Luciana; Stefanon, Ivanita; Alonso, María Jesus; Salaices, Mercedes; Valentim Vassallo, Dalton

2012-01-01

Environmental contamination has exposed humans to various metal agents, including mercury. This exposure is more common than expected, and the health consequences of such exposure remain unclear. For many years, mercury was used in a wide variety of human activities, and now, exposure to this metal from both natural and artificial sources is significantly increasing. Many studies show that high exposure to mercury induces changes in the central nervous system, potentially resulting in irritability, fatigue, behavioral changes, tremors, headaches, hearing and cognitive loss, dysarthria, incoordination, hallucinations, and death. In the cardiovascular system, mercury induces hypertension in humans and animals that has wide-ranging consequences, including alterations in endothelial function. The results described in this paper indicate that mercury exposure, even at low doses, affects endothelial and cardiovascular function. As a result, the reference values defining the limits for the absence of danger should be reduced. PMID:22811600

How best to capture the respiratory consequences of prematurity?

PubMed

Ciuffini, Francesca; Robertson, Colin F; Tingay, David G

2018-03-31

Chronic respiratory morbidity is a common complication of premature birth, generally defined by the presence of bronchopulmonary dysplasia, both clinically and in trials of respiratory therapies. However, recent data have highlighted that bronchopulmonary dysplasia does not correlate with chronic respiratory morbidity in older children born preterm. Longitudinally evaluating pulmonary morbidity from early life through to childhood provides a more rational method of defining the continuum of chronic respiratory morbidity of prematurity, and offers new insights into the efficacy of neonatal respiratory interventions. The changing nature of preterm lung disease suggests that a multimodal approach using dynamic lung function assessment will be needed to assess the efficacy of a neonatal respiratory therapy and predict the long-term respiratory consequences of premature birth. Our aim is to review the literature regarding the long-term respiratory outcomes of neonatal respiratory strategies, the difficulties of assessing dynamic lung function in infants, and potential new solutions. Copyright ©ERS 2018.

ANTECEDENT VERSUS CONSEQUENT EVENTS AS PREDICTORS OF PROBLEM BEHAVIOR

PubMed Central

Camp, Erin M; Iwata, Brian A; Hammond, Jennifer L; Bloom, Sarah E

2009-01-01

Comparisons of results from descriptive and functional analyses of problem behavior generally have shown poor correspondence. Most descriptive analyses have focused on relations between consequent events and behavior, and it has been noted that attention is a common consequence for problem behavior even though it may not be a functional reinforcer. Because attention may be prescribed simply as a means of stopping serious problem behavior, it is possible that naturally occurring antecedent events (establishing operations) might be better predictors of problem behavior than consequences. We conducted descriptive and functional analyses of the problem behaviors of 7 participants. Conditional probabilities based on combined antecedent and consequent events showed correspondence with the functional analysis data for 4 of the 7 participants, but antecedent events were no better than consequent events in identifying the function of problem behavior. PMID:19949538

Integrated modelling for the evaluation of infiltration effects.

PubMed

Schulz, N; Baur, R; Krebs, P

2005-01-01

The objective of the present study is the estimation of the potential benefits of sewer pipe rehabilitation for the performance of the drainage system and the wastewater treatment plant (WWTP) as well as for the receiving water quality. The relation of sewer system status and the infiltration rate is assessed based on statistical analysis of 470 km of CCTV (Closed Circuit Television) inspected sewers of the city of Dresden. The potential reduction of infiltration rates and the consequent performance improvements of the urban wastewater system are simulated as a function of rehabilitation activities in the network. The integrated model is applied to an artificial system with input from a real sewer network. In this paper, the general design of the integrated model and its data requirements are presented. For an exemplary study, the consequences of the simulations are discussed with respect to the prioritisation of rehabilitation activities in the network.

Getting quantitative about consequences of cross-ecosystem resource subsidies on recipient consumers

USGS Publications Warehouse

Richardson, John S.; Wipfli, Mark S.

2016-01-01

Most studies of cross-ecosystem resource subsidies have demonstrated positive effects on recipient consumer populations, often with very large effect sizes. However, it is important to move beyond these initial addition–exclusion experiments to consider the quantitative consequences for populations across gradients in the rates and quality of resource inputs. In our introduction to this special issue, we describe at least four potential models that describe functional relationships between subsidy input rates and consumer responses, most of them asymptotic. Here we aim to advance our quantitative understanding of how subsidy inputs influence recipient consumers and their communities. In the papers following, fish were either the recipient consumers or the subsidy as carcasses of anadromous species. Advancing general, predictive models will enable us to further consider what other factors are potentially co-limiting (e.g., nutrients, other population interactions, physical habitat, etc.) and better integrate resource subsidies into consumer–resource, biophysical dynamics models.

Confinement of Radioactive Materials at Defense Nuclear Facilities

DTIC Science & Technology

2004-10-01

The design of defense nuclear facilities includes systems whose reliable operation is vital to the protection of the public, workers, and the...final safety-class barrier to the release of hazardous materials with potentially serious public consequences. The Defense Nuclear Facilities Safety...the public at certain defense nuclear facilities . This change has resulted in downgrading of the functional safety classification of confinement

The head injured adolescent: a case report and review of the issues.

PubMed

Reiter, S; Kutcher, S P

1990-11-01

Closed head injuries in adolescents are a common problem with potentially disastrous consequences to multiple areas of functioning. Through a case presentation and literature review, this paper considers treatment issues and research applications in an adolescent population with closed head injuries. Suggestions for understanding the symptom constellations are made and directions for future research and service delivery are given.

Functional characterization of cytochrome P450-derived epoxyeicosatrienoic acids in adipogenesis and obesity.

PubMed

Zha, Weibin; Edin, Matthew L; Vendrov, Kimberly C; Schuck, Robert N; Lih, Fred B; Jat, Jawahar Lal; Bradbury, J Alyce; DeGraff, Laura M; Hua, Kunjie; Tomer, Kenneth B; Falck, John R; Zeldin, Darryl C; Lee, Craig R

2014-10-01

Adipogenesis plays a critical role in the initiation and progression of obesity. Although cytochrome P450 (CYP)-derived epoxyeicosatrienoic acids (EETs) have emerged as a potential therapeutic target for cardiometabolic disease, the functional contribution of EETs to adipogenesis and the pathogenesis of obesity remain poorly understood. Our studies demonstrated that induction of adipogenesis in differentiated 3T3-L1 cells (in vitro) and obesity-associated adipose expansion in high-fat diet (HFD)-fed mice (in vivo) significantly dysregulate the CYP epoxygenase pathway and evoke a marked suppression of adipose-derived EET levels. Subsequent in vitro experiments demonstrated that exogenous EET analog administration elicits potent anti-adipogenic effects via inhibition of the early phase of adipogenesis. Furthermore, EET analog administration to mice significantly mitigated HFD-induced weight gain, adipose tissue expansion, pro-adipogenic gene expression, and glucose intolerance. Collectively, these findings suggest that suppression of EET bioavailability in adipose tissue is a key pathological consequence of obesity, and strategies that promote the protective effects of EETs in adipose tissue offer enormous therapeutic potential for obesity and its downstream pathological consequences. Copyright © 2014 by the American Society for Biochemistry and Molecular Biology, Inc.

Programming of the appetite-regulating neural network: a link between maternal overnutrition and the programming of obesity?

PubMed

Mühlhäusler, B S

2007-01-01

The concept of a functional foetal "appetite regulatory neural network" is a new and potentially critical one. There is a growing body of evidence showing that the nutritional environment to which the foetus is exposed during prenatal and perinatal development has long-term consequences for the function of the appetite-regulating neural network and therefore the way in which an individual regulates energy balance throughout later life. This is of particular importance in the context of evidence obtained from a wide range of epidemiological studies, which have shown that individuals exposed to an elevated nutrient supply before birth have an increased risk of becoming obese as children and adults. This review summarises the key pieces of experimental evidence, by our group and others, that have contributed to our current understanding of the programming of appetite, and highlights the important questions that are yet to be answered. It is clear that this area of research has the potential to generate, within the next few years, interventions that could begin to alleviate the adverse long-term consequences of being exposed to an elevated nutrient supply before birth.

Impaired decision making under ambiguity but not under risk in individuals with pathological buying-behavioral and psychophysiological evidence.

PubMed

Trotzke, Patrick; Starcke, Katrin; Pedersen, Anya; Müller, Astrid; Brand, Matthias

2015-09-30

Pathological buying (PB) is described as dysfunctional buying behavior, associated with harmful consequences. It is discussed whether decision-making deficits are related to PB, because affected individuals often choose the short-term rewarding option of buying despite persistent negative long-term consequences. We investigated 30 patients suffering from PB and 30 matched control participants with two different decision-making tasks: the Iowa Gambling Task (IGT) measures decisions under ambiguity and involves emotional feedback processing, whereas the Game of Dice Task (GDT) measures decisions under risk and can be solved strategically. Potential emotional and cognitive correlates of decision making were investigated by assessing skin conductance response (SCR) and executive functioning. In comparison to the control participants, the patients showed more disadvantageous decisions under ambiguity in the IGT. These data were supported by the SCR results: patients failed to generate SCRs that usually occur before disadvantageous decisions. The physiological and behavioral performance on decisions under risk and executive functioning did not differ between groups. Thus, deficits in emotional feedback processing might be one potential factor in etiology and pathogenesis of PB and should be considered in theory and treatment. Copyright © 2015. Published by Elsevier Ireland Ltd.

Resolving TYK2 locus genotype-to-phenotype differences in autoimmunity

PubMed Central

Dendrou, Calliope A.; Cortes, Adrian; Shipman, Lydia; Evans, Hayley G.; Attfield, Kathrine E.; Jostins, Luke; Barber, Thomas; Kaur, Gurman; Kuttikkatte, Subita Balaram; Leach, Oliver A.; Desel, Christiane; Faergeman, Soren L.; Cheeseman, Jane; Neville, Matt J.; Sawcer, Stephen; Compston, Alastair; Johnson, Adam R.; Everett, Christine; Bell, John I.; Karpe, Fredrik; Ultsch, Mark; Eigenbrot, Charles; McVean, Gil; Fugger, Lars

2017-01-01

Thousands of genetic variants have been identified that contribute to the development of complex diseases, but determining how to fully elucidate their biological consequences for translation into clinical benefit is challenging. Conflicting evidence regarding the functional impact of genetic variants in the tyrosine kinase 2 (TYK2) gene, which is differentially associated with common autoimmune diseases, currently obscures the potential of TYK2 as a therapeutic target. We aimed to resolve this conflict by performing genetic meta-analysis across disorders, subsequent molecular, cellular, in vivo and structural functional follow-up and epidemiological studies. Our data revealed a protective homozygous effect that defined a signaling optimum between autoimmunity and immunodeficiency and identified TYK2 as a potential drug target for multiple autoimmune disorders. PMID:27807284

Human performance consequences of stages and levels of automation: an integrated meta-analysis.

PubMed

Onnasch, Linda; Wickens, Christopher D; Li, Huiyang; Manzey, Dietrich

2014-05-01

We investigated how automation-induced human performance consequences depended on the degree of automation (DOA). Function allocation between human and automation can be represented in terms of the stages and levels taxonomy proposed by Parasuraman, Sheridan, and Wickens. Higher DOAs are achieved both by later stages and higher levels within stages. A meta-analysis based on data of 18 experiments examines the mediating effects of DOA on routine system performance, performance when the automation fails, workload, and situation awareness (SA). The effects of DOA on these measures are summarized by level of statistical significance. We found (a) a clear automation benefit for routine system performance with increasing DOA, (b) a similar but weaker pattern for workload when automation functioned properly, and (c) a negative impact of higher DOA on failure system performance and SA. Most interesting was the finding that negative consequences of automation seem to be most likely when DOA moved across a critical boundary, which was identified between automation supporting information analysis and automation supporting action selection. Results support the proposed cost-benefit trade-off with regard to DOA. It seems that routine performance and workload on one hand, and the potential loss of SA and manual skills on the other hand, directly trade off and that appropriate function allocation can serve only one of the two aspects. Findings contribute to the body of research on adequate function allocation by providing an overall picture through quantitatively combining data from a variety of studies across varying domains.

Clinical review: Cardiovascular consequences of ovarian disruption: a focus on functional hypothalamic amenorrhea in physically active women.

PubMed

O'Donnell, Emma; Goodman, Jack M; Harvey, Paula J

2011-12-01

Evidence indicates that hypoestrogenemia is linked with accelerated progression of atherosclerosis. Premenopausal women presenting with ovulatory disruption due to functional hypothalamic amenorrhea (FHA) are characterized by hypoestrogenemia. One common and reversible form of FHA in association with energy deficiency is exercise-associated amenorrhea (EAA). Articles were found via PubMed search for both original and review articles based on peer review publications between 1974 and 2011 reporting on cardiovascular changes in women with FHA, with emphasis placed on women with EAA. Despite participation in regular exercise training, hypoestrogenic women with EAA demonstrate paradoxical changes in cardiovascular function, including endothelial dysfunction, a known permissive factor for the progression and development of atherosclerosis. Such alterations suggest that the beneficial effects of regular exercise training on vascular function are obviated in the face of hypoestrogenemia. The long-term cardiovascular consequences of altered vascular function in response to ovulatory disruption in women with EAA remain to be determined. Retrospective data, however, suggest premature development and progression of coronary artery disease in older premenopausal women reporting a history of hypothalamic ovulatory disruption. Importantly, in women with EAA, estrogen therapy, folic acid supplementation without change in menstrual status, and resumption of menses restores endothelial function. In this review, we focus on the influence of hypoestrogenemia in association with energy deficiency in mediating changes in cardiovascular function in women with EAA, including endothelial function, regional blood flow, lipid profile, and autonomic control of blood pressure, heart rate, and baroreflex sensitivity. The influence of exercise training is also considered. With the premenopausal years typically considered to be cardioprotective in association with normal ovarian function, ovarian disruption in women with EAA is of importance. Further investigation of the short-term, and potentially long-term, cardiovascular consequences of hypoestrogenemia in women with EAA is recommended.

Next generation interatomic potentials for condensed systems

NASA Astrophysics Data System (ADS)

Handley, Christopher Michael; Behler, Jörg

2014-07-01

The computer simulation of condensed systems is a challenging task. While electronic structure methods like density-functional theory (DFT) usually provide a good compromise between accuracy and efficiency, they are computationally very demanding and thus applicable only to systems containing up to a few hundred atoms. Unfortunately, many interesting problems require simulations to be performed on much larger systems involving thousands of atoms or more. Consequently, more efficient methods are urgently needed, and a lot of effort has been spent on the development of a large variety of potentials enabling simulations with significantly extended time and length scales. Most commonly, these potentials are based on physically motivated functional forms and thus perform very well for the applications they have been designed for. On the other hand, they are often highly system-specific and thus cannot easily be transferred from one system to another. Moreover, their numerical accuracy is restricted by the intrinsic limitations of the imposed functional forms. In recent years, several novel types of potentials have emerged, which are not based on physical considerations. Instead, they aim to reproduce a set of reference electronic structure data as accurately as possible by using very general and flexible functional forms. In this review we will survey a number of these methods. While they differ in the choice of the employed mathematical functions, they all have in common that they provide high-quality potential-energy surfaces, while the efficiency is comparable to conventional empirical potentials. It has been demonstrated that in many cases these potentials now offer a very interesting new approach to study complex systems with hitherto unreached accuracy.

[Consequences of tobacco, cocaine and cannabis consumption during pregnancy on the pregnancy itself, on the newborn and on child development: A review].

PubMed

Lamy, S; Laqueille, X; Thibaut, F

2015-06-01

Substance use has increased worldwide. Based on these data, we may think that substance use has also increased during pregnancy, but epidemiological data are scarce in this population. The potential consequences of tobacco, cocaine or cannabis use during pregnancy are a major public health concern. The combined use of different substances during pregnancy may have serious consequences on the pregnancy and on child development. In this paper, we will describe the potential consequences for the newborn, child and adolescent after being exposed to tobacco, cannabis and cocaine in utero. For this purpose, we will review all retrospective and prospective studies (in English and French) referenced in PubMed reporting on the somatic or psychiatric consequences of alcohol, tobacco and drug consumption by pregnant women on newborn and children. Consumption during pregnancy was assessed in these studies using simple questionnaires, biomarkers analysis or both. Generally speaking, these pregnancies are at high risk for both the mother and the foetus: for example, an increased risk of miscarriage or of reduced length of gestation, an increased risk of uterine apoplexy and placenta praevia, more premature births and/or hypotrophy were reported. The occurrence of a newborn's withdrawal syndrome may be misdiagnosed. Many consequences on child development may be observed such as growth disorders, learning or motor disorders, language disorders, cognitive disorders (attention, memory, executive functions), attention deficit disorders with impulsivity or with hyperactivity (ADHD), and memory disorders. The prevalence of depressive or anxiety disorders may also be increased in these children. The risk of addictive disorders or schizophrenia in children exposed in utero to illicit drugs or tobacco is still unknown. The combined use of different substances increases, consequently it is difficult to disentangle the consequences on child development of each of the drugs used during pregnancy owing to potential interactions between these drugs. The consequences on child development will also depend on the dose and on the time of drug use during pregnancy. The National Institute of Drug Abuse reported that 75% of the infants exposed in utero to one or more substances will present medical problems during childhood, as compared to only 27% of the non-exposed infants. However, the medical consequences are still a matter of controversies. Methodological biases, such as the use of different rating scales among studies, and the heterogeneity of the populations included are main limitations. Further studies are needed using larger cohorts and longer follow-up periods. Copyright © 2014 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.

Short- and long-term health consequences of sleep disruption.

PubMed

Medic, Goran; Wille, Micheline; Hemels, Michiel Eh

2017-01-01

Sleep plays a vital role in brain function and systemic physiology across many body systems. Problems with sleep are widely prevalent and include deficits in quantity and quality of sleep; sleep problems that impact the continuity of sleep are collectively referred to as sleep disruptions. Numerous factors contribute to sleep disruption, ranging from lifestyle and environmental factors to sleep disorders and other medical conditions. Sleep disruptions have substantial adverse short- and long-term health consequences. A literature search was conducted to provide a nonsystematic review of these health consequences (this review was designed to be nonsystematic to better focus on the topics of interest due to the myriad parameters affected by sleep). Sleep disruption is associated with increased activity of the sympathetic nervous system and hypothalamic-pituitary-adrenal axis, metabolic effects, changes in circadian rhythms, and proinflammatory responses. In otherwise healthy adults, short-term consequences of sleep disruption include increased stress responsivity, somatic pain, reduced quality of life, emotional distress and mood disorders, and cognitive, memory, and performance deficits. For adolescents, psychosocial health, school performance, and risk-taking behaviors are impacted by sleep disruption. Behavioral problems and cognitive functioning are associated with sleep disruption in children. Long-term consequences of sleep disruption in otherwise healthy individuals include hypertension, dyslipidemia, cardiovascular disease, weight-related issues, metabolic syndrome, type 2 diabetes mellitus, and colorectal cancer. All-cause mortality is also increased in men with sleep disturbances. For those with underlying medical conditions, sleep disruption may diminish the health-related quality of life of children and adolescents and may worsen the severity of common gastrointestinal disorders. As a result of the potential consequences of sleep disruption, health care professionals should be cognizant of how managing underlying medical conditions may help to optimize sleep continuity and consider prescribing interventions that minimize sleep disruption.

Short- and long-term health consequences of sleep disruption

PubMed Central

Medic, Goran; Wille, Micheline; Hemels, Michiel EH

2017-01-01

Sleep plays a vital role in brain function and systemic physiology across many body systems. Problems with sleep are widely prevalent and include deficits in quantity and quality of sleep; sleep problems that impact the continuity of sleep are collectively referred to as sleep disruptions. Numerous factors contribute to sleep disruption, ranging from lifestyle and environmental factors to sleep disorders and other medical conditions. Sleep disruptions have substantial adverse short- and long-term health consequences. A literature search was conducted to provide a nonsystematic review of these health consequences (this review was designed to be nonsystematic to better focus on the topics of interest due to the myriad parameters affected by sleep). Sleep disruption is associated with increased activity of the sympathetic nervous system and hypothalamic–pituitary–adrenal axis, metabolic effects, changes in circadian rhythms, and proinflammatory responses. In otherwise healthy adults, short-term consequences of sleep disruption include increased stress responsivity, somatic pain, reduced quality of life, emotional distress and mood disorders, and cognitive, memory, and performance deficits. For adolescents, psychosocial health, school performance, and risk-taking behaviors are impacted by sleep disruption. Behavioral problems and cognitive functioning are associated with sleep disruption in children. Long-term consequences of sleep disruption in otherwise healthy individuals include hypertension, dyslipidemia, cardiovascular disease, weight-related issues, metabolic syndrome, type 2 diabetes mellitus, and colorectal cancer. All-cause mortality is also increased in men with sleep disturbances. For those with underlying medical conditions, sleep disruption may diminish the health-related quality of life of children and adolescents and may worsen the severity of common gastrointestinal disorders. As a result of the potential consequences of sleep disruption, health care professionals should be cognizant of how managing underlying medical conditions may help to optimize sleep continuity and consider prescribing interventions that minimize sleep disruption. PMID:28579842

Let thy left brain know what thy right brain doeth: Inter-hemispheric compensation of functional deficits after brain damage.

PubMed

Bartolomeo, Paolo; Thiebaut de Schotten, Michel

2016-12-01

Recent evidence revealed the importance of inter-hemispheric communication for the compensation of functional deficits after brain damage. This review summarises the biological consequences observed using histology as well as the longitudinal findings measured with magnetic resonance imaging methods in brain damaged animals and patients. In particular, we discuss the impact of post-stroke brain hyperactivity on functional recovery in relation to time. The reviewed evidence also suggests that the proportion of the preserved functional network both in the lesioned and in the intact hemispheres, rather than the simple lesion location, determines the extent of functional recovery. Hence, future research exploring longitudinal changes in patients with brain damage may unveil potential biomarkers underlying functional recovery. Copyright © 2016 Elsevier Ltd. All rights reserved.

Ground-state energies and highest occupied eigenvalues of atoms in exchange-only density-functional theory

NASA Astrophysics Data System (ADS)

Li, Yan; Harbola, Manoj K.; Krieger, J. B.; Sahni, Viraht

1989-11-01

The exchange-correlation potential of the Kohn-Sham density-functional theory has recently been interpreted as the work required to move an electron against the electric field of its Fermi-Coulomb hole charge distribution. In this paper we present self-consistent results for ground-state total energies and highest occupied eigenvalues of closed subshell atoms as obtained by this formalism in the exchange-only approximation. The total energies, which are an upper bound, lie within 50 ppm of Hartree-Fock theory for atoms heavier than Be. The highest occupied eigenvalues, as a consequence of this interpretation, approximate well the experimental ionization potentials. In addition, the self-consistently calculated exchange potentials are very close to those of Talman and co-workers [J. D. Talman and W. F. Shadwick, Phys. Rev. A 14, 36 (1976); K. Aashamar, T. M. Luke, and J. D. Talman, At. Data Nucl. Data Tables 22, 443 (1978)].

Psychological and social consequences after reconstruction of upper extremity trauma: methods of detection and management.

PubMed

Galanakos, Spyridon P; Bot, Arjan G J; Zoubos, Aristides B; Soucacos, Panayotis N

2014-03-01

Upper extremity trauma and resulting disability is a stressful event and can affect a patient's personality. Several studies have shown that this injury type has serious psychological and/or social consequences. We systematically reviewed the evidence on the consequences of disability after a complex trauma (combination of soft tissue, osseous, vascular, and nerve involvement) of the upper extremity. We tried to find out the potential crucial factors that could determine the final hand function. In addition, we considered the challenges that need to be addressed to eliminate the adverse or negative effects that arise from upper limb trauma. In the literature, there is a growing interest to study changes in patients' quality of life and return to work. Psychological morbidity is an important part of patients' perceived general health. These issues could play an important role in the final functional outcome of the therapy. An early identification and treatment of trauma-related distress in patients may prevent progression of psychological pathology and mitigate negative effects on general health status. It may be important to evaluate the amount of psychological distress when caring for patients with hand injuries. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

JPRS Report, Soviet Union, International Affairs.

DTIC Science & Technology

1987-11-27

becoming very relevant in this connection. One direct consequence is the need for closer interaction not only of the technical and production potential... personal computers, systems for numeric programmed control for functional machine tools and flexible produc- tion modules, programmable master... personality of the collective director— his enterprising nature, his ability to work in a new way (or his willing- ness to learn). "Even today many

Human inversions and their functional consequences

PubMed Central

Puig, Marta; Casillas, Sònia; Villatoro, Sergi

2015-01-01

Polymorphic inversions are a type of structural variants that are difficult to analyze owing to their balanced nature and the location of breakpoints within complex repeated regions. So far, only a handful of inversions have been studied in detail in humans and current knowledge about their possible functional effects is still limited. However, inversions have been related to phenotypic changes and adaptation in multiple species. In this review, we summarize the evidences of the functional impact of inversions in the human genome. First, given that inversions have been shown to inhibit recombination in heterokaryotes, chromosomes displaying different orientation are expected to evolve independently and this may lead to distinct gene-expression patterns. Second, inversions have a role as disease-causing mutations both by directly affecting gene structure or regulation in different ways, and by predisposing to other secondary arrangements in the offspring of inversion carriers. Finally, several inversions show signals of being selected during human evolution. These findings illustrate the potential of inversions to have phenotypic consequences also in humans and emphasize the importance of their inclusion in genome-wide association studies. PMID:25998059

Neonatal Brain Hemorrhage (NBH) of Prematurity: Translational Mechanisms of the Vascular-Neural Network

PubMed Central

Lekic, Tim; Klebe, Damon; Poblete, Roy; Krafft, Paul R.; Rolland, William B.; Tang, Jiping; Zhang, John H.

2015-01-01

Neonatal brain hemorrhage (NBH) of prematurity is an unfortunate consequence of preterm birth. Complications result in shunt dependence and long-term structural changes such as post-hemorrhagic hydrocephalus, periventricular leukomalacia, gliosis, and neurological dysfunction. Several animal models are available to study this condition, and many basic mechanisms, etiological factors, and outcome consequences, are becoming understood. NBH is an important clinical condition, of which treatment may potentially circumvent shunt complication, and improve functional recovery (cerebral palsy, and cognitive impairments). This review highlights key pathophysiological findings of the neonatal vascular-neural network in the context of molecular mechanisms targeting the post-hemorrhagic hydrocephalus affecting this vulnerable infant population. PMID:25620100

Superfluidity or supersolidity as a consequence of off-diagonal long-range order

NASA Astrophysics Data System (ADS)

Shi, Yu

2005-07-01

We present a general derivation of Hess-Fairbank effect or nonclassical rotational inertial (NCRI), i.e., the refusal to rotate with its container, as well as the quantization of angular momentum, as consequences of off-diagonal long-range order (ODLRO) in an interacting Bose system. Afterwards, the path integral formulation of superfluid density is rederived without ignoring the centrifugal potential. Finally and in particular, for a class of variational wave functions used for solid helium, treating the constraint of single-valuedness boundary condition carefully, we show that there is no ODLRO and, especially, demonstrate explicitly that NCRI cannot be possessed in absence of defects, even though there exist zero-point motion and exchange effect.

Mechanisms and consequences of alternative polyadenylation

PubMed Central

Di Giammartino, Dafne Campigli; Nishida, Kensei; Manley, James L.

2011-01-01

Summary Alternative polyadenylation (APA) is emerging as a widespread mechanism used to control gene expression. Like alternative splicing, usage of alternative poly(A) sites allows a single gene to encode multiple mRNA transcripts. In some cases, this changes the mRNA coding potential; in other cases, the code remains unchanged but the 3’UTR length is altered, influencing the fate of mRNAs in several ways, for example, by altering the availability of RNA binding protein sites and microRNA binding sites. The mechansims governing both global and gene-specific APA are only starting to be deciphered. Here we review what is known about these mechanisms and the functional consequences of alternative polyadenlyation. PMID:21925375

Sedentary Screen Time and Left Ventricular Structure and Function: the CARDIA Study

PubMed Central

Gibbs, Bethany Barone; Reis, Jared P.; Schelbert, Erik B.; Craft, Lynette L.; Sidney, Steve; Lima, Joao; Lewis, Cora E.

2013-01-01

Sedentary screen time (watching TV or using a computer) predicts cardiovascular outcomes independently from moderate and vigorous physical activity and could impact left ventricular structure and function through the adverse consequences of sedentary behavior. Purpose To determine whether sedentary screen time is associated with measures of left ventricular structure and function. Methods The Coronary Artery Risk Development in Young Adults (CARDIA) Study measured screen time by questionnaire and left ventricular structure and function by echocardiography in 2,854 black and white participants, aged 43–55 years, in 2010–2011. Generalized linear models evaluated cross-sectional trends for echocardiography measures across higher categories of screen time and adjusting for demographics, smoking, alcohol, and physical activity. Further models adjusted for potential intermediate factors (blood pressure, antihypertensive medication use, diabetes, and body mass index (BMI). Results The relationship between screen time and left ventricular mass(LVM) differed in blacks vs. whites. Among whites, higher screen time was associated with larger LVM (P<0.001), after adjustment for height, demographics, and lifestyle variables. Associations between screen time and LVM persisted when adjusting for blood pressure, antihypertensive medication use, and diabetes (P=0.008) but not with additional adjustment for BMI (P=0.503). Similar relationships were observed for screen time with LVM indexed to height2.7, relative wall thickness, and mass-to-volume ratio. Screen time was not associated with left ventricular structure among blacks or left ventricular function in either race group. Conclusions Sedentary screen time is associated with greater LVM in white adults and this relationship was largely explained by higher overall adiposity. The lack of association in blacks supports a potential qualitative difference in the cardiovascular consequences of sedentary screen-based behavior. PMID:23863618

Ecological Immunology through the Lens of Exercise Immunology: New Perspective on the Links between Physical Activity and Immune Function and Disease Susceptibility in Wild Animals.

PubMed

van Dijk, Jacintha G B; Matson, Kevin D

2016-08-01

Locomotion and other physical activities by free-living animals may influence immune function and disease susceptibility. This influence may be a consequence of energetic trade-offs or other mechanisms that are often, but not always, inseparably linked to an animal's life history (e.g., flight and migration). Ecological immunology has mainly focused on these life-history trade-offs, overlooking the possible effects of physical activity per se on immune function and disease susceptibility. In this review, we explore the field of exercise immunology, which examines the impact of exercise on immune function and disease susceptibility in humans, with the aim of presenting new perspectives that might be transferable to ecological immunology. First, we explore key concepts in exercise immunology that could be extended to animals. Next, we investigate the concept "exercise" in animals, and propose the use of "physical activity" instead. We briefly discuss methods used in animals to quantify physical activity in terms of energy expenditure and summarize several examples of animals engaging in physical activity. Then, we highlight potential consequences of physical activity on immune function and disease susceptibility in animals, together with an overview of animal studies that examine these links. Finally, we explore and discuss the potential for incorporating perspectives from exercise immunology into ecological immunology. Such integration could help advance our understanding of human and animal health and contribute new ideas to budding "One Health" initiatives. © The Author 2016. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email: journals.permissions@oup.com.

Variant Interpretation: Functional Assays to the Rescue.

PubMed

Starita, Lea M; Ahituv, Nadav; Dunham, Maitreya J; Kitzman, Jacob O; Roth, Frederick P; Seelig, Georg; Shendure, Jay; Fowler, Douglas M

2017-09-07

Classical genetic approaches for interpreting variants, such as case-control or co-segregation studies, require finding many individuals with each variant. Because the overwhelming majority of variants are present in only a few living humans, this strategy has clear limits. Fully realizing the clinical potential of genetics requires that we accurately infer pathogenicity even for rare or private variation. Many computational approaches to predicting variant effects have been developed, but they can identify only a small fraction of pathogenic variants with the high confidence that is required in the clinic. Experimentally measuring a variant's functional consequences can provide clearer guidance, but individual assays performed only after the discovery of the variant are both time and resource intensive. Here, we discuss how multiplex assays of variant effect (MAVEs) can be used to measure the functional consequences of all possible variants in disease-relevant loci for a variety of molecular and cellular phenotypes. The resulting large-scale functional data can be combined with machine learning and clinical knowledge for the development of "lookup tables" of accurate pathogenicity predictions. A coordinated effort to produce, analyze, and disseminate large-scale functional data generated by multiplex assays could be essential to addressing the variant-interpretation crisis. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Production of bioactive substances by intestinal bacteria as a basis for explaining probiotic mechanisms: bacteriocins and conjugated linoleic acid.

PubMed

O'Shea, Eileen F; Cotter, Paul D; Stanton, Catherine; Ross, R Paul; Hill, Colin

2012-01-16

The mechanisms by which intestinal bacteria achieve their associated health benefits can be complex and multifaceted. In this respect, the diverse microbial composition of the human gastrointestinal tract (GIT) provides an almost unlimited potential source of bioactive substances (pharmabiotics) which can directly or indirectly affect human health. Bacteriocins and fatty acids are just two examples of pharmabiotic substances which may contribute to probiotic functionality within the mammalian GIT. Bacteriocin production is believed to confer producing strains with a competitive advantage within complex microbial environments as a consequence of their associated antimicrobial activity. This has the potential to enable the establishment and prevalence of producing strains as well as directly inhibiting pathogens within the GIT. Consequently, these antimicrobial peptides and the associated intestinal producing strains may be exploited to beneficially influence microbial populations. Intestinal bacteria are also known to produce a diverse array of health-promoting fatty acids. Indeed, certain strains of intestinal bifidobacteria have been shown to produce conjugated linoleic acid (CLA), a fatty acid which has been associated with a variety of systemic health-promoting effects. Recently, the ability to modulate the fatty acid composition of the liver and adipose tissue of the host upon oral administration of CLA-producing bifidobacteria and lactobacilli was demonstrated in a murine model. Importantly, this implies a potential therapeutic role for probiotics in the treatment of certain metabolic and immunoinflammatory disorders. Such examples serve to highlight the potential contribution of pharmabiotic production to probiotic functionality in relation to human health maintenance. Copyright © 2011 Elsevier B.V. All rights reserved.

Ecological consequences of invasion across the freshwater-marine transition in a warming world.

PubMed

Crespo, Daniel; Solan, Martin; Leston, Sara; Pardal, Miguel A; Dolbeth, Marina

2018-02-01

The freshwater-marine transition that characterizes an estuarine system can provide multiple entry options for invading species, yet the relative importance of this gradient in determining the functional contribution of invading species has received little attention. The ecological consequences of species invasion are routinely evaluated within a freshwater versus marine context, even though many invasive species can inhabit a wide range of salinities. We investigate the functional consequences of different sizes of Corbicula fluminea -an invasive species able to adapt to a wide range of temperatures and salinity-across the freshwater-marine transition in the presence versus absence of warming. Specifically, we characterize how C. fluminea affect fluid and particle transport, important processes in mediating nutrient cycling (NH 4 -N, NO 3 -N, PO 4 -P). Results showed that sediment particle reworking (bioturbation) tends to be influenced by size and to a lesser extent, temperature and salinity; nutrient concentrations are influenced by different interactions between all variables (salinity, temperature, and size class). Our findings demonstrate the highly context-dependent nature of the ecosystem consequences of invasion and highlight the potential for species to simultaneously occupy multiple components of an ecosystem. Recognizing of this aspect of invasibility is fundamental to management and conservation efforts, particularly as freshwater and marine systems tend to be compartmentalized rather than be treated as a contiguous unit. We conclude that more comprehensive appreciation of the distribution of invasive species across adjacent habitats and different seasons is urgently needed to allow the true extent of biological introductions, and their ecological consequences, to be fully realized.

The Effects of Consequence Manipulation during Functional Analysis of Problem Behavior Maintained by Negative Reinforcement

ERIC Educational Resources Information Center

Potoczak, Kathryn; Carr, James E.; Michael, Jack

2007-01-01

Two distinct analytic methods have been used to identify the function of problem behavior. The antecedent-behavior-consequence (ABC) method (Iwata, Dorsey, Slifer, Bauman, & Richman, 1982/1994) includes the delivery of consequences for problem behavior. The AB method (Carr & Durand, 1985) does not include consequence delivery, instead relying…

Recovery of microbial communities and carbon cycling processes following drought manipulation in southern California

NASA Astrophysics Data System (ADS)

Allison, S. D.; Martiny, J. B. H.; Martiny, A.; Berlemont, R.; Treseder, K. K.; Goulden, M.; Brodie, E.

2016-12-01

Predicting the functioning of microbial communities under changing environmental conditions remains a key challenge in Earth system science. Metagenomics and other high-throughput molecular approaches can help address this challenge by revealing the functional potential of microbial communities. We coupled metagenomics with models and experimental manipulations to address microbial responses to drought in a California grassland ecosystem along with the consequences for carbon cycling. We developed an approach for extracting trait information from metagenomic data and asked: 1) What is the phylogenetic structure of drought response traits? 2) What is the relationship between these traits and those involved in carbohydrate degradation? 3) How do both classes of traits vary seasonally and with precipitation manipulation? 4) How resilient are these traits in the face of perturbation? We found that drought response traits are phylogenetically conserved at an equivalent of 5-8% ribosomal RNA gene sequence dissimilarity. Experimental drought treatment selected for the genetic potential to degrade starch, xylan, and mixed polysaccharides, suggesting a link between drought response and carbon cycling traits. In addition, microbial communities exposed to experimental drought showed a reduced potential to degrade plant biomass. Particularly among bacteria, seasonal drought had a larger impact on microbial composition, abundance, and carbohydrate-degrading genes compared to experimental drought. Bacterial communities were also more resilient to drought perturbation than fungal communities, which showed legacies of drought perturbation for up to three years. Altogether, these findings imply that microbial communities exhibit trait diversity that facilitates resilience but with substantial time lags and consequences for carbon turnover. This information is being used to inform new trait-based models that address the challenge of predicting microbial functioning under precipitation change.

Nature and biosynthesis of galacto-oligosaccharides related to oligosaccharides in human breast milk

PubMed Central

Intanon, Montira; Arreola, Sheryl Lozel; Pham, Ngoc Hung; Kneifel, Wolfgang; Haltrich, Dietmar; Nguyen, Thu-Ha

2014-01-01

Human milk oligosaccharides (HMO) are prominent among the functional components of human breast milk. While HMO have potential applications in both infants and adults, this potential is limited by the difficulties in manufacturing these complex structures. Consequently, functional alternatives such as galacto-oligosaccharides are under investigation, and nowadays, infant formulae are supplemented with galacto-oligosaccharides to mimic the biological effects of HMO. Recently, approaches toward the production of defined human milk oligosaccharide structures using microbial, fermentative methods employing single, appropriately engineered microorganisms were introduced. Furthermore, galactose-containing hetero-oligosaccharides have attracted an increasing amount of attention because they are structurally more closely related to HMO. The synthesis of these novel oligosaccharides, which resemble the core of HMO, is of great interest for applications in the food industry. PMID:24571717

Resolving TYK2 locus genotype-to-phenotype differences in autoimmunity.

PubMed

Dendrou, Calliope A; Cortes, Adrian; Shipman, Lydia; Evans, Hayley G; Attfield, Kathrine E; Jostins, Luke; Barber, Thomas; Kaur, Gurman; Kuttikkatte, Subita Balaram; Leach, Oliver A; Desel, Christiane; Faergeman, Soren L; Cheeseman, Jane; Neville, Matt J; Sawcer, Stephen; Compston, Alastair; Johnson, Adam R; Everett, Christine; Bell, John I; Karpe, Fredrik; Ultsch, Mark; Eigenbrot, Charles; McVean, Gil; Fugger, Lars

2016-11-02

Thousands of genetic variants have been identified, which contribute to the development of complex diseases, but determining how to elucidate their biological consequences for translation into clinical benefit is challenging. Conflicting evidence regarding the functional impact of genetic variants in the tyrosine kinase 2 (TYK2) gene, which is differentially associated with common autoimmune diseases, currently obscures the potential of TYK2 as a therapeutic target. We aimed to resolve this conflict by performing genetic meta-analysis across disorders; subsequent molecular, cellular, in vivo, and structural functional follow-up; and epidemiological studies. Our data revealed a protective homozygous effect that defined a signaling optimum between autoimmunity and immunodeficiency and identified TYK2 as a potential drug target for certain common autoimmune disorders. Copyright © 2016, American Association for the Advancement of Science.

Progranulin: at the interface of neurodegenerative and metabolic diseases.

PubMed

Nguyen, Andrew D; Nguyen, Thi A; Martens, Lauren Herl; Mitic, Laura L; Farese, Robert V

2013-12-01

Progranulin is a widely expressed, cysteine-rich, secreted glycoprotein originally discovered for its growth factor-like properties. Its subsequent identification as a causative gene for frontotemporal dementia (FTD), a devastating early-onset neurodegenerative disease, has catalyzed a surge of new discoveries about progranulin function in the brain. More recently, progranulin was recognized as an adipokine involved in diet-induced obesity and insulin resistance, revealing its metabolic function. We review here progranulin biology in both neurodegenerative and metabolic diseases. In particular, we highlight the growth factor-like, trophic, and anti-inflammatory properties of progranulin as potential unifying themes in these seemingly divergent conditions. We also discuss potential therapeutic options for raising progranulin levels to treat progranulin-deficient FTD, as well as the possible consequences of such treatment. Copyright © 2013 Elsevier Ltd. All rights reserved.

Progranulin: At the interface of neurodegenerative and metabolic diseases

PubMed Central

Nguyen, Andrew D.; Nguyen, Thi A.; Martens, Lauren Herl; Mitic, Laura L.; Farese, Robert V.

2013-01-01

Progranulin is a widely expressed, cysteine-rich, secreted glycoprotein originally discovered for its growth factor–like properties. Its subsequent identification as a causative gene for frontotemporal dementia (FTD), a devastating early-onset neurodegenerative disease, has catalyzed a surge of new discoveries about progranulin’s function in the brain. More recently, progranulin was recognized as an adipokine involved in diet-induced obesity and insulin resistance, revealing its metabolic function. Here, we review progranulin biology in both neurodegenerative and metabolic diseases. In particular, we highlight progranulin’s growth factor–like, trophic, and anti-inflammatory properties as potential unifying themes in these seemingly divergent conditions. We also discuss potential therapeutic options for raising progranulin levels to treat progranulin-deficient FTD, as well as the possible consequences of such treatment. PMID:24035620

Worry spreads: interpersonal transfer of problem-related anxiety.

PubMed

Parkinson, Brian; Simons, Gwenda

2012-01-01

This paper distinguishes processes potentially contributing to interpersonal anxiety transfer, including object-directed social appraisal, empathic worry, and anxiety contagion, and reviews evidence for their operation. We argue that these anxiety-transfer processes may be exploited strategically when attempting to regulate relationship partners' emotion. More generally, anxiety may serve as either a warning signal to other people about threat (alerting function) or an appeal for emotional support or practical help (comfort-seeking function). Tensions between these two interpersonal functions may account for mutually incongruent interpersonal responses to expressed anxiety, including mistargeted interpersonal regulation attempts. Because worry waxes and wanes over time as a function of other people's ongoing reactions, interpersonal interventions may help to alleviate some of its maladaptive consequences.

Non-invasive Brain Stimulation: Probing Intracortical Circuits and Improving Cognition in the Aging Brain

PubMed Central

Gomes-Osman, Joyce; Indahlastari, Aprinda; Fried, Peter J.; Cabral, Danylo L. F.; Rice, Jordyn; Nissim, Nicole R.; Aksu, Serkan; McLaren, Molly E.; Woods, Adam J.

2018-01-01

The impact of cognitive aging on brain function and structure is complex, and the relationship between aging-related structural changes and cognitive function are not fully understood. Physiological and pathological changes to the aging brain are highly variable, making it difficult to estimate a cognitive trajectory with which to monitor the conversion to cognitive decline. Beyond the information on the structural and functional consequences of cognitive aging gained from brain imaging and neuropsychological studies, non-invasive brain stimulation techniques such as transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) can enable stimulation of the human brain in vivo, offering useful insights into the functional integrity of intracortical circuits using electrophysiology and neuromodulation. TMS measurements can be used to identify and monitor changes in cortical reactivity, the integrity of inhibitory and excitatory intracortical circuits, the mechanisms of long-term potentiation (LTP)/depression-like plasticity and central cholinergic function. Repetitive TMS and tDCS can be used to modulate neuronal excitability and enhance cortical function, and thus offer a potential means to slow or reverse cognitive decline. This review will summarize and critically appraise relevant literature regarding the use of TMS and tDCS to probe cortical areas affected by the aging brain, and as potential therapeutic tools to improve cognitive function in the aging population. Challenges arising from intra-individual differences, limited reproducibility, and methodological differences will be discussed.

Untargeted metabolomics unravels functionalities of phosphorylation sites in Saccharomyces cerevisiae.

PubMed

Raguz Nakic, Zrinka; Seisenbacher, Gerhard; Posas, Francesc; Sauer, Uwe

2016-11-15

Coordinated through a complex network of kinases and phosphatases, protein phosphorylation regulates essentially all cellular processes in eukaryotes. Recent advances in proteomics enable detection of thousands of phosphorylation sites (phosphosites) in single experiments. However, functionality of the vast majority of these sites remains unclear and we lack suitable approaches to evaluate functional relevance at a pace that matches their detection. Here, we assess functionality of 26 phosphosites by introducing phosphodeletion and phosphomimic mutations in 25 metabolic enzymes and regulators from the TOR and HOG signaling pathway in Saccharomyces cerevisiae by phenotypic analysis and untargeted metabolomics. We show that metabolomics largely outperforms growth analysis and recovers 10 out of the 13 previously characterized phosphosites and suggests functionality for several novel sites, including S79 on the TOR regulatory protein Tip41. We analyze metabolic profiles to identify consequences underlying regulatory phosphorylation events and detecting glycerol metabolism to have a so far unknown influence on arginine metabolism via phosphoregulation of the glycerol dehydrogenases. Further, we also find S508 in the MAPKK Pbs2 as a potential link for cross-talking between HOG signaling and the cell wall integrity pathway. We demonstrate that metabolic profiles can be exploited for gaining insight into regulatory consequences and biological roles of phosphosites. Altogether, untargeted metabolomics is a fast, sensitive and informative approach appropriate for future large-scale functional analyses of phosphosites.

Covalent bonds are created by the drive of electron waves to lower their kinetic energy through expansion

PubMed Central

Schmidt, Michael W.; Ivanic, Joseph; Ruedenberg, Klaus

2014-01-01

An analysis based on the variation principle shows that in the molecules H2+, H2, B2, C2, N2, O2, F2, covalent bonding is driven by the attenuation of the kinetic energy that results from the delocalization of the electronic wave function. For molecular geometries around the equilibrium distance, two features of the wave function contribute to this delocalization: (i) Superposition of atomic orbitals extends the electronic wave function from one atom to two or more atoms; (ii) intra-atomic contraction of the atomic orbitals further increases the inter-atomic delocalization. The inter-atomic kinetic energy lowering that (perhaps counter-intuitively) is a consequence of the intra-atomic contractions drives these contractions (which per se would increase the energy). Since the contractions necessarily encompass both, the intra-atomic kinetic and potential energy changes (which add to a positive total), the fact that the intra-atomic potential energy change renders the total potential binding energy negative does not alter the fact that it is the kinetic delocalization energy that drives the bond formation. PMID:24880263

Covalent bonds are created by the drive of electron waves to lower their kinetic energy through expansion.

PubMed

Schmidt, Michael W; Ivanic, Joseph; Ruedenberg, Klaus

2014-05-28

An analysis based on the variation principle shows that in the molecules H2 (+), H2, B2, C2, N2, O2, F2, covalent bonding is driven by the attenuation of the kinetic energy that results from the delocalization of the electronic wave function. For molecular geometries around the equilibrium distance, two features of the wave function contribute to this delocalization: (i) Superposition of atomic orbitals extends the electronic wave function from one atom to two or more atoms; (ii) intra-atomic contraction of the atomic orbitals further increases the inter-atomic delocalization. The inter-atomic kinetic energy lowering that (perhaps counter-intuitively) is a consequence of the intra-atomic contractions drives these contractions (which per se would increase the energy). Since the contractions necessarily encompass both, the intra-atomic kinetic and potential energy changes (which add to a positive total), the fact that the intra-atomic potential energy change renders the total potential binding energy negative does not alter the fact that it is the kinetic delocalization energy that drives the bond formation.

Reclaiming caring in nursing leadership: a deconstruction of leadership using a Habermasian lens.

PubMed

Stewart, Lee; Holmes, Colin; Usher, Kim

2012-01-01

Nursing leaders function in an environment of increasing demands coupled with decreasing resources. This paper explores the landscape of nursing leadership from a critical theory perspective, particularly Habermas's theory of communicative action. We not only deconstruct contemporary nursing leadership, discussing the potential negative consequences for those who fulfil roles of both 'nurse' and 'leader', but also offer possibilities for a more positive future.

N cycling in SPRUCE (Spruce Peatlands Response Under ...

EPA Pesticide Factsheets

Peatlands located in boreal regions make up a third of global wetland area and are expected to have the highest temperature increases in response to climate change. As climate warms, we expect peat decomposition may accelerate, altering the cycling of nitrogen. Alterations in the nitrogen cycle can have consequences on NO3, NH4 availability or pollution, and potentially increase nitrous oxide (N2O) emissions, a persistent greenhouse gas (GHG). These consequences can cascade to altering whole ecosystem functions and effecting human health.We are investigating nitrogen cycling response to elevated temperature and CO2 in a boreal peatland. Spruce and Peatland Responses Under Climate and Environmental Change (SPRUCE) project initiated soil warming in 2014 in ten peatland mesocosms (five temperature treatments from ambient (+0°C) to +9°C) and elevated CO2 in half of the mesocosms in 2016. Peat cores at three depths (acrotelm, catotelm, deep peat) were analyzed in the laboratory for denitrification, nitrification, and ammonification. We expect denitrification, nitrification, and ammonification rates to increase, and denitrification efficiency to decrease with rising temperatures- potentially contaminating water resources with NO3, NH4 and increase N2O concentrations in our atmosphere. This research will enhance the scientific understanding of how nitrogen cycling, an important functional eco-service, responds under environmental conditions including elevated CO2

High Functioning Autism Spectrum Disorders in Adults: Consequences for Primary Caregivers Compared to Schizophrenia and Depression

ERIC Educational Resources Information Center

Grootscholten, Inge A. C.; van Wijngaarden, Bob; Kan, Cornelis C.

2018-01-01

Primary caregivers experience consequences from being in close contact to a person with autism spectrum disorder (ASD). This study used the Involvement Evaluation Questionnaire to explore the level of consequences of 104 caregivers involved with adults with High Functioning ASD (HF-ASD) and compared these with the consequences reported by…

Timely Diagnosis for Alzheimer's Disease: A Literature Review on Benefits and Challenges.

PubMed

Dubois, Bruno; Padovani, Alessandro; Scheltens, Philip; Rossi, Andrea; Dell'Agnello, Grazia

2016-01-01

Timely diagnosis of Alzheimer's disease (AD) refers to a diagnosis at the stage when patients come to the attention of clinicians because of concerns about changes in cognition, behavior, or functioning and can be still free of dementia and functionally independent. To comprehensively review existing scientific evidence on the benefits and potential challenges of making a timely diagnosis of AD. Relevant studies were identified by searching electronic databases (Medline, Embase) and bibliographies for studies published in English between 1 January 2000 and 2 June 2014 on the consequences of a timely diagnosis of AD. Nine studies were identified that investigated the consequences of diagnosing AD at the initial stages; none were specifically focused on prodromal AD. A timely diagnosis potentially offers the opportunities of early intervention, implementation of coordinated care plans, better management of symptoms, patient safety, cost savings, and postponement of institutionalization. Barriers to making a timely diagnosis include stigma, suicide risk, lack of training, diagnostic uncertainty, shortage of specialized diagnostic services, and the reluctance of healthcare providers to make a diagnosis when no effective disease-modifying options are available. Despite its potential benefits, few published studies have explored the advantages or risks of a timely diagnosis of AD. In light of the cultural shift toward diagnosis at the initial stage of the disease continuum, when the patient does not yet have dementia, more investigations are needed to evaluate the benefits and address the barriers that may impede making a timely AD diagnosis.

Computer simulation of ledge formation and ledge interaction for the silicon (111) free surface

NASA Technical Reports Server (NTRS)

Balamane, H.; Halicioglu, T.; Tiller, W. A.

1987-01-01

Both strip and triangular clusters, composed of 2 -1 -1 line ledges, have been simulated on the Si (111) surface. The long-range ledge-ledge interaction and the surface stress tensor distribution have been evaluated for these two pill-box geometries using a semiempirical potential-energy function that incorporates both two-body and three-body contributions. The consequences of the ledge-ledge interaction on two-dimensional nucleation for Si (111) has been evaluated as a function of Si adatom supersaturation and shown to differ significantly from conventional theory, where such interaction is neglected.

Toward an operant model of power in organizations

PubMed Central

Goltz, Sonia M.

2003-01-01

The purpose of this paper is to suggest that behavior analysis can help to explain social power. In this approach, an individual's potential for influence is thought to be partially a function of his or her access to stimuli that can be used as consequences. This access can occur either through direct authority or indirectly through social networks and exchanges. Social power is also thought to be a function of an individual's skill in delivering the stimuli in ways that will have the most impact on behavior. A number of predictions about power based on an operant approach are offered. PMID:22478398

Current state of cartilage tissue engineering

PubMed Central

Tuli, Richard; Li, Wan-Ju; Tuan, Rocky S

2003-01-01

Damage to cartilage is of great clinical consequence given the tissue's limited intrinsic potential for healing. Current treatments for cartilage repair are less than satisfactory, and rarely restore full function or return the tissue to its native normal state. The rapidly emerging field of tissue engineering holds great promise for the generation of functional cartilage tissue substitutes. The general approach involves a biocompatible, structurally and mechanically sound scaffold, with an appropriate cell source, which is loaded with bioactive molecules that promote cellular differentiation and/or maturation. This review highlights aspects of current progress in cartilage tissue engineering. PMID:12932283

Neuroethics vs neurophysiologically and neuropsychologically uninformed influences in child-rearing, education, emerging hunter-gatherers, and artificial intelligence models of the brain.

PubMed

Pontius, A A

1993-04-01

Potentially negative long-term consequences in four areas are emphasized, if specific neuromaturational, neurophysiological, and neuropsychological facts within a neurodevelopmental and ecological context are neglected in normal functional levels of child development and maturational lag of the frontal lobe system in "Attention Deficit Disorder," in education (reading/writing and arithmetic), in assessment of cognitive functioning in hunter-gatherer populations, specifically modified in the service of their survival, and in constructing computer models of the brain, neglecting consciousness and intentionality as criticized recently by Searle.

Chronic early life stress induced by limited bedding and nesting (LBN) material in rodents: critical considerations of methodology, outcomes and translational potential.

PubMed

Walker, Claire-Dominique; Bath, Kevin G; Joels, Marian; Korosi, Aniko; Larauche, Muriel; Lucassen, Paul J; Morris, Margaret J; Raineki, Charlis; Roth, Tania L; Sullivan, Regina M; Taché, Yvette; Baram, Tallie Z

2017-09-01

The immediate and long-term effects of exposure to early life stress (ELS) have been documented in humans and animal models. Even relatively brief periods of stress during the first 10 days of life in rodents can impact later behavioral regulation and the vulnerability to develop adult pathologies, in particular an impairment of cognitive functions and neurogenesis, but also modified social, emotional, and conditioned fear responses. The development of preclinical models of ELS exposure allows the examination of mechanisms and testing of therapeutic approaches that are not possible in humans. Here, we describe limited bedding and nesting (LBN) procedures, with models that produce altered maternal behavior ranging from fragmentation of care to maltreatment of infants. The purpose of this paper is to discuss important issues related to the implementation of this chronic ELS procedure and to describe some of the most prominent endpoints and consequences, focusing on areas of convergence between laboratories. Effects on the hypothalamic-pituitary adrenal (HPA) axis, gut axis and metabolism are presented in addition to changes in cognitive and emotional functions. Interestingly, recent data have suggested a strong sex difference in some of the reported consequences of the LBN paradigm, with females being more resilient in general than males. As both the chronic and intermittent variants of the LBN procedure have profound consequences on the offspring with minimal external intervention from the investigator, this model is advantageous ecologically and has a large translational potential. In addition to the direct effect of ELS on neurodevelopmental outcomes, exposure to adverse early environments can also have intergenerational impacts on mental health and function in subsequent generation offspring. Thus, advancing our understanding of the effect of ELS on brain and behavioral development is of critical concern for the health and wellbeing of both the current population, and for generations to come.

Multiple molecular effect pathways of an environmental oestrogen in fish.

PubMed

Filby, Amy L; Thorpe, Karen L; Tyler, Charles R

2006-08-01

Complex interrelationships in the signalling of oestrogenic effects mean that environmental oestrogens present in the aquatic environment have the potential to disrupt physiological function in fish in a more complex manner than portrayed in the present literature. Taking a broader approach to investigate the possible effect pathways and the likely consequences of environmental oestrogen exposure in fish, the effects of 17beta-oestradiol (E(2)) were studied on the expression of a suite of genes which interact to mediate growth, development and thyroid and interrenal function (growth hormone GH (gh), GH receptor (ghr ), insulin-like growth factor (IGF-I) (igf1), IGF-I receptor (igf1r ), thyroid hormone receptors-alpha (thra) and -beta (thrb) and glucocorticoid receptor (gr )) together with the expression analyses of sex-steroid receptors and ten other genes centrally involved in sexual development and reproduction in fathead minnow (fhm; Pimephales promelas). Exposure of adult fhm to 35 ng E(2)/l for 14 days induced classic oestrogen biomarker responses (hepatic oestrogen receptor 1 and plasma vitellogenin), and impacted on the reproductive axis, feminising "male" steroidogenic enzyme expression profiles and suppressing genes involved in testis differentiation. However, E(2) also triggered a cascade of responses for gh, ghr, igf1, igf1r, thra, thrb and gr in the pituitary, brain, liver, gonad and gill, with potential consequences for the functioning of many physiological processes, not just reproduction. Molecular responses to E(2) were complex, with most genes showing differential responses between tissues and sexes. For example, igf1 expression increased in brain but decreased in gill on exposure to E(2), and responded in an opposite way in males compared with females in liver, gonad and pituitary. These findings demonstrate the importance of developing a deeper understanding of the endocrine interactions for unravelling the mechanisms of environmental oestrogen action and predicting the likely health consequences.

Unacknowledged Rape: The Influences of Child Sexual Abuse and Personality Traits.

PubMed

Wilson, Laura C; Scarpa, Angela

2015-01-01

Evidence supports that the majority of young women who experience sexual victimization that meets the legal definition of rape do not label their experiences as rape--this has been termed unacknowledged rape. In a sample of 77 young adult women, the odds of unacknowledged rape significantly increased as a function of less severe child sexual abuse histories and greater levels of dysfunctional personality traits. Potential explanations for these findings as well as clinical implications are discussed. Because of the potential psychological and societal consequences of unacknowledged rape, it is vital that researchers continue to examine this phenomenon.

Potential consequences of clinical application of artificial gametes: a systematic review of stakeholder views.

PubMed

Hendriks, Saskia; Dondorp, Wybo; de Wert, Guido; Hamer, Geert; Repping, Sjoerd; Dancet, Eline A F

2015-01-01

Recent progress in the formation of artificial gametes, i.e. gametes generated from progenitors or somatic cells, has led to scientific and societal discussion about their use in medically assisted reproduction. In animals, live births have already been achieved using artificial gametes of varying (cell type) sources and biological research seems to be progressing steadily toward clinical application in humans. Artificial gametes could potentially help not only infertile heterosexual couples of reproductive age of which one or both partners lacks functional gametes, but also post-menopausal women and same-sex couples, to conceive a child who will be genetically related to them. But as clinical application of these new technologies may have wider societal consequences, a proactive consideration of the possible impact seems timely and important. This review aims to contribute to this by providing a systematic overview of the potential consequences of clinical application of artificial gametes anticipated by different stakeholders. The electronic database 'Medline/Pubmed' was systematically searched with medical subject heading terms (MesH) for articles published in English between January 1970 and December 2013. Articles were selected based on eligibility and reference lists of eligible studies were hand searched. The reported potential consequences of clinical application of artificial gametes were extracted from the articles and were grouped into categories by content analysis. Per category, we noted which stakeholders referred to which potential consequences, based on author affiliations and, if applicable, study participants. The systematic search yielded 2424 articles, and 84 studies were included after screening. Nine positive consequences, 21 specific consequences requiring consideration and 22 recommendations referring to clinical application of artificial gametes were documented. All positive consequences, consequences requiring consideration and recommendations could be categorized under the following eight objectives to be safeguarded during clinical application of artificial gametes: (i) timing the implementation of new treatments correctly, (ii) meeting 'plausible demands of patients', (iii) improving and safeguarding public health, (iv) promoting the progress of medical science in the interest of future patients, (v) providing treatments that are morally acceptable for the general public, (vi) controlling medical practice, (vii) offering treatments that allow acquisition of informed consent and (viii) funding treatments fairly. Professionals specialized in biomedical science, science journalists and professionals specialized in ethics all addressed these eight objectives on artificial gametes, whereas professionals specialized in law or political science addressed seven objectives. Although one study reported on the perspective of parents of under-aged patients on three objectives, the perspectives of patients themselves were not reported by the reviewed literature. Of course, clinical introduction of artificial gametes should only be considered on the basis of reassuring outcomes of appropriate preclinical effectiveness and safety studies. In addition, potential users' views on the desirability and acceptability of artificial gametes should be studied before clinical introduction. A societal debate including all stakeholders is needed to determine the relative importance of all arguments in favor of and against the introduction of artificial gametes into clinical practice. More broadly, establishing pre-implementation processes for new medical techniques is relevant for all fields of medicine. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The Consequences of the Consequences

PubMed Central

Carragher, Marcella; Foster, Abby

2017-01-01

Understanding the impact of the environment on the participation of people with aphasia depends on one's perspective. A long-term perspective provides a unique insight into the myriad of ways in which the environment can influence the participation of people living with aphasia over decades. In this article, the authors present the real-life story of “Hank,” who has lived with aphasia for more than 15 years. The authors consider how 2 different conceptual frameworks—the International Classification of Functioning, Disability and Health and the Social Determinants of Health—account for Hank's experience. The International Classification of Functioning, Disability and Health is useful to conceptualize the range of factors that influence living with aphasia at a particular point in time. In contrast, the Social Determinants of Health is useful to conceptualize the cumulative impact of living with aphasia on long-term health and well-being. Viewing aphasia as a social condition that impacts social determinants of health has potentially wide ranging implications for service design and delivery and the role of speech–language pathologists. PMID:28232769

Functional effects of CCL3L1 copy number

PubMed Central

Carpenter, Danielle; McIntosh, Richard S; Pleass, Richard J; Armour, John AL

2012-01-01

Copy number variation (CNV) is becoming increasingly important as a feature of human variation in disease susceptibility studies. However, the consequences of copy number variation are not so well understood. Here we present data exploring the functional consequences of copy number variation of CCL3L1 in 55 independent UK samples with no known clinical phenotypes. Copy number of CCL3L1 was determined by the paralogue ratio test (PRT), and expression levels of MIP-1α and mRNA from stimulated monocytes were measured and analysed. The data show no statistically significant association of MIP-1α protein levels with copy number. However, there was a significant correlation between copy number and CCL3L1:CCL3 mRNA ratio. The data also provide evidence that expression of CCL3 predominates in both protein and mRNA, and therefore the observed variation of CCL3 is potentially more important biologically than that of copy number variation of CCL3L1. PMID:22476153

Functional effects of CCL3L1 copy number.

PubMed

Carpenter, D; McIntosh, R S; Pleass, R J; Armour, J A L

2012-07-01

Copy number variation (CNV) is becoming increasingly important as a feature of human variation in disease susceptibility studies. However, the consequences of CNV are not so well understood. Here, we present data exploring the functional consequences of CNV of CCL3L1 in 55 independent UK samples with no known clinical phenotypes. The copy number of CCL3L1 was determined by the paralogue ratio test, and expression levels of macrophage inflammatory protein-1α (MIP-1α) and mRNA from stimulated monocytes were measured and analysed. The data show no statistically significant association of MIP-1α protein levels with copy number. However, there was a significant correlation between copy number and CCL3L1:CCL3 mRNA ratio. The data also provide evidence that expression of CCL3 predominates in both protein and mRNA, and therefore the observed variation of CCL3 is potentially more important biologically than that of CNV of CCL3L1.

Heparan Sulfates Support Pyramidal Cell Excitability, Synaptic Plasticity, and Context Discrimination

PubMed Central

Minge, Daniel; Senkov, Oleg; Kaushik, Rahul; Herde, Michel K.; Tikhobrazova, Olga; Wulff, Andreas B.; Mironov, Andrey; van Kuppevelt, Toin H.; Oosterhof, Arie; Kochlamazashvili, Gaga

2017-01-01

Abstract Heparan sulfate (HS) proteoglycans represent a major component of the extracellular matrix and are critical for brain development. However, their function in the mature brain remains to be characterized. Here, acute enzymatic digestion of HS side chains was used to uncover how HSs support hippocampal function in vitro and in vivo. We found that long-term potentiation (LTP) of synaptic transmission at CA3–CA1 Schaffer collateral synapses was impaired after removal of highly sulfated HSs with heparinase 1. This reduction was associated with decreased Ca2+ influx during LTP induction, which was the consequence of a reduced excitability of CA1 pyramidal neurons. At the subcellular level, heparinase treatment resulted in reorganization of the distal axon initial segment, as detected by a reduction in ankyrin G expression. In vivo, digestion of HSs impaired context discrimination in a fear conditioning paradigm and oscillatory network activity in the low theta band after fear conditioning. Thus, HSs maintain neuronal excitability and, as a consequence, support synaptic plasticity and learning. PMID:28119345

The consequences of fetal growth restriction on brain structure and neurodevelopmental outcome.

PubMed

Miller, Suzanne L; Huppi, Petra S; Mallard, Carina

2016-02-15

Fetal growth restriction (FGR) is a significant complication of pregnancy describing a fetus that does not grow to full potential due to pathological compromise. FGR affects 3-9% of pregnancies in high-income countries, and is a leading cause of perinatal mortality and morbidity. Placental insufficiency is the principal cause of FGR, resulting in chronic fetal hypoxia. This hypoxia induces a fetal adaptive response of cardiac output redistribution to favour vital organs, including the brain, and is in consequence called brain sparing. Despite this, it is now apparent that brain sparing does not ensure normal brain development in growth-restricted fetuses. In this review we have brought together available evidence from human and experimental animal studies to describe the complex changes in brain structure and function that occur as a consequence of FGR. In both humans and animals, neurodevelopmental outcomes are influenced by the timing of the onset of FGR, the severity of FGR, and gestational age at delivery. FGR is broadly associated with reduced total brain volume and altered cortical volume and structure, decreased total number of cells and myelination deficits. Brain connectivity is also impaired, evidenced by neuronal migration deficits, reduced dendritic processes, and less efficient networks with decreased long-range connections. Subsequent to these structural alterations, short- and long-term functional consequences have been described in school children who had FGR, most commonly including problems in motor skills, cognition, memory and neuropsychological dysfunctions. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

The injury List of All Deficits (LOAD) Framework--conceptualizing the full range of deficits and adverse outcomes following injury and violence.

PubMed

Lyons, Ronan A; Finch, Caroline F; McClure, Rod; van Beeck, Ed; Macey, Steven

2010-09-01

Over recent years, there has been increasing recognition that the burden of injuries and violence includes more than just the direct and indirect monetary costs associated with their medical outcomes. However, quantification of the total burden has been seriously hampered by lack of a framework for considering the range of outcomes which comprise the burden, poor identification of the outcomes and their imprecise measurement. This article proposes a new conceptual framework, the List of All Deficits (or LOAD) Framework, that has been developed from extensive expert discussion and consensus meetings to facilitate the measurement of the full burden of injuries and violence. The LOAD Framework recognises the multidimensional nature of injury burden across individual, family and societal domains. This classification of potential consequences of injury was built on the International Classification of Functioning concept of disability. Examples of empirical support for each consequence were obtained from the scientific literature. Determining the multidimensional injury burden requires the assessment and combination of 20 domains of potential consequences. The resulting LOAD Framework classification and concept diagram describes 12 groups of injury consequences for individuals, three for family and close friends and five for wider society. Understanding the extent of the negative implications (or deficits) of injury, through application of the LOAD Framework, is needed to put existing burden of injury studies into context and to highlight the inter-relationship between the direct and indirect burden of injury relative to other conditions.

The consequences of Campylobacter infection.

PubMed

O'Brien, Sarah J

2017-01-01

The purpose of this review is to provide an update on the clinical, public health and economic consequences of Campylobacter infection. Campylobacter is a leading bacterial cause of food-related illness. Its importance is enhanced by the chronic sequelae that can result from acute infection. Recent advances include a new clinical classification system for neurological sequelae with the aim of speeding accurate diagnosis and appropriate treatment, a better understanding of the mechanisms underlying postinfectious functional gastrointestinal disorders, the emergence of Campylobacter concisus and Campylobacter showae as potential aetiological agents in inflammatory bowel disease, a new mechanism for antimicrobial resistance in campylobacters and a better appreciation of the economic costs. Campylobacter infection is very common and can lead to serious chronic sequelae and considerable personal, healthcare and societal costs.

Unrealized potential and residual consequences of electronic prescribing on pharmacy workflow in the outpatient pharmacy.

PubMed

Nanji, Karen C; Rothschild, Jeffrey M; Boehne, Jennifer J; Keohane, Carol A; Ash, Joan S; Poon, Eric G

2014-01-01

Electronic prescribing systems have often been promoted as a tool for reducing medication errors and adverse drug events. Recent evidence has revealed that adoption of electronic prescribing systems can lead to unintended consequences such as the introduction of new errors. The purpose of this study is to identify and characterize the unrealized potential and residual consequences of electronic prescribing on pharmacy workflow in an outpatient pharmacy. A multidisciplinary team conducted direct observations of workflow in an independent pharmacy and semi-structured interviews with pharmacy staff members about their perceptions of the unrealized potential and residual consequences of electronic prescribing systems. We used qualitative methods to iteratively analyze text data using a grounded theory approach, and derive a list of major themes and subthemes related to the unrealized potential and residual consequences of electronic prescribing. We identified the following five themes: Communication, workflow disruption, cost, technology, and opportunity for new errors. These contained 26 unique subthemes representing different facets of our observations and the pharmacy staff's perceptions of the unrealized potential and residual consequences of electronic prescribing. We offer targeted solutions to improve electronic prescribing systems by addressing the unrealized potential and residual consequences that we identified. These recommendations may be applied not only to improve staff perceptions of electronic prescribing systems but also to improve the design and/or selection of these systems in order to optimize communication and workflow within pharmacies while minimizing both cost and the potential for the introduction of new errors.

Structure-based conformational preferences of amino acids

PubMed Central

Koehl, Patrice; Levitt, Michael

1999-01-01

Proteins can be very tolerant to amino acid substitution, even within their core. Understanding the factors responsible for this behavior is of critical importance for protein engineering and design. Mutations in proteins have been quantified in terms of the changes in stability they induce. For example, guest residues in specific secondary structures have been used as probes of conformational preferences of amino acids, yielding propensity scales. Predicting these amino acid propensities would be a good test of any new potential energy functions used to mimic protein stability. We have recently developed a protein design procedure that optimizes whole sequences for a given target conformation based on the knowledge of the template backbone and on a semiempirical potential energy function. This energy function is purely physical, including steric interactions based on a Lennard-Jones potential, electrostatics based on a Coulomb potential, and hydrophobicity in the form of an environment free energy based on accessible surface area and interatomic contact areas. Sequences designed by this procedure for 10 different proteins were analyzed to extract conformational preferences for amino acids. The resulting structure-based propensity scales show significant agreements with experimental propensity scale values, both for α-helices and β-sheets. These results indicate that amino acid conformational preferences are a natural consequence of the potential energy we use. This confirms the accuracy of our potential and indicates that such preferences should not be added as a design criterion. PMID:10535955

An animal model of functional electrical stimulation: evidence that the central nervous system modulates the consequences of training

PubMed Central

Hook, MA; Grau, JW

2011-01-01

Study Design Review of how spinal neurons can modulate the consequences of functional electrical stimulation (FES) in an animal model. Methods Spinal effects of FES are examined in male Sprague–Dawley rats transected at the second thoracic vertebra. The rats are exposed to FES training 24–48 h after surgery. Experimental manipulations of stimulation parameters, combined with physiological and pharmacological procedures, are used to examine the potential role of spinal neurons. Results The isolated spinal cord is inherently capable of learning the response–outcome relations imposed in FES training contingencies. Adaptive behavioral modifications are observed when an outcome (electrical stimulation) is contingent on a behavioral response. In contrast, a lack of correlation between the response and outcome in training produces a learning deficit in the spinal cord, rendering it incapable of adaptive learning for up to 48 h. The N-methyl-D-aspartic acid receptor appears to mediate both the adaptive plasticity and loss of plasticity, seen in this spinal model. Conclusion The behavioral effects observed with FES therapies are not simply due to the direct (motor) consequences of stimulation elicited by the activation of efferent motor neurons and/or selected muscles. FES training has the capacity to shape inherent spinal circuits and to produce a long-lasting behavioral modification. Further understanding of the spinal mechanisms underlying adaptive behavioral modification will be integral for establishing functional neural connections in a regenerating spinal system. PMID:17700514

Social media use of older adults: a mini-review.

PubMed

Leist, Anja K

2013-01-01

Maintaining social relationships has been defined as a core element of aging well. With a considerable amount of older adults living alone, social media provides the possibility to engage in meaningful social contact, e.g. by joining online social networks and online discussion forums. The review encompasses current knowledge of prerequisites in social media use of older adults such as functional capacity, information and communications technology-related knowledge, and favorable attitudes towards social media. Then, the potential of social media use for clinical practice and possible negative consequences are outlined. Literature on social media use from a gerontological perspective was reviewed in July and August 2012. Online communities are suitable for providing and receiving social support when confronted with a difficult life situation, regardless of geographical location or time. From a practitioner's perspective, social media can be used to advance health-related knowledge such as information on prevention, diagnosis, and treatment of specific conditions and disorders. Further positive consequences have been shown to be overcoming loneliness, relieving stress, and raising feelings of control and self-efficacy. Possible negative consequences could be misuse of personal data as well as the distribution and uncritical adoption of potentially harmful information via online communities. The potential of social media in clinical practice is reflected in a wide range of intervention possibilities for older adults. However, with the rise of social media, new threats emerge for older adults as well. Copyright © 2013 S. Karger AG, Basel.

Sexual Assertiveness Mediates the Associations Between Partner Facilitative Responses and Sexual Outcomes in Women With Provoked Vestibulodynia.

PubMed

McNicoll, Gabrielle; Corsini-Munt, Serena; O Rosen, Natalie; McDuff, Pierre; Bergeron, Sophie

2017-10-03

Provoked vestibulodynia (PVD) is a recurrent idiopathic vulvo-vaginal pain associated with negative sexual and psychological consequences. Facilitative partner responses to pain are currently receiving empirical attention because they are positively associated with women's sexual outcomes. However, the mechanisms through which facilitative responses to pain are associated with these outcomes have not been examined. One potential mechanism is sexual assertiveness, which has been found to be associated with better sexual function and satisfaction in women with PVD. The present study examined whether women's sexual assertiveness mediated the association between women's perception of facilitative partner responses and women's sexual function and satisfaction. Women (N = 140) with PVD symptomatology completed self-reported questionnaires evaluating their perception of their partners' facilitative responses, and their own sexual assertiveness, sexual function, and sexual satisfaction. Dependent measures were sexual function measured by the Female Sexual Function Index and sexual satisfaction assessed by the Global Measure of Sexual Satisfaction Scale. Results indicated that women's higher sexual assertiveness mediated the association between their greater perceived facilitative partner responses and their improved sexual function and satisfaction. Findings suggest a potential mechanism through which partner responses may be associated with women's sexual outcomes.

Gaps in clinical prevention and treatment for alcohol use disorders: costs, consequences, and strategies.

PubMed

Willenbring, Mark L

2013-01-01

Heavy drinking causes significant morbidity, premature mortality, and other social and economic burdens on society, prompting numerous prevention and treatment efforts to avoid or ameliorate the prevalence of heavy drinking and its consequences. However, the impact on public health of current selective (i.e., clinical) prevention and treatment strategies is unclear. Screening and brief counseling for at-risk drinkers in ambulatory primary care has the strongest evidence for efficacy, and some evidence indicates this approach is cost-effective and reduces excess morbidity and dysfunction. Widespread implementation of screening and brief counseling of nondependent heavy drinkers outside of the medical context has the potential to have a large public health impact. For people with functional dependence, no appropriate treatment and prevention approaches currently exist, although such strategies might be able to prevent or reduce the morbidity and other harmful consequences associated with the condition before its eventual natural resolution. For people with alcohol use disorders, particularly severe and recurrent dependence, treatment studies have shown improvement in the short term. However, there is no compelling evidence that treatment of alcohol use disorders has resulted in reductions in overall disease burden. More research is needed on ways to address functional alcohol dependence as well as severe and recurrent alcohol dependence.

A methodology for assessing deployment trauma and its consequences in OEF/OIF/OND veterans: The TRACTS longitudinal prospective cohort study

PubMed Central

McGlinchey, Regina E.; Milberg, William P.; Fonda, Jennifer R.; Fortier, Catherine Brawn

2017-01-01

Many US veterans of Afghanistan and Iraq have multiple physical and psychiatric problems. A major focus of research has been on determining the effects of mild Traumatic Brain Injury (mTBI), but mTBI is rarely diagnosed in the absence of co-occurring conditions such as blast exposure, post-traumatic stress disorder (PTSD), depression, substance abuse, etc. These potentially interactive psychological and physical conditions produce complex patterns of cognitive, psychological, and physical symptoms that impede civilian reintegration and complicate efficient and effective treatment planning. The Translational Research Center for TBI and Stress Disorders (TRACTS) has developed a multidisciplinary approach to the assessment of deployment trauma and its consequences in veterans of these wars. The prospective TRACTS longitudinal cohort study conducts state-of-the-art assessments in the domains of biomedical function, lifetime head trauma, psychological function encompassing deployment experience and lifetime exposure to traumatic events, neuropsychological function, and structural and functional neuroimaging. The TRACTS longitudinal cohort study is the first of its kind to comprehensively evaluate lifetime incidence of TBI and PTSD in these veterans, in addition to those incurred during military deployment. The protocol has begun to reveal information that will help improve understanding of the complex pathophysiology associated with co-occurring mTBI and related stress disorders. PMID:28211592

Quantum mechanics on phase space and the Coulomb potential

NASA Astrophysics Data System (ADS)

Campos, P.; Martins, M. G. R.; Vianna, J. D. M.

2017-04-01

Symplectic quantum mechanics (SMQ) makes possible to derive the Wigner function without the use of the Liouville-von Neumann equation. In this formulation of the quantum theory the Galilei Lie algebra is constructed using the Weyl (or star) product with Q ˆ = q ⋆ = q +iħ/2∂p , P ˆ = p ⋆ = p -iħ/2∂q, and the Schrödinger equation is rewritten in phase space; in consequence physical applications involving the Coulomb potential present some specific difficulties. Within this context, in order to treat the Schrödinger equation in phase space, a procedure based on the Levi-Civita (or Bohlin) transformation is presented and applied to two-dimensional (2D) hydrogen atom. Amplitudes of probability in phase space and the correspondent Wigner quasi-distribution functions are derived and discussed.

Analyzing structure-function relationships of artificial and cancer-associated PARP1 variants by reconstituting TALEN-generated HeLa PARP1 knock-out cells.

PubMed

Rank, Lisa; Veith, Sebastian; Gwosch, Eva C; Demgenski, Janine; Ganz, Magdalena; Jongmans, Marjolijn C; Vogel, Christopher; Fischbach, Arthur; Buerger, Stefanie; Fischer, Jan M F; Zubel, Tabea; Stier, Anna; Renner, Christina; Schmalz, Michael; Beneke, Sascha; Groettrup, Marcus; Kuiper, Roland P; Bürkle, Alexander; Ferrando-May, Elisa; Mangerich, Aswin

2016-12-01

Genotoxic stress activates PARP1, resulting in the post-translational modification of proteins with poly(ADP-ribose) (PAR). We genetically deleted PARP1 in one of the most widely used human cell systems, i.e. HeLa cells, via TALEN-mediated gene targeting. After comprehensive characterization of these cells during genotoxic stress, we analyzed structure-function relationships of PARP1 by reconstituting PARP1 KO cells with a series of PARP1 variants. Firstly, we verified that the PARP1\\E988K mutant exhibits mono-ADP-ribosylation activity and we demonstrate that the PARP1\\L713F mutant is constitutively active in cells. Secondly, both mutants exhibit distinct recruitment kinetics to sites of laser-induced DNA damage, which can potentially be attributed to non-covalent PARP1-PAR interaction via several PAR binding motifs. Thirdly, both mutants had distinct functional consequences in cellular patho-physiology, i.e. PARP1\\L713F expression triggered apoptosis, whereas PARP1\\E988K reconstitution caused a DNA-damage-induced G2 arrest. Importantly, both effects could be rescued by PARP inhibitor treatment, indicating distinct cellular consequences of constitutive PARylation and mono(ADP-ribosyl)ation. Finally, we demonstrate that the cancer-associated PARP1 SNP variant (V762A) as well as a newly identified inherited PARP1 mutation (F304L\\V762A) present in a patient with pediatric colorectal carcinoma exhibit altered biochemical and cellular properties, thereby potentially supporting human carcinogenesis. Together, we establish a novel cellular model for PARylation research, by revealing strong structure-function relationships of natural and artificial PARP1 variants. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Analyzing structure–function relationships of artificial and cancer-associated PARP1 variants by reconstituting TALEN-generated HeLa PARP1 knock-out cells

PubMed Central

Rank, Lisa; Veith, Sebastian; Gwosch, Eva C.; Demgenski, Janine; Ganz, Magdalena; Jongmans, Marjolijn C.; Vogel, Christopher; Fischbach, Arthur; Buerger, Stefanie; Fischer, Jan M.F.; Zubel, Tabea; Stier, Anna; Renner, Christina; Schmalz, Michael; Beneke, Sascha; Groettrup, Marcus; Kuiper, Roland P.; Bürkle, Alexander; Ferrando-May, Elisa; Mangerich, Aswin

2016-01-01

Genotoxic stress activates PARP1, resulting in the post-translational modification of proteins with poly(ADP-ribose) (PAR). We genetically deleted PARP1 in one of the most widely used human cell systems, i.e. HeLa cells, via TALEN-mediated gene targeting. After comprehensive characterization of these cells during genotoxic stress, we analyzed structure–function relationships of PARP1 by reconstituting PARP1 KO cells with a series of PARP1 variants. Firstly, we verified that the PARP1\\E988K mutant exhibits mono-ADP-ribosylation activity and we demonstrate that the PARP1\\L713F mutant is constitutively active in cells. Secondly, both mutants exhibit distinct recruitment kinetics to sites of laser-induced DNA damage, which can potentially be attributed to non-covalent PARP1–PAR interaction via several PAR binding motifs. Thirdly, both mutants had distinct functional consequences in cellular patho-physiology, i.e. PARP1\\L713F expression triggered apoptosis, whereas PARP1\\E988K reconstitution caused a DNA-damage-induced G2 arrest. Importantly, both effects could be rescued by PARP inhibitor treatment, indicating distinct cellular consequences of constitutive PARylation and mono(ADP-ribosyl)ation. Finally, we demonstrate that the cancer-associated PARP1 SNP variant (V762A) as well as a newly identified inherited PARP1 mutation (F304L\\V762A) present in a patient with pediatric colorectal carcinoma exhibit altered biochemical and cellular properties, thereby potentially supporting human carcinogenesis. Together, we establish a novel cellular model for PARylation research, by revealing strong structure–function relationships of natural and artificial PARP1 variants. PMID:27694308

Positive and Negative Reinforcement Effects on Behavior in a Three-Person Microsociety.

DTIC Science & Technology

1983-12-01

Per-hour earning potential uas roughly equivalent among the groups. Prdr The consequences of ompletlng a work trip were varied to assess the effects ...31 abandoned his previously established pattern. These effects are attributable, at least In part, to the style of alternating work that the... working under aversive control. These effects suggest that the functional properties of work (C-.h. oonsequences) were far more significant to the group

A Comparison of Descriptive and Functional Analyses of Inappropriate Mealtime Behavior.

PubMed

Borrero, Carrie S W; England, Jennie D; Sarcia, Ben; Woods, Julia N

2016-12-01

In recent years, rather than being used to assess the potential function of a response, descriptive assessment methods have been applied to evaluate potential consequences or contingencies for problem behavior (Borrero, Woods, Borrero, Masler, & Lesser in Journal of Applied Behavior Analysis, 43 , 71-88. doi: 10.1901/jaba.2010.43-71, 2010) or to assist with designing baseline conditions to approximate caregiver behavior (Casey et al. in Behavior Modification, 33 , 537-558. doi: 10.1177/0145445509341457, 2009). It has been shown that descriptive assessments of some forms of problem behavior (e.g., self-injury, aggression) are not good indicators of behavioral function and should not be used exclusively when conducting functional behavior assessments (Thompson & Iwata in Journal of Applied Behavior Analysis, 40 , 333-338. doi: 10.1901/jaba.2007.56.06/epdf, 2007). However, the extent to which descriptive assessments of inappropriate mealtime behavior can predict behavioral function is not yet clear. We conducted descriptive assessments of inappropriate mealtime behavior and compared the results to functional analyses for ten children with severe food refusal. Results showed that, for 71 % of participants, the descriptive and functional analyses matched. These results suggest that the correspondence between descriptive and functional analyses, at least for inappropriate mealtime behavior, may be higher than that for other forms of problem behavior.

Microcalcifications in breast cancer: novel insights into the molecular mechanism and functional consequence of mammary mineralisation

PubMed Central

Cox, R F; Hernandez-Santana, A; Ramdass, S; McMahon, G; Harmey, J H; Morgan, M P

2012-01-01

Background: Mammographic microcalcifications represent one of the most reliable features of nonpalpable breast cancer yet remain largely unexplored and poorly understood. Methods: We report a novel model to investigate the in vitro mineralisation potential of a panel of mammary cell lines. Primary mammary tumours were produced by implanting tumourigenic cells into the mammary fat pads of female BALB/c mice. Results: Hydroxyapatite (HA) was deposited only by the tumourigenic cell lines, indicating mineralisation potential may be associated with cell phenotype in this in vitro model. We propose a mechanism for mammary mineralisation, which suggests that the balance between enhancers and inhibitors of physiological mineralisation are disrupted. Inhibition of alkaline phosphatase and phosphate transport prevented mineralisation, demonstrating that mineralisation is an active cell-mediated process. Hydroxyapatite was found to enhance in vitro tumour cell migration, while calcium oxalate had no effect, highlighting potential consequences of calcium deposition. In addition, HA was also deposited in primary mammary tumours produced by implanting the tumourigenic cells into the mammary fat pads of female BALB/c mice. Conclusion: This work indicates that formation of mammary HA is a cell-specific regulated process, which creates an osteomimetic niche potentially enhancing breast tumour progression. Our findings point to the cells mineralisation potential and the microenvironment regulating it, as a significant feature of breast tumour development. PMID:22233923

Hippocampal 5-HT Input Regulates Memory Formation and Schaffer Collateral Excitation.

PubMed

Teixeira, Catia M; Rosen, Zev B; Suri, Deepika; Sun, Qian; Hersh, Marc; Sargin, Derya; Dincheva, Iva; Morgan, Ashlea A; Spivack, Stephen; Krok, Anne C; Hirschfeld-Stoler, Tessa; Lambe, Evelyn K; Siegelbaum, Steven A; Ansorge, Mark S

2018-06-06

The efficacy and duration of memory storage is regulated by neuromodulatory transmitter actions. While the modulatory transmitter serotonin (5-HT) plays an important role in implicit forms of memory in the invertebrate Aplysia, its function in explicit memory mediated by the mammalian hippocampus is less clear. Specifically, the consequences elicited by the spatio-temporal gradient of endogenous 5-HT release are not known. Here we applied optogenetic techniques in mice to gain insight into this fundamental biological process. We find that activation of serotonergic terminals in the hippocampal CA1 region both potentiates excitatory transmission at CA3-to-CA1 synapses and enhances spatial memory. Conversely, optogenetic silencing of CA1 5-HT terminals inhibits spatial memory. We furthermore find that synaptic potentiation is mediated by 5-HT4 receptors and that systemic modulation of 5-HT4 receptor function can bidirectionally impact memory formation. Collectively, these data reveal powerful modulatory influence of serotonergic synaptic input on hippocampal function and memory formation. Copyright © 2018 Elsevier Inc. All rights reserved.

Modified Holographic Ricci Dark Energy in Chameleon Brans-Dicke Cosmology and Its Thermodynamic Consequence

NASA Astrophysics Data System (ADS)

Jawad, A.; Chattopadhyay, S.; Bhattacharya, S.; Pasqua, A.

2015-04-01

The objective of this paper is to discuss the Chameleon Brans-Dicke gravity with non-minimally matter coupling of scalar field. We take modified Holographic Ricci dark energy model in this gravity with its energy density in interaction with energy density of cold dark matter. We assume power-law ansatz for scale factor and scalar field to discuss potential as well as coupling functions in the evolving universe. These reconstructed functions are plotted versus scalar field and time for different values of power component of scale factor n. We observe that potential and coupling functions represent increasing behavior, in particular, consistent results for a specific value of n. Finally, we have examined validity of the generalized second law of thermodynamics and we have observed its validity for all values of n. The financial Supported from Department of Science and Technology, Govt. of India under Project Grant No. SR/FTP/PS-167/2011 is thankfully acknowledged by SC

Multi-Lagrangians for integrable systems

NASA Astrophysics Data System (ADS)

Nutku, Y.; Pavlov, M. V.

2002-03-01

We propose a general scheme to construct multiple Lagrangians for completely integrable nonlinear evolution equations that admit multi-Hamiltonian structure. The recursion operator plays a fundamental role in this construction. We use a conserved quantity higher/lower than the Hamiltonian in the potential part of the new Lagrangian and determine the corresponding kinetic terms by generating the appropriate momentum map. This leads to some remarkable new developments. We show that nonlinear evolutionary systems that admit N-fold first order local Hamiltonian structure can be cast into variational form with 2N-1 Lagrangians which will be local functionals of Clebsch potentials. This number increases to 3N-2 when the Miura transformation is invertible. Furthermore we construct a new Lagrangian for polytropic gas dynamics in 1+1 dimensions which is a free, local functional of the physical field variables, namely density and velocity, thus dispensing with the necessity of introducing Clebsch potentials entirely. This is a consequence of bi-Hamiltonian structure with a compatible pair of first and third order Hamiltonian operators derived from Sheftel's recursion operator.

Human mast cell and airway smooth muscle cell interactions: implications for asthma.

PubMed

Page, S; Ammit, A J; Black, J L; Armour, C L

2001-12-01

Asthma is characterized by inflammation, hyperresponsiveness, and remodeling of the airway. Human mast cells (HMCs) play a central role in all of these changes by releasing mediators that cause exaggerated bronchoconstriction, induce human airway smooth muscle (HASM) cell proliferation, and recruit and activate inflammatory cells. Moreover, the number of HMCs present on asthmatic HASM is increased compared with that on nonasthmatic HASM. HASM cells also have the potential to actively participate in the inflammatory process by synthesizing cytokines and chemokines and expressing surface molecules, which have the capacity to perpetuate the inflammatory mechanisms present in asthma. This review specifically examines how the mediators of HMCs have the capacity to modulate many functions of HASM; how the synthetic function of HASM, particularly through the release and expression of stem cell factor, has the potential to influence HMC number and activation in an extraordinarily potent and proinflammatory manner; and how these interactions between HMCs and HASM have potential consequences for airway structure and inflammation relevant to the disease process of asthma.

Dielectric response of an inhomogeneous quasi-two-dimensional electron gas

NASA Astrophysics Data System (ADS)

Fernández-Velicia, F. J.; García-Moliner, F.; Velasco, V. R.

1996-01-01

The solution of the integral equation required to invert the dielectric function of a confined quasi-two-dimensional electron gas is studied by means of a formal analysis which yields a convergent algorithm. The dielectric function can then be inverted in real space for an arbitrary number of populated subbands and taking into account the effect of intersubband excitations involving empty subbands to any desired degree of accuracy. Plasma modes and screened potential can then be easily studied by using a basis which bears out explicitly the consequences of symmetry in symmetric systems. A model calculation of dynamical screening at frequencies of the order of those of confined polar optical modes in usual GaAs wells indicates that the empty states may play a quite significant role and the screened potential, explicitly obtained in real space, may exhibit a great variety of behaviors: the sign of the potential may change and its magnitude may be either reduced (ordinary screening) or enhanced (antiscreening).

sRNA antitoxins: more than one way to repress a toxin.

PubMed

Wen, Jia; Fozo, Elizabeth M

2014-08-04

Bacterial toxin-antitoxin loci consist of two genes: one encodes a potentially toxic protein, and the second, an antitoxin to repress its function or expression. The antitoxin can either be an RNA or a protein. For type I and type III loci, the antitoxins are RNAs; however, they have very different modes of action. Type I antitoxins repress toxin protein expression through interacting with the toxin mRNA, thereby targeting the mRNA for degradation or preventing its translation or both; type III antitoxins directly bind to the toxin protein, sequestering it. Along with these two very different modes of action for the antitoxin, there are differences in the functions of the toxin proteins and the mobility of these loci between species. Within this review, we discuss the major differences as to how the RNAs repress toxin activity, the potential consequences for utilizing different regulatory strategies, as well as the confirmed and potential biological roles for these loci across bacterial species.

Influence of the confinement potential on the size-dependent optical response of metallic nanometric particles

NASA Astrophysics Data System (ADS)

Zapata-Herrera, Mario; Camacho, Ángela S.; Ramírez, Hanz Y.

2018-06-01

In this paper, different confinement potential approaches are considered in the simulation of size effects on the optical response of silver spheres with radii at the few nanometer scale. By numerically obtaining dielectric functions from different sets of eigenenergies and eigenstates, we simulate the absorption spectrum and the field enhancement factor for nanoparticles of various sizes, within a quantum framework for both infinite and finite potentials. The simulations show significant dependence on the sphere radius of the dipolar surface plasmon resonance, as a direct consequence of energy discretization associated to the strong confinement experienced by conduction electrons in small nanospheres. Considerable reliance of the calculated optical features on the chosen wave functions and transition energies is evidenced, so that discrepancies in the plasmon resonance frequencies obtained with the three studied models reach up to above 30%. Our results are in agreement with reported measurements and shade light on the puzzling shift of the plasmon resonance in metallic nanospheres.

Segmental Duplication, Microinversion, and Gene Loss Associated with a Complex Inversion Breakpoint Region in Drosophila

PubMed Central

Calvete, Oriol; González, Josefa; Betrán, Esther; Ruiz, Alfredo

2012-01-01

Chromosomal inversions are usually portrayed as simple two-breakpoint rearrangements changing gene order but not gene number or structure. However, increasing evidence suggests that inversion breakpoints may often have a complex structure and entail gene duplications with potential functional consequences. Here, we used a combination of different techniques to investigate the breakpoint structure and the functional consequences of a complex rearrangement fixed in Drosophila buzzatii and comprising two tandemly arranged inversions sharing the middle breakpoint: 2m and 2n. By comparing the sequence in the breakpoint regions between D. buzzatii (inverted chromosome) and D. mojavensis (noninverted chromosome), we corroborate the breakpoint reuse at the molecular level and infer that inversion 2m was associated with a duplication of a ∼13 kb segment and likely generated by staggered breaks plus repair by nonhomologous end joining. The duplicated segment contained the gene CG4673, involved in nuclear transport, and its two nested genes CG5071 and CG5079. Interestingly, we found that other than the inversion and the associated duplication, both breakpoints suffered additional rearrangements, that is, the proximal breakpoint experienced a microinversion event associated at both ends with a 121-bp long duplication that contains a promoter. As a consequence of all these different rearrangements, CG5079 has been lost from the genome, CG5071 is now a single copy nonnested gene, and CG4673 has a transcript ∼9 kb shorter and seems to have acquired a more complex gene regulation. Our results illustrate the complex effects of chromosomal rearrangements and highlight the need of complementing genomic approaches with detailed sequence-level and functional analyses of breakpoint regions if we are to fully understand genome structure, function, and evolutionary dynamics. PMID:22328714

The Intimate and Controversial Relationship between Voltage Gated Proton Channels and the Phagocyte NADPH Oxidase

PubMed Central

DeCoursey, Thomas E.

2016-01-01

Summary One of the most fascinating and exciting periods in my scientific career entailed dissecting the symbiotic relationship between two membrane transporters, the NADPH oxidase complex and voltage gated proton channels (HV1). By the time I entered this field, there had already been substantial progress toward understanding NADPH oxidase, but HV1 were known only to a tiny handful of cognoscenti around the world. Having identified the first proton currents in mammalian cells in 1991, I needed to find a clear function for these molecules if the work was to become fundable. The then-recent discoveries of Henderson, Chappell, and colleagues in 1987–1988 that led them to hypothesize interactions of both molecules during the respiratory burst of phagocytes provided an excellent opportunity. In a nutshell, both transporters function by moving electrical charge across the membrane: NADPH oxidase moves electrons and HV1 moves protons. The consequences of electrogenic NADPH oxidase activity on both membrane potential and pH strongly self-limit this enzyme. Fortunately, both consequences specifically activate HV1, and HV1 activity counteracts both consequences, a kind of yin-yang relationship. Notwithstanding a decade starting in 1995 when many believed the opposite, these are two separate molecules that function independently despite their being functionally interdependent in phagocytes. The relationship between NADPH oxidase and HV1 has become a paradigm that somewhat surprisingly has now extended well beyond the phagocyte NADPH oxidase -- an industrial strength producer of reactive oxygen species (ROS) -- to myriad other cells that produce orders of magnitude less ROS for signaling purposes. These cells with their seven NADPH oxidase (NOX) isoforms provide a vast realm of mechanistic obscurity that will occupy future studies for years to come. PMID:27558336

Obstructive sleep apnea: current perspectives

PubMed Central

Osman, Amal M; Carter, Sophie G; Carberry, Jayne C; Eckert, Danny J

2018-01-01

The prevalence of obstructive sleep apnea (OSA) continues to rise. So too do the health, safety, and economic consequences. On an individual level, the causes and consequences of OSA can vary substantially between patients. In recent years, four key contributors to OSA pathogenesis or “phenotypes” have been characterized. These include a narrow, crowded, or collapsible upper airway “anatomical compromise” and “non-anatomical” contributors such as ineffective pharyngeal dilator muscle function during sleep, a low threshold for arousal to airway narrowing during sleep, and unstable control of breathing (high loop gain). Each of these phenotypes is a target for therapy. This review summarizes the latest knowledge on the different contributors to OSA with a focus on measurement techniques including emerging clinical tools designed to facilitate translation of new cause-driven targeted approaches to treat OSA. The potential for some of the specific pathophysiological causes of OSA to drive some of the key symptoms and consequences of OSA is also highlighted. PMID:29416383

The value of eutherian-marsupial comparisons for understanding the function of glucocorticoids in female mammal reproduction.

PubMed

Fanson, Kerry V; Parrott, Marissa L

2015-11-01

This article is part of a Special Issue "SBN 2014". Chronic stress is known to inhibit female reproductive function. Consequently, it is often assumed that glucocorticoid (GC) concentrations should be negatively correlated with reproductive success because of the role they play in stress physiology. In contrast, a growing body of evidence indicates that GCs play an active role in promoting reproductive function. It is precisely because GCs are so integral to the entire process that disruptions to adrenal activity have negative consequences for reproduction. The goal of this paper is to draw attention to the increasing evidence showing that increases in adrenal activity are important for healthy female reproduction. Furthermore, we outline several hypotheses about the functional role(s) that GCs may play in mediating reproduction and argue that comparative studies between eutherian and marsupial mammals, which exhibit some pronounced differences in reproductive physiology, may be particularly useful for testing different hypotheses about the functional role of GCs in reproduction. Much of our current thinking about GCs and reproduction comes from research involving stress-induced levels of GCs and has led to broad assumptions about the effects of GCs on reproduction. Unfortunately, this has left a gaping hole in our knowledge about basal GC levels and how they may influence reproductive function, thereby preventing a broader understanding of adrenal physiology and obscuring potential solutions for reproductive dysfunction. Copyright © 2015 Elsevier Inc. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lindgren, Ingvar; Salomonson, Sten

The locality theorem in density-functional theory (DFT) states that the functional derivative of the Hohenberg-Kohn universal functional can be expressed as a local multiplicative potential function, and this is the basis of DFT and of the successful Kohn-Sham model. Nesbet has in several papers [Phys. Rev. A 58, R12 (1998); ibid.65, 010502 (2001); Adv. Quant. Chem, 43, 1 (2003)] claimed that this theorem is in conflict with fundamental quantum physics, and as a consequence that the Hohenberg-Kohn theory cannot be generally valid. We have commented upon these works [Comment, Phys. Rev. A 67, 056501 (2003)] and recently extended the argumentsmore » [Adv. Quantum Chem. 43, 95 (2003)]. We have shown that there is no such conflict and that the locality theorem is inherently exact. In the present work we have furthermore verified this numerically by constructing a local Kohn-Sham potential for the 1s2s{sup 3}S state of helium that generates the many-body electron density and shown that the corresponding 2s Kohn-Sham orbital eigenvalue agrees with the ionization energy to nine digits. Similar result is obtained with the Hartree-Fock density. Therefore, in addition to verifying the locality theorem, this result also confirms the so-called ionization-potential theorem.« less

Functional Consequence of Distal Brachioradialis Tendon Release: A Biomechanical Study

PubMed Central

Tirrell, Timothy F.; Franko, Orrin I.; Bhola, Siddharth; Hentzen, Eric R.; Abrams, Reid A.; Lieber, Richard L.

2013-01-01

Purpose Open reduction and internal fixation of distal radius fractures often necessitates release of the brachioradialis from the radial styloid. However, this common procedure has the potential to decrease elbow flexion strength. To determine the potential morbidity associated with brachioradialis release, we measured the change in elbow torque as a function of incremental release of the brachioradialis insertion footprint. Methods In 5 upper extremity cadaveric specimens, the brachioradialis tendon was systematically released from the radius, and the resultant effect on brachioradialis elbow flexion torque was measured. Release distance was defined as the distance between the release point and the tip of the radial styloid. Results Brachioradialis elbow flexion torque dropped to 95%, 90% and 86% of its original value at release distances of 27mm, 46mm, and 52mm, respectively. Importantly, brachioradialis torque remained above 80% of its original value at release distances up to 7 centimeters. Conclusions Our data demonstrate that release of the brachioradialis tendon from its insertion has minor effects on its ability to transmit force to the distal radius. Clinical Relevance These data may imply that release of the distal brachioradialis tendon during distal radius open reduction internal fixation can be performed without meaningful functional consequences to elbow flexion torque. Even at large release distances, overall elbow flexion torque loss after brachioradialis release would be expected to be less than 5% due to the much larger contributions of the biceps and brachialis. Use of the brachioradialis as a tendon transfer donor should not be limited by concerns of elbow flexion loss, and the tendon could be considered as an autograft donor. PMID:23528425

Functional metagenomics of oil-impacted mangrove sediments reveals high abundance of hydrolases of biotechnological interest.

PubMed

Ottoni, Júlia Ronzella; Cabral, Lucélia; de Sousa, Sanderson Tarciso Pereira; Júnior, Gileno Vieira Lacerda; Domingos, Daniela Ferreira; Soares Junior, Fábio Lino; da Silva, Mylenne Calciolari Pinheiro; Marcon, Joelma; Dias, Armando Cavalcante Franco; de Melo, Itamar Soares; de Souza, Anete Pereira; Andreote, Fernando Dini; de Oliveira, Valéria Maia

2017-07-01

Mangroves are located in coastal wetlands and are susceptible to the consequences of oil spills, what may threaten the diversity of microorganisms responsible for the nutrient cycling and the consequent ecosystem functioning. Previous reports show that high concentration of oil favors the incidence of epoxide hydrolases and haloalkane dehalogenases in mangroves. This finding has guided the goals of this study in an attempt to broaden the analysis to other hydrolases and thereby verify whether oil contamination interferes with the prevalence of particular hydrolases and their assigned microorganisms. For this, an in-depth survey of the taxonomic and functional microbial diversity recovered in a fosmid library (Library_Oil Mgv) constructed from oil-impacted Brazilian mangrove sediment was carried out. Fosmid DNA of the whole library was extracted and submitted to Illumina HiSeq sequencing. The resulting Library Oil_Mgv dataset was further compared with those obtained by direct sequencing of environmental DNA from Brazilian mangroves (from distinct regions and affected by distinct sources of contamination), focusing on hydrolases with potential use in biotechnological processes. The most abundant hydrolases found were proteases, esterases and amylases, with similar occurrence profile in all datasets. The main microbial groups harboring such hydrolase-encoding genes were distinct in each mangrove, and in the fosmid library these enzymes were mainly assigned to Chloroflexaceae (for amylases), Planctomycetaceae (for esterases) and Bradyrhizobiaceae (for proteases). Assembly and analysis of Library_Oil Mgv reads revealed three potentially novel enzymes, one epoxide hydrolase, one xylanase and one amylase, to be further investigated via heterologous expression assays.

Anesthesia and perioperative stress: consequences on neural networks and postoperative behaviors.

PubMed

Borsook, David; George, Edward; Kussman, Barry; Becerra, Lino

2010-12-01

Anesthesia is a state of drug-induced unconsciousness with suppression of sensory perception, and consists of both hypnotic and analgesic components. The anesthesiologist monitors the clinical response to noxious stimuli and adjusts drug dosage(s) to achieve an adequate depth of anesthesia, with the aim of reducing operative stress. Acute stress in the perioperative period has four major contributors: anxiety, pain, the surgical stress response, and the potential neurotoxicity of anesthetic agents. Any or all of these may act deleteriously on multiple systems in the brain and have known significant effects on brain regions such as the hippocampus and the hypothalamic-pituitary-adrenal axis. Perioperative stress on the nervous system and the resultant central nervous system (CNS) changes are likely to be causative for altered behaviors that are seen postoperatively, including chronic pain, posttraumatic stress disorder, and learning difficulties. Improving the ability of the anesthesiologist to control all four components of acute perioperative stress could potentially reduce the negative impact of surgery on the brain. Currently, there is no objective measurement for any of these stressors. The development and application of objective measures for perioperative stressors is the first step towards controlling these risk factors and eliminating or reducing their serious postoperative consequences. In this paper we review known and likely effects of perioperative stressors on brain systems and how they may play a significant role in altered postoperative behaviors. We discuss the role of current (and developing) measures of brain function and their potential for monitoring perioperative stress, with an emphasis on functional neuroimaging. Copyright © 2010 Elsevier Ltd. All rights reserved.

Respiratory muscle function and exercise limitation in patients with chronic obstructive pulmonary disease: a review.

PubMed

Charususin, Noppawan; Dacha, Sauwaluk; Gosselink, Rik; Decramer, Marc; Von Leupoldt, Andreas; Reijnders, Thomas; Louvaris, Zafeiris; Langer, Daniel

2018-01-01

Respiratory muscle dysfunction is common and contributes to dyspnea and exercise limitation in patients with chronic obstructive pulmonary disease (COPD). Improving dynamic function of respiratory muscles during exercise might help to reduce symptoms and improve exercise capacity. Areas covered: The aims of this review are to 1) summarize physiological mechanisms linking respiratory muscle dysfunction to dyspnea and exercise limitation; 2) provide an overview of available therapeutic approaches to better maintain load-capacity balance of respiratory muscles during exercise; and 3) to summarize current knowledge on potential mechanisms explaining effects of interventions aimed at optimizing dynamic respiratory muscle function with a special focus on inspiratory muscle training. Expert commentary: Several mechanisms which are potentially linking improvements in dynamic respiratory muscle function to symptomatic and functional benefits have not been studied so far in COPD patients. Examples of underexplored areas include the study of neural processes related to the relief of acute dyspnea and the competition between respiratory and peripheral muscles for limited energy supplies during exercise. Novel methodologies are available to non-invasively study these mechanisms. Better insights into the consequences of dynamic respiratory muscle dysfunction will hopefully contribute to further refine and individualize therapeutic approaches in patients with COPD.

Connecting the dots: developing a holistic picture of children's health.

PubMed

2008-11-01

Current definitions of child health transcend the historical biomedical model, which largely equated health with the absence of disease. Scientific evidence indicates that child health is best defined as the optimization of a child's developmental potential and functional capacity with interventions focused on maximizing protective factors and minimizing risk factors. This approach to child health recognizes the interplay among physical, cognitive, social, and emotional development and stresses the lifelong consequences of deficits in these developmental areas.

Collection of ions

DOEpatents

Orr, Christopher Henry; Luff, Craig Janson; Dockray, Thomas; Macarthur, Duncan Whittemore; Bounds, John Alan; Koster, James E.

2001-01-01

The apparatus and method provide an improved technique for detecting ions as the area from which ions are attracted to a detector is increased, consequently increasing the number of ions detected. This is achieved by providing the outer electrodes of the detector connected to the electrical potential, together with alternate intermediate electrodes. The other intermediate electrodes and preferably the housing are grounded. The technique renders such detection techniques more sensitive and gives them a lower threshold at which they can function.

Mobile phones and sleep - A review

NASA Astrophysics Data System (ADS)

Supe, Sanjay S.

2010-01-01

The increasing use of mobile phones has raised concerns regarding the potential health effects of exposure to the radiofrequency electromagnetic fields. An increasing amount research related to mobile phone use has focussed on the possible effects of mobile phone exposure on human brain activity and function. In particular, the use of sleep research has become a more widely used technique for assessing the possible effects of mobile phones on human health and wellbeing especially in the investigation of potential changes in sleep architecture resulting from mobile phone use. Acute exposure to a mobile phone prior to sleep significantly enhances electroencephalogram spectral power in the sleep spindle frequency range. This mobile phone-induced enhancement in spectral power is largely transitory and does not linger throughout the night. Furthermore, a reduction in rapid eye movement sleep latency following mobile phone exposure was also found, although interestingly, neither this change in rapid eye movement sleep latency or the enhancement in spectral power following mobile phone exposure, led to changes in the overall quality of sleep. In conclusion, a short exposure to the radiofrequency electromagnetic fields emitted by a mobile phone handset immediately prior to sleep is sufficient to induce changes in brain activity in the initial part of sleep. The consequences or functional significance of this effect are currently unknown and it would be premature to draw conclusions about possible health consequences.

Improving Collaborative Behaviour Planning in Adult Auditory Rehabilitation: Development of the I-PLAN Intervention Using the Behaviour Change Wheel.

PubMed

Barker, Fiona; Lusignan, Simon de; Deborah, Cooke

2018-05-18

The consequences of poorly managed hearing loss can be ameliorated with hearing aid use but rates of use are sub-optimal. The impact of audiologist behaviour on subsequent use, particularly over the long term, is unknown. This study aimed to describe the role of the behaviour change wheel in developing an intervention to introduce and embed particular clinical behaviours into adult hearing aid fitting consultations, within the framework of the Medical Research Council guidance on complex interventions. Following the steps of the behaviour change wheel, audiologist behaviours that might influence hearing aid use were identified based on a systematic review and qualitative work with audiologists. An analysis, using the COM-B model, identified potential drivers of the target behaviours. This was used to select intervention functions and behaviour change techniques likely to influence behaviour in this context. The target behaviours were as follows: giving information about the benefits of hearing aid use and the negative consequences of non-use, providing prompts for use and engaging in collaborative behavioural planning for use. The behavioural analysis suggested that psychological capability, opportunity and motivation were potential drivers of these behaviours. The intervention functions of education, coercion, training, environmental restructuring, modelling and enablement were selected and combined to develop a single complex intervention that seeks to address the target behaviours.

Species-specific effects of soil fauna on fungal foraging and decomposition.

PubMed

Crowther, Thomas W; Boddy, Lynne; Jones, T Hefin

2011-10-01

Decomposer fungi are primary decomposing agents in terrestrial soils. Their mycelial networks play an important role in nutrient mineralisation and distribution, but are also nutritious resources for various soil invertebrates. Global climate change is predicted to alter the diversity and community composition of these soil fauna. To understand whether changes in invertebrate species diversity are likely to affect fungal-mediated decomposition, this study compared the grazing potentials of different invertebrate taxa and functional groups. Specifically, the grazing impacts of seven invertebrate taxa on the growth and spatial distribution of six basidiomycete fungi growing from beech wood blocks in soil microcosms were explored. Wood decay rates by fungi were also compared. The consequences of grazing were both taxon- and species-specific. Generally, macro-invertebrates caused the greatest damage, while meso- and micro-invertebrates often stimulated mycelial growth. Invertebrate size, preferences and population dynamics are likely to influence grazing potentials. Effects of grazing varied between fungi, with mycelial morphology and biochemistry possibly influencing susceptibility. Heavy grazing indirectly increased fungal-mediated wood decomposition. Changes in invertebrate community composition are predicted to have consequences for fungal growth, activity and community structure in woodland soils. Abiotic climate change factors including CO(2) and temperature affect mycelial productivity directly, but the indirect effects, mediated through changes in the soil invertebrate community, may be equally important in controlling ecosystem functioning.

An Evaluation of the Relative Effectiveness of Function-Based Consequent and Antecedent Interventions in a Preschool Setting

ERIC Educational Resources Information Center

von Schulz, Jonna H.; Dufrene, Brad A.; LaBrot, Zachary C.; Tingstrom, Daniel H.; Olmi, D. Joe; Radley, Keith; Mitchell, Rachel; Maldonado, Aimee

2018-01-01

Although there is substantial functional behavioral assessment (FBA) literature suggesting that function-based interventions are effective for improving problem behavior, only a limited number of studies have examined the effectiveness of function-based antecedent versus consequent interventions. Additionally, although there has been a recent…

Under the influence of Facebook? Excess use of social networking sites and drinking motives, consequences, and attitudes in college students

PubMed Central

Hormes, Julia M.

2016-01-01

Background and aims Excessive use of social networking sites (SNS) has recently been conceptualized as a behavioral addiction (i.e., “disordered SNS use”) using key criteria for the diagnosis of substance dependence and shown to be associated with a variety of impairments in psychosocial functioning, including an increased risk of problem drinking. This study sought to characterize associations between “disordered SNS use” and attitudes towards alcohol, drinking motives, and adverse consequences resulting from alcohol use in young adults. Methods Undergraduate students (n = 537, 64.0% female, mean age = 19.63 years, SD = 4.24) reported on their use of SNSs and completed the Alcohol Use Disorders Identification Test, Temptation and Restraint Inventory, Approach and Avoidance of Alcohol and Drinking Motives Questionnaires, and Drinker Inventory of Consequences. Results Respondents meeting previously established criteria for “disordered SNS use” were significantly more likely to use alcohol to cope with negative affect and to conform to perceived social norms, reported significantly more conflicting (i.e., simultaneous positive and negative) attitudes towards alcohol, and had experienced significantly more, and more frequent adverse consequences from drinking in their inter- and intrapersonal, physical, and social functioning, compared to individuals without problems related to SNS use. Discussion and conclusions Findings add to an emerging body of literature suggesting a link between excess or maladaptive SNS use and problems related to alcohol in young adults and point to emotion dysregulation and coping motives as potential shared risk factors for substance and behavioral addictions in this demographic. PMID:28092186

Under the influence of Facebook? Excess use of social networking sites and drinking motives, consequences, and attitudes in college students.

PubMed

Hormes, Julia M

2016-03-01

Background and aims Excessive use of social networking sites (SNS) has recently been conceptualized as a behavioral addiction (i.e., "disordered SNS use") using key criteria for the diagnosis of substance dependence and shown to be associated with a variety of impairments in psychosocial functioning, including an increased risk of problem drinking. This study sought to characterize associations between "disordered SNS use" and attitudes towards alcohol, drinking motives, and adverse consequences resulting from alcohol use in young adults. Methods Undergraduate students (n = 537, 64.0% female, mean age = 19.63 years, SD = 4.24) reported on their use of SNSs and completed the Alcohol Use Disorders Identification Test, Temptation and Restraint Inventory, Approach and Avoidance of Alcohol and Drinking Motives Questionnaires, and Drinker Inventory of Consequences. Results Respondents meeting previously established criteria for "disordered SNS use" were significantly more likely to use alcohol to cope with negative affect and to conform to perceived social norms, reported significantly more conflicting (i.e., simultaneous positive and negative) attitudes towards alcohol, and had experienced significantly more, and more frequent adverse consequences from drinking in their inter- and intrapersonal, physical, and social functioning, compared to individuals without problems related to SNS use. Discussion and conclusions Findings add to an emerging body of literature suggesting a link between excess or maladaptive SNS use and problems related to alcohol in young adults and point to emotion dysregulation and coping motives as potential shared risk factors for substance and behavioral addictions in this demographic.

In Your Face: Risk of Punishment Enhances Cognitive Control and Error-Related Activity in the Corrugator Supercilii Muscle.

PubMed

Lindström, Björn R; Mattsson-Mårn, Isak Berglund; Golkar, Armita; Olsson, Andreas

2013-01-01

Cognitive control is needed when mistakes have consequences, especially when such consequences are potentially harmful. However, little is known about how the aversive consequences of deficient control affect behavior. To address this issue, participants performed a two-choice response time task where error commissions were expected to be punished by electric shocks during certain blocks. By manipulating (1) the perceived punishment risk (no, low, high) associated with error commissions, and (2) response conflict (low, high), we showed that motivation to avoid punishment enhanced performance during high response conflict. As a novel index of the processes enabling successful cognitive control under threat, we explored electromyographic activity in the corrugator supercilii (cEMG) muscle of the upper face. The corrugator supercilii is partially controlled by the anterior midcingulate cortex (aMCC) which is sensitive to negative affect, pain and cognitive control. As hypothesized, the cEMG exhibited several key similarities with the core temporal and functional characteristics of the Error-Related Negativity (ERN) ERP component, the hallmark index of cognitive control elicited by performance errors, and which has been linked to the aMCC. The cEMG was amplified within 100 ms of error commissions (the same time-window as the ERN), particularly during the high punishment risk condition where errors would be most aversive. Furthermore, similar to the ERN, the magnitude of error cEMG predicted post-error response time slowing. Our results suggest that cEMG activity can serve as an index of avoidance motivated control, which is instrumental to adaptive cognitive control when consequences are potentially harmful.

In Your Face: Risk of Punishment Enhances Cognitive Control and Error-Related Activity in the Corrugator Supercilii Muscle

PubMed Central

Lindström, Björn R.; Mattsson-Mårn, Isak Berglund; Golkar, Armita; Olsson, Andreas

2013-01-01

Cognitive control is needed when mistakes have consequences, especially when such consequences are potentially harmful. However, little is known about how the aversive consequences of deficient control affect behavior. To address this issue, participants performed a two-choice response time task where error commissions were expected to be punished by electric shocks during certain blocks. By manipulating (1) the perceived punishment risk (no, low, high) associated with error commissions, and (2) response conflict (low, high), we showed that motivation to avoid punishment enhanced performance during high response conflict. As a novel index of the processes enabling successful cognitive control under threat, we explored electromyographic activity in the corrugator supercilii (cEMG) muscle of the upper face. The corrugator supercilii is partially controlled by the anterior midcingulate cortex (aMCC) which is sensitive to negative affect, pain and cognitive control. As hypothesized, the cEMG exhibited several key similarities with the core temporal and functional characteristics of the Error-Related Negativity (ERN) ERP component, the hallmark index of cognitive control elicited by performance errors, and which has been linked to the aMCC. The cEMG was amplified within 100 ms of error commissions (the same time-window as the ERN), particularly during the high punishment risk condition where errors would be most aversive. Furthermore, similar to the ERN, the magnitude of error cEMG predicted post-error response time slowing. Our results suggest that cEMG activity can serve as an index of avoidance motivated control, which is instrumental to adaptive cognitive control when consequences are potentially harmful. PMID:23840356

Intermuscular Fat: A Review of the Consequences and Causes

PubMed Central

Marcus, Robin L.; LaStayo, Paul C.; Ryan, Alice S.

2014-01-01

Muscle's structural composition is an important factor underlying muscle strength and physical function in older adults. There is an increasing amount of research to support the clear disassociation between the loss of muscle lean tissue mass and strength with aging. This disassociation implies that factors in addition to lean muscle mass are responsible for the decreases in strength and function seen with aging. Intermuscular adipose tissue (IMAT) is a significant predictor of both muscle function and mobility function in older adults and across a wide variety of comorbid conditions such as stroke, spinal cord injury, diabetes, and COPD. IMAT is also implicated in metabolic dysfunction such as insulin resistance. The purpose of this narrative review is to provide a review of the implications of increased IMAT levels in metabolic, muscle, and mobility function. Potential treatment options to mitigate increasing levels of IMAT will also be discussed. PMID:24527032

Declining resilience of ecosystem functions under biodiversity loss.

PubMed

Oliver, Tom H; Isaac, Nick J B; August, Tom A; Woodcock, Ben A; Roy, David B; Bullock, James M

2015-12-08

The composition of species communities is changing rapidly through drivers such as habitat loss and climate change, with potentially serious consequences for the resilience of ecosystem functions on which humans depend. To assess such changes in resilience, we analyse trends in the frequency of species in Great Britain that provide key ecosystem functions--specifically decomposition, carbon sequestration, pollination, pest control and cultural values. For 4,424 species over four decades, there have been significant net declines among animal species that provide pollination, pest control and cultural values. Groups providing decomposition and carbon sequestration remain relatively stable, as fewer species are in decline and these are offset by large numbers of new arrivals into Great Britain. While there is general concern about degradation of a wide range of ecosystem functions, our results suggest actions should focus on particular functions for which there is evidence of substantial erosion of their resilience.

Automated identification of functional dynamic networks from X-ray crystallography

PubMed Central

van den Bedem, Henry; Bhabha, Gira; Yang, Kun; Wright, Peter E.; Fraser, James S.

2013-01-01

Protein function often depends on the exchange between conformational substates. Allosteric ligand binding or distal mutations can stabilize specific active site conformations and consequently alter protein function. In addition to comparing independently determined X-ray crystal structures, alternative conformations observed at low levels of electron density have the potential to provide mechanistic insights into conformational dynamics. Here, we report a new multi-conformer contact network algorithm (CONTACT) that identifies networks of conformationally heterogeneous residues directly from high-resolution X-ray crystallography data. Contact networks in Escherichia coli dihydrofolate reductase (ecDHFR) predict the long-range pattern of NMR chemical shift perturbations of an allosteric mutation. A comparison of contact networks in wild type and mutant ecDHFR suggests how mutations that alter optimized networks of coordinated motions can impair catalytic function. Thus, CONTACT-guided mutagenesis will allow the structure-dynamics-function relationship to be exploited in protein engineering and design. PMID:23913260

Giant mitochondria do not fuse and exchange their contents with normal mitochondria

DOE Office of Scientific and Technical Information (OSTI.GOV)

Navratil, Marian; Terman, Alexei; Arriaga, Edgar A.

2008-01-01

Giant mitochondria accumulate within aged or diseased postmitotic cells as a consequence of insufficient autophagy, which is normally responsible for mitochondrial degradation. We report that giant mitochondria accumulating in cultured rat myoblasts due to inhibition of autophagy have low inner membrane potential and do not fuse with each other or with normal mitochondria. In addition to the low inner mitochondrial membrane potential in giant mitochondria, the quantity of the OPA1 mitochondrial fusion protein in these mitochondria was low, but the abundance of mitofusin-2 (Mfn2) remained unchanged. The combination of these factors may explain the lack of mitochondrial fusion in giantmore » mitochondria and imply that the dysfunctional giant mitochondria cannot restore their function by fusing and exchanging their contents with fully functional mitochondria. These findings have important implications for understanding the mechanisms of accumulation of age-related mitochondrial damage in postmitotic cells.« less

IGF-1, the cross road of the nutritional, inflammatory and hormonal pathways to frailty.

PubMed

Maggio, Marcello; De Vita, Francesca; Lauretani, Fulvio; Buttò, Valeria; Bondi, Giuliana; Cattabiani, Chiara; Nouvenne, Antonio; Meschi, Tiziana; Dall'Aglio, Elisabetta; Ceda, Gian Paolo

2013-10-21

The decline in functional capacity is a heterogeneous phenomenon in the elderly. An accelerated ageing determines a frail status. It results in an increased vulnerability to stressors for decreased physiological reserves. The early identification of a frail status is essential for preventing loss of functional capacity, and its clinical consequences. Frailty and mobility limitation result from an interplay of different pathways including multiple anabolic deficiency, inflammation, oxidative stress, and a poor nutritional status. However, the age-related decline in insulin-like growth factor 1 (IGF-1) bioactivity deserves special attention as it could represent the ideal crossroad of endocrine, inflammatory, and nutritional pathways to frailty. Several minerals, namely magnesium, selenium, and zinc, appear to be important determinants of IGF-1 bioactivity. This review aims to provide an overview of the potential usefulness of nutrients modulating IGF-1 as potential therapeutic targets in the prevention of mobility limitation occurring in frail older subjects.

Functional genomic Landscape of Human Breast Cancer drivers, vulnerabilities, and resistance

PubMed Central

Marcotte, Richard; Sayad, Azin; Brown, Kevin R.; Sanchez-Garcia, Felix; Reimand, Jüri; Haider, Maliha; Virtanen, Carl; Bradner, James E.; Bader, Gary D.; Mills, Gordon B.; Pe’er, Dana; Moffat, Jason; Neel, Benjamin G.

2016-01-01

Summary Large-scale genomic studies have identified multiple somatic aberrations in breast cancer, including copy number alterations, and point mutations. Still, identifying causal variants and emergent vulnerabilities that arise as a consequence of genetic alterations remain major challenges. We performed whole genome shRNA “dropout screens” on 77 breast cancer cell lines. Using a hierarchical linear regression algorithm to score our screen results and integrate them with accompanying detailed genetic and proteomic information, we identify vulnerabilities in breast cancer, including candidate “drivers,” and reveal general functional genomic properties of cancer cells. Comparisons of gene essentiality with drug sensitivity data suggest potential resistance mechanisms, effects of existing anti-cancer drugs, and opportunities for combination therapy. Finally, we demonstrate the utility of this large dataset by identifying BRD4 as a potential target in luminal breast cancer, and PIK3CA mutations as a resistance determinant for BET-inhibitors. PMID:26771497

Mesenchymal stem-cell potential in cartilage repair: an update

PubMed Central

Mazor, M; Lespessailles, E; Coursier, R; Daniellou, R; Best, T M; Toumi, H

2014-01-01

Articular cartilage damage and subsequent degeneration are a frequent occurrence in synovial joints. Treatment of these lesions is a challenge because this tissue is incapable of quality repair and/or regeneration to its native state. Non-operative treatments endeavour to control symptoms and include anti-inflammatory medications, viscosupplementation, bracing, orthotics and activity modification. Classical surgical techniques for articular cartilage lesions are frequently insufficient in restoring normal anatomy and function and in many cases, it has not been possible to achieve the desired results. Consequently, researchers and clinicians are focusing on alternative methods for cartilage preservation and repair. Recently, cell-based therapy has become a key focus of tissue engineering research to achieve functional replacement of articular cartilage. The present manuscript is a brief review of stem cells and their potential in the treatment of early OA (i.e. articular cartilage pathology) and recent progress in the field. PMID:25353372

Functional consequences of climate change-induced plant species loss in a tallgrass prairie.

PubMed

Craine, Joseph M; Nippert, Jesse B; Towne, E Gene; Tucker, Sally; Kembel, Steven W; Skibbe, Adam; McLauchlan, Kendra K

2011-04-01

Future climate change is likely to reduce the floristic diversity of grasslands. Yet the potential consequences of climate-induced plant species losses for the functioning of these ecosystems are poorly understood. We investigated how climate change might alter the functional composition of grasslands for Konza Prairie, a diverse tallgrass prairie in central North America. With species-specific climate envelopes, we show that a reduction in mean annual precipitation would preferentially remove species that are more abundant in the more productive lowland positions at Konza. As such, decreases in precipitation could reduce productivity not only by reducing water availability but by also removing species that inhabit the most productive areas and respond the most to climate variability. In support of this prediction, data on species abundance at Konza over 16 years show that species that are more abundant in lowlands than uplands are preferentially reduced in years with low precipitation. Climate change is likely to also preferentially remove species from particular functional groups and clades. For example, warming is forecast to preferentially remove perennials over annuals as well as Cyperaceae species. Despite these predictions, climate change is unlikely to unilaterally alter the functional composition of the tallgrass prairie flora, as many functional traits such as physiological drought tolerance and maximum photosynthetic rates showed little relationship with climate envelope parameters. In all, although climatic drying would indirectly alter grassland productivity through species loss patterns, the insurance afforded by biodiversity to ecosystem function is likely to be sustained in the face of climate change.

Impact of Substance Messages in Music Videos on Youth: Beware the Influence of Connectedness and Its Potential Prevention-Shielding Effect.

PubMed

Russell, Cristel Antonia; Régnier-Denois, Véronique; Chapoton, Boris; Buhrau, Denise

2017-09-01

Two studies were conducted to investigate the role of connectedness with music videos in affecting youths' beliefs about substances (alcohol and tobacco) embedded therein and the potential for a prevention message to limit the impact of these images. The first study used cross-sectional data from a national sample of 1,023 adolescents (54.3% male) to evaluate the relationship between youths' consumption of music videos and their beliefs about the consequences of consuming alcohol and tobacco. A controlled experiment with 151 participants (57% male) then tested whether exposure to smoking in a video affects youths' smoking beliefs and the preventive potential of a pre-video warning. Connectedness to music videos, not overall amount of viewing, is the main correlate of beliefs about the positive outcomes of consuming alcohol/tobacco. A single exposure to a music video with smoking images can increase beliefs that smoking leads to positive consequences, and connected viewers are especially receptive to these images. Alerting youths to the presence of substance messages in a video leads to differential results as a function of connectedness. Many youths spend hours every day watching music videos in which positive visuals about drinking and smoking abound. Rather than the quantity of viewing, it is the degree to which youths immerse themselves in these music videos that enhances their beliefs that smoking and drinking have positive consequences. Interventions that warn youths about the presence of substances in music videos can minimize their influence, but youths highly connected with the music video content are especially resistant to warnings.

Heparan Sulfates Support Pyramidal Cell Excitability, Synaptic Plasticity, and Context Discrimination.

PubMed

Minge, Daniel; Senkov, Oleg; Kaushik, Rahul; Herde, Michel K; Tikhobrazova, Olga; Wulff, Andreas B; Mironov, Andrey; van Kuppevelt, Toin H; Oosterhof, Arie; Kochlamazashvili, Gaga; Dityatev, Alexander; Henneberger, Christian

2017-02-01

Heparan sulfate (HS) proteoglycans represent a major component of the extracellular matrix and are critical for brain development. However, their function in the mature brain remains to be characterized. Here, acute enzymatic digestion of HS side chains was used to uncover how HSs support hippocampal function in vitro and in vivo. We found that long-term potentiation (LTP) of synaptic transmission at CA3-CA1 Schaffer collateral synapses was impaired after removal of highly sulfated HSs with heparinase 1. This reduction was associated with decreased Ca2+ influx during LTP induction, which was the consequence of a reduced excitability of CA1 pyramidal neurons. At the subcellular level, heparinase treatment resulted in reorganization of the distal axon initial segment, as detected by a reduction in ankyrin G expression. In vivo, digestion of HSs impaired context discrimination in a fear conditioning paradigm and oscillatory network activity in the low theta band after fear conditioning. Thus, HSs maintain neuronal excitability and, as a consequence, support synaptic plasticity and learning. © The Author 2017. Published by Oxford University Press.

HSP90 Shapes the Consequences of Human Genetic Variation.

PubMed

Karras, Georgios I; Yi, Song; Sahni, Nidhi; Fischer, Máté; Xie, Jenny; Vidal, Marc; D'Andrea, Alan D; Whitesell, Luke; Lindquist, Susan

2017-02-23

HSP90 acts as a protein-folding buffer that shapes the manifestations of genetic variation in model organisms. Whether HSP90 influences the consequences of mutations in humans, potentially modifying the clinical course of genetic diseases, remains unknown. By mining data for >1,500 disease-causing mutants, we found a strong correlation between reduced phenotypic severity and a dominant (HSP90 ≥ HSP70) increase in mutant engagement by HSP90. Examining the cancer predisposition syndrome Fanconi anemia in depth revealed that mutant FANCA proteins engaged predominantly by HSP70 had severely compromised function. In contrast, the function of less severe mutants was preserved by a dominant increase in HSP90 binding. Reducing HSP90's buffering capacity with inhibitors or febrile temperatures destabilized HSP90-buffered mutants, exacerbating FA-related chemosensitivities. Strikingly, a compensatory FANCA somatic mutation from an "experiment of nature" in monozygotic twins both prevented anemia and reduced HSP90 binding. These findings provide one plausible mechanism for the variable expressivity and environmental sensitivity of genetic diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

Reconstructing ecosystem functions of the active microbial community of the Baltic Sea oxygen depleted sediments.

PubMed

Thureborn, Petter; Franzetti, Andrea; Lundin, Daniel; Sjöling, Sara

2016-01-01

Baltic Sea deep water and sediments hold one of the largest anthropogenically induced hypoxic areas in the world. High nutrient input and low water exchange result in eutrophication and oxygen depletion below the halocline. As a consequence at Landsort Deep, the deepest point of the Baltic Sea, anoxia in the sediments has been a persistent condition over the past decades. Given that microbial communities are drivers of essential ecosystem functions we investigated the microbial community metabolisms and functions of oxygen depleted Landsort Deep sediments by metatranscriptomics. Results show substantial expression of genes involved in protein metabolism demonstrating that the Landsort Deep sediment microbial community is active. Identified expressed gene suites of metabolic pathways with importance for carbon transformation including fermentation, dissimilatory sulphate reduction and methanogenesis were identified. The presence of transcripts for these metabolic processes suggests a potential for heterotrophic-autotrophic community synergism and indicates active mineralisation of the organic matter deposited at the sediment as a consequence of the eutrophication process. Furthermore, cyanobacteria, probably deposited from the water column, are transcriptionally active in the anoxic sediment at this depth. Results also reveal high abundance of transcripts encoding integron integrases. These results provide insight into the activity of the microbial community of the anoxic sediment at the deepest point of the Baltic Sea and its possible role in ecosystem functioning.

What cost mitochondria? The maintenance of functional mitochondrial DNA within and across generations

PubMed Central

Aanen, Duur K.; Spelbrink, Johannes N.; Beekman, Madeleine

2014-01-01

The peculiar biology of mitochondrial DNA (mtDNA) potentially has detrimental consequences for organismal health and lifespan. Typically, eukaryotic cells contain multiple mitochondria, each with multiple mtDNA genomes. The high copy number of mtDNA implies that selection on mtDNA functionality is relaxed. Furthermore, because mtDNA replication is not strictly regulated, within-cell selection may favour mtDNA variants with a replication advantage, but a deleterious effect on cell fitness. The opportunities for selfish mtDNA mutations to spread are restricted by various organism-level adaptations, such as uniparental transmission, germline mtDNA bottlenecks, germline selection and, during somatic growth, regular alternation between fusion and fission of mitochondria. These mechanisms are all hypothesized to maintain functional mtDNA. However, the strength of selection for maintenance of functional mtDNA progressively declines with age, resulting in age-related diseases. Furthermore, organismal adaptations that most probably evolved to restrict the opportunities for selfish mtDNA create secondary problems. Owing to predominantly maternal mtDNA transmission, recombination among mtDNA from different individuals is highly restricted or absent, reducing the scope for repair. Moreover, maternal inheritance precludes selection against mtDNA variants with male-specific effects. We finish by discussing the consequences of life-history differences among taxa with respect to mtDNA evolution and make a case for the use of microorganisms to experimentally manipulate levels of selection. PMID:24864309

Prenatal marijuana exposure impacts executive functioning into young adulthood: An fMRI study.

PubMed

Smith, Andra M; Mioduszewski, Ola; Hatchard, Taylor; Byron-Alhassan, Aziza; Fall, Carley; Fried, Peter A

Understanding the potentially harmful long term consequences of prenatal marijuana exposure is important given the increase in number of pregnant women smoking marijuana to relieve morning sickness. Altered executive functioning is one area of research that has suggested negative consequences of prenatal marijuana exposure into adolescence. Investigating if these findings continue into young adulthood and exploring the neural basis of these effects was the purpose of this research. Thirty one young adults (ages 18-22years) from the longitudinal Ottawa Prenatal Prospective Study (OPPS) underwent functional magnetic resonance imaging (fMRI) during four tasks; 1) Visuospatial 2-Back, 2) Go/NoGo, 3) Letter 2-Back and 4) Counting Stroop task. Sixteen participants were prenatally exposed to marijuana while 15 had no prenatal marijuana exposure. Task performance was similar for both groups but blood flow was significantly different between the groups. This paper presents the results for all 4 tasks, highlighting the consistently increased left posterior brain activity in the prenatally exposed group compared with the control group. These alterations in neurophysiological functioning of young adults prenatally exposed to marijuana emphasizes the importance of education for women in child bearing years, as well as for policy makers and physicians interested in the welfare of both the pregnant women and their offspring's future success. Copyright © 2016 Elsevier Inc. All rights reserved.

Reconstructing ecosystem functions of the active microbial community of the Baltic Sea oxygen depleted sediments

PubMed Central

Franzetti, Andrea; Lundin, Daniel; Sjöling, Sara

2016-01-01

Baltic Sea deep water and sediments hold one of the largest anthropogenically induced hypoxic areas in the world. High nutrient input and low water exchange result in eutrophication and oxygen depletion below the halocline. As a consequence at Landsort Deep, the deepest point of the Baltic Sea, anoxia in the sediments has been a persistent condition over the past decades. Given that microbial communities are drivers of essential ecosystem functions we investigated the microbial community metabolisms and functions of oxygen depleted Landsort Deep sediments by metatranscriptomics. Results show substantial expression of genes involved in protein metabolism demonstrating that the Landsort Deep sediment microbial community is active. Identified expressed gene suites of metabolic pathways with importance for carbon transformation including fermentation, dissimilatory sulphate reduction and methanogenesis were identified. The presence of transcripts for these metabolic processes suggests a potential for heterotrophic-autotrophic community synergism and indicates active mineralisation of the organic matter deposited at the sediment as a consequence of the eutrophication process. Furthermore, cyanobacteria, probably deposited from the water column, are transcriptionally active in the anoxic sediment at this depth. Results also reveal high abundance of transcripts encoding integron integrases. These results provide insight into the activity of the microbial community of the anoxic sediment at the deepest point of the Baltic Sea and its possible role in ecosystem functioning. PMID:26823996

Enhancers of Polycomb EPC1 and EPC2 sustain the oncogenic potential of MLL leukemia stem cells

PubMed Central

Huang, Xu; Spencer, Gary J; Lynch, James T; Ciceri, Filippo; Somerville, Tim D D; Somervaille, Tim C P

2013-01-01

Through a targeted knockdown (KD) screen of chromatin regulatory genes we identified the EP400 complex components EPC1 and EPC2 as critical oncogenic co-factors in acute myeloid leukemia (AML). EPC1 and EPC2 were required for the clonogenic potential of human AML cells of multiple molecular subtypes. Focusing on MLL-mutated AML as an exemplar, Epc1 or Epc2 KD induced apoptosis of murine MLL-AF9 AML cells and abolished leukemia stem cell potential. By contrast, normal hematopoietic stem and progenitor cells (HSPC) were spared. Similar selectivity was observed for human primary AML cells versus normal CD34+ HSPC. In keeping with these distinct functional consequences, Epc1 or Epc2 KD induced divergent transcriptional consequences in murine MLL-AF9 granulocyte-macrophage progenitor-like (GMP) cells versus normal GMP, with a signature of increased MYC activity in leukemic but not normal cells. This was caused by accumulation of MYC protein and was also observed following KD of other EP400 complex genes. Pharmacological inhibition of MYC:MAX dimerization, or concomitant MYC KD, reduced apoptosis following EPC1 KD, linking the accumulation of MYC to cell death. Therefore EPC1 and EPC2 are components of a complex which directly or indirectly serves to prevent MYC accumulation and AML cell apoptosis, thus sustaining oncogenic potential. PMID:24166297

Quantum mechanics of a constrained particle

NASA Astrophysics Data System (ADS)

da Costa, R. C. T.

1981-04-01

The motion of a particle rigidly bounded to a surface is discussed, considering the Schrödinger equation of a free particle constrained to move, by the action of an external potential, in an infinitely thin sheet of the ordinary three-dimensional space. Contrary to what seems to be the general belief expressed in the literature, this limiting process gives a perfectly well-defined result, provided that we take some simple precautions in the definition of the potentials and wave functions. It can then be shown that the wave function splits into two parts: the normal part, which contains the infinite energies required by the uncertainty principle, and a tangent part which contains "surface potentials" depending both on the Gaussian and mean curvatures. An immediate consequence of these results is the existence of different quantum mechanical properties for two isometric surfaces, as can be seen from the bound state which appears along the edge of a folded (but not stretched) plane. The fact that this surface potential is not a bending invariant (cannot be expressed as a function of the components of the metric tensor and their derivatives) is also interesting from the more general point of view of the quantum mechanics in curved spaces, since it can never be obtained from the classical Lagrangian of an a priori constrained particle without substantial modifications in the usual quantization procedures. Similar calculations are also presented for the case of a particle bounded to a curve. The properties of the constraining spatial potential, necessary to a meaningful limiting process, are discussed in some detail, and, as expected, the resulting Schrödinger equation contains a "linear potential" which is a function of the curvature.

Nonlinear spectral singularities for confined nonlinearities.

PubMed

Mostafazadeh, Ali

2013-06-28

We introduce a notion of spectral singularity that applies for a general class of nonlinear Schrödinger operators involving a confined nonlinearity. The presence of the nonlinearity does not break the parity-reflection symmetry of spectral singularities but makes them amplitude dependent. Nonlinear spectral singularities are, therefore, associated with a resonance effect that produces amplified waves with a specific amplitude-wavelength profile. We explore the consequences of this phenomenon for a complex δ-function potential that is subject to a general confined nonlinearity.

British Military Mission (BMM) to Greece, 1942-44

DTIC Science & Technology

2009-05-21

Terrorism. Failure to take into account and accurately assess political and military actions in such environments can lead to unintended consequences ...such environments can lead to unintended consequences (potential civil war) affecting the stability of a country. Accurate assessment of the political...take into account and accurately assess political and military actions in such environments can lead to unintended consequences (potential civil war

Dominant β-catenin mutations cause intellectual disability with recognizable syndromic features

PubMed Central

Tucci, Valter; Kleefstra, Tjitske; Hardy, Andrea; Heise, Ines; Maggi, Silvia; Willemsen, Marjolein H.; Hilton, Helen; Esapa, Chris; Simon, Michelle; Buenavista, Maria-Teresa; McGuffin, Liam J.; Vizor, Lucie; Dodero, Luca; Tsaftaris, Sotirios; Romero, Rosario; Nillesen, Willy N.; Vissers, Lisenka E.L.M.; Kempers, Marlies J.; Vulto-van Silfhout, Anneke T.; Iqbal, Zafar; Orlando, Marta; Maccione, Alessandro; Lassi, Glenda; Farisello, Pasqualina; Contestabile, Andrea; Tinarelli, Federico; Nieus, Thierry; Raimondi, Andrea; Greco, Barbara; Cantatore, Daniela; Gasparini, Laura; Berdondini, Luca; Bifone, Angelo; Gozzi, Alessandro; Wells, Sara; Nolan, Patrick M.

2014-01-01

The recent identification of multiple dominant mutations in the gene encoding β-catenin in both humans and mice has enabled exploration of the molecular and cellular basis of β-catenin function in cognitive impairment. In humans, β-catenin mutations that cause a spectrum of neurodevelopmental disorders have been identified. We identified de novo β-catenin mutations in patients with intellectual disability, carefully characterized their phenotypes, and were able to define a recognizable intellectual disability syndrome. In parallel, characterization of a chemically mutagenized mouse line that displays features similar to those of human patients with β-catenin mutations enabled us to investigate the consequences of β-catenin dysfunction through development and into adulthood. The mouse mutant, designated batface (Bfc), carries a Thr653Lys substitution in the C-terminal armadillo repeat of β-catenin and displayed a reduced affinity for membrane-associated cadherins. In association with this decreased cadherin interaction, we found that the mutation results in decreased intrahemispheric connections, with deficits in dendritic branching, long-term potentiation, and cognitive function. Our study provides in vivo evidence that dominant mutations in β-catenin underlie losses in its adhesion-related functions, which leads to severe consequences, including intellectual disability, childhood hypotonia, progressive spasticity of lower limbs, and abnormal craniofacial features in adults. PMID:24614104

Phosphatidic acid in neuronal development: a node for membrane and cytoskeleton rearrangements.

PubMed

Ammar, Mohamed-Raafet; Kassas, Nawal; Bader, Marie-France; Vitale, Nicolas

2014-12-01

Phosphatidic acid (PA) is the simplest phospholipid naturally existing in all-living organisms. It constitutes only a minor fraction of the total cell lipids but has attracted considerable attention being both a lipid second messenger and a modulator of membrane shape. The pleiotropic functions of PA are the direct consequence of its very simple chemical structure consisting of only two acyl chains linked by ester bonds to two adjacent hydroxyl groups of glycerol, whose remaining hydroxyl group is esterified with a phosphomonoester group. Hence the small phosphate head group of PA gives it the shape of a cone providing flexibility and negative curvatures in the context of a lipid bilayer. In addition, the negatively charged phosphomonoester headgroup of PA is unique because it can potentially carry one or two negative charges playing a role in the recruitment of positively charged molecules to biomembranes. In consequence, PA has been proposed to play various key cellular functions. In the brain, a fine balance between cell growth, migration and differentiation, and cell death is required to sculpt the nervous system during development. In this review, we will summarize the various functions that have been proposed for PA in neuronal development. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Decoupling Coupled Constraints Through Utility Design

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, N; Marden, JR

2014-08-01

Several multiagent systems exemplify the need for establishing distributed control laws that ensure the resulting agents' collective behavior satisfies a given coupled constraint. This technical note focuses on the design of such control laws through a game-theoretic framework. In particular, this technical note provides two systematic methodologies for the design of local agent objective functions that guarantee all resulting Nash equilibria optimize the system level objective while also satisfying a given coupled constraint. Furthermore, the designed local agent objective functions fit into the framework of state based potential games. Consequently, one can appeal to existing results in game-theoretic learning tomore » derive a distributed process that guarantees the agents will reach such an equilibrium.« less

A New Pathogenesis of Albuminuria: Role of Transcytosis.

PubMed

He, Fang-Fang; Gong, Yi; Li, Zhen-Qiong; Wu, Liang; Jiang, Hua-Jun; Su, Hua; Zhang, Chun; Wang, Yu-Mei

2018-06-15

Transcytosis is an important intracellular transport process by which multicellular organisms selectively move cargoes from apical to basolateral membranes without disrupting cellular homeostasis. In kidney, macromolecular components in the serum, such as albumin, low-density lipoprotein and immunoglobulins, pass through the glomerular filtration barrier (GFB) and proximal tubular cells (PTCs) by transcytosis. Protein transcytosis plays a vital role in the pathology of albuminuria, which causes progressive destruction of the GFB structure and function. However, the pathophysiological consequences of protein transcytosis in the kidney remain largely unknown. This article summarizes recent researches on the regulation of albumin transcytosis across the GFB and PTCs in both physiological and pathological conditions. Understanding the mechanism of albumin transcytosis may reveal potential therapeutic targets for prevention or alleviation of the pathological consequences of albuminuria. © 2018 The Author(s). Published by S. Karger AG, Basel.

Stochastic Consequence Analysis for Waste Leaks

DOE Office of Scientific and Technical Information (OSTI.GOV)

HEY, B.E.

This analysis evaluates the radiological consequences of potential Hanford Tank Farm waste transfer leaks. These include ex-tank leaks into structures, underneath the soil, and exposed to the atmosphere. It also includes potential misroutes, tank overflow

Integrative self-assembly of functional hybrid nanoconstructs by inorganic wrapping of single biomolecules, biomolecule arrays and organic supramolecular assemblies

NASA Astrophysics Data System (ADS)

Patil, Avinash J.; Li, Mei; Mann, Stephen

2013-07-01

Synthesis of functional hybrid nanoscale objects has been a core focus of the rapidly progressing field of nanomaterials science. In particular, there has been significant interest in the integration of evolutionally optimized biological systems such as proteins, DNA, virus particles and cells with functional inorganic building blocks to construct mesoscopic architectures and nanostructured materials. However, in many cases the fragile nature of the biomolecules seriously constrains their potential applications. As a consequence, there is an on-going quest for the development of novel strategies to modulate the thermal and chemical stabilities, and performance of biomolecules under adverse conditions. This feature article highlights new methods of ``inorganic molecular wrapping'' of single or multiple protein molecules, individual double-stranded DNA helices, lipid bilayer vesicles and self-assembled organic dye superstructures using inorganic building blocks to produce bio-inorganic nanoconstructs with core-shell type structures. We show that spatial isolation of the functional biological nanostructures as ``armour-plated'' enzyme molecules or polynucleotide strands not only maintains their intact structure and biochemical properties, but also enables the fabrication of novel hybrid nanomaterials for potential applications in diverse areas of bionanotechnology.

Targeting complement-mediated immunoregulation for cancer immunotherapy.

PubMed

Kolev, Martin; Markiewski, Maciej M

2018-06-01

Complement was initially discovered as an assembly of plasma proteins "complementing" the cytolytic activity of antibodies. However, our current knowledge places this complex system of several plasma proteins, receptors, and regulators in the center of innate immunity as a bridge between the initial innate responses and adaptive immune reactions. Consequently, complement appears to be pivotal for elimination of pathogens, not only as an early response defense, but by directing the subsequent adaptive immune response. The discovery of functional intracellular complement and its roles in cellular metabolism opened novel avenues for research and potential therapeutic implications. The recent studies demonstrating immunoregulatory functions of complement in the tumor microenvironment and the premetastatic niche shifted the paradigm on our understanding of functions of the complement system in regulating immunity. Several complement proteins, through their interaction with cells in the tumor microenvironment and in metastasis-targeted organs, contribute to modulating tumor growth, antitumor immunity, angiogenesis, and therefore, the overall progression of malignancy and, perhaps, responsiveness of cancer to different therapies. Here, we focus on recent progress in our understanding of immunostimulatory vs. immunoregulatory functions of complement and potential applications of these findings to the design of novel therapies for cancer patients. Copyright © 2018 Elsevier Ltd. All rights reserved.

Multiscale model within-host and between-host for viral infectious diseases.

PubMed

Almocera, Alexis Erich S; Nguyen, Van Kinh; Hernandez-Vargas, Esteban A

2018-05-08

Multiscale models possess the potential to uncover new insights into infectious diseases. Here, a rigorous stability analysis of a multiscale model within-host and between-host is presented. The within-host model describes viral replication and the respective immune response while disease transmission is represented by a susceptible-infected model. The bridging of scales from within- to between-host considered transmission as a function of the viral load. Consequently, stability and bifurcation analyses were developed coupling the two basic reproduction numbers [Formula: see text] and [Formula: see text] for the within- and the between-host subsystems, respectively. Local stability results for each subsystem, including a unique stable equilibrium point, recapitulate classical approaches to infection and epidemic control. Using a Lyapunov function, global stability of the between-host system was obtained. Our main result was the derivation of the [Formula: see text] as an increasing function of [Formula: see text]. Numerical analyses reveal that a Michaelis-Menten form based on the virus is more likely to recapitulate the behavior between the scales than a form directly proportional to the virus. Our work contributes basic understandings of the two models and casts light on the potential effects of the coupling function on linking the two scales.

Integrative self-assembly of functional hybrid nanoconstructs by inorganic wrapping of single biomolecules, biomolecule arrays and organic supramolecular assemblies.

PubMed

Patil, Avinash J; Li, Mei; Mann, Stephen

2013-08-21

Synthesis of functional hybrid nanoscale objects has been a core focus of the rapidly progressing field of nanomaterials science. In particular, there has been significant interest in the integration of evolutionally optimized biological systems such as proteins, DNA, virus particles and cells with functional inorganic building blocks to construct mesoscopic architectures and nanostructured materials. However, in many cases the fragile nature of the biomolecules seriously constrains their potential applications. As a consequence, there is an on-going quest for the development of novel strategies to modulate the thermal and chemical stabilities, and performance of biomolecules under adverse conditions. This feature article highlights new methods of "inorganic molecular wrapping" of single or multiple protein molecules, individual double-stranded DNA helices, lipid bilayer vesicles and self-assembled organic dye superstructures using inorganic building blocks to produce bio-inorganic nanoconstructs with core-shell type structures. We show that spatial isolation of the functional biological nanostructures as "armour-plated" enzyme molecules or polynucleotide strands not only maintains their intact structure and biochemical properties, but also enables the fabrication of novel hybrid nanomaterials for potential applications in diverse areas of bionanotechnology.

A Theoretical Mechanism of Szilard Engine Function in Nucleic Acids and the Implications for Quantum Coherence in Biological Systems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Matthew Mihelic, F.

2010-12-22

Nucleic acids theoretically possess a Szilard engine function that can convert the energy associated with the Shannon entropy of molecules for which they have coded recognition, into the useful work of geometric reconfiguration of the nucleic acid molecule. This function is logically reversible because its mechanism is literally and physically constructed out of the information necessary to reduce the Shannon entropy of such molecules, which means that this information exists on both sides of the theoretical engine, and because information is retained in the geometric degrees of freedom of the nucleic acid molecule, a quantum gate is formed through whichmore » multi-state nucleic acid qubits can interact. Entangled biophotons emitted as a consequence of symmetry breaking nucleic acid Szilard engine (NASE) function can be used to coordinate relative positioning of different nucleic acid locations, both within and between cells, thus providing the potential for quantum coherence of an entire biological system. Theoretical implications of understanding biological systems as such 'quantum adaptive systems' include the potential for multi-agent based quantum computing, and a better understanding of systemic pathologies such as cancer, as being related to a loss of systemic quantum coherence.« less

A Theoretical Mechanism of Szilard Engine Function in Nucleic Acids and the Implications for Quantum Coherence in Biological Systems

NASA Astrophysics Data System (ADS)

Matthew Mihelic, F.

2010-12-01

Nucleic acids theoretically possess a Szilard engine function that can convert the energy associated with the Shannon entropy of molecules for which they have coded recognition, into the useful work of geometric reconfiguration of the nucleic acid molecule. This function is logically reversible because its mechanism is literally and physically constructed out of the information necessary to reduce the Shannon entropy of such molecules, which means that this information exists on both sides of the theoretical engine, and because information is retained in the geometric degrees of freedom of the nucleic acid molecule, a quantum gate is formed through which multi-state nucleic acid qubits can interact. Entangled biophotons emitted as a consequence of symmetry breaking nucleic acid Szilard engine (NASE) function can be used to coordinate relative positioning of different nucleic acid locations, both within and between cells, thus providing the potential for quantum coherence of an entire biological system. Theoretical implications of understanding biological systems as such "quantum adaptive systems" include the potential for multi-agent based quantum computing, and a better understanding of systemic pathologies such as cancer, as being related to a loss of systemic quantum coherence.

Heavy ion beam probe operation in time varying equilibria of improved confinement reversed field pinch discharges.

PubMed

Demers, D R; Chen, X; Schoch, P M; Fimognari, P J

2010-10-01

Operation of a heavy ion beam probe (HIBP) on a reversed field pinch is unique from other toroidal applications because the magnetic field is more temporal and largely produced by plasma current. Improved confinement, produced through the transient application of a poloidal electric field which leads to a reduction of dynamo activity, exhibits gradual changes in equilibrium plasma quantities. A consequence of this is sweeping of the HIBP trajectories by the dynamic magnetic field, resulting in motion of the sample volume. In addition, the plasma potential evolves with the magnetic equilibrium. Measurement of the potential as a function of time is thus a combination of temporal changes of the equilibrium and motion of the sample volume. A frequent additional complication is a nonideal balance of ion current on the detectors resulting from changes in the beam trajectory (magnetic field) and energy (plasma potential). This necessitates use of data selection criteria. Nevertheless, the HIBP on the Madison Symmetric Torus has acquired measurements as a function of time throughout improved confinement. A technique developed to infer the potential in the improved confinement reversed field pinch from HIBP data in light of the time varying plasma equilibrium will be discussed.

Expression, Localization of SUMO-1, and Analyses of Potential SUMOylated Proteins in Bubalus bubalis Spermatozoa

PubMed Central

Brohi, Rahim Dad; Wang, Li; Hassine, Najla Ben; Cao, Jing; Talpur, Hira Sajjad; Wu, Di; Huang, Chun-Jie; Rehman, Zia-Ur; Bhattarai, Dinesh; Huo, Li-Jun

2017-01-01

Mature spermatozoa have highly condensed DNA that is essentially silent both transcriptionally and translationally. Therefore, post translational modifications are very important for regulating sperm motility, morphology, and for male fertility in general. Protein sumoylation was recently demonstrated in human and rodent spermatozoa, with potential consequences for sperm motility and DNA integrity. We examined the expression and localization of small ubiquitin-related modifier-1 (SUMO-1) in the sperm of water buffalo (Bubalus bubalis) using immunofluorescence analysis. We confirmed the expression of SUMO-1 in the acrosome. We further found that SUMO-1 was lost if the acrosome reaction was induced by calcium ionophore A23187. Proteins modified or conjugated by SUMO-1 in water buffalo sperm were pulled down and analyzed by mass spectrometry. Sixty proteins were identified, including proteins important for sperm morphology and motility, such as relaxin receptors and cytoskeletal proteins, including tubulin chains, actins, and dyneins. Forty-six proteins were predicted as potential sumoylation targets. The expression of SUMO-1 in the acrosome region of water buffalo sperm and the identification of potentially SUMOylated proteins important for sperm function implicates sumoylation as a crucial PTM related to sperm function. PMID:28659810

A nuclear ribosomal DNA pseudogene in triatomines opens a new research field of fundamental and applied implications in Chagas disease.

PubMed

Zuriaga, María Angeles; Mas-Coma, Santiago; Bargues, María Dolores

2015-05-01

A pseudogene, designated as "ps(5.8S+ITS-2)", paralogous to the 5.8S gene and internal transcribed spacer (ITS)-2 of the nuclear ribosomal DNA (rDNA), has been recently found in many triatomine species distributed throughout North America, Central America and northern South America. Among characteristics used as criteria for pseudogene verification, secondary structures and free energy are highlighted, showing a lower fit between minimum free energy, partition function and centroid structures, although in given cases the fit only appeared to be slightly lower. The unique characteristics of "ps(5.8S+ITS-2)" as a processed or retrotransposed pseudogenic unit of the ghost type are reviewed, with emphasis on its potential functionality compared to the functionality of genes and spacers of the normal rDNA operon. Besides the technical problem of the risk for erroneous sequence results, the usefulness of "ps(5.8S+ITS-2)" for specimen classification, phylogenetic analyses and systematic/taxonomic studies should be highlighted, based on consistence and retention index values, which in pseudogenic sequence trees were higher than in functional sequence trees. Additionally, intraindividual, interpopulational and interspecific differences in pseudogene amount and the fact that it is a pseudogene in the nuclear rDNA suggests a potential relationships with fitness, behaviour and adaptability of triatomine vectors and consequently its potential utility in Chagas disease epidemiology and control.

Predicting the Effect of Mutations on Protein-Protein Binding Interactions through Structure-Based Interface Profiles

PubMed Central

Brender, Jeffrey R.; Zhang, Yang

2015-01-01

The formation of protein-protein complexes is essential for proteins to perform their physiological functions in the cell. Mutations that prevent the proper formation of the correct complexes can have serious consequences for the associated cellular processes. Since experimental determination of protein-protein binding affinity remains difficult when performed on a large scale, computational methods for predicting the consequences of mutations on binding affinity are highly desirable. We show that a scoring function based on interface structure profiles collected from analogous protein-protein interactions in the PDB is a powerful predictor of protein binding affinity changes upon mutation. As a standalone feature, the differences between the interface profile score of the mutant and wild-type proteins has an accuracy equivalent to the best all-atom potentials, despite being two orders of magnitude faster once the profile has been constructed. Due to its unique sensitivity in collecting the evolutionary profiles of analogous binding interactions and the high speed of calculation, the interface profile score has additional advantages as a complementary feature to combine with physics-based potentials for improving the accuracy of composite scoring approaches. By incorporating the sequence-derived and residue-level coarse-grained potentials with the interface structure profile score, a composite model was constructed through the random forest training, which generates a Pearson correlation coefficient >0.8 between the predicted and observed binding free-energy changes upon mutation. This accuracy is comparable to, or outperforms in most cases, the current best methods, but does not require high-resolution full-atomic models of the mutant structures. The binding interface profiling approach should find useful application in human-disease mutation recognition and protein interface design studies. PMID:26506533

Computational Models of Neuronal Biophysics and the Characterization of Potential Neuropharmacological Targets

PubMed Central

Ferrante, Michele; Blackwell, Kim T.; Migliore, Michele; Ascoli, Giorgio A.

2012-01-01

The identification and characterization of potential pharmacological targets in neurology and psychiatry is a fundamental problem at the intersection between medicinal chemistry and the neurosciences. Exciting new techniques in proteomics and genomics have fostered rapid progress, opening numerous questions as to the functional consequences of ligand binding at the systems level. Psycho- and neuro-active drugs typically work in nerve cells by affecting one or more aspects of electrophysiological activity. Thus, an integrated understanding of neuropharmacological agents requires bridging the gap between their molecular mechanisms and the biophysical determinants of neuronal function. Computational neuroscience and bioinformatics can play a major role in this functional connection. Robust quantitative models exist describing all major active membrane properties under endogenous and exogenous chemical control. These include voltage-dependent ionic channels (sodium, potassium, calcium, etc.), synaptic receptor channels (e.g. glutamatergic, GABAergic, cholinergic), and G protein coupled signaling pathways (protein kinases, phosphatases, and other enzymatic cascades). This brief review of neuromolecular medicine from the computational perspective provides compelling examples of how simulations can elucidate, explain, and predict the effect of chemical agonists, antagonists, and modulators in the nervous system. PMID:18855673

Levetiracetam as a possible contributor to acute kidney injury.

PubMed

Spengler, Danielle C; Montouris, Georgia D; Hohler, Anna D

2014-08-01

Levetiracetam is an antiepileptic medication that has been reported to be both well-tolerated and effective in treating generalized tonic-clonic, myoclonic, and partial-onset seizures. The adverse effects most commonly reported in tolerability trials include somnolence, fatigue/asthenia, headaches, dizziness, and nausea. However, there have been a few reports suggesting possible detrimental effects of levetiracetam on renal function. Here we describe the case of a previously healthy 23-year-old female patient who developed acute kidney injury 1 day after the initiation of levetiracetam therapy for new-onset seizures. Based on the time course of the patient's rise in serum creatinine and the exclusion of other causes, this case suggests that levetiracetam use contributed to the acute kidney injury. Levetiracetam is a widely used drug that has been reported to be generally tolerable and effective; however, it has the potential to negatively affect renal function. This potential consequence of therapy should be considered when deciding whether or not to prescribe this medication, and renal function should be monitored during treatment. Copyright © 2014 Elsevier HS Journals, Inc. All rights reserved.

Prototype for Automatable, Dielectrophoretically-Accessed Intracellular Membrane–Potential Measurements by Metal Electrodes

PubMed Central

Sukhorukov, Vladimir L.; Zimmermann, Dirk

2013-01-01

Abstract Functional access to membrane proteins, for example, ion channels, of individual cells is an important prerequisite in drug discovery studies. The highly sophisticated patch-clamp method is widely used for electrogenic membrane proteins, but is demanding for the operator, and its automation remains challenging. The dielectrophoretically-accessed, intracellular membrane–potential measurement (DAIMM) method is a new technique showing high potential for automation of electrophysiological data recording in the whole-cell configuration. A cell suspension is brought between a mm-scaled planar electrode and a μm-scaled tip electrode, placed opposite to each other. Due to the asymmetric electrode configuration, the application of alternating electric fields (1–5 MHz) provokes a dielectrophoretic force acting on the target cell. As a consequence, the cell is accelerated and pierced by the tip electrode, hence functioning as the internal (working) electrode. We used the light-gated cation channel Channelrhodopsin-2 as a reporter protein expressed in HEK293 cells to characterize the DAIMM method in comparison with the patch-clamp technique. PMID:22994967

Thermodynamics of charged dilatonic BTZ black holes in rainbow gravity

NASA Astrophysics Data System (ADS)

Dehghani, M.

2018-02-01

In this paper, the charged three-dimensional Einstein's theory coupled to a dilatonic field has been considered in the rainbow gravity. The dilatonic potential has been written as the linear combination of two Liouville-type potentials. Four new classes of charged dilatonic rainbow black hole solutions, as the exact solution to the coupled field equations of the energy dependent space time, have been obtained. Two of them are correspond to the Coulomb's electric field and the others are consequences of a modified Coulomb's law. Total charge and mass as well as the entropy, temperature and electric potential of the new charged black holes have been calculated in the presence of rainbow functions. Although the thermodynamic quantities are affected by the rainbow functions, it has been found that the first law of black hole thermodynamics is still valid for all of the new black hole solutions. At the final stage, making use of the canonical ensemble method and regarding the black hole heat capacity, the thermal stability or phase transition of the new rainbow black hole solutions have been analyzed.

The potential of protein-nanomaterial interaction for advanced drug delivery.

PubMed

Peng, Qiang; Mu, Huiling

2016-03-10

Nanomaterials, like nanoparticles, micelles, nano-sheets, nanotubes and quantum dots, have great potentials in biomedical fields. However, their delivery is highly limited by the formation of protein corona upon interaction with endogenous proteins. This new identity, instead of nanomaterial itself, would be the real substance the organs and cells firstly encounter. Consequently, the behavior of nanomaterials in vivo is uncontrollable and some undesired effects may occur, like rapid clearance from blood stream; risk of capillary blockage; loss of targeting capacity; and potential toxicity. Therefore, protein-nanomaterial interaction is a great challenge for nanomaterial systems and should be inhibited. However, this interaction can also be used to functionalize nanomaterials by forming a selected protein corona. Unlike other decoration using exogenous molecules, nanomaterials functionalized by selected protein corona using endogenous proteins would have greater promise for clinical use. In this review, we aim to provide a comprehensive understanding of protein-nanomaterial interaction. Importantly, a discussion about how to use such interaction is launched and some possible applications of such interaction for advanced drug delivery are presented. Copyright © 2016 Elsevier B.V. All rights reserved.

Functional Analysis of Episodic Self-Injury Correlated with Recurrent Otitis Media.

ERIC Educational Resources Information Center

O'Reilly, Mark F.

1997-01-01

A functional analysis examined the consequences that maintained episodic self-injury and the relationship between those consequences and otitis media for a 26-month-old child with developmental disabilities. Results indicated that self-injury occurred only during periods of otitis media and may have served as a sensory escape function. (Author/CR)

Joint statistics of strongly correlated neurons via dimensionality reduction

NASA Astrophysics Data System (ADS)

Deniz, Taşkın; Rotter, Stefan

2017-06-01

The relative timing of action potentials in neurons recorded from local cortical networks often shows a non-trivial dependence, which is then quantified by cross-correlation functions. Theoretical models emphasize that such spike train correlations are an inevitable consequence of two neurons being part of the same network and sharing some synaptic input. For non-linear neuron models, however, explicit correlation functions are difficult to compute analytically, and perturbative methods work only for weak shared input. In order to treat strong correlations, we suggest here an alternative non-perturbative method. Specifically, we study the case of two leaky integrate-and-fire neurons with strong shared input. Correlation functions derived from simulated spike trains fit our theoretical predictions very accurately. Using our method, we computed the non-linear correlation transfer as well as correlation functions that are asymmetric due to inhomogeneous intrinsic parameters or unequal input.

Biomaterials Made from Coiled-Coil Peptides.

PubMed

Conticello, Vincent; Hughes, Spencer; Modlin, Charles

The development of biomaterials designed for specific applications is an important objective in personalized medicine. While the breadth and prominence of biomaterials have increased exponentially over the past decades, critical challenges remain to be addressed, particularly in the development of biomaterials that exhibit highly specific functions. These functional properties are often encoded within the molecular structure of the component molecules. Proteins, as a consequence of their structural specificity, represent useful substrates for the construction of functional biomaterials through rational design. This chapter provides an in-depth survey of biomaterials constructed from coiled-coils, one of the best-understood protein structural motifs. We discuss the utility of this structurally diverse and functionally tunable class of proteins for the creation of novel biomaterials. This discussion illustrates the progress that has been made in the development of coiled-coil biomaterials by showcasing studies that bridge the gap between the academic science and potential technological impact.

From anatomy to function: diagnosis of atherosclerotic renal artery stenosis.

PubMed

Odudu, Aghogho; Vassallo, Diana; Kalra, Philip A

2015-12-01

Atherosclerotic renal artery stenosis (ARAS) affects 7% of the over 65 s and will be increasingly common with an ageing population. ARAS obstructs normal renal perfusion with adverse renal and cardiovascular consequences. Drug therapy is directed at reducing atherosclerotic risk. Two recent major trials of revascularization for ARAS showed that clinical outcomes were not improved beyond those offered by optimal drug therapy in most patients. This reflects experimental data showing that restoration of blood flow alone may not attenuate a cascade of tissue injury. A shift from anatomic to functional imaging of ARAS coupled to novel therapies might improve clinical outcomes in selected patients. This review outlines the case for separately assessing hemodynamic significance of arterial stenosis and functional reserve of renal parenchymal tissue. The authors consider current and emerging diagnostic techniques for ARAS and their potential to allow individualized and functionally directed treatments.

Time-dependent local potential in a Tomonaga-Luttinger liquid

NASA Astrophysics Data System (ADS)

Kamar, Naushad Ahmad; Giamarchi, Thierry

2017-12-01

We study the energy deposition in a one-dimensional interacting quantum system with a pointlike potential modulated in amplitude. The pointlike potential at position x =0 has a constant part and a small oscillation in time with a frequency ω . We use bosonization, renormalization group, and linear response theory to calculate the corresponding energy deposition. It exhibits a power law behavior as a function of the frequency that reflects the Tomonaga-Luttinger liquid (TLL) nature of the system. Depending on the interactions in the system, characterized by the TLL parameter K of the system, a crossover between weak and strong coupling for the backscattering due to the potential is possible. We compute the frequency scale ω*, at which such crossover exists. We find that the energy deposition due to the backscattering shows different exponents for K >1 and K <1 . We discuss possible experimental consequences, in the context of cold atomic gases, of our theoretical results.

Long-term psychosocial consequences of surgical congenital malformations.

PubMed

Diseth, Trond H; Emblem, Ragnhild

2017-10-01

Surgical congenital malformations often represent years of treatment, large number of hospital stays, treatment procedures, and long-term functional sequels affecting patients' psychosocial functioning. Both functional defects and psychosocial difficulties that occur commonly in childhood may pass through adolescence on to adulthood. This overview presents reports published over the past 3 decades to elucidate the long-term psychosocial consequences of surgical congenital malformations. Literature searches conducted on PubMed database revealed that less than 1% of all the records of surgical congenital malformations described long-term psychosocial consequences, but with diverse findings. This inconsistency may be due to methodological differences or deficiencies; especially in study design, patient sampling, and methods. Most of the studies revealed that the functional deficits may have great impact on patients' mental health, psychosocial functioning, and QoL; both short- and long-term negative consequences. Factors other than functional problems, e.g., repeated anesthesia, multiple hospitalization, traumatic treatment procedures, and parental dysfunctioning, may also predict long-term mental health and psychosocial functioning. Through multidisciplinary approach, pediatric surgeons should also be aware of deficits in emotional and psychosocial functioning. To achieve overall optimal psychosocial functioning, the challenge is to find a compromise between physically optimal treatment procedures and procedures that are not psychologically detrimental. Copyright © 2017. Published by Elsevier Inc.

Cardiovascular Consequences of Metabolic Syndrome

PubMed Central

Tune, Johnathan D.; Goodwill, Adam G.; Sassoon, Daniel J.; Mather, Kieren J.

2017-01-01

The metabolic syndrome (MetS) is defined as the concurrence of obesity-associated cardiovascular risk factors including abdominal obesity, impaired glucose tolerance, hypertriglyceridemia, decreased HDL cholesterol, and/or hypertension. Earlier conceptualizations of the MetS focused on insulin resistance as a core feature, and it is clearly coincident with the above list of features. Each component of the MetS is an independent risk factor for cardiovascular disease and the combination of these risk factors elevates rates and severity of cardiovascular disease, related to a spectrum of cardiovascular conditions including microvascular dysfunction, coronary atherosclerosis and calcification, cardiac dysfunction, myocardial infarction, and heart failure. While advances in understanding the etiology and consequences of this complex disorder have been made, the underlying pathophysiologic mechanisms remain incompletely understood, and it is unclear how these concurrent risk factors conspire to produce the variety of obesity-associated adverse cardiovascular diseases. In this review we highlight current knowledge regarding the pathophysiologic consequences of obesity and the MetS on cardiovascular function and disease, including considerations of potential physiologic and molecular mechanisms that may contribute to these adverse outcomes. PMID:28130064

Elderly persons with ICU-acquired weakness: the potential role for β-hydroxy-β-methylbutyrate (HMB) supplementation?

PubMed

Rahman, Adam; Wilund, Kenneth; Fitschen, Peter J; Jeejeebhoy, Khursheed; Agarwala, Ravi; Drover, John W; Mourtzakis, Marina

2014-07-01

Intensive care unit (ICU)-acquired weakness is common and characterized by muscle loss, weakness, and paralysis. It is associated with poor short-term outcomes, including increased mortality, but the consequences of reduced long-term outcomes, including decreased physical function and quality of life, can be just as devastating. ICU-acquired weakness is particularly relevant to elderly patients who are increasingly consuming ICU resources and are at increased risk for ICU-acquired weakness and complications, including mortality. Elderly patients often enter critical illness with reduced muscle mass and function and are also at increased risk for accelerated disuse atrophy with acute illness. Increasingly, intensivists and researchers are focusing on strategies and therapies aimed at improving long-term neuromuscular function. β-Hydroxy-β-methylbutyrate (HMB), an ergogenic supplement, has shown efficacy in elderly patients and certain clinical populations in counteracting muscle loss. The present review discusses ICU-acquired weakness, as well as the unique physiology of muscle loss and skeletal muscle function in elderly patients, and then summarizes the evidence for HMB in elderly patients and in clinical populations. We subsequently postulate on the potential role and strategies in studying HMB in elderly ICU patients to improve muscle mass and function. © 2013 American Society for Parenteral and Enteral Nutrition.

Sexual Outcomes and Satisfaction with Hysterectomy: Influence of Patient Education

PubMed Central

Bradford, Andrea; Meston, Cindy

2010-01-01

Introduction Many women experience improved sexual function after hysterectomy. However, a sizeable minority of women report worsened sexual function after the surgery, and concerns about the effect of surgery on sexual function are common among women planning to undergo hysterectomy. Aim The present study examined the role of education about the potential sexual consequences of hysterectomy in predicting self-reported outcomes and satisfaction with the procedure. Methods We conducted a cross-sectional survey of 204 women who had undergone simple hysterectomy in the preceding 3–12 months. Participants volunteered in response to a Web-based advertisement. Main Outcome Measures Participants indicated their current sexual function using the Female Sexual Function Index (FSFI), and reported positive and negative sexual outcomes experienced after hysterectomy using a checklist. Participants also completed questionnaire items regarding satisfaction with hysterectomy and education from their physicians about sexual risks and benefits prior to surgery. Results Current sexual function scores were related to self-reports of positive and negative sexual outcomes following hysterectomy and overall satisfaction with hysterectomy. Education from a physician about possible adverse sexual outcomes was largely unrelated to self-reports of having experienced those outcomes. However, education about possible negative sexual outcomes predicted overall satisfaction with hysterectomy when controlling for self-reports of positive and negative sexual outcomes. Conclusion Education about potential negative sexual outcomes after surgery may enhance satisfaction with hysterectomy, independent of whether negative sexual outcomes were experienced. Including a discussion of potential sexual changes after surgery may enhance the benefits of presurgical counseling prior to hysterectomy. PMID:17087803

Kinetic features and non-stationary electron trapping in paraxial magnetic nozzles

NASA Astrophysics Data System (ADS)

Sánchez-Arriaga, G.; Zhou, J.; Ahedo, E.; Martínez-Sánchez, M.; Ramos, J. J.

2018-03-01

The paraxial expansion of a collisionless plasma jet into vacuum, guided by a magnetic nozzle, is studied with an Eulerian and non-stationary Vlasov-Poisson solver. Parametric analyzes varying the magnetic field expansion rate, the size of the simulation box, and the electrostatic potential fall are presented. After choosing the potential fall leading to a zero net current beam, the steady states of the simulations exhibit a quasi-neutral region followed by a downstream sheath. The latter, an unavoidable consequence of the finite size of the computational domain, does not affect the quasi-neutral region if the box size is chosen appropriately. The steady state presents a strong decay of the perpendicular temperature of the electrons, whose profile versus the inverse of the magnetic field does not depend on the expansion rate within the quasi-neutral region. As a consequence, the electron distribution function is highly anisotropic downstream. The simulations revealed that the ions reach a higher velocity during the transient than in the steady state and their distribution functions are not far from mono-energetic. The density percentage of the population of electrons trapped during the transient, which is computed self-consistently by the code, is up to 25% of the total electron density in the quasi-neutral region. It is demonstrated that the exact amount depends on the history of the system and the steady state is not unique. Nevertheless, the amount of trapped electrons is smaller than the one assumed heuristically by kinetic stationary theories.

Neural indicators of interpersonal anger as cause and consequence of combat training stress symptoms.

PubMed

Gilam, G; Lin, T; Fruchter, E; Hendler, T

2017-07-01

Angry outbursts are an important feature of various stress-related disorders, and commonly lead to aggression towards other people. Findings regarding interpersonal anger have linked the ventromedial prefrontal cortex (vmPFC) to anger regulation and the locus coeruleus (LC) to aggression. Both regions were previously associated with traumatic and chronic stress symptoms, yet it is unclear if their functionality represents a consequence of, or possibly also a cause for, stress symptoms. Here we investigated the relationship between the neural trajectory of these indicators of anger and the development and manifestation of stress symptoms. A total of 46 males (29 soldiers, 17 civilians) participated in a prospective functional magnetic resonance imaging experiment in which they played a modified interpersonal anger-provoking Ultimatum Game (UG) at two-points. Soldiers were tested at the beginning and end of combat training, while civilians were tested at the beginning and end of civil service. We assumed that combat training would induce chronic stress and result in increased stress symptoms. Soldiers showed an increase in stress symptoms following combat training while civilians showed no such change following civil service. All participants were angered by the modified UG irrespective of time point. Higher post-combat training stress symptoms were associated with lower pre-combat training vmPFC activation and with higher activation increase in the LC between pre- and post-combat training. Results suggest that during anger-provoking social interactions, flawed vmPFC functionality may serve as a causal risk factor for the development of stress symptoms, and heightened reactivity of the LC possibly reflects a consequence of stress-inducing combat training. These findings provide potential neural targets for therapeutic intervention and inoculation for stress-related psychopathological manifestations of anger.

Soils are sensitive reactors - do we need a paradigm change towards a more sustainable soil use?

NASA Astrophysics Data System (ADS)

Horn, Rainer; Holthusen, Dörthe

2015-04-01

The aim of the lecture is to clarify the effect of soil management and the consequences of physical degradation on processes like soil aggregation and changes in the accessibility and functionality of structured soils. If due to soil management strategies the internal soil strength will be exceeded by external stresses applied not only the available pore space is reduced while the solid mass is increased but especially the pore continuity and the accessibility of exchange places for nutrients or heavy metals are altered. In addition, the root distribution in soils becomes not only reduced but also unevenly distributed which again hinders the possibility to evenly uptake plant available water and nutrient out of the pores. The applied stresses also create an anisotropic arrangement of the pores and their functions and also result in a more pronounced lateral mass transport by surface runoff including soil erosion by water and wind. Thus, also the water balance on all scales (from the pedon to the catchment) shows an increased water loss by evaporation and surface water while the groundwater recharge and the transpiration rates are reduced. If we analyze the scale dependency of nutrient adsorption and desorption phenomena it has to be stated, that the accessibility of exchange places within soil aggregates are the better the more structured and the more rigid these aggregates are, while with increasing mechanical stress applied aggregates are deformed and as a consequences they become less porous with a severe differentiation between the outer and the inner part of the aggregate volume. On the bulk soil scale, we can analyze the platy structure as a visible hint for anthropogenic soil degradation which affects amongst others also the ion exchange processes. Furthermore an uneven aeration within such degraded soils results in a very pronounced anoxia on all scales (from the aggregate to the hectare scale) which can be quantified not only by corresponding measurements of the spatial distribution of redox potential values. In recent studies under "normal" wheeling conditions in arable fields and also in harvested forest sites it was proofed that Eh values close to 0 mV or even a methane emission have to be expected (with consequences for the global warming). Finally anoxic conditions also affect the redox induced mobilization of Fe and Mn which even results in a more rapid soil development with consequences also for yield and further soil functions. Consequently a shift to a more sustainable landuse or soil management strategy is urgently requested in order to prevent a further soil degradation. The scenario of peak soil must and can be prevented by a more site specific soil management. In the lecture, these effects will be discussed as well as a soil protection guide line (based on the German soil protection law) will be presented in order to prevent further irreversible soil degradation phenomena. Keywords: mechanical strength, mechanical stress and strain effects soil degradation, pore functions, ad-/desorption processes, redox potential, anoxia;, global change

Bidirectional Homeostatic Regulation of a Depression-Related Brain State by Gamma-Aminobutyric Acidergic Deficits and Ketamine Treatment.

PubMed

Ren, Zhen; Pribiag, Horia; Jefferson, Sarah J; Shorey, Matthew; Fuchs, Thomas; Stellwagen, David; Luscher, Bernhard

2016-09-15

Major depressive disorder is increasingly recognized to involve functional deficits in both gamma-aminobutyric acid (GABA)ergic and glutamatergic synaptic transmission. To elucidate the relationship between these phenotypes, we used GABAA receptor γ2 subunit heterozygous (γ2(+/-)) mice, which we previously characterized as a model animal with construct, face, and predictive validity for major depressive disorder. To assess possible consequences of GABAergic deficits on glutamatergic transmission, we quantitated the cell surface expression of N-methyl-D-aspartate (NMDA)-type and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-type glutamate receptors and the function of synapses in the hippocampus and medial prefrontal cortex of γ2(+/-) mice. We also analyzed the effects of an acute dose of the experimental antidepressant ketamine on all these parameters in γ2(+/-) versus wild-type mice. Modest defects in GABAergic synaptic transmission of γ2(+/-) mice resulted in a strikingly prominent homeostatic-like reduction in the cell surface expression of NMDA-type and AMPA-type glutamate receptors, along with prominent functional impairment of glutamatergic synapses in the hippocampus and medial prefrontal cortex. A single subanesthetic dose of ketamine normalized glutamate receptor expression and synaptic function of γ2(+/-) mice to wild-type levels for a prolonged period, along with antidepressant-like behavioral consequences selectively in γ2(+/-) mice. The GABAergic synapses of γ2(+/-) mice were potentiated by ketamine in parallel but only in the medial prefrontal cortex. Depressive-like brain states that are caused by GABAergic deficits involve a homeostatic-like reduction of glutamatergic transmission that is reversible by an acute, subanesthetic dose of ketamine, along with regionally selective potentiation of GABAergic synapses. The data merge the GABAergic and glutamatergic deficit hypotheses of major depressive disorder. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

TGIF1 is a potential candidate gene for high myopia in ethnic Kashmiri population.

PubMed

Ahmed, Ishfaq; Rasool, Shabhat; Jan, Tariq; Qureshi, Tariq; Naykoo, Niyaz A; Andrabi, Khurshid I

2014-03-01

High myopia is a complex disorder that imposes serious consequences on ocular health. Linkage analysis has identified several genetic loci with a series of potential candidate genes that reveal an ambiguous pattern of association with high myopia due to population heterogeneity. We have accordingly chosen to examine the prospect of association of one such gene [transforming growth β-induced factor 1 (TGIF1)] in population that is purely ethnic (Kashmiri) and represents a homogeneous cohort from Northern India. Cases with high myopia with a spherical equivalent of ≥-6 diopters (D) and emmetropic controls with spherical equivalent within ±0.5 D in one or both eyes represented by a sample size of 212 ethnic Kashmiri subjects and 239 matched controls. Genomic DNA was genotyped for sequence variations in TGIF1 gene and allele frequencies tested for Hardy-Weinberg disequilibrium. Potential association was evaluated using χ(2) or Fisher's exact test. Two previously reported missense variations C > T, rs4468717 (first base of codon 143) changing proline to serine and rs2229333 (second base of codon 143) changing proline to leucine were identified in exon 10 of TGIF1. Both variations exhibited possibly significant (p < 0.05) association with the disease phenotype. Since the variant allele frequency of both the single-nucleotide polymorphisms in cases is higher than controls with odds ratio greater than 1.Therefore, variant allele of both the single-nucleotide polymorphisms represents the possible risk factor for myopia in the Kashmiri population. In silico predictions show that substitutions are likely to have an impact on the structure and functional properties of the protein, making it imperative to understand their functional consequences in relation to high myopia. TGIF1 is a relevant candidate gene with potential to contribute in the genesis of high myopia.

Identifying unintended consequences of quality indicators: a qualitative study.

PubMed

Lester, Helen E; Hannon, Kerin L; Campbell, Stephen M

2011-12-01

For the first 5 years of the UK primary care pay for performance scheme, the Quality and Outcomes Framework (QOF), quality indicators were introduced without piloting. However, in 2009, potential new indicators were piloted in a nationally representative sample of practices. This paper describes an in-depth exploration of family physician, nurse and other primary-care practice staff views of the value of piloting with a particular focus on unintended consequences of 13 potential new QOF indicators. Fifty-seven family-practice professionals were interviewed in 24 representative practices across England. Almost all interviewees emphasised the value of piloting in terms of an opportunity to identify unintended consequences of potential QOF indicators in 'real world' settings with staff who deliver day-to-day care to patients. Four particular types of unintended consequences were identified: measure fixation, tunnel vision, misinterpretation and potential gaming. 'Measure fixation,' an inappropriate attention on isolated aspects of care, appeared to be the key unintended consequence. In particular, if the palliative care indicator had been introduced without piloting, this might have incentivised poorer care in a minority of practices with potential harm to vulnerable patients. It is important to identify concerns and experiences about unintended consequences of indicators at an early stage when there is time to remove or adapt problem indicators. Since the UK government currently spends over £1 billion each year on QOF, the £150,000 spent on each piloting cohort (0.0005% of the total QOF budget) appears to be good value for money.

Heat Shock Protein 70: Roles in Multiple Sclerosis

PubMed Central

Mansilla, María José; Montalban, Xavier; Espejo, Carmen

2012-01-01

Heat shock proteins (HSP) have long been considered intracellular chaperones that possess housekeeping and cytoprotective functions. Consequently, HSP overexpression was proposed as a potential therapy for neurodegenerative diseases characterized by the accumulation or aggregation of abnormal proteins. Recently, the discovery that cells release HSP with the capacity to trigger proinflammatory as well as immunoregulatory responses has focused attention on investigating the role of HSP in chronic inflammatory autoimmune diseases such as multiple sclerosis (MS). To date, the most relevant HSP is the inducible Hsp70, which exhibits both cytoprotectant and immunoregulatory functions. Several studies have presented contradictory evidence concerning the involvement of Hsp70 in MS or experimental autoimmune encephalomyelitis (EAE), the MS animal model. In this review, we dissect the functions of Hsp70 and discuss the controversial data concerning the role of Hsp70 in MS and EAE. PMID:22669475

On the solution of integral equations with a generalized cauchy kernal

NASA Technical Reports Server (NTRS)

Kaya, A. C.; Erdogan, F.

1986-01-01

A certain class of singular integral equations that may arise from the mixed boundary value problems in nonhonogeneous materials is considered. The distinguishing feature of these equations is that in addition to the Cauchy singularity, the kernels contain terms that are singular only at the end points. In the form of the singular integral equations adopted, the density function is a potential or a displacement and consequently the kernal has strong singularities of the form (t-x)(-2), x(n-2) (t+x)(n), (n is = or 2, 0 x, t b). The complex function theory is used to determine the fundamental function of the problem for the general case and a simple numerical technique is described to solve the integral equation. Two examples from the theory of elasticity are then considered to show the application of the technique.

Cognitive engineering models in space systems

NASA Technical Reports Server (NTRS)

Mitchell, Christine M.

1992-01-01

NASA space systems, including mission operations on the ground and in space, are complex, dynamic, predominantly automated systems in which the human operator is a supervisory controller. The human operator monitors and fine-tunes computer-based control systems and is responsible for ensuring safe and efficient system operation. In such systems, the potential consequences of human mistakes and errors may be very large, and low probability of such events is likely. Thus, models of cognitive functions in complex systems are needed to describe human performance and form the theoretical basis of operator workstation design, including displays, controls, and decision support aids. The operator function model represents normative operator behavior-expected operator activities given current system state. The extension of the theoretical structure of the operator function model and its application to NASA Johnson mission operations and space station applications is discussed.

Effects of Marijuana Use on Brain Structure and Function: Neuroimaging Findings from a Neurodevelopmental Perspective

PubMed Central

Brumback, T.; Castro, N.; Jacobus, J.; Tapert, S.

2016-01-01

Marijuana, behind only tobacco and alcohol, is the most popular recreational drug in America with prevalence rates of use rising over the past decade. A wide range of research has highlighted neurocognitive deficits associated with marijuana use, particularly when initiated during childhood or adolescence. Neuroimaging, describing alterations to brain structure and function, has begun to provide a picture of possible mechanisms associated with the deleterious effects of marijuana use. This chapter provides a neurodevelopmental framework from which recent data on brain structural and functional abnormalities associated with marijuana use is reviewed. Based on the current data, we provide aims for future studies to more clearly delineate the effects of marijuana on the developing brain and to define underlying mechanisms of the potential long-term negative consequences of marijuana use. PMID:27503447

Allergic rhinitis: more than just a stuffy nose.

PubMed

Borres, Magnus P

2009-07-01

Allergic rhinitis is more than just sneezing and an itchy nose. Complications of this disease are numerous and can have a significant impact, both mentally and physically. That is why it is important not only to detect, investigate and treat allergic rhinitis but also to actively identify potential complications. Mental functions such as learning, sleep and activity levels can deteriorate, and the eustachian tubes, sinuses and airway functions can be affected. Otitis, sinusitis and asthma are overrepresented among individuals who suffer from allergic rhinitis. This article highlights how allergic rhinitis can affect cognitive functions, and what consequences this can have on school performance, work and quality of life. Health professionals and school personnel need to increase their awareness of the ramifications of this disease and actively work to prevent deterioration in both academic achievement and workplace productivity.

Epidermal Growth Factor Receptor Transactivation: Mechanisms, Pathophysiology, and Potential Therapies in the Cardiovascular System.

PubMed

Forrester, Steven J; Kawai, Tatsuo; O'Brien, Shannon; Thomas, Walter; Harris, Raymond C; Eguchi, Satoru

2016-01-01

Epidermal growth factor receptor (EGFR) activation impacts the physiology and pathophysiology of the cardiovascular system, and inhibition of EGFR activity is emerging as a potential therapeutic strategy to treat diseases including hypertension, cardiac hypertrophy, renal fibrosis, and abdominal aortic aneurysm. The capacity of G protein-coupled receptor (GPCR) agonists, such as angiotensin II (AngII), to promote EGFR signaling is called transactivation and is well described, yet delineating the molecular processes and functional relevance of this crosstalk has been challenging. Moreover, these critical findings are dispersed among many different fields. The aim of our review is to highlight recent advancements in defining the signaling cascades and downstream consequences of EGFR transactivation in the cardiovascular renal system. We also focus on studies that link EGFR transactivation to animal models of the disease, and we discuss potential therapeutic applications.

The intimate and controversial relationship between voltage-gated proton channels and the phagocyte NADPH oxidase.

PubMed

DeCoursey, Thomas E

2016-09-01

One of the most fascinating and exciting periods in my scientific career entailed dissecting the symbiotic relationship between two membrane transporters, the Nicotinamide adenine dinucleotide phosphate reduced form (NADPH) oxidase complex and voltage-gated proton channels (HV 1). By the time I entered this field, there had already been substantial progress toward understanding NADPH oxidase, but HV 1 were known only to a tiny handful of cognoscenti around the world. Having identified the first proton currents in mammalian cells in 1991, I needed to find a clear function for these molecules if the work was to become fundable. The then-recent discoveries of Henderson, Chappell, and colleagues in 1987-1988 that led them to hypothesize interactions of both molecules during the respiratory burst of phagocytes provided an excellent opportunity. In a nutshell, both transporters function by moving electrical charge across the membrane: NADPH oxidase moves electrons and HV 1 moves protons. The consequences of electrogenic NADPH oxidase activity on both membrane potential and pH strongly self-limit this enzyme. Fortunately, both consequences specifically activate HV 1, and HV 1 activity counteracts both consequences, a kind of yin-yang relationship. Notwithstanding a decade starting in 1995 when many believed the opposite, these are two separate molecules that function independently despite their being functionally interdependent in phagocytes. The relationship between NADPH oxidase and HV 1 has become a paradigm that somewhat surprisingly has now extended well beyond the phagocyte NADPH oxidase - an industrial strength producer of reactive oxygen species (ROS) - to myriad other cells that produce orders of magnitude less ROS for signaling purposes. These cells with their seven NADPH oxidase (NOX) isoforms provide a vast realm of mechanistic obscurity that will occupy future studies for years to come. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

On the v-representability of ensemble densities of electron systems

NASA Astrophysics Data System (ADS)

Gonis, A.; Däne, M.

2018-05-01

Analogously to the case at zero temperature, where the density of the ground state of an interacting many-particle system determines uniquely (within an arbitrary additive constant) the external potential acting on the system, the thermal average of the density over an ensemble defined by the Boltzmann distribution at the minimum of the thermodynamic potential, or the free energy, determines the external potential uniquely (and not just modulo a constant) acting on a system described by this thermodynamic potential or free energy. The paper describes a formal procedure that generates the domain of a constrained search over general ensembles (at zero or elevated temperatures) that lead to a given density, including as a special case a density thermally averaged at a given temperature, and in the case of a v-representable density determines the external potential leading to the ensemble density. As an immediate consequence of the general formalism, the concept of v-representability is extended beyond the hitherto discussed case of ground state densities to encompass excited states as well. Specific application to thermally averaged densities solves the v-representability problem in connection with the Mermin functional in a manner analogous to that in which this problem was recently settled with respect to the Hohenberg and Kohn functional. The main formalism is illustrated with numerical results for ensembles of one-dimensional, non-interacting systems of particles under a harmonic potential.

On the v-representability of ensemble densities of electron systems

DOE PAGES

Gonis, A.; Dane, M.

2017-12-30

Analogously to the case at zero temperature, where the density of the ground state of an interacting many-particle system determines uniquely (within an arbitrary additive constant) the external potential acting on the system, the thermal average of the density over an ensemble defined by the Boltzmann distribution at the minimum of the thermodynamic potential, or the free energy, determines the external potential uniquely (and not just modulo a constant) acting on a system described by this thermodynamic potential or free energy. The study describes a formal procedure that generates the domain of a constrained search over general ensembles (at zeromore » or elevated temperatures) that lead to a given density, including as a special case a density thermally averaged at a given temperature, and in the case of a v-representable density determines the external potential leading to the ensemble density. As an immediate consequence of the general formalism, the concept of v-representability is extended beyond the hitherto discussed case of ground state densities to encompass excited states as well. Specific application to thermally averaged densities solves the v-representability problem in connection with the Mermin functional in a manner analogous to that in which this problem was recently settled with respect to the Hohenberg and Kohn functional. Finally, the main formalism is illustrated with numerical results for ensembles of one-dimensional, non-interacting systems of particles under a harmonic potential.« less

New computational methods reveal tRNA identity element divergence between Proteobacteria and Cyanobacteria.

PubMed

Freyhult, Eva; Cui, Yuanyuan; Nilsson, Olle; Ardell, David H

2007-10-01

There are at least 21 subfunctional classes of tRNAs in most cells that, despite a very highly conserved and compact common structure, must interact specifically with different cliques of proteins or cause grave organismal consequences. Protein recognition of specific tRNA substrates is achieved in part through class-restricted tRNA features called tRNA identity determinants. In earlier work we used TFAM, a statistical classifier of tRNA function, to show evidence of unexpectedly large diversity among bacteria in tRNA identity determinants. We also created a data reduction technique called function logos to visualize identity determinants for a given taxon. Here we show evidence that determinants for lysylated isoleucine tRNAs are not the same in Proteobacteria as in other bacterial groups including the Cyanobacteria. Consistent with this, the lysylating biosynthetic enzyme TilS lacks a C-terminal domain in Cyanobacteria that is present in Proteobacteria. We present here, using function logos, a map estimating all potential identity determinants generally operational in Cyanobacteria and Proteobacteria. To further isolate the differences in potential tRNA identity determinants between Proteobacteria and Cyanobacteria, we created two new data reduction visualizations to contrast sequence and function logos between two taxa. One, called Information Difference logos (ID logos), shows the evolutionary gain or retention of functional information associated to features in one lineage. The other, Kullback-Leibler divergence Difference logos (KLD logos), shows recruitments or shifts in the functional associations of features, especially those informative in both lineages. We used these new logos to specifically isolate and visualize the differences in potential tRNA identity determinants between Proteobacteria and Cyanobacteria. Our graphical results point to numerous differences in potential tRNA identity determinants between these groups. Although more differences in general are explained by shifts in functional association rather than gains or losses, the apparent identity differences in lysylated isoleucine tRNAs appear to have evolved through both mechanisms.

Potential implications of Luria's work for the neuropsychology of epilepsy and epilepsy surgery: A perspective for re-examination.

PubMed

Patrikelis, Panayiotis; Lucci, Giuliana; Siatouni, Anna; Verentzioti, Anastasia; Alexoudi, Athanasia; Gatzonis, Stylianos

2017-07-01

The pioneeristic work of Alexander Romanovic Luria into the field of human neuropsychology offered eminent contributions to clinical praxis by providing theory guided methods and instruments for the study of higher cortical functions. However, lots of this knowledge corpus either remains untranslated and thus inaccessible, or in some cases selectively overlooked by academic authorities and consequently not passed to the future generations of experts. Although Luria was not exclusively devoted to the study of epilepsy, his theories and clinical approaches actually penetrate the whole neuropathology spectrum. His holistic and systemic approach to the brain sounds nowadays more than opportune and consistent with the network approach of the modern neuroimaging era. As to epilepsy, the logic underlying the Lurian approach (cognitive functions organized into complex functional systems with intra- and/or inter-hemispheric distribution, as opposed to the modularistic view of the brain) seems consistent with our current knowledge in epileptology with respect to epileptic networks, as well as the modern construct of the functional deficit zone. These contributions seem to be highly promising for the neuropsychology of epilepsy and epilepsy surgery, since they provide clinicians with valuable methods and theories to assist them in the localization -and lateralization- of cognitive deficits. Consequently they are of great applicability in the context of the preoperative neuropsychological monitoring of patients candidates for epilepsy surgery, where neuropsychologist are called upon to provide surgeons with anatomical data. Copyright © 2017 Elsevier Inc. All rights reserved.

Consequences of cancer treatments on adult hippocampal neurogenesis: implications for cognitive function and depressive symptoms

PubMed Central

Pereira Dias, Gisele; Hollywood, Ronan; Bevilaqua, Mário Cesar do Nascimento; da Silveira da Luz, Anna Claudia Domingos; Hindges, Robert; Nardi, Antonio Egidio; Thuret, Sandrine

2014-01-01

The human brain is capable of generating new functional neurons throughout life, a phenomenon known as adult neurogenesis. The generation of new neurons is sustained throughout adulthood due to the proliferation and differentiation of adult neural stem cells. This process in humans is uniquely located in the subgranular zone of the dentate gyrus in the hippocampus. Adult hippocampal neurogenesis (AHN) is thought to play a major role in hippocampus-dependent functions, such as spatial awareness, long-term memory, emotionality, and mood. The overall aim of current treatments for cancer (such as radiotherapy and chemotherapy) is to prevent aberrant cell division of cell populations associated with malignancy. However, the treatments in question are absolutist in nature and hence inhibit all cell division. An unintended consequence of this cessation of cell division is the impairment of adult neural stem cell proliferation and AHN. Patients undergoing treatment for cancerous malignancies often display specific forms of memory deficits, as well as depressive symptoms. This review aims to discuss the effects of cancer treatments on AHN and propose a link between the inhibition of the neurogenetic process in the hippocampus and the advent of the cognitive and mood-based deficits observed in patients and animal models undergoing cancer therapies. Possible evidence for coadjuvant interventions aiming to protect neural cells, and subsequently the mood and cognitive functions they regulate, from the ablative effects of cancer treatment are discussed as potential clinical tools to improve mental health among cancer patients. PMID:24470543

Consequences of cancer treatments on adult hippocampal neurogenesis: implications for cognitive function and depressive symptoms.

PubMed

Pereira Dias, Gisele; Hollywood, Ronan; Bevilaqua, Mário Cesar do Nascimento; da Luz, Anna Claudia Domingos da Silveira; Hindges, Robert; Nardi, Antonio Egidio; Thuret, Sandrine

2014-04-01

The human brain is capable of generating new functional neurons throughout life, a phenomenon known as adult neurogenesis. The generation of new neurons is sustained throughout adulthood due to the proliferation and differentiation of adult neural stem cells. This process in humans is uniquely located in the subgranular zone of the dentate gyrus in the hippocampus. Adult hippocampal neurogenesis (AHN) is thought to play a major role in hippocampus-dependent functions, such as spatial awareness, long-term memory, emotionality, and mood. The overall aim of current treatments for cancer (such as radiotherapy and chemotherapy) is to prevent aberrant cell division of cell populations associated with malignancy. However, the treatments in question are absolutist in nature and hence inhibit all cell division. An unintended consequence of this cessation of cell division is the impairment of adult neural stem cell proliferation and AHN. Patients undergoing treatment for cancerous malignancies often display specific forms of memory deficits, as well as depressive symptoms. This review aims to discuss the effects of cancer treatments on AHN and propose a link between the inhibition of the neurogenetic process in the hippocampus and the advent of the cognitive and mood-based deficits observed in patients and animal models undergoing cancer therapies. Possible evidence for coadjuvant interventions aiming to protect neural cells, and subsequently the mood and cognitive functions they regulate, from the ablative effects of cancer treatment are discussed as potential clinical tools to improve mental health among cancer patients.

Global change-driven effects on dissolved organic matter composition: Implications for food webs of northern lakes.

PubMed

Creed, Irena F; Bergström, Ann-Kristin; Trick, Charles G; Grimm, Nancy B; Hessen, Dag O; Karlsson, Jan; Kidd, Karen A; Kritzberg, Emma; McKnight, Diane M; Freeman, Erika C; Senar, Oscar E; Andersson, Agneta; Ask, Jenny; Berggren, Martin; Cherif, Mehdi; Giesler, Reiner; Hotchkiss, Erin R; Kortelainen, Pirkko; Palta, Monica M; Vrede, Tobias; Weyhenmeyer, Gesa A

2018-03-15

Northern ecosystems are experiencing some of the most dramatic impacts of global change on Earth. Rising temperatures, hydrological intensification, changes in atmospheric acid deposition and associated acidification recovery, and changes in vegetative cover are resulting in fundamental changes in terrestrial-aquatic biogeochemical linkages. The effects of global change are readily observed in alterations in the supply of dissolved organic matter (DOM)-the messenger between terrestrial and lake ecosystems-with potentially profound effects on the structure and function of lakes. Northern terrestrial ecosystems contain substantial stores of organic matter and filter or funnel DOM, affecting the timing and magnitude of DOM delivery to surface waters. This terrestrial DOM is processed in streams, rivers, and lakes, ultimately shifting its composition, stoichiometry, and bioavailability. Here, we explore the potential consequences of these global change-driven effects for lake food webs at northern latitudes. Notably, we provide evidence that increased allochthonous DOM supply to lakes is overwhelming increased autochthonous DOM supply that potentially results from earlier ice-out and a longer growing season. Furthermore, we assess the potential implications of this shift for the nutritional quality of autotrophs in terms of their stoichiometry, fatty acid composition, toxin production, and methylmercury concentration, and therefore, contaminant transfer through the food web. We conclude that global change in northern regions leads not only to reduced primary productivity but also to nutritionally poorer lake food webs, with discernible consequences for the trophic web to fish and humans. © 2018 John Wiley & Sons Ltd.

An approach to modeling the consequences of beech mortality from beech bark disease

Treesearch

Harry T. Valentine

1983-01-01

Changes to an extant model of forest growth and transition that allow an evaluation of the consequences of beech bark disease are outlined. Required are a function to scale beech growth for the effects of beech bark disease, a function to predict beech mortality from beech bark disease, and a function that predicts root-sprout regeneration of beech.

A model-free characterization of recurrences in stationary time series

NASA Astrophysics Data System (ADS)

Chicheportiche, Rémy; Chakraborti, Anirban

2017-05-01

Study of recurrences in earthquakes, climate, financial time-series, etc. is crucial to better forecast disasters and limit their consequences. Most of the previous phenomenological studies of recurrences have involved only a long-ranged autocorrelation function, and ignored the multi-scaling properties induced by potential higher order dependencies. We argue that copulas is a natural model-free framework to study non-linear dependencies in time series and related concepts like recurrences. Consequently, we arrive at the facts that (i) non-linear dependences do impact both the statistics and dynamics of recurrence times, and (ii) the scaling arguments for the unconditional distribution may not be applicable. Hence, fitting and/or simulating the intertemporal distribution of recurrence intervals is very much system specific, and cannot actually benefit from universal features, in contrast to the previous claims. This has important implications in epilepsy prognosis and financial risk management applications.

Renal Aging: Causes and Consequences

PubMed Central

Hughes, Jeremy; Ferenbach, David A.

2017-01-01

Individuals age >65 years old are the fastest expanding population demographic throughout the developed world. Consequently, more aged patients than before are receiving diagnoses of impaired renal function and nephrosclerosis—age–associated histologic changes in the kidneys. Recent studies have shown that the aged kidney undergoes a range of structural changes and has altered transcriptomic, hemodynamic, and physiologic behavior at rest and in response to renal insults. These changes impair the ability of the kidney to withstand and recover from injury, contributing to the high susceptibility of the aged population to AKI and their increased propensity to develop subsequent progressive CKD. In this review, we examine these features of the aged kidney and explore the various validated and putative pathways contributing to the changes observed with aging in both experimental animal models and humans. We also discuss the potential for additional study to increase understanding of the aged kidney and lead to novel therapeutic strategies. PMID:28143966

Loss of Mass and Stability of Galaxies in Modified Newtonian Dynamics

NASA Astrophysics Data System (ADS)

Wu, Xufen; Zhao, HongSheng; Famaey, Benoit; Gentile, G.; Tiret, O.; Combes, F.; Angus, G. W.; Robin, A. C.

2007-08-01

The self-binding energy and stability of a galaxy in MOND-based gravity are curiously decreasing functions of its center-of-mass acceleration (of the order of 10-12 to 10-10 m s-2) toward neighboring mass concentrations. A tentative indication of this breaking of the strong equivalence principle in field galaxies is the RAVE-observed escape speed in the Milky Way. Another consequence is that satellites of field galaxies will move on nearly Keplerian orbits at large radii (100-500 kpc), with a declining speed below the asymptotically constant naive MOND prediction. But the consequences of an environment-sensitive gravity are even more severe in clusters, where member galaxies accelerate fast; no dark halo-like potential is present to support galaxies, meaning that extended axisymmetric disks of gas and stars are likely unstable. These predicted reappearances of asymptotic Keplerian velocity curves and disappearances of ``stereotypic galaxies'' in clusters are falsifiable with targeted surveys.

A red orange extract modulates the vascular response to a recreational dive: a pilot study on the effect of anthocyanins on the physiological consequences of scuba diving.

PubMed

Balestra, C; Cimino, F; Theunissen, S; Snoeck, T; Provyn, S; Canali, R; Bonina, A; Virgili, F

2016-09-01

Nutritional antioxidants have been proposed as an expedient strategy to counter the potentially deleterious effects of scuba diving on endothelial function, flow-mediated dilation (FMD) and heart function. Sixteen volunteers performing a single standard dive (20 min at 33 m) according to US Navy diving procedures were randomly assigned to two groups: one was administered with two doses of 200 mg of an anthocyanins (AC)-rich extract from red oranges, 12 and 4 h before diving. Anthocyanins supplementation significantly modulated the effects of diving on haematocrit, body water distribution and FMD. AC administration significantly reduces the potentially harmful endothelial effects of a recreational single dive. The lack of any significant effect on the most common markers of plasma antioxidant capacity suggests that the mechanism underlying this protective activity is independent of the putative antioxidant effect of AC and possibly involves cellular signalling modulation of the response to high oxygen.

Spatio-temporal patterns of major bacterial groups in alpine waters.

PubMed

Freimann, Remo; Bürgmann, Helmut; Findlay, Stuart E G; Robinson, Christopher T

2014-01-01

Glacial alpine landscapes are undergoing rapid transformation due to changes in climate. The loss of glacial ice mass has directly influenced hydrologic characteristics of alpine floodplains. Consequently, hyporheic sediment conditions are likely to change in the future as surface waters fed by glacial water (kryal) become groundwater dominated (krenal). Such environmental shifts may subsequently change bacterial community structure and thus potential ecosystem functioning. We quantitatively investigated the structure of major bacterial groups in glacial and groundwater-fed streams in three alpine floodplains during different hydrologic periods. Our results show the importance of several physico-chemical variables that reflect local geological characteristics as well as water source in structuring bacterial groups. For instance, Alpha-, Betaproteobacteria and Cytophaga-Flavobacteria were influenced by pH, conductivity and temperature as well as by inorganic and organic carbon compounds, whereas phosphorous compounds and nitrate showed specific influence on single bacterial groups. These results can be used to predict future bacterial group shifts, and potential ecosystem functioning, in alpine landscapes under environmental transformation.

IGF-1, the Cross Road of the Nutritional, Inflammatory and Hormonal Pathways to Frailty

PubMed Central

Maggio, Marcello; De Vita, Francesca; Lauretani, Fulvio; Buttò, Valeria; Bondi, Giuliana; Cattabiani, Chiara; Nouvenne, Antonio; Meschi, Tiziana; Dall’Aglio, Elisabetta; Ceda, Gian Paolo

2013-01-01

The decline in functional capacity is a heterogeneous phenomenon in the elderly. An accelerated ageing determines a frail status. It results in an increased vulnerability to stressors for decreased physiological reserves. The early identification of a frail status is essential for preventing loss of functional capacity, and its clinical consequences. Frailty and mobility limitation result from an interplay of different pathways including multiple anabolic deficiency, inflammation, oxidative stress, and a poor nutritional status. However, the age-related decline in insulin-like growth factor 1 (IGF-1) bioactivity deserves special attention as it could represent the ideal crossroad of endocrine, inflammatory, and nutritional pathways to frailty. Several minerals, namely magnesium, selenium, and zinc, appear to be important determinants of IGF-1 bioactivity. This review aims to provide an overview of the potential usefulness of nutrients modulating IGF-1 as potential therapeutic targets in the prevention of mobility limitation occurring in frail older subjects. PMID:24152751

DOE Office of Scientific and Technical Information (OSTI.GOV)

Verma, Prakash; Bartlett, Rodney J., E-mail: bartlett@qtp.ufl.edu

Core excitation energies are computed with time-dependent density functional theory (TD-DFT) using the ionization energy corrected exchange and correlation potential QTP(0,0). QTP(0,0) provides C, N, and O K-edge spectra to about an electron volt. A mean absolute error (MAE) of 0.77 and a maximum error of 2.6 eV is observed for QTP(0,0) for many small molecules. TD-DFT based on QTP (0,0) is then used to describe the core-excitation spectra of the 22 amino acids. TD-DFT with conventional functionals greatly underestimates core excitation energies, largely due to the significant error in the Kohn-Sham occupied eigenvalues. To the contrary, the ionization energymore » corrected potential, QTP(0,0), provides excellent approximations (MAE of 0.53 eV) for core ionization energies as eigenvalues of the Kohn-Sham equations. As a consequence, core excitation energies are accurately described with QTP(0,0), as are the core ionization energies important in X-ray photoionization spectra or electron spectroscopy for chemical analysis.« less

Functional Genomic Landscape of Human Breast Cancer Drivers, Vulnerabilities, and Resistance.

PubMed

Marcotte, Richard; Sayad, Azin; Brown, Kevin R; Sanchez-Garcia, Felix; Reimand, Jüri; Haider, Maliha; Virtanen, Carl; Bradner, James E; Bader, Gary D; Mills, Gordon B; Pe'er, Dana; Moffat, Jason; Neel, Benjamin G

2016-01-14

Large-scale genomic studies have identified multiple somatic aberrations in breast cancer, including copy number alterations and point mutations. Still, identifying causal variants and emergent vulnerabilities that arise as a consequence of genetic alterations remain major challenges. We performed whole-genome small hairpin RNA (shRNA) "dropout screens" on 77 breast cancer cell lines. Using a hierarchical linear regression algorithm to score our screen results and integrate them with accompanying detailed genetic and proteomic information, we identify vulnerabilities in breast cancer, including candidate "drivers," and reveal general functional genomic properties of cancer cells. Comparisons of gene essentiality with drug sensitivity data suggest potential resistance mechanisms, effects of existing anti-cancer drugs, and opportunities for combination therapy. Finally, we demonstrate the utility of this large dataset by identifying BRD4 as a potential target in luminal breast cancer and PIK3CA mutations as a resistance determinant for BET-inhibitors. Copyright © 2016 Elsevier Inc. All rights reserved.

Natural biopolymer-based nanocomposite films for packaging applications.

PubMed

Rhim, Jong-Whan; Ng, Perry K W

2007-01-01

Concerns on environmental waste problems caused by non-biodegradable petrochemical-based plastic packaging materials as well as the consumer's demand for high quality food products has caused an increasing interest in developing biodegradable packaging materials using annually renewable natural biopolymers such as polysaccharides and proteins. Inherent shortcomings of natural polymer-based packaging materials such as low mechanical properties and low water resistance can be recovered by applying a nanocomposite technology. Polymer nanocomposites, especially natural biopolymer-layered silicate nanocomposites, exhibit markedly improved packaging properties due to their nanometer size dispersion. These improvements include increased modulus and strength, decreased gas permeability, and increased water resistance. Additionally, biologically active ingredients can be added to impart the desired functional properties to the resulting packaging materials. Consequently, natural biopolymer-based nanocomposite packaging materials with bio-functional properties have a huge potential for application in the active food packaging industry. In this review, recent advances in the preparation of natural biopolymer-based films and their nanocomposites, and their potential use in packaging applications are addressed.

Evolutionarily Conserved, Multitasking TRP Channels: Lessons from Worms and Flies

PubMed Central

Venkatachalam, Kartik; Luo, Junjie; Montell, Craig

2015-01-01

The Transient Receptor Potential (TRP) channel family is comprised of a large group of cation-permeable channels, which display an extraordinary diversity of roles in sensory signaling. TRPs allow animals to detect chemicals, mechanical force, light, and changes in temperature. Consequently, these channels control a plethora of animal behaviors. Moreover, their functions are not limited to the classical senses, as they are cellular sensors, which are critical for ionic homeostasis and metabolism. Two genetically tractable invertebrate model organisms, Caenorhabditis elegans and Drosophila melanogaster, have led the way in revealing a wide array of sensory roles and behaviors that depend on TRP channels. Two overriding themes have emerged from these studies. First, TRPs are multitasking proteins, and second, many functions and modes of activation of these channels are evolutionarily conserved, including some that were formerly thought to be unique to invertebrates, such as phototransduction. Thus, worms and flies offer the potential to decipher roles for mammalian TRPs, which would otherwise not be suspected. PMID:24961975

The system N transporter SN2 doubles as a transmitter precursor furnisher and a potential regulator of NMDA receptors.

PubMed

Hamdani, El Hassan; Gudbrandsen, Marius; Bjørkmo, Mona; Chaudhry, Farrukh Abbas

2012-11-01

Activation of NMDA receptor requires two co-agonists, glutamate and glycine. Despite its intrinsic role in brain functions molecular mechanisms involved in glutamate replenishment and identification of the origin of glycine have eluded characterization. We have performed direct measurements of glycine flux by SN2 (Slc38a5; also known as SNAT5), executed extensive electrophysiological characterization as well as implemented ratiometric analyses to show that SN2 transport resembles SN1 in mechanism but differ in functional implications. We report that rat SN2 mediates electroneutral and bidirectional transport of glutamine and glycine at perisynaptic astroglial membranes. Sophisticated coupled and uncoupled movements of H(+) differentially associate with glutamine and glycine transport by SN2 and regulate pH(i) and the release mode of the transporter. Consequently, SN2 doubles as a transmitter precursor furnisher and a potential regulator of NMDA receptors. Copyright © 2012 Wiley Periodicals, Inc.

Corrosion consequences of microfouling in water reclamation systems

NASA Technical Reports Server (NTRS)

Ford, Tim; Mitchell, Ralph

1991-01-01

This paper examines the potential fouling and corrosion problems associated with microbial film formation throughout the water reclamation system (WRS) designed for the Space Station Freedom. It is shown that the use of advanced metal sputtering techiques combined with image analysis and FTIR spectroscopy will present realistic solutions for investigating the formation and function of biofilm on different alloys, the subsequent corrosion, and the efficiency of different treatments. These techniques, used in combination with electrochemical measurements of corrosion, will provide a powerful approach to examinations of materials considered for use in the WRS.

DISC1 genetics, biology and psychiatric illness

PubMed Central

THOMSON, Pippa A.; MALAVASI, Elise L.V.; GRÜNEWALD, Ellen; SOARES, Dinesh C.; BORKOWSKA, Malgorzata; MILLAR, J. Kirsty

2012-01-01

Psychiatric disorders are highly heritable, and in many individuals likely arise from the combined effects of genes and the environment. A substantial body of evidence points towards DISC1 being one of the genes that influence risk of schizophrenia, bipolar disorder and depression, and functional studies of DISC1 consequently have the potential to reveal much about the pathways that lead to major mental illness. Here, we review the evidence that DISC1 influences disease risk through effects upon multiple critical pathways in the developing and adult brain. PMID:23550053

Functional consequences of realistic biodiversity changes in a marine ecosystem

PubMed Central

Bracken, Matthew E. S.; Friberg, Sara E.; Gonzalez-Dorantes, Cirse A.; Williams, Susan L.

2008-01-01

Declines in biodiversity have prompted concern over the consequences of species loss for the goods and services provided by natural ecosystems. However, relatively few studies have evaluated the functional consequences of realistic, nonrandom changes in biodiversity. Instead, most designs have used randomly selected assemblages from a local species pool to construct diversity gradients. It is therefore difficult, based on current evidence, to predict the functional consequences of realistic declines in biodiversity. In this study, we used tide pool microcosms to demonstrate that the effects of real-world changes in biodiversity may be very different from those of random diversity changes. Specifically, we measured the relationship between the diversity of a seaweed assemblage and its ability to use nitrogen, a key limiting nutrient in nearshore marine systems. We quantified nitrogen uptake using both experimental and model seaweed assemblages and found that natural increases in diversity resulted in enhanced rates of nitrogen use, whereas random diversity changes had no effect on nitrogen uptake. Our results suggest that understanding the real-world consequences of declining biodiversity will require addressing changes in species performance along natural diversity gradients and understanding the relationships between species' susceptibility to loss and their contributions to ecosystem functioning. PMID:18195375

Smoker-free workplace policies: developing a model of public health consequences of workplace policies barring employment to smokers.

PubMed

Houle, B; Siegel, M

2009-02-01

A marked shift in tobacco-related workplace health promotion intervention involves the adoption of policies barring employment to smokers. We discuss the potential public health consequences of these policies on those affected-smokers, their families, the surrounding community and society at large. We find a lack of published evidence evaluating the effectiveness and consequences of these policies. By developing a model of policy effects, we outline possible unintended consequences. With such large gaps in the evidence base and the potential for deleterious consequences, we argue for increased discussion about the use of smoker-free employment policies as a public health intervention and for increased engagement of employers by the public health community in worksite health promotion.

Restoration of facial symmetry in a patient with bell palsy using a modified maxillary complete denture: a case report.

PubMed

Bagchi, Gautam; Nath, Dilip Kumar

2012-01-01

Permanent facial paralysis can be devastating for a patient. Modern society's emphasis on appearance and physical beauty contributes to this problem and often leads to isolation of patients embarrassed by their appearance. Lagophthalmos with ocular exposure, loss of oral competence with resultant drooling, alar collapse with nasal airway obstruction, and difficulties with mastication and speech production are all potential consequences of facial paralysis. Affected patients are confronted with both a cosmetic defect and the functional deficits associated with loss of facial nerve function. In this case history report, a modified maxillary complete denture permitted a patient with Bell palsy to carry on daily activities with minimal facial distortion, pain, speech difficulty, and associated emotional trauma.

Neurophysiological Changes Measured Using Somatosensory Evoked Potentials.

PubMed

Macerollo, Antonella; Brown, Matt J N; Kilner, James M; Chen, Robert

2018-05-01

Measurements of somatosensory evoked potentials (SEPs), recorded using electroencephalography during different phases of movement, have been fundamental in understanding the neurophysiological changes related to motor control. SEP recordings have also been used to investigate adaptive plasticity changes in somatosensory processing related to active and observational motor learning tasks. Combining noninvasive brain stimulation with SEP recordings and intracranial SEP depth recordings, including recordings from deep brain stimulation electrodes, has been critical in identifying neural areas involved in specific temporal stages of somatosensory processing. Consequently, this fundamental information has furthered our understanding of the maladaptive plasticity changes related to pathophysiology of diseases characterized by abnormal movements, such as Parkinson's disease, dystonia, and functional movement disorders. Crown Copyright © 2018. Published by Elsevier Ltd. All rights reserved.

Tachyon with an inverse power-law potential in a braneworld cosmology

NASA Astrophysics Data System (ADS)

Bilić, Neven; Domazet, Silvije; Djordjevic, Goran S.

2017-08-01

We study a tachyon cosmological model based on the dynamics of a 3-brane in the bulk of the second Randall-Sundrum model extended to more general warp functions. A well known prototype of such a generalization is the bulk with a selfinteracting scalar field. As a consequence of a generalized bulk geometry the cosmology on the observer brane is modified by the scale dependent four-dimensional gravitational constant. In particular, we study a power law warp factor which generates an inverse power-law potential V\\propto \\varphi-n of the tachyon field φ. We find a critical power n cr that divides two subclasses with distinct asymptotic behaviors: a dust universe for n>n_cr and a quasi de Sitter universe for 0.

Consistent effects of biodiversity loss on multifunctionality across contrasting ecosystems.

PubMed

Fanin, Nicolas; Gundale, Michael J; Farrell, Mark; Ciobanu, Marcel; Baldock, Jeff A; Nilsson, Marie-Charlotte; Kardol, Paul; Wardle, David A

2018-02-01

Understanding how loss of biodiversity affects ecosystem functioning, and thus the delivery of ecosystem goods and services, has become increasingly necessary in a changing world. Considerable recent attention has focused on predicting how biodiversity loss simultaneously impacts multiple ecosystem functions (that is, ecosystem multifunctionality), but the ways in which these effects vary across ecosystems remain unclear. Here, we report the results of two 19-year plant diversity manipulation experiments, each established across a strong environmental gradient. Although the effects of plant and associated fungal diversity loss on individual functions frequently differed among ecosystems, the consequences of biodiversity loss for multifunctionality were relatively invariant. However, the context-dependency of biodiversity effects also worked in opposing directions for different individual functions, meaning that similar multifunctionality values across contrasting ecosystems could potentially mask important differences in the effects of biodiversity on functioning among ecosystems. Our findings highlight that an understanding of the relative contribution of species or functional groups to individual ecosystem functions among contrasting ecosystems and their interactions (that is, complementarity versus competition) is critical for guiding management efforts aimed at maintaining ecosystem multifunctionality and the delivery of multiple ecosystem services.

Undermining and Strengthening Social Networks through Network Modification

PubMed Central

Mellon, Jonathan; Yoder, Jordan; Evans, Daniel

2016-01-01

Social networks have well documented effects at the individual and aggregate level. Consequently it is often useful to understand how an attempt to influence a network will change its structure and consequently achieve other goals. We develop a framework for network modification that allows for arbitrary objective functions, types of modification (e.g. edge weight addition, edge weight removal, node removal, and covariate value change), and recovery mechanisms (i.e. how a network responds to interventions). The framework outlined in this paper helps both to situate the existing work on network interventions but also opens up many new possibilities for intervening in networks. In particular use two case studies to highlight the potential impact of empirically calibrating the objective function and network recovery mechanisms as well as showing how interventions beyond node removal can be optimised. First, we simulate an optimal removal of nodes from the Noordin terrorist network in order to reduce the expected number of attacks (based on empirically predicting the terrorist collaboration network from multiple types of network ties). Second, we simulate optimally strengthening ties within entrepreneurial ecosystems in six developing countries. In both cases we estimate ERGM models to simulate how a network will endogenously evolve after intervention. PMID:27703198

Rapid recovery from the effects of early monocular deprivation is enabled by temporary inactivation of the retinas.

PubMed

Fong, Ming-Fai; Mitchell, Donald E; Duffy, Kevin R; Bear, Mark F

2016-12-06

A half-century of research on the consequences of monocular deprivation (MD) in animals has revealed a great deal about the pathophysiology of amblyopia. MD initiates synaptic changes in the visual cortex that reduce acuity and binocular vision by causing neurons to lose responsiveness to the deprived eye. However, much less is known about how deprivation-induced synaptic modifications can be reversed to restore normal visual function. One theoretically motivated hypothesis is that a period of inactivity can reduce the threshold for synaptic potentiation such that subsequent visual experience promotes synaptic strengthening and increased responsiveness in the visual cortex. Here we have reduced this idea to practice in two species. In young mice, we show that the otherwise stable loss of cortical responsiveness caused by MD is reversed when binocular visual experience follows temporary anesthetic inactivation of the retinas. In 3-mo-old kittens, we show that a severe impairment of visual acuity is also fully reversed by binocular experience following treatment and, further, that prolonged retinal inactivation alone can erase anatomical consequences of MD. We conclude that temporary retinal inactivation represents a highly efficacious means to promote recovery of function.

Undermining and Strengthening Social Networks through Network Modification.

PubMed

Mellon, Jonathan; Yoder, Jordan; Evans, Daniel

2016-10-05

Social networks have well documented effects at the individual and aggregate level. Consequently it is often useful to understand how an attempt to influence a network will change its structure and consequently achieve other goals. We develop a framework for network modification that allows for arbitrary objective functions, types of modification (e.g. edge weight addition, edge weight removal, node removal, and covariate value change), and recovery mechanisms (i.e. how a network responds to interventions). The framework outlined in this paper helps both to situate the existing work on network interventions but also opens up many new possibilities for intervening in networks. In particular use two case studies to highlight the potential impact of empirically calibrating the objective function and network recovery mechanisms as well as showing how interventions beyond node removal can be optimised. First, we simulate an optimal removal of nodes from the Noordin terrorist network in order to reduce the expected number of attacks (based on empirically predicting the terrorist collaboration network from multiple types of network ties). Second, we simulate optimally strengthening ties within entrepreneurial ecosystems in six developing countries. In both cases we estimate ERGM models to simulate how a network will endogenously evolve after intervention.

Undermining and Strengthening Social Networks through Network Modification

NASA Astrophysics Data System (ADS)

Mellon, Jonathan; Yoder, Jordan; Evans, Daniel

2016-10-01

Social networks have well documented effects at the individual and aggregate level. Consequently it is often useful to understand how an attempt to influence a network will change its structure and consequently achieve other goals. We develop a framework for network modification that allows for arbitrary objective functions, types of modification (e.g. edge weight addition, edge weight removal, node removal, and covariate value change), and recovery mechanisms (i.e. how a network responds to interventions). The framework outlined in this paper helps both to situate the existing work on network interventions but also opens up many new possibilities for intervening in networks. In particular use two case studies to highlight the potential impact of empirically calibrating the objective function and network recovery mechanisms as well as showing how interventions beyond node removal can be optimised. First, we simulate an optimal removal of nodes from the Noordin terrorist network in order to reduce the expected number of attacks (based on empirically predicting the terrorist collaboration network from multiple types of network ties). Second, we simulate optimally strengthening ties within entrepreneurial ecosystems in six developing countries. In both cases we estimate ERGM models to simulate how a network will endogenously evolve after intervention.

Fitness Consequences of Boldness in Juvenile and Adult Largemouth Bass.

PubMed

Ballew, Nicholas G; Mittelbach, Gary G; Scribner, Kim T

2017-04-01

To date, most studies investigating the relationship between personality traits and fitness have focused on a single measure of fitness (such as survival) at a specific life stage. However, many personality traits likely have multiple effects on fitness, potentially operating across different functional contexts and stages of development. Here, we address the fitness consequences of boldness, under seminatural conditions, across life stages and functional contexts in largemouth bass (Micropterus salmoides). Specifically, we report the effect of boldness on (1) juvenile survivorship in an outdoor pond containing natural prey and predators and (2) adult reproductive success in three outdoor ponds across three reproductive seasons (years). Juvenile survival was negatively affected by boldness, with bolder juveniles having a lower probability of survival than shyer juveniles. In contrast, bolder adult male bass had greater reproductive success than their shyer male counterparts. Female reproductive success was not affected by boldness. These findings demonstrate that boldness can affect fitness differently across life stages. Further, boldness was highly consistent across years and significantly heritable, which suggests that boldness has a genetic component. Thus, our results support theory suggesting that fitness trade-offs across life stages may contribute to the maintenance of personality variation within populations.

Cytochrome b 6 f function and localization, phosphorylation state of thylakoid membrane proteins and consequences on cyclic electron flow.

PubMed

Dumas, Louis; Chazaux, Marie; Peltier, Gilles; Johnson, Xenie; Alric, Jean

2016-09-01

Both the structure and the protein composition of thylakoid membranes have an impact on light harvesting and electron transfer in the photosynthetic chain. Thylakoid membranes form stacks and lamellae where photosystem II and photosystem I localize, respectively. Light-harvesting complexes II can be associated to either PSII or PSI depending on the redox state of the plastoquinone pool, and their distribution is governed by state transitions. Upon state transitions, the thylakoid ultrastructure and lateral distribution of proteins along the membrane are subject to significant rearrangements. In addition, quinone diffusion is limited to membrane microdomains and the cytochrome b 6 f complex localizes either to PSII-containing grana stacks or PSI-containing stroma lamellae. Here, we discuss possible similarities or differences between green algae and C3 plants on the functional consequences of such heterogeneities in the photosynthetic electron transport chain and propose a model in which quinones, accepting electrons either from PSII (linear flow) or NDH/PGR pathways (cyclic flow), represent a crucial control point. Our aim is to give an integrated description of these processes and discuss their potential roles in the balance between linear and cyclic electron flows.

A birds-eye view of biological connectivity in mangrove systems

NASA Astrophysics Data System (ADS)

Buelow, Christina; Sheaves, Marcus

2015-01-01

Considerable advances in understanding of biological connectivity have flowed from studies of fish-facilitated connectivity within the coastal ecosystem mosaic. However, there are limits to the information that fish can provide on connectivity. Mangrove-bird communities have the potential to connect coastal habitats in different ways and at different scales than fish, so incorporation of these links into our models of coastal ecosystem mosaics affords the opportunity to greatly increase the breadth of our understanding. We review the habitat and foraging requirements of mangrove-bird functional groups to understand how bird use of mangroves facilitates biological connectivity in coastal ecosystem mosaics, and how that connectivity adds to the diversity and complexity of ecological processes in mangrove ecosystems. Avian biological connectivity is primarily characterized by foraging behavior and habitat/resource requirements. Therefore, the consequence of bird links for coastal ecosystem functioning largely depends on patterns of habitat use and foraging, and potentially influences nutrient cycling, top-down control and genetic information linkage. Habitats that experience concentrated bird guano deposition have high levels of nitrogen and phosphorus, placing particular importance on the consequences of avian nutrient translocation and subsidization for coastal ecosystem functioning. High mobility allows mangrove-bird communities to link mangrove forests to other mangrove, terrestrial and marine-pelagic systems. Therefore, the spatial scale of coastal connectivity facilitated by birds is substantially more extensive than fish-facilitated connectivity. In particular, migratory birds link habitats at regional, continental and inter-continental scales as they travel among seasonally available feeding areas from breeding grounds to non-breeding grounds; scales at which there are few fish equivalents. Knowledge of the nature and patterns of fish connectivity have contributed to shifting the initial, historical perception of mangrove-ecosystem functioning from that of a simple system based on nutrient and energy retention, to a view that includes fish-facilitated energy export. In a similar way, understanding the nature and implications of mangrove connectivity through bird movements and migrations affords new possibilities for revising our view of the extent of functional links between mangroves and other ecosystems.

The paradox of the modern mass media: probably the major source of social cohesion in liberal democracies, even though its content is often socially divisive.

PubMed

Charlton, Bruce G

2006-01-01

The modern mass media (MM) is often regarded a mixture between a trivial waste of time and resources, and a dangerously subversive system tending to promote social division and community breakdown. But these negative evaluations are difficult to square with the fact that those countries with the largest mass media include the most modernized and powerful nations. It seems more plausible that the MM is serving some useful - perhaps vital - function. I suggest that modern mass media function as the main source of social cohesion in liberal democracies. The paradox is that this cohesive function is sustained in a context of frequently divisive media content. This media function evolved because modern MM produce an excess of media communications in a context of consumer choice which generates competition for public attention both within- and between-media. Competition has led the media to become increasingly specialized at gaining and retaining public attention. Social cohesion is the consequence of the mass media continually drawing public attention to itself, and to the extremely large, internally complex and interconnected nature of the MM system. The means by which attention is attracted are almost arbitrary, encompassing both novelty and familiarity and evoking a wide range of emotions both positive and negative. Driven to seek competitive advantage, modern mass media produce a wide range of material to cater to a vast range of interests; thereby engaging a great variety of individuals and social groupings. The consequence is that media content is typically self-contradictory and includes content which is offensive and potentially divisive; since what grabs the interest of some may offend or repel others. For instance, young men must be socially engaged, since they are potentially the most violent social group, yet the interests of young men include material that the majority of the population would find excessively aggressive, disrespectful, subversive or sexual. If the mass media is effectively to perform its crucial function of enabling social cohesion among a diverse and differentiated population, then modern liberal democracies need a broad margin of toleration and a widespread psychological capacity to endure dissent and disagreement.

Immunotoxicological effects of JP-8 jet fuel exposure.

PubMed

Harris, D T; Sakiestewa, D; Robledo, R F; Witten, M

1997-01-01

Chronic exposure to jet fuel has been shown to have adverse effects on human liver function, to cause emotional dysfunction, to cause abnormal electroencephalograms, to cause shortened attention spans, and to decrease sensorimotor speed (3-5). Due to the decision by the United States Air Force to implement the widespread use of JP-8 jet fuel in its operations, a thorough understanding of its potential effects upon exposed personnel is both critical and necessary. Exposure to potential environmental toxicants such as JP-8 may have significant effects on host systems beyond those readily visible (e.g., physiology, cardiology, respiratory, etc.); e.g., the immune system. Significant changes in immune consequences, even if short-lived, may have serious consequences for the exposed host that may impinge affect susceptibility to infectious agents. Major alterations in immune function that are long-lasting may result in an increased likelihood of development and/or progression of cancer, as well as autoimmune diseases. In the current study mice were exposed for 1h/day for 7 days to varying concentrations of aerosolized JP-8 jet fuel to simulate occupational exposures. Twenty-four hours after the last exposure the mice were analyzed for effects on their immune systems. It was observed that even at exposure concentrations as low as 100 mg/m3 detrimental effects on the immune system occurred. Decreases in viable immune cell numbers and immune organ weights were found. Jet fuel exposure resulted in losses of different immune cell subpopulations depending upon the immune organ being examined. Further, JP-8 exposure resulted in significantly decreased immune function, as analyzed by mitogenesis assays. Suppressed immune function could not be overcome by the addition of exogenous growth factors known to stimulate immune function. Thus, short-term, low concentration exposure of mice to JP-8 jet fuel caused significant toxicological effects on the immune system. It appears that the immune system may be the most sensitive indicator of toxicological damage due to JP-8 exposure, as effects were seen at concentrations of jet fuel that did not evidence change in other biological systems. Such changes may have significant effects on the health of the exposed individual.

The human Nav1.5 F1486 deletion associated with long QT syndrome leads to impaired sodium channel inactivation and reduced lidocaine sensitivity

PubMed Central

Song, Weihua; Xiao, Yucheng; Chen, Hanying; Ashpole, Nicole M; Piekarz, Andrew D; Ma, Peilin; Hudmon, Andy; Cummins, Theodore R; Shou, Weinian

2012-01-01

The deletion of phenylalanine 1486 (F1486del) in the human cardiac voltage-gated sodium channel (hNav1.5) is associated with fatal long QT (LQT) syndrome. In this study we determined how F1486del impairs the functional properties of hNav1.5 and alters action potential firing in heterologous expression systems (human embryonic kidney (HEK) 293 cells) and their native cardiomyocyte background. Cells expressing hNav1.5-F1486del exhibited a loss-of-function alteration, reflected by an 80% reduction of peak current density, and several gain-of-function alterations, including reduced channel inactivation, enlarged window current, substantial augmentation of persistent late sodium current and an increase in ramp current. We also observed substantial action potential duration (APD) prolongation and prominent early afterdepolarizations (EADs) in neonatal cardiomyocytes expressing the F1486del channels, as well as in computer simulations of myocyte activity. In addition, lidocaine sensitivity was dramatically reduced, which probably contributed to the poor therapeutic outcome observed in the patient carrying the hNav1.5-F1486del mutation. Therefore, despite the significant reduction in peak current density, the F1486del mutation also leads to substantial gain-of-function alterations that are sufficient to cause APD prolongation and EADs, the predominant characteristic of LQTs. These data demonstrate that hNav1.5 mutations can have complex functional consequences and highlight the importance of identifying the specific molecular defect when evaluating potential treatments for individuals with prolonged QT intervals. PMID:22826127

Trophic level, successional age and trait matching determine specialization of deadwood-based interaction networks of saproxylic beetles

PubMed Central

Gossner, Martin M.; Grass, Ingo; Arnstadt, Tobias; Hofrichter, Martin; Floren, Andreas; Linsenmair, Karl Eduard; Weisser, Wolfgang W.; Steffan-Dewenter, Ingolf

2017-01-01

The specialization of ecological networks provides important insights into possible consequences of biodiversity loss for ecosystem functioning. However, mostly mutualistic and antagonistic interactions of living organisms have been studied, whereas detritivore networks and their successional changes are largely unexplored. We studied the interactions of saproxylic (deadwood-dependent) beetles with their dead host trees. In a large-scale experiment, 764 logs of 13 tree species were exposed to analyse network structure of three trophic groups of saproxylic beetles over 3 successional years. We found remarkably high specialization of deadwood-feeding xylophages and lower specialization of fungivorous and predatory species. During deadwood succession, community composition, network specialization and network robustness changed differently for the functional groups. To reveal potential drivers of network specialization, we linked species' functional traits to their network roles, and tested for trait matching between plant (i.e. chemical compounds) and beetle (i.e. body size) traits. We found that both plant and animal traits are major drivers of species specialization, and that trait matching can be more important in explaining interactions than neutral processes reflecting species abundance distributions. High network specialization in the early successional stage and decreasing network robustness during succession indicate vulnerability of detritivore networks to reduced tree species diversity and beetle extinctions, with unknown consequences for wood decomposition and nutrient cycling. PMID:28469020

Contrasting soil microbial community functional structures in two major landscapes of the Tibetan alpine meadow

DOE PAGES

Chu, Houjuan; Wang, Shiping; Yue, Haowei; ...

2014-07-07

The grassland and shrubland are two major landscapes of the Tibetan alpine meadow, a region very sensitive to the impact of global warming and anthropogenic perturbation. Herein, we report a study showing that a majority of differences in soil microbial community functional structures, measured by a functional gene array named GeoChip 4.0, in two adjacent shrubland and grassland areas, were explainable by environmental properties, suggesting that the harsh environments in the alpine grassland rendered niche adaptation important. Furthermore, genes involved in labile carbon degradation were more abundant in the shrubland than those of the grassland but genes involved in recalcitrantmore » carbon degradation were less abundant, which was conducive to long-term carbon storage and sequestration in the shrubland despite low soil organic carbon content. In addition, genes of anerobic nitrogen cycling processes such as denitrification and dissimilatory nitrogen reduction were more abundant, shifting soil nitrogen cycling toward ammonium biosynthesis and consequently leading to higher soil ammonium contents. In conclusion, we also noted higher abundances of stress genes responsive to nitrogen limitation and oxygen limitation, which might be attributed to low total nitrogen and higher water contents in the shrubland. Together, these results provide mechanistic knowledge about microbial linkages to soil carbon and nitrogen storage and potential consequences of vegetation shifts in the Tibetan alpine meadow.« less

Emerging roles of the spliceosomal machinery in myelodysplastic syndromes and other hematological disorders.

PubMed

Visconte, V; Makishima, H; Maciejewski, J P; Tiu, R V

2012-12-01

In humans, the majority of all protein-coding transcripts contain introns that are removed by mRNA splicing carried out by spliceosomes. Mutations in the spliceosome machinery have recently been identified using whole-exome/genome technologies in myelodysplastic syndromes (MDS) and in other hematological disorders. Alterations in splicing factor 3 subunit b1 (SF3b1) were the first spliceosomal mutations described, immediately followed by identification of other splicing factor mutations, including U2 small nuclear RNA auxillary factor 1 (U2AF1) and serine arginine-rich splicing factor 2 (SRSF2). SF3b1/U2AF1/SRSF2 mutations occur at varying frequencies in different disease subtypes, each contributing to differences in survival outcomes. However, the exact functional consequences of these spliceosomal mutations in the pathogenesis of MDS and other hematological malignancies remain largely unknown and subject to intense investigation. For SF3b1, a gain of function mutation may offer the promise of new targeted therapies for diseases that carry this molecular abnormality that can potentially lead to cure. This review aims to provide a comprehensive overview of the emerging role of the spliceosome machinery in the biology of MDS/hematological disorders with an emphasis on the functional consequences of mutations, their clinical significance, and perspectives on how they may influence our understanding and management of diseases affected by these mutations.

Emerging roles of the spliceosomal machinery in myelodysplastic syndromes and other hematologic disorders

PubMed Central

Visconte, V; Makishima, H; Maciejewski, JP; Tiu, RV

2013-01-01

In humans, the majority of all protein-coding transcripts contain introns that are removed by mRNA splicing carried out by spliceosomes. Mutations in the spliceosome machinery have recently been identified using whole exome/genome technologies in myelodysplastic syndromes (MDS) and in other hematologic disorders. Alterations in Splicing Factor 3 Subunit b1 (SF3b1) were the first spliceosomal mutations described, immediately followed by identification of other splicing factor mutations, including U2 Small Nuclear RNA Auxillary Factor 1 (U2AF1) and Serine Arginine Rich Splicing Factor 2 (SRSF2). SF3b1/U2AF1/SRSF2 mutations occur at varying frequencies in different disease subtypes, each contributing to differences in survival outcomes. However, the exact functional consequences of these spliceosomal mutations in the pathogenesis of MDS and other hematologic malignancies remain largely unknown and subject to intense investigation. For SF3b1, a gain of function mutation may offer the promise of new targeted therapies for diseases that carry this molecular abnormality that can potentially lead to cure. This review aims to provide a comprehensive overview of the emerging role of the spliceosome machinery in the biology of MDS/hematologic disorders with an emphasis on the functional consequences of mutations, their clinical significance, and perspectives on how they may influence our understanding and management of diseases affected by these mutations. PMID:22678168

Survey of Costs Arising From Potential Radionuclide Scattering Events

DOE Office of Scientific and Technical Information (OSTI.GOV)

Luna, R.E.; Pe, Ph.D.; Yoshimura, H.R.

The potential effects from scattering radioactive materials in public places include health, social, and economic consequences. These are substantial consequences relative to potential terror activities that include use of radioactive material dispersal devices (RDDs). Such an event with radionuclides released and deposited on surfaces outside and inside people's residences and places of work, commerce, and recreation will require decisions on how to recover from the event. One aspect of those decisions will be the cost to clean up the residual radioactive contamination to make the area functional again versus abandonment and/or razing and rebuilding. Development of cleanup processes have beenmore » the subject of experiment from the beginning of the nuclear age, but formalized cost breakdowns are relatively rare and mostly applicable to long term releases in non-public sites. Pre-event cleanup cost estimation of cost for cleanup of radioactive materials released to the public environment is an issue that has seen sporadic activity over the last 20 to 30 years. This paper will briefly review several of the more important efforts to estimate the costs of remediation or razing and reconstruction of radioactively contaminated areas. The cost estimates for such recoveries will be compared in terms of 2005 dollars for the sake of consistency. Dependence of cost estimates on population density and needed degree of decontamination will be shown to be quite strong in the overall presentation of the data. (authors)« less

System Safety and the Unintended Consequence

NASA Technical Reports Server (NTRS)

Watson, Clifford

2012-01-01

The analysis and identification of risks often result in design changes or modification of operational steps. This paper identifies the potential of unintended consequences as an over-looked result of these changes. Examples of societal changes such as prohibition, regulatory changes including mandating lifeboats on passenger ships, and engineering proposals or design changes to automobiles and spaceflight hardware are used to demonstrate that the System Safety Engineer must be cognizant of the potential for unintended consequences as a result of an analysis. Conclusions of the report indicate the need for additional foresight and consideration of the potential effects of analysis-driven design, processing changes, and/or operational modifications.

On the trends of Fukui potential and hardness potential derivatives in isolated atoms vs. atoms in molecules.

PubMed

Bhattacharjee, Rituparna; Roy, Ram Kinkar

2014-10-28

In the present study, trends of electronic contribution to molecular electrostatic potential [Vel(r¯)(r=0)], Fukui potential [v(+)f|(r=0) and v(-)f|(r=0)] and hardness potential derivatives [Δ(+)h(k) and Δ(-)h(k)] for isolated atoms as well as atoms in molecules are investigated. The generated numerical values of these three reactivity descriptors in these two electronically different situations are critically analyzed through the relevant formalism. Values of Vel(r¯) (when r → 0, i.e., on the nucleus) are higher for atoms in molecules than that of isolated atoms. In contrast, higher values of v(+)|(r=0) and v(-)|(r=0) are observed for isolated atoms compared to the values for atoms in a molecule. However, no such regular trend is observed for the Δ(+)h(k) and Δ(-)h(k) values, which is attributed to the uncertainty in the Fukui function values of atoms in molecules. The sum of Fukui potential and the sum of hardness potential derivatives in molecules are also critically analyzed, which shows the efficacy of orbital relaxation effects in quantifying the values of these parameters. The chemical consequence of the observed trends of these descriptors in interpreting electron delocalization, electronic relaxation and non-negativity of atomic Fukui function indices is also touched upon. Several commonly used molecules containing carbon as well as heteroatoms are chosen to make the investigation more insightful.

Male fertility potential alteration in rheumatic diseases: a systematic review.

PubMed

Tiseo, Bruno Camargo; Cocuzza, Marcello; Bonfa, Eloisa; Srougi, Miguel; Silva, Clovis A

2016-01-01

Improved targeted therapies for rheumatic diseases were developed recently resulting in a better prognosis for affected patients. Nowadays, patients are living longer and with improved quality of life, including fertility potential. These patients are affected by impaired reproductive function and the causes are often multifactorial related to particularities of each disease. This review highlights how rheumatic diseases and their management affect testicular function and male fertility. A systematic review of literature of all published data after 1970 was conducted. Data was collected about fertility abnormalities in male patients with systemic lupus erythematosus, rheumatoid arthritis, dermatomyositis, ankylosing spondylitis, Behçet disease and gout. Two independent researchers carried out the search in online databases. A total of 19 articles were included addressing the following diseases: 7 systemic lupus erythematosus, 6 Behçet disease, 4 ankylosing spondylitis, 2 rheumatoid arthritis, 2 dermatomyositis and one gout. Systemic lupus erythematosus clearly affects gonadal function impairing spermatogenesis mainly due to antisperm antibodies and cyclophosphamide therapy. Behçet disease, gout and ankylosing spondylitis patients, including those under anti-TNF therapy in the latter disease, do not seem to have reduced fertility whereas in dermatomyositis, the fertility potential is hampered by disease activity and by alkylating agents. Data regarding rheumatoid arthritis is scarce, gonadal dysfunction observed as consequence of disease activity and antisperm antibodies. Reduced fertility potential is not uncommon. Its frequency and severity vary among the different rheumatic diseases. Permanent infertility is rare and often associated with alkylating agent therapy.

Constraints on physiological function associated with branch architecture and wood density in tropical forest trees.

PubMed

Meinzer, Frederick C; Campanello, Paula I; Domec, Jean-Christophe; Genoveva Gatti, M; Goldstein, Guillermo; Villalobos-Vega, Randol; Woodruff, David R

2008-11-01

This study examined how leaf and stem functional traits related to gas exchange and water balance scale with two potential proxies for tree hydraulic architecture: the leaf area:sapwood area ratio (A(L):A(S)) and wood density (rho(w)). We studied the upper crowns of individuals of 15 tropical forest tree species at two sites in Panama with contrasting moisture regimes and forest types. Transpiration and maximum photosynthetic electron transport rate (ETR(max)) per unit leaf area declined sharply with increasing A(L):A(S), as did the ratio of ETR(max) to leaf N content, an index of photosynthetic nitrogen-use efficiency. Midday leaf water potential, bulk leaf osmotic potential at zero turgor, branch xylem specific conductivity, leaf-specific conductivity and stem and leaf capacitance all declined with increasing rho(w). At the branch scale, A(L):A(S) and total leaf N content per unit sapwood area increased with rho(w), resulting in a 30% increase in ETR(max) per unit sapwood area with a doubling of rho(w). These compensatory adjustments in A(L):A(S), N allocation and potential photosynthetic capacity at the branch level were insufficient to completely offset the increased carbon costs of producing denser wood, and exacerbated the negative impact of increasing rho(w) on branch hydraulics and leaf water status. The suite of tree functional and architectural traits studied appeared to be constrained by the hydraulic and mechanical consequences of variation in rho(w).

Safety of Patient Mobilization and Rehabilitation in the Intensive Care Unit. Systematic Review with Meta-Analysis.

PubMed

Nydahl, Peter; Sricharoenchai, Thiti; Chandra, Saurabh; Kundt, Firuzan Sari; Huang, Minxuan; Fischill, Magdalena; Needham, Dale M

2017-05-01

Early mobilization and rehabilitation of patients in intensive care units (ICUs) may improve physical function, and reduce the duration of delirium, mechanical ventilation, and ICU length of stay. However, safety concerns are an important barrier to widespread implementation. To synthesize safety data regarding patient mobilization and rehabilitation in the ICU, including falls, removal of endotracheal tubes, removal or dysfunction of intravascular catheters, removal of other catheters/tubes, cardiac arrest, hemodynamic changes, and desaturation. Systematic literature review, including searches of five databases. Eligible studies evaluated patients who received mobilization-related interventions in the ICU. Exclusion criteria included: (1) case series with fewer than 10 patients; (2) majority of patients under 18 years of age; and (3) data not reported to permit calculation of incidence of safety events. Number of patients, mobilization/rehabilitation sessions, potential safety events, and events with negative consequences (e.g., requiring intervention or additional therapy). Heterogeneity was assessed by I 2 statistics, and bias assessed by the Newcastle-Ottawa Scale and Cochrane risk of bias assessment. The literature search identified 20,660 titles. There were 48 eligible publications evaluating 7,546 patients, with 583 potential safety events occurring in 22,351 mobilization/rehabilitation sessions. There was a total of 583 (2.6%) potential safety events with heterogeneity in the definitions for these events. For the safety event types that could be meta-analyzed, pooled incidences per 1,000 mobilization/rehabilitation sessions (95% confidence interval), were: hemodynamic changes, 3.8 (1.3-11.4), and desaturation, 1.9 (0.9-4.3). A total of 24 studies of 3,404 patients reported on any consequences of potential safety events (e.g., needing to increase dose of vasopressor due to mobility-related hypotension), with a frequency of 0.6% in 14,398 mobilization/rehabilitation sessions. Patient mobilization and physical rehabilitation in the ICU appears safe, with a low incidence of potential safety events, and only rare events having any consequences for patient management. Heterogeneity in the definition of safety events across studies emphasizes the importance of implementing existing consensus-based definitions.

RMP Guidance for Warehouses - Chapter 4: Offsite Consequence Analysis

EPA Pesticide Factsheets

Offsite consequence analysis (OCA) informs government and the public about potential consequences of an accidental toxic or flammable chemical release at your facility, and consists of a worst-case release scenario and alternative release scenarios.

Neonatal seizures alter NMDA glutamate receptor GluN2A and 3A subunit expression and function in hippocampal CA1 neurons

PubMed Central

Zhou, Chengwen; Sun, Hongyu; Klein, Peter M.; Jensen, Frances E.

2015-01-01

Neonatal seizures are commonly caused by hypoxic and/or ischemic injury during birth and can lead to long-term epilepsy and cognitive deficits. In a rodent hypoxic seizure (HS) model, we have previously demonstrated a critical role for seizure-induced enhancement of the AMPA subtype of glutamate receptor (GluA) in epileptogenesis and cognitive consequences, in part due to GluA maturational upregulation of expression. Similarly, as the expression and function of the N-Methyl-D-aspartate (NMDA) subtype of glutamate receptor (GluN) is also developmentally controlled, we examined how early life seizures during the critical period of synaptogenesis could modify GluN development and function. In a postnatal day (P)10 rat model of neonatal seizures, we found that seizures could alter GluN2/3 subunit composition of GluNs and physiological function of synaptic GluNs. In hippocampal slices removed from rats within 48–96 h following seizures, the amplitudes of synaptic GluN-mediated evoked excitatory postsynaptic currents (eEPSCs) were elevated in CA1 pyramidal neurons. Moreover, GluN eEPSCs showed a decreased sensitivity to GluN2B selective antagonists and decreased Mg2+ sensitivity at negative holding potentials, indicating a higher proportion of GluN2A and GluN3A subunit function, respectively. These physiological findings were accompanied by a concurrent increase in GluN2A phosphorylation and GluN3A protein. These results suggest that altered GluN function and expression could potentially contribute to future epileptogenesis following neonatal seizures, and may represent potential therapeutic targets for the blockade of future epileptogenesis in the developing brain. PMID:26441533

Acute administration of ivacaftor to people with cystic fibrosis and a G551D-CFTR mutation reveals smooth muscle abnormalities

PubMed Central

Adam, Ryan J.; Hisert, Katherine B.; Dodd, Jonathan D.; Grogan, Brenda; Launspach, Janice L.; Barnes, Janel K.; Gallagher, Charles G.; Sieren, Jered P.; Gross, Thomas J.; Fischer, Anthony J.; Cavanaugh, Joseph E.; Hoffman, Eric A.; Singh, Pradeep K.; Welsh, Michael J.; McKone, Edward F.; Stoltz, David A.

2016-01-01

BACKGROUND. Airflow obstruction is common in cystic fibrosis (CF), yet the underlying pathogenesis remains incompletely understood. People with CF often exhibit airway hyperresponsiveness, CF transmembrane conductance regulator (CFTR) is present in airway smooth muscle (ASM), and ASM from newborn CF pigs has increased contractile tone, suggesting that loss of CFTR causes a primary defect in ASM function. We hypothesized that restoring CFTR activity would decrease smooth muscle tone in people with CF. METHODS. To increase or potentiate CFTR function, we administered ivacaftor to 12 adults with CF with the G551D-CFTR mutation; ivacaftor stimulates G551D-CFTR function. We studied people before and immediately after initiation of ivacaftor (48 hours) to minimize secondary consequences of CFTR restoration. We tested smooth muscle function by investigating spirometry, airway distensibility, and vascular tone. RESULTS. Ivacaftor rapidly restored CFTR function, indicated by reduced sweat chloride concentration. Airflow obstruction and air trapping also improved. Airway distensibility increased in airways less than 4.5 mm but not in larger-sized airways. To assess smooth muscle function in a tissue outside the lung, we measured vascular pulse wave velocity (PWV) and augmentation index, which both decreased following CFTR potentiation. Finally, change in distensibility of <4.5-mm airways correlated with changes in PWV. CONCLUSIONS. Acute CFTR potentiation provided a unique opportunity to investigate CFTR-dependent mechanisms of CF pathogenesis. The rapid effects of ivacaftor on airway distensibility and vascular tone suggest that CFTR dysfunction may directly cause increased smooth muscle tone in people with CF and that ivacaftor may relax smooth muscle. FUNDING. This work was funded in part from an unrestricted grant from the Vertex Investigator-Initiated Studies Program. PMID:27158673

Proteome-wide search for functional motifs altered in tumors: Prediction of nuclear export signals inactivated by cancer-related mutations

PubMed Central

Prieto, Gorka; Fullaondo, Asier; Rodríguez, Jose A.

2016-01-01

Large-scale sequencing projects are uncovering a growing number of missense mutations in human tumors. Understanding the phenotypic consequences of these alterations represents a formidable challenge. In silico prediction of functionally relevant amino acid motifs disrupted by cancer mutations could provide insight into the potential impact of a mutation, and guide functional tests. We have previously described Wregex, a tool for the identification of potential functional motifs, such as nuclear export signals (NESs), in proteins. Here, we present an improved version that allows motif prediction to be combined with data from large repositories, such as the Catalogue of Somatic Mutations in Cancer (COSMIC), and to be applied to a whole proteome scale. As an example, we have searched the human proteome for candidate NES motifs that could be altered by cancer-related mutations included in the COSMIC database. A subset of the candidate NESs identified was experimentally tested using an in vivo nuclear export assay. A significant proportion of the selected motifs exhibited nuclear export activity, which was abrogated by the COSMIC mutations. In addition, our search identified a cancer mutation that inactivates the NES of the human deubiquitinase USP21, and leads to the aberrant accumulation of this protein in the nucleus. PMID:27174732

Thiol-reactive amphiphilic block copolymer for coating gold nanoparticles with neutral and functionable surfaces

PubMed Central

Chen, Hongwei; Zou, Hao; Paholak, Hayley J.; Ito, Masayuki; Qian, Wei; Che, Yong; Sun, Duxin

2014-01-01

Nanoparticles designed for biomedical applications are often coated with polymers containing reactive functional groups, such as –COOH and –NH2, to conjugate targeting ligands or drugs. However, introducing highly charged surfaces promotes binding of the nanoparticles to biomolecules in biological systems through ionic interactions, causing the nanoparticles to aggregate in biological environments and consequently undergo strong non-specific binding to off-target cells and tissues. Developing a unique polymer with neutral surfaces that can be further functionalized directly would be critical to develop suitable nanomaterials for nanomedicine. Here, we report a thiol-reactive amphiphilic block copolymer poly(ethylene oxide)-block-poly(pyridyldisulfide ethylmeth acrylate) (PEO-b-PPDSM) for coating gold nanoparticles (AuNPs). The resultant polymer-coated AuNPs have almost neutral surfaces with slightly negative zeta potentials from -10 to 0 mV over a wide pH range from 2 to 12. Although the zeta potential is close to zero we show that the PEO-b-PPDSM copolymer-coated AuNPs have both good stability in various physiological conditions and reduced non-specific adsorption of proteins/biomolecules. Because of the multiple pyridyldisulfide groups on the PPDSM block, these individually dispersed nanocomplexes with an overall hydrodynamic size around 43.8 nm can be directly functionalized via disulfide-thiol exchange chemistry. PMID:24729795

College Alcohol Beliefs and Drinking Consequences: A Multiple Mediation Analysis of Norms, Expectancies, and Willingness to Experience Drinking Consequences

ERIC Educational Resources Information Center

Osberg, Timothy M.; Boyer, Amber

2018-01-01

Objective: We explored the potential mediating role of willingness to experience drinking consequences and other traditional alcohol outcome predictors (descriptive norms, injunctive norms, positive alcohol expectancies) in explaining the association between college alcohol beliefs1 (CABs) and the actual experience of drinking consequences among…

Observational Consequences of an Interacting Multiverse

NASA Astrophysics Data System (ADS)

Robles-Pérez, Salvador

2017-05-01

The observability of the multiverse is at the very root of its physical significance as a scientific proposal. In this conference we present, within the third quantization formalism, an interacting scheme between the wave functions of different universes and analyze the effects of some particular values of the coupling function. One of the main consequences of the interaction between universes can be the appearance of a pre-inflationary stage in the evolution of the universes that might leave observable consequences in the properties of the CMB.

Behavior Management: Examining the Functions of Behavior

ERIC Educational Resources Information Center

Alstot, Andrew E.; Alstot, Crystal D.

2015-01-01

Appropriate student behavior is essential for the success of a physical education lesson. Despite using effective proactive management strategies, teachers may need to also use reactive techniques to reduce problem behaviors by applying suitable consequences. For these consequences to be effective, they must be aligned with the function, or cause,…

Smoker-Free Workplace Policies: Developing a Model of Public Health Consequences of Workplace Policies Barring Employment to Smokers

PubMed Central

Houle, Brian; Siegel, Michael

2009-01-01

A marked shift in tobacco-related workplace health promotion intervention involves the adoption of policies barring employment to smokers. We discuss the potential public health consequences of these policies on those affected – smokers, their families, the surrounding community, and society at large. We find a lack of published evidence evaluating the effectiveness and consequences of these policies. By developing a model of policy effects, we outline possible unintended consequences. With such large gaps in the evidence base and the potential for deleterious consequences, we argue for increased discussion about the use of smoker-free employment policies as a public health intervention and for increased engagement of employers by the public health community in worksite health promotion. PMID:19168490

An Interdisciplinary Meta-Analysis of the Potential Antecedents, Correlates, and Consequences of Protege Perceptions of Mentoring

ERIC Educational Resources Information Center

Eby, Lillian Turner de Tormes; Allen, Tammy D.; Hoffman, Brian J.; Baranik, Lisa E.; Sauer, Julia B.; Baldwin, Sean; Morrison, M. Ashley; Kinkade, Katie M.; Maher, Charleen P.; Curtis, Sara; Evans, Sarah C.

2013-01-01

This meta-analysis summarized youth, academic, and workplace research on the potential antecedents (demographics, human capital, and relationship attributes), correlates (interaction frequency, relationship length, performance, motivation, and social capital), and consequences (attitudinal, behavioral, career-related, and health-related outcomes)…

Catecholamines and cognition after traumatic brain injury

PubMed Central

Jenkins, Peter O.; Mehta, Mitul A.

2016-01-01

Abstract Cognitive problems are one of the main causes of ongoing disability after traumatic brain injury. The heterogeneity of the injuries sustained and the variability of the resulting cognitive deficits makes treating these problems difficult. Identifying the underlying pathology allows a targeted treatment approach aimed at cognitive enhancement. For example, damage to neuromodulatory neurotransmitter systems is common after traumatic brain injury and is an important cause of cognitive impairment. Here, we discuss the evidence implicating disruption of the catecholamines (dopamine and noradrenaline) and review the efficacy of catecholaminergic drugs in treating post-traumatic brain injury cognitive impairments. The response to these therapies is often variable, a likely consequence of the heterogeneous patterns of injury as well as a non-linear relationship between catecholamine levels and cognitive functions. This individual variability means that measuring the structure and function of a person’s catecholaminergic systems is likely to allow more refined therapy. Advanced structural and molecular imaging techniques offer the potential to identify disruption to the catecholaminergic systems and to provide a direct measure of catecholamine levels. In addition, measures of structural and functional connectivity can be used to identify common patterns of injury and to measure the functioning of brain ‘networks’ that are important for normal cognitive functioning. As the catecholamine systems modulate these cognitive networks, these measures could potentially be used to stratify treatment selection and monitor response to treatment in a more sophisticated manner. PMID:27256296

The Role for Dietary Omega-3 Fatty Acids Supplementation in Older Adults

PubMed Central

Molfino, Alessio; Gioia, Gianfranco; Fanelli, Filippo Rossi; Muscaritoli, Maurizio

2014-01-01

Optimal nutrition is one of the most important determinants of healthier ageing, reducing the risk of disability, maintaining mental and physical functions, and thus preserving and ensuring a better quality of life. Dietary intake and nutrient absorption decline with age, thus increasing the risk of malnutrition, morbidity and mortality. Specific nutrients, particularly long-chain omega-3 polyunsaturated fatty acids (PUFAs), might have the potential of preventing and reducing co-morbidities in older adults. Omega-3 PUFAs are able to modulate inflammation, hyperlipidemia, platelet aggregation, and hypertension. Different mechanisms contribute to these effects, including conditioning cell membrane function and composition, eicosanoid production, and gene expression. The present review analyzes the influence of omega-3 PUFAs status and intake on brain function, cardiovascular system, immune function, muscle performance and bone health in older adults. Omega-3 FAs may have substantial benefits in reducing the risk of cognitive decline in older people. The available data encourage higher intakes of omega-3 PUFAs in the diet or via specific supplements. More studies are needed to confirm the role of omega-3 FAs in maintaining bone health and preventing the loss of muscle mass and function associated with ageing. In summary, omega-3 PUFAs are now identified as potential key nutrients, safe and effective in the treatment and prevention of several negative consequences of ageing. PMID:25285409

Ciprofloxacin and statin interaction: a cautionary tale of rhabdomyolysis.

PubMed

Goldie, Fraser Charles; Brogan, Amy; Boyle, James Graham

2016-07-28

A 62-year-old woman presented to hospital, on general practitioner (GP) advice, with a 15-day history of slowly progressing muscle weakness. Results showed newly deranged liver function and creatine kinase (CK) of >24 000. Prior medical history includes previous myocardial infarction and recurrent urinary tract infection. 4 days prior to symptom onset, the patient developed typical urinary tract infection symptoms, treated with ciprofloxacin. The patient had been taking simvastatin (40 mg nocte) for 13 years and had never previously taken ciprofloxacin. Initial management included intravenous crystalloid fluids and discontinuation of simvastatin. CK level fell, liver function slowly improved and renal function remained stable. Muscle weakness improved and the patient became independently able to perform activities of daily living. While the interactions between statins and other antibiotics are well documented, the interaction between statins and ciprofloxacin is less so. The consequences of this interaction can have potentially serious outcomes. 2016 BMJ Publishing Group Ltd.

Global profiling of lysine reactivity and ligandability in the human proteome

NASA Astrophysics Data System (ADS)

Hacker, Stephan M.; Backus, Keriann M.; Lazear, Michael R.; Forli, Stefano; Correia, Bruno E.; Cravatt, Benjamin F.

2017-12-01

Nucleophilic amino acids make important contributions to protein function, including performing key roles in catalysis and serving as sites for post-translational modification. Electrophilic groups that target amino-acid nucleophiles have been used to create covalent ligands and drugs, but have, so far, been mainly limited to cysteine and serine. Here, we report a chemical proteomic platform for the global and quantitative analysis of lysine residues in native biological systems. We have quantified, in total, more than 9,000 lysines in human cell proteomes and have identified several hundred residues with heightened reactivity that are enriched at protein functional sites and can frequently be targeted by electrophilic small molecules. We have also discovered lysine-reactive fragment electrophiles that inhibit enzymes by active site and allosteric mechanisms, as well as disrupt protein-protein interactions in transcriptional regulatory complexes, emphasizing the broad potential and diverse functional consequences of liganding lysine residues throughout the human proteome.

Interactive Contributions of Cumulative Peer Stress and Executive Function Deficits to Depression in Early Adolescence.

PubMed

Agoston, Anna M; Rudolph, Karen D

2016-01-01

Exposure to peer stress contributes to adolescent depression, yet not all youth experience these effects. Thus, it is important to identify individual differences that shape the consequences of peer stress. This research investigated the interactive contribution of cumulative peer stress during childhood (second-fifth grades) and executive function (EF) deficits to depression during early adolescence (sixth grade). Youth (267 girls, 227 boys; X̄ age at Wave 1 = 7.95, SD = .37) completed questionnaires and semi-structured interviews to assess peer stress and depression, respectively; teachers completed the Behavior Rating Scale of Executive Function to assess everyday performance in several EF domains. As anticipated, exposure to peer stress in childhood predicted heightened sixth-grade depression in girls but not boys with higher levels of EF deficits. This study extends theory and research on individual differences in vulnerability to adolescent depression, in turn elucidating potential intervention targets.

On the solution of integral equations with a generalized cauchy kernel

NASA Technical Reports Server (NTRS)

Kaya, A. C.; Erdogan, F.

1986-01-01

In this paper a certain class of singular integral equations that may arise from the mixed boundary value problems in nonhomogeneous materials is considered. The distinguishing feature of these equations is that in addition to the Cauchy singularity, the kernels contain terms that are singular only at the end points. In the form of the singular integral equations adopted, the density function is a potential or a displacement and consequently the kernel has strong singularities of the form (t-x) sup-2, x sup n-2 (t+x) sup n, (n or = 2, 0x,tb). The complex function theory is used to determine the fundamental function of the problem for the general case and a simple numerical technique is described to solve the integral equation. Two examples from the theory of elasticity are then considered to show the application of the technique.

An Affect-Centered Model of the Psyche and its Consequences for a New Understanding of Nonlinear Psychodynamics

NASA Astrophysics Data System (ADS)

Ciompi, Luc

At variance with a purely cognitivistic approach, an affect-centered model of mental functioning called `fractal affect-logic' is presented on the basis of current emotional-psychological and neurobiological research. Functionally integrated feeling-thinking-behaving programs generated by action appear in this model as the basic `building blocks' of the psyche. Affects are understood as the essential source of energy that mobilises and organises both linear and nonlinear affective-cognitive dynamics, under the influence of appropriate control parameters and order parameters. Global patterns of affective-cognitive functioning form dissipative structures in the sense of Prigogine, with affect-specific attractors and repulsors, bifurcations, high sensitivity for initial conditions and a fractal overall structure that may be represented in a complex potential landscape of variable configuration. This concept opens new possibilities of understanding normal and pathological psychodynamics and sociodynamics, with numerous practical and theoretical implications.

Adaptability as the key to success for the ubiquitous marine nitrite oxidizer Nitrococcus

PubMed Central

Füssel, Jessika; Lücker, Sebastian; Yilmaz, Pelin; Nowka, Boris; van Kessel, Maartje A. H. J.; Bourceau, Patric; Hach, Philipp F.; Littmann, Sten; Berg, Jasmine; Spieck, Eva; Daims, Holger; Kuypers, Marcel M. M.; Lam, Phyllis

2017-01-01

Nitrite-oxidizing bacteria (NOB) have conventionally been regarded as a highly specialized functional group responsible for the production of nitrate in the environment. However, recent culture-based studies suggest that they have the capacity to lead alternative lifestyles, but direct environmental evidence for the contribution of marine nitrite oxidizers to other processes has been lacking to date. We report on the alternative biogeochemical functions, worldwide distribution, and sometimes high abundance of the marine NOB Nitrococcus. These largely overlooked bacteria are capable of not only oxidizing nitrite but also reducing nitrate and producing nitrous oxide, an ozone-depleting agent and greenhouse gas. Furthermore, Nitrococcus can aerobically oxidize sulfide, thereby also engaging in the sulfur cycle. In the currently fast-changing global oceans, these findings highlight the potential functional switches these ubiquitous bacteria can perform in various biogeochemical cycles, each with distinct or even contrasting consequences. PMID:29109973

RNA editing in Drosophila melanogaster: new targets and functionalconsequences

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stapleton, Mark; Carlson, Joseph W.; Celniker, Susan E.

2006-09-05

Adenosine deaminases that act on RNA (ADARs) catalyze the site-specific conversion of adenosine to inosine in primary mRNA transcripts. These re-coding events affect coding potential, splice-sites, and stability of mature mRNAs. ADAR is an essential gene and studies in mouse, C. elegans, and Drosophila suggest its primary function is to modify adult behavior by altering signaling components in the nervous system. By comparing the sequence of isogenic cDNAs to genomic DNA, we have identified and experimentally verified 27 new targets of Drosophila ADAR. Our analyses lead us to identify new classes of genes whose transcripts are targets of ADAR includingmore » components of the actin cytoskeleton, and genes involved in ion homeostasis and signal transduction. Our results indicate that editing in Drosophila increases the diversity of the proteome, and does so in a manner that has direct functional consequences on protein function.« less

Chia Oil Extraction Coproduct as a Potential New Ingredient for the Food Industry: Chemical, Physicochemical, Techno-Functional and Antioxidant Properties.

PubMed

Fernández-López, Juana; Lucas-González, Raquel; Viuda-Martos, Manuel; Sayas-Barberá, Estrella; Pérez-Alvarez, José Angel

2018-06-01

The aim of this work was to characterize the coproduct obtained from chia oil production (cold-pressing) with a view to its possible application in new food product development. For this characterization, the following determinations were made: proximate composition, physicochemical analysis, techno-functional properties, total phenolic and flavonoid content, polyphenolic profile and antioxidant capacity (using four different methods). Chia coproduct showed significantly higher levels of proteins and total dietary fiber and lower levels of fats than chia seeds, pointing to the promising nature of this coproduct as an ingredient of food formulations since it remains a source of high biological value proteins and total dietary fiber (as chia seeds themselves) but with a lower energy value. This chia coproduct presents similar techno-functional properties to the original chia seeds and significantly higher levels of polyphenolic compounds and, consequently, higher antioxidant activity.

Interactive Contributions of Cumulative Peer Stress and Executive Function Deficits to Depression in Early Adolescence

PubMed Central

Agoston, Anna M.; Rudolph, Karen D.

2017-01-01

Exposure to peer stress contributes to adolescent depression, yet not all youth experience these effects. Thus, it is important to identify individual differences that shape the consequences of peer stress. This research investigated the interactive contribution of cumulative peer stress during childhood (second-fifth grades) and executive function (EF) deficits to depression during early adolescence (sixth grade). Youth (267 girls, 227 boys; X̄age at Wave 1 = 7.95, SD = .37) completed questionnaires and semi-structured interviews to assess peer stress and depression, respectively; teachers completed the Behavior Rating Scale of Executive Function to assess everyday performance in several EF domains. As anticipated, exposure to peer stress in childhood predicted heightened sixth-grade depression in girls but not boys with higher levels of EF deficits. This study extends theory and research on individual differences in vulnerability to adolescent depression, in turn elucidating potential intervention targets. PMID:28936024

Global profiling of lysine reactivity and ligandability in the human proteome.

PubMed

Hacker, Stephan M; Backus, Keriann M; Lazear, Michael R; Forli, Stefano; Correia, Bruno E; Cravatt, Benjamin F

2017-12-01

Nucleophilic amino acids make important contributions to protein function, including performing key roles in catalysis and serving as sites for post-translational modification. Electrophilic groups that target amino-acid nucleophiles have been used to create covalent ligands and drugs, but have, so far, been mainly limited to cysteine and serine. Here, we report a chemical proteomic platform for the global and quantitative analysis of lysine residues in native biological systems. We have quantified, in total, more than 9,000 lysines in human cell proteomes and have identified several hundred residues with heightened reactivity that are enriched at protein functional sites and can frequently be targeted by electrophilic small molecules. We have also discovered lysine-reactive fragment electrophiles that inhibit enzymes by active site and allosteric mechanisms, as well as disrupt protein-protein interactions in transcriptional regulatory complexes, emphasizing the broad potential and diverse functional consequences of liganding lysine residues throughout the human proteome.

Prebiotics: A Potential Treatment Strategy for the Chemotherapy-damaged Gut?

PubMed

Wang, Hanru; Geier, Mark S; Howarth, Gordon S

2016-01-01

Mucositis, characterized by ulcerative lesions along the alimentary tract, is a common consequence of many chemotherapy regimens. Chemotherapy negatively disrupts the intestinal microbiota, resulting in increased numbers of potentially pathogenic bacteria, such as Clostridia and Enterobacteriaceae, and decreased numbers of "beneficial" bacteria, such as Lactobacilli and Bifidobacteria. Agents capable of restoring homeostasis in the bowel microbiota could, therefore, be applicable to mucositis. Prebiotics are indigestible compounds, commonly oligosaccharides, that seek to reverse chemotherapy-induced intestinal dysbiosis through selective colonization of the intestinal microbiota by probiotic bacteria. In addition, evidence is emerging that certain prebiotics contribute to nutrient digestibility and absorption, modulate intestinal barrier function through effects on mucin expression, and also modify mucosal immune responses, possibly via inflammasome-mediated processes. This review examines the known mechanisms of prebiotic action, and explores their potential for reducing the severity of chemotherapy-induced mucositis in the intestine.

EGFR transactivation: mechanisms, pathophysiology and potential therapies in cardiovascular system

PubMed Central

Forrester, Steven J.; Kawai, Tatsuo; Elliott, Katherine J.; O’Brien, Shannon; Thomas, Walter; Harris, Raymond C.; Eguchi, Satoru

2017-01-01

Accumulating studies suggest that the epidermal growth factor receptor (EGFR) activation is associated with the physiology and pathophysiology of the cardiovascular system, and inhibition of EGFR activity is emerging as a potential therapeutic strategy to treat diseases, including hypertension, cardiac hypertrophy, renal fibrosis and abdominal aortic aneurysm. The capacity of G protein-coupled receptor (GPCR) agonists, such as angiotensin II (AngII), to promote EGFR signaling is well described – a process termed EGFR “transactivation” – yet delineating the molecular processes and functional relevance of this crosstalk has been challenging. Moreover, these critical findings are dispersed among many different fields. The aim of our review is to highlight the recent advancement of the signaling cascades and downstream consequences of EGFR transactivation within the cardiovascular renal system in vitro and in vivo. We will also focus on linking EGFR transactivation to animal models of the disease as well as the potential therapeutic applications. PMID:26566153

Stokes' theorem, gauge symmetry and the time-dependent Aharonov-Bohm effect

DOE Office of Scientific and Technical Information (OSTI.GOV)

Macdougall, James, E-mail: jbm34@mail.fresnostate.edu; Singleton, Douglas, E-mail: dougs@csufresno.edu

2014-04-15

Stokes' theorem is investigated in the context of the time-dependent Aharonov-Bohm effect—the two-slit quantum interference experiment with a time varying solenoid between the slits. The time varying solenoid produces an electric field which leads to an additional phase shift which is found to exactly cancel the time-dependent part of the usual magnetic Aharonov-Bohm phase shift. This electric field arises from a combination of a non-single valued scalar potential and/or a 3-vector potential. The gauge transformation which leads to the scalar and 3-vector potentials for the electric field is non-single valued. This feature is connected with the non-simply connected topology ofmore » the Aharonov-Bohm set-up. The non-single valued nature of the gauge transformation function has interesting consequences for the 4-dimensional Stokes' theorem for the time-dependent Aharonov-Bohm effect. An experimental test of these conclusions is proposed.« less

Mapping influenza transmission in the ferret model to transmission in humans

PubMed Central

Buhnerkempe, Michael G; Gostic, Katelyn; Park, Miran; Ahsan, Prianna; Belser, Jessica A; Lloyd-Smith, James O

2015-01-01

The controversy surrounding 'gain-of-function' experiments on high-consequence avian influenza viruses has highlighted the role of ferret transmission experiments in studying the transmission potential of novel influenza strains. However, the mapping between influenza transmission in ferrets and in humans is unsubstantiated. We address this gap by compiling and analyzing 240 estimates of influenza transmission in ferrets and humans. We demonstrate that estimates of ferret secondary attack rate (SAR) explain 66% of the variation in human SAR estimates at the subtype level. Further analysis shows that ferret transmission experiments have potential to identify influenza viruses of concern for epidemic spread in humans, though small sample sizes and biological uncertainties prevent definitive classification of human transmissibility. Thus, ferret transmission experiments provide valid predictions of pandemic potential of novel influenza strains, though results should continue to be corroborated by targeted virological and epidemiological research. DOI: http://dx.doi.org/10.7554/eLife.07969.001 PMID:26329460

Exploring the functional significance of sterol glycosyltransferase enzymes.

PubMed

Singh, Gaurav; Dhar, Yogeshwar Vikram; Asif, Mehar Hasan; Misra, Pratibha

2018-01-01

Steroidal alkaloids (SAs) are widely synthesized and distributed in plants manifesting as natural produce endowed with potential for medicinal, pesticidal and other high-value usages. Glycosylation of these SAs raises complex and diverse glycosides in plant cells that indeed govern numerous functional aspects. During the glycosylation process of these valuable metabolites, the addition of carbohydrate molecule(s) is catalyzed by enzymes known as sterol glycosyltransferases (SGTs), commonly referred to as UGTs, leading to the production of steryl glycosides (SGs). The ratio of SGs and nonglyco-conjugated SAs are different in different plant species, however, their biosynthesis in the cell is controlled by different environmental factors. The aim of this review is to evaluate the current SGT enzyme research and the functional consequences of glycomodification of SAs on the physiology and plant development, which together are associated with the plant's primary processes. Pharmaceutical, industrial, and other potential uses of saponins have also been discussed and their use in therapeutics has been unveiled by in silico analysis. The field of biotransformation or conversion of nonglycosylated to glycosylated phytosterols by the activity of SGTs, making them soluble, available and more useful for humankind is the new field of interest towards drug therapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Contribution of nematodes to the structure and function of the soil food web.

PubMed

Ferris, Howard

2010-03-01

As carbon and energy flow through the soil food web they are depleted by the metabolic and production functions of organisms. To be sustained, a "long" food web, with a large biomass at higher trophic levels, must receive a high rate of rhizodeposition or detrital subsidy, or be top-populated by organisms of slow growth and long life cycle. Disturbed soil food webs tend to be bottom heavy and recalcitrant to restoration due to the slow growth of upper predator populations, physical and chemical constraints of the soil matrix, biological imbalances, and the relatively low mobility and invasion potential of soil organisms. The functional roles of nematodes, determined by their metabolic and behavioral activities, may be categorized as ecosystem services, disservices or effect-neutral. Among the disservices attributable to nematodes are overgrazing, which diminishes services of prey organisms, and plant-damaging herbivory, which reduces carbon fixation and availability to other organisms in the food web. Unfortunately, management to ameliorate potential disservices of certain nematodes results in unintended but long-lasting diminution of the services of others. Beneficial roles of nematodes may be enhanced by environmental stewardship that fosters greater biodiversity and, consequently, complementarity and continuity of their services.

Structure and capacitance of an electric double layer of an asymmetric valency dimer electrolyte: A comparison of the density functional theory with Monte Carlo simulations

DOE PAGES

Henderson, Douglas; Silvestre-Alcantara, Whasington; Kaja, Monika; ...

2016-08-18

Here, the density functional theory is applied to a study of the structure and differential capacitance of a planar electric double layer formed by a valency asymmetric mixture of charged dimers and monomers. The dimer consists of two tangentially tethered hard spheres of equal diameters of which one is charged and the other is neutral, while the monomer is a charged hard sphere of the same size. The dimer electrolyte is next to a uniformly charged, smooth planar electrode. The electrode-particle singlet distributions, the mean electrostatic potential, and the differential capacitance for the model double layer are evaluated for amore » 2:1/1:2 valency electrolyte at a given concentration. Important consequences of asymmetry in charges and in ion shapes are (i) a finite, non-zero potential of zero charge, and (ii) asymmetric shaped 2:1 and 1:2 capacitance curves which are not mirror images of each other. Comparisons of the density functional results with the corresponding Monte Carlo simulations show the theoretical predictions to be in good agreement with the simulations overall except near zero surface charge.« less

Modulation of mitochondrial metabolism as a biochemical trait in blood feeding organisms: the redox vampire hypothesis redux.

PubMed

Ferreira, Caroline M; Oliveira, Matheus P; Paes, Marcia C; Oliveira, Marcus F

2018-06-01

Hematophagous organisms undergo remarkable metabolic changes during the blood digestion process, increasing fermentative glucose metabolism, and reducing respiratory rates, both consequence of functional mitochondrial remodeling. Here, we review the pathways involved in energy metabolism and mitochondrial functionality in a comparative framework across different hematophagous species, and consider how these processes regulate redox homeostasis during blood digestion. The trend across distinct species indicate that a switch in energy metabolism might represent an important defensive mechanism to avoid the potential harmful interaction of oxidants generated from aerobic energy metabolism with products derived from blood digestion. Indeed, in insect vectors, blood feeding transiently reduces respiratory rates and oxidant production, irrespective of tissue and insect model. On the other hand, a different scenario is observed in several unrelated parasite species when exposed to blood digestion products, as respiratory rates reduce and mitochondrial oxidant production increase. The emerging picture indicates that re-wiring of energy metabolism, through reduced mitochondrial function, culminates in improved tolerance to redox insults and seems to represent a key step for hematophagous organisms to cope with the overwhelming and potentially toxic blood meal. © 2018 International Federation for Cell Biology.

A comprehensive and conservative approach for the restoration of abrasion and erosion. Part I: concepts and clinical rationale for early intervention using adhesive techniques.

PubMed

Dietschi, Didier; Argente, Ana

2011-01-01

Tooth wear represents a frequent pathology with multifactorial origins. Behavioral changes, unbalanced diet, various medical conditions and medications inducing acid regurgitation or influencing saliva composition and flow rate, trigger tooth erosion. Awake and sleep bruxism, which are widespread nowadays with functional disorders, induce attrition. It has become increasingly important to diagnose early signs of tooth wear so that proper preventive, and if needed, restorative measures are taken. Such disorders have biological, functional, and also esthetic consequences. Following a comprehensive clinical evaluation, treatment objectives, such as a proper occlusal and anatomical scheme as well as a pleasing smile line, are usually set on models with an anterior teeth full-mouth waxup, depending on the severity of tissue loss. Based on the new vertical dimension of occlusion (VDO), combinations of direct and indirect restorations can then help to reestablish anatomy and function. The use of adhesive techniques and resin composites has demonstrated its potential, in particular for the treatment of moderate tooth wear. Part I of this article reviews recent knowledge and clinical concepts dealing with the various forms of early restorative interventions and their potential to restrict ongoing tissue destruction.

CRISPR: express delivery to any DNA address.

PubMed

Peterson, A

2017-01-01

The sudden emergence and worldwide adoption of CRISPR gene-editing technology confronts humanity with unprecedented opportunities and choices. CRISPR's transformative impact on our future understanding of biology, along with its potential to unleash control over the most fundamental of biological processes, is predictable by already achieved applications. Although its origin, composition, and function were revealed only recently, close to 3000 CRISPR-based publications have appeared including insightful and diversely focused reviews referenced here. Adding further to scientific and public awareness, a recent symposium addressed the ethical implications of interfacing CRISPR technology and human biology. However, the magnitude of CRISPR's rapidly emerging power mandates its broadest assessment. Only with the participation of a diverse and informed community can the most effective and humanity-positive CRISPR applications be defined. This brief review is aimed at those with little previous exposure to the CRISPR revolution. The molecules that constitute CRISPR's core components and their functional organization are described along with how the mechanism has been harnessed to edit genome structure and modulate gene function. Additionally, a glimpse into CRISPR's potential to unleash genetic changes with far-reaching consequences is presented. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Napping: A public health issue. From epidemiological to laboratory studies.

PubMed

Faraut, Brice; Andrillon, Thomas; Vecchierini, Marie-Françoise; Leger, Damien

2017-10-01

Sleep specialists have proposed measures to counteract the negative short- and long-term consequences of sleep debt, and some have suggested the nap as a potential and powerful "public health tool". Here, we address this countermeasure aspect of napping viewed as an action against sleep deprivation rather than an action associated with poor health. We review the physiological functions that have been associated positively with napping in both public health and clinical settings (sleep-related accidents, work and school, and cardiovascular risk) and in laboratory-based studies with potential public health issues (cognitive performance, stress, immune function and pain sensitivity). We also discuss the circumstances in which napping-depending on several factors, including nap duration, frequency, and age-could be a potential public health tool and a countermeasure for sleep loss in terms of reducing accidents and cardiovascular events and improving sleep-restriction-sensitive working performance. However, the impact of napping and the nature of the sleep stage(s) involved still need to be evaluated, especially from the perspective of coping strategies in populations with chronic sleep debt, such as night and shift workers. Copyright © 2016 Elsevier Ltd. All rights reserved.

Rye and Wheat Bran Extracts Isolated with Pressurized Solvents Increase Oxidative Stability and Antioxidant Potential of Beef Meat Hamburgers.

PubMed

Šulniūtė, Vaida; Jaime, Isabel; Rovira, Jordi; Venskutonis, Petras Rimantas

2016-02-01

Rye and wheat bran extracts containing phenolic compounds and demonstrating high DPPH• (2,2-diphenyl-1-picrylhydrazyl), ABTS(•+) (2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) scavenging and oxygen radical absorbance capacities (ORAC) were tested in beef hamburgers as possible functional ingredients. Bran extracts significantly increased the indicators of antioxidant potential of meat products and their global antioxidant response (GAR) during physiological in vitro digestion. The extracts also inhibited the formation of oxidation products, hexanal and malondialdehyde, of hamburgers during their storage; however, they did not have significant effect on the growth of microorganisms. Hamburgers with 0.8% wheat bran extract demonstrated the highest antioxidant potential. Some effects of bran extracts on other quality characteristics such as pH, color, formation of metmyoglobin were also observed, however, these effects did not have negative influence on the overall sensory evaluation score of hamburgers. Consequently, the use of bran extracts in meat products may be considered as promising means of increasing oxidative product stability and enriching with functional ingredients which might possess health benefits. © 2016 Institute of Food Technologists®

Sleep, Plasticity and the Pathophysiology of Neurodevelopmental Disorders: The Potential Roles of Protein Synthesis and Other Cellular Processes

PubMed Central

Picchioni, Dante; Reith, R. Michelle; Nadel, Jeffrey L.; Smith, Carolyn B.

2014-01-01

Sleep is important for neural plasticity, and plasticity underlies sleep-dependent memory consolidation. It is widely appreciated that protein synthesis plays an essential role in neural plasticity. Studies of sleep-dependent memory and sleep-dependent plasticity have begun to examine alterations in these functions in populations with neurological and psychiatric disorders. Such an approach acknowledges that disordered sleep may have functional consequences during wakefulness. Although neurodevelopmental disorders are not considered to be sleep disorders per se, recent data has revealed that sleep abnormalities are among the most prevalent and common symptoms and may contribute to the progression of these disorders. The main goal of this review is to highlight the role of disordered sleep in the pathology of neurodevelopmental disorders and to examine some potential mechanisms by which sleep-dependent plasticity may be altered. We will also briefly attempt to extend the same logic to the other end of the developmental spectrum and describe a potential role of disordered sleep in the pathology of neurodegenerative diseases. We conclude by discussing ongoing studies that might provide a more integrative approach to the study of sleep, plasticity, and neurodevelopmental disorders. PMID:24839550

Invasive aquarium fish transform ecosystem nutrient dynamics

PubMed Central

Capps, Krista A.; Flecker, Alexander S.

2013-01-01

Trade of ornamental aquatic species is a multi-billion dollar industry responsible for the introduction of myriad fishes into novel ecosystems. Although aquarium invaders have the potential to alter ecosystem function, regulation of the trade is minimal and little is known about the ecosystem-level consequences of invasion for all but a small number of aquarium species. Here, we demonstrate how ecological stoichiometry can be used as a framework to identify aquarium invaders with the potential to modify ecosystem processes. We show that explosive growth of an introduced population of stoichiometrically unique, phosphorus (P)-rich catfish in a river in southern Mexico significantly transformed stream nutrient dynamics by altering nutrient storage and remineralization rates. Notably, changes varied between elements; the P-rich fish acted as net sinks of P and net remineralizers of nitrogen. Results from this study suggest species-specific stoichiometry may be insightful for understanding how invasive species modify nutrient dynamics when their population densities and elemental composition differ substantially from native organisms. Risk analysis for potential aquarium imports should consider species traits such as body stoichiometry, which may increase the likelihood that an invasion will alter the structure and function of ecosystems. PMID:23966642

Unintended Consequences of Wearable Sensor Use in Healthcare. Contribution of the IMIA Wearable Sensors in Healthcare WG.

PubMed

Schukat, M; McCaldin, D; Wang, K; Schreier, G; Lovell, N H; Marschollek, M; Redmond, S J

2016-11-10

As wearable sensors take the consumer market by storm, and medical device manufacturers move to make their devices wireless and appropriate for ambulatory use, this revolution brings with it some unintended consequences, which we aim to discuss in this paper. We discuss some important unintended consequences, both beneficial and unwanted, which relate to: modifications of behavior; creation and use of big data sets; new security vulnerabilities; and unforeseen challenges faced by regulatory authorities, struggling to keep pace with recent innovations. Where possible, we proposed potential solutions to unwanted consequences. Intelligent and inclusive design processes may mitigate unintended modifications in behavior. For big data, legislating access to and use of these data will be a legal and political challenge in the years ahead, as we trade the health benefits of wearable sensors against the risk to our privacy. The wireless and personal nature of wearable sensors also exposes them to a number of unique security vulnerabilities. Regulation plays an important role in managing these security risks, but also has the dual responsibility of ensuring that wearable devices are fit for purpose. However, the burden of validating the function and security of medical devices is becoming infeasible for regulators, given the many software apps and wearable sensors entering the market each year, which are only a subset of an even larger 'internet of things'. Wearable sensors may serve to improve wellbeing, but we must be vigilant against the occurrence of unintended consequences. With collaboration between device manufacturers, regulators, and end-users, we balance the risk of unintended consequences occurring against the incredible benefit that wearable sensors promise to bring to the world.

Unintended Consequences of Wearable Sensor Use in Healthcare

PubMed Central

McCaldin, D.; Wang, K.; Schreier, G.; Lovell, N. H.; Marschollek, M.; Redmond, S. J.

2016-01-01

Summary Objectives As wearable sensors take the consumer market by storm, and medical device manufacturers move to make their devices wireless and appropriate for ambulatory use, this revolution brings with it some unintended consequences, which we aim to discuss in this paper. Methods We discuss some important unintended consequences, both beneficial and unwanted, which relate to: modifications of behavior; creation and use of big data sets; new security vulnerabilities; and unforeseen challenges faced by regulatory authorities, struggling to keep pace with recent innovations. Where possible, we proposed potential solutions to unwanted consequences. Results Intelligent and inclusive design processes may mitigate unintended modifications in behavior. For big data, legislating access to and use of these data will be a legal and political challenge in the years ahead, as we trade the health benefits of wearable sensors against the risk to our privacy. The wireless and personal nature of wearable sensors also exposes them to a number of unique security vulnerabilities. Regulation plays an important role in managing these security risks, but also has the dual responsibility of ensuring that wearable devices are fit for purpose. However, the burden of validating the function and security of medical devices is becoming infeasible for regulators, given the many software apps and wearable sensors entering the market each year, which are only a subset of an even larger ‘internet of things’. Conclusion Wearable sensors may serve to improve wellbeing, but we must be vigilant against the occurrence of unintended consequences. With collaboration between device manufacturers, regulators, and end-users, we balance the risk of unintended consequences occurring against the incredible benefit that wearable sensors promise to bring to the world. PMID:27830234

Polymerase γ gene POLG determines the risk of sodium valproate-induced liver toxicity.

PubMed

Stewart, Joanna D; Horvath, Rita; Baruffini, Enrico; Ferrero, Iliana; Bulst, Stefanie; Watkins, Paul B; Fontana, Robert J; Day, Christopher P; Chinnery, Patrick F

2010-11-01

Sodium valproate (VPA) is widely used throughout the world to treat epilepsy, migraine, chronic headache, bipolar disorder, and as adjuvant chemotherapy. VPA toxicity is an uncommon but potentially fatal cause of idiosyncratic liver injury. Rare mutations in POLG, which codes for the mitochondrial DNA polymerase γ (polγ), cause Alpers-Huttenlocher syndrome (AHS). AHS is a neurometabolic disorder associated with an increased risk of developing fatal VPA hepatotoxicity. We therefore set out to determine whether common genetic variants in POLG explain why some otherwise healthy individuals develop VPA hepatotoxicity. We carried out a prospective study of subjects enrolled in the Drug Induced Liver Injury Network (DILIN) from 2004 to 2008 through five US centers. POLG was sequenced and the functional consequences of VPA and novel POLG variants were evaluated in primary human cell lines and the yeast model system Saccharomyces cerevisiae. Heterozygous genetic variation in POLG was strongly associated with VPA-induced liver toxicity (odds ratio = 23.6, 95% confidence interval [CI] = 8.4-65.8, P = 5.1 × 10⁻⁷). This was principally due to the p.Q1236H substitution which compromised polγ function in yeast. Therapeutic doses of VPA inhibited human cellular proliferation and high doses caused nonapoptotic cell death, which was not mediated through mitochondrial DNA depletion, mutation, or a defect of fatty acid metabolism. These findings implicate impaired liver regeneration in VPA toxicity and show that prospective genetic testing of POLG will identify individuals at high risk of this potentially fatal consequence of treatment.

POLG determines the risk of sodium valproate induced liver toxicity

PubMed Central

Stewart, Joanna D.; Horvath, Rita; Baruffini, Enrico; Ferrero, Iliana; Bulst, Stefanie; Watkins, Paul B.; Fontana, Robert J.; Day, Christopher P.; Chinnery, Patrick F.

2013-01-01

Sodium valproate (VPA) is widely used throughout the world to treat epilepsy, migraine, chronic headache, bipolar disorder, and as adjuvant chemotherapy. VPA toxicity is an uncommon but potentially fatal cause of idiosyncratic liver injury. Rare mutations in POLG, which codes for the mitochondrial DNA polymerase γ (polγ), cause the Alpers-Huttenlocher syndrome (AHS). AHS is a neurometabolic disorder associated with an increased risk of developing fatal VPA-hepatotoxicity. We therefore set out to determine whether common genetic variants in POLG explain why some otherwise healthy individuals develop VPA-hepatotoxicity. We carried out a prospective study of subjects enrolled in the Drug Induced Liver Injury Network (DILIN) from 2004 to 2008 through five US centres. POLG was sequenced and the functional consequences of VPA and novel POLG variants were evaluated in primary human cell lines and the yeast model system Saccharomyces cerevisiae. Heterozygous genetic variation in POLG was strongly associated with VPA-induced liver toxicity (odds ratio = 23.6, 95% CI = 8.4 – 65.8, P = 5.1 × 10−7). This was principally due to the p.Q1236H substitution which compromised polγ function in yeast. Therapeutic doses of VPA inhibited human cellular proliferation, and high doses caused non-apoptotic cell death which was not mediated through mitochondrial DNA depletion, mutation, or a defect of fatty acid metabolism. These findings implicate impaired liver regeneration in VPA toxicity, and show that prospective genetic testing of POLG will identify individuals at high risk of this potentially fatal consequence of treatment. PMID:21038416

Functional Consequences of Repeated Organophosphate Exposure: Potential Non-Cholinergic Mechanisms

PubMed Central

Terry, A.V.

2012-01-01

The class of chemicals known as the “organophosphates” (OPs) comprises many of the most common agricultural and commercial pesticides that are used worldwide as well as the highly toxic chemical warfare agents. The mechanism of the acute toxicity of OPs in both target and non-target organisms is primarily attributed to inhibitory actions on various forms of cholinesterase leading to excessive peripheral and central cholinergic activity. However, there is now substantial evidence that this canonical (cholinesterase-based) mechanism cannot alone account for the wide-variety of adverse consequences of OP exposure that have been described, especially those associated with repeated exposures to levels that produce no overt signs of acute toxicity. This type of exposure has been associated with prolonged impairments in attention, memory, and other domains of cognition, as well as chronic illnesses where these symptoms are manifested (e.g., Gulf War Illness, Alzheimer’s disease). Due to their highly reactive nature, it is not surprising that OPs might alter the function of a number of enzymes and proteins (in addition to cholinesterase). However, the wide variety of long-term neuropsychiatric symptoms that have been associated with OPs suggests that some basic or fundamental neuronal process was adversely affected during the exposure period. The purpose of this review is to discuss several non-cholinesterase targets of OPs that might affect such fundamental processes and includes cytoskeletal and motor proteins involved in axonal transport, neurotrophins and their receptors, and mitochondria (especially their morphology and movement in axons). Potential therapeutic implications of these OP interactions are also discussed. PMID:22465060

Functional consequences of prolactin signalling in endothelial cells: a potential link with angiogenesis in pathophysiology?

PubMed Central

Reuwer, Anne Q; Nowak-Sliwinska, Patrycja; Mans, Laurie A; van der Loos, Chris M; von der Thüsen, Jan H; Twickler, Marcel Th B; Spek, C Arnold; Goffin, Vincent; Griffioen, Arjan W; Borensztajn, Keren S

2012-01-01

Prolactin is best known as the polypeptide anterior pituitary hormone, which regulates the development of the mammary gland. However, it became clear over the last decade that prolactin contributes to a broad range of pathologies, including breast cancer. Prolactin is also involved in angiogenesis via the release of pro-angiogenic factors by leukocytes and epithelial cells. However, whether prolactin also influences endothelial cells, and whether there are functional consequences of prolactin-induced signalling in the perspective of angiogenesis, remains so far elusive. In the present study, we show that prolactin induces phosphorylation of ERK1/2 and STAT5 and induces tube formation of endothelial cells on Matrigel. These effects are blocked by a specific prolactin receptor antagonist, del1-9-G129R-hPRL. Moreover, in an in vivo model of the chorioallantoic membrane of the chicken embryo, prolactin enhances vessel density and the tortuosity of the vasculature and pillar formation, which are hallmarks of intussusceptive angiogenesis. Interestingly, while prolactin has only little effect on endothelial cell proliferation, it markedly stimulates endothelial cell migration. Again, migration was reverted by del1-9-G129R-hPRL, indicating a direct effect of prolactin on its receptor. Immunohistochemistry and spectral imaging revealed that the prolactin receptor is present in the microvasculature of human breast carcinoma tissue. Altogether, these results suggest that prolactin may directly stimulate angiogenesis, which could be one of the mechanisms by which prolactin contributes to breast cancer progression, thereby providing a potential tool for intervention. PMID:22128761

Methods and Protocols for Developing Prion Vaccines.

PubMed

Marciniuk, Kristen; Taschuk, Ryan; Napper, Scott

2016-01-01

Prion diseases denote a distinct form of infectivity that is based in the misfolding of a self-protein (PrP(C)) into a pathological, infectious conformation (PrP(Sc)). Efforts to develop vaccines for prion diseases have been complicated by the potential dangers that are associated with induction of immune responses against a self-protein. As a consequence, there is considerable appeal for vaccines that specifically target the misfolded prion conformation. Such conformation-specific immunotherapy is made possible through the identification of vaccine targets (epitopes) that are exclusively presented as a consequence of misfolding. An immune response directed against these targets, termed disease-specific epitopes (DSEs), has the potential to spare the function of the native form of the protein while clearing, or neutralizing, the infectious isomer. Although identification of DSEs represents a critical first step in the induction of conformation-specific immune responses, substantial efforts are required to translate these targets into functional vaccines. Due to the poor immunogenicity that is inherent to self-proteins, and that is often associated with short peptides, substantial efforts are required to overcome tolerance-to-self and maximize the resultant immune response following DSE-based immunization. This often includes optimization of target sequences in terms of immunogenicity and development of effective formulation and delivery strategies for the associated peptides. Further, these vaccines must satisfy additional criteria from perspectives of specificity (PrP(C) vs. PrP(Sc)) and safety (antibody-induced template-driven misfolding of PrP(C)). The emphasis of this report is on the steps required to translate DSEs into prion vaccines and subsequent evaluation of the resulting immune responses.

As fathers and felons: explaining the effects of current and recent incarceration on major depression.

PubMed

Turney, Kristin; Wildeman, Christopher; Schnittker, Jason

2012-01-01

Dramatic increases in the American imprisonment rate since the mid-1970s have important implications for the life chances of minority men with low educational attainment, including for their health. Although a large literature has considered the collateral consequences of incarceration for a variety of outcomes, studies concerned with health have several limitations: Most focus exclusively on physical health; those concerned with mental health only consider current incarceration or previous incarceration, but never both; some are cross-sectional; many fail to consider mechanisms; and virtually all neglect the role of family processes, thereby overlooking the social roles current and former prisoners inhabit. In this article, we use stress process theory to extend this research by first considering the association between incarceration and major depression and then considering potential mechanisms that explain this association. Results from the Fragile Families and Child Wellbeing Study (N = 3,107) show current and recent incarceration are substantially associated with the risk of major depression, suggesting both immediate and short-term implications. In addition, consistent with stress proliferation theory, the results show the well-known consequences of incarceration for socioeconomic status and family functioning partly explain these associations, suggesting the link between incarceration and depression depends heavily on the consequences of incarceration for economic and social reintegration, not only the direct psychological consequences of confinement.

Hemorheological alterations in sickle cell anemia and their clinical consequences - The role of genetic modulators.

PubMed

Silva, Marisa; Vargas, Sofia; Coelho, Andreia; Dias, Alexandra; Ferreira, Teresa; Morais, Anabela; Maia, Raquel; Kjöllerström, Paula; Lavinha, João; Faustino, Paula

2016-01-01

Sickle cell anemia (SCA) is an autosomal recessive disease caused by the HBB:c.20A>T mutation that leads to hemoglobin S synthesis. The disease presents with high clinical heterogeneity characterized by chronic hemolysis, recurrent episodes of vaso-oclusion and infection. This work aimed to characterize by in silico studies some genetic modulators of severe hemolysis and stroke risk in children with SCA, and understand their consequences at the hemorheological level.Association studies were performed between hemolysis biomarkers as well as the degree of cerebral vasculopathy and the inheritance of several polymorphic regions in genes related with vascular cell adhesion and vascular tonus in pediatric SCA patients. In silico tools (e.g. MatInspector) were applied to investigate the main variant consequences.Variants in vascular adhesion molecule-1 (VCAM1) gene promoter and endothelial nitric oxide synthase (NOS3) gene were significantly associated with higher degree of hemolysis and stroke events. They potentially modify transcription factor binding sites (e.g. VCAM1 rs1409419_T allele may lead to an EVI1 gain) or disturb the corresponding protein structure/function. Our findings emphasize the relevance of genetic variation in modulating the disease severity due to their effect on gene expression or modification of protein biological activities related with sickled erythrocyte/endothelial interactions and consequent hemorheological abnormalities.

Assessing the Potential Environmental Consequences of a New Energetic Material: A Phased Approach

DTIC Science & Technology

2007-12-01

Melting point • Ionization potential (2) QSAR approaches can also be used to estimate toxicological impact. Toxicity QSAR models can often... TOXICOLOGY STUDY NO. 87-XE-03N3-05 ASSESSING THE POTENTIAL ENVIRONMENTAL CONSEQUENCES OF A NEW ENERGETIC MATERIAL: A PHASED APPROACH...SEPTEMBER 2005 Published: December 2007 Approved for public release; distribution unlimited. Toxicology Study No. 87-XE-03N3-05

[On the necessity to distinguishing judgment from subjective choice in the cognitive neuroscience of morality].

PubMed

Tassy, Sébastien

2011-10-01

Recently, cognitive neuroscience has shed new light on our understanding of the neural underpinning of humans' morality. These findings allow for a fundamental questioning and rethinking of the alleged dichotomy between reason and emotion, that has profoundly shaped both moral philosophy and moral psychology. Functional neuroimaging and neuropsychology studies have provided strong arguments favoring a dynamic and interdependent interaction between rational and emotional processes in the brain. Yet another fundamental issue remains largely unexplored: the dissociation between certain behaviours and the moral judgments that seem to precede them. The importance of this dissociation was highlighted in a study of psychopathic patients during which they preserved their moral judgments while frequently engaging in completely non moral behaviour. Such dissociation could result from the cognitive difference between an objective moral judgement with no personal consequence, and a subjective behavioural choice that has effective or potential personal consequences. Consequently, the results of moral dilemma experiments would differ widely depending whether they explore objective or subjective moral evaluations. That these evaluations involve two distinct neural processes should be taken into account when exploring the neural bases of human morality. © 2011 médecine/sciences – Inserm / SRMS.

Ecosystems and Land Use Change

NASA Astrophysics Data System (ADS)

DeFries, Ruth S.; Asner, Gregory P.; Houghton, Richard A.

Land use is at the center of one of the most vexing challenges for the coming decades: to provide enough food, fiber and shelter for the world's population; raise the standard of living for the billion people currently below the poverty line; and simultaneously sustain the world's ecosystems for use by humans and other species. The intended consequence of cropland expansion, urban growth, and other land use changes is to satisfy demands from the increasing appetite of the world's population. Unintended consequences, however, can alter ecological processes and have far-reaching and long-term effects that potentially compromise the basic functioning of ecosystems. Recently, the scientific community has begun to confront such issues. Several national and international programs have been at the forefront of scientific enquiry on the causes and consequences of land use change, including: the Land Use and Land Cover Change Program of the National Aeronautics and Space Administration, the Land Use program element in the interagency U.S. Climate Change Science Program, and the International Geosphere-Biosphere's Land Use and Cover Change (LUCC) core project. The result has been significant advances in understanding the complex socioeconomic, technological, and biophysical factors that drive land use change worldwide.

Preface

NASA Astrophysics Data System (ADS)

DeFries, Ruth S.; Asner, Gregory P.; Houghton, Richard A.

Land use is at the center of one of the most vexing challenges for the coming decades: to provide enough food, fiber and shelter for the world's population; raise the standard of living for the billion people currently below the poverty line; and simultaneously sustain the world's ecosystems for use by humans and other species. The intended consequence of cropland expansion, urban growth, and other land use changes is to satisfy demands from the increasing appetite of the world's population. Unintended consequences, however, can alter ecological processes and have far-reaching and long-term effects that potentially compromise the basic functioning of ecosystems. Recently, the scientific community has begun to confront such issues. Several national and international programs have been at the forefront of scientific enquiry on the causes and consequences of land use change, including: the Land Use and Land Cover Change Program of the National Aeronautics and Space Administration, the Land Use program element in the interagency U.S. Climate Change Science Program, and the International Geosphere-Biosphere's Land Use and Cover Change (LUCC) core project. The result has been significant advances in understanding the complex socioeconomic, technological, and biophysical factors that drive land use change worldwide.

Ecological consequences of colony structure in dynamic ant nest networks.

PubMed

Ellis, Samuel; Franks, Daniel W; Robinson, Elva J H

2017-02-01

Access to resources depends on an individual's position within the environment. This is particularly important to animals that invest heavily in nest construction, such as social insects. Many ant species have a polydomous nesting strategy: a single colony inhabits several spatially separated nests, often exchanging resources between the nests. Different nests in a polydomous colony potentially have differential access to resources, but the ecological consequences of this are unclear. In this study, we investigate how nest survival and budding in polydomous wood ant ( Formica lugubris ) colonies are affected by being part of a multi-nest system. Using field data and novel analytical approaches combining survival models with dynamic network analysis, we show that the survival and budding of nests within a polydomous colony are affected by their position in the nest network structure. Specifically, we find that the flow of resources through a nest, which is based on its position within the wider nest network, determines a nest's likelihood of surviving and of founding new nests. Our results highlight how apparently disparate entities in a biological system can be integrated into a functional ecological unit. We also demonstrate how position within a dynamic network structure can have important ecological consequences.

Neural correlates of decision making with explicit information about probabilities and incentives in elderly healthy subjects.

PubMed

Labudda, Kirsten; Woermann, Friedrich G; Mertens, Markus; Pohlmann-Eden, Bernd; Markowitsch, Hans J; Brand, Matthias

2008-06-01

Recent functional neuroimaging and lesion studies demonstrate the involvement of the orbitofrontal/ventromedial prefrontal cortex as a key structure in decision making processes. This region seems to be particularly crucial when contingencies between options and consequences are unknown but have to be learned by the use of feedback following previous decisions (decision making under ambiguity). However, little is known about the neural correlates of decision making under risk conditions in which information about probabilities and potential outcomes is given. In the present study, we used functional magnetic resonance imaging to measure blood-oxygenation-level-dependent (BOLD) responses in 12 subjects during a decision making task. This task provided explicit information about probabilities and associated potential incentives. The responses were compared to BOLD signals in a control condition without information about incentives. In contrast to previous decision making studies, we completely removed the outcome phase following a decision to exclude the potential influence of feedback previously received on current decisions. The results indicate that the integration of information about probabilities and incentives leads to activations within the dorsolateral prefrontal cortex, the posterior parietal lobe, the anterior cingulate and the right lingual gyrus. We assume that this pattern of activation is due to the involvement of executive functions, conflict detection mechanisms and arithmetic operations during the deliberation phase of decisional processes that are based on explicit information.

Construction of the landscape for multi-stable systems: Potential landscape, quasi-potential, A-type integral and beyond

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhou, Peijie, E-mail: cliffzhou@pku.edu.cn; Li, Tiejun, E-mail: tieli@pku.edu.cn

Motivated by the famous Waddington’s epigenetic landscape metaphor in developmental biology, biophysicists and applied mathematicians made different proposals to construct the landscape for multi-stable complex systems. We aim to summarize and elucidate the relationships among these theories from a mathematical point of view. We systematically investigate and compare three different but closely related realizations in the recent literature: the Wang’s potential landscape theory from steady state distribution of stochastic differential equations (SDEs), the Freidlin-Wentzell quasi-potential from the large deviation theory, and the construction through SDE decomposition and A-type integral. We revisit that the quasi-potential is the zero noise limit ofmore » the potential landscape, and the potential function in the third proposal coincides with the quasi-potential. We compare the difference between local and global quasi-potential through the viewpoint of exchange of limit order for time and noise amplitude. We argue that local quasi-potentials are responsible for getting transition rates between neighboring stable states, while the global quasi-potential mainly characterizes the residence time of the states as the system reaches stationarity. The difference between these two is prominent when the transitivity property is broken. The most probable transition path by minimizing the Onsager-Machlup or Freidlin-Wentzell action functional is also discussed. As a consequence of the established connections among different proposals, we arrive at the novel result which guarantees the existence of SDE decomposition while denies its uniqueness in general cases. It is, therefore, clarified that the A-type integral is more appropriate to be applied to the decomposed SDEs rather than its primitive form as believed by previous researchers. Our results contribute to a deeper understanding of landscape theories for biological systems.« less

Construction of the landscape for multi-stable systems: Potential landscape, quasi-potential, A-type integral and beyond

NASA Astrophysics Data System (ADS)

Zhou, Peijie; Li, Tiejun

2016-03-01

Motivated by the famous Waddington's epigenetic landscape metaphor in developmental biology, biophysicists and applied mathematicians made different proposals to construct the landscape for multi-stable complex systems. We aim to summarize and elucidate the relationships among these theories from a mathematical point of view. We systematically investigate and compare three different but closely related realizations in the recent literature: the Wang's potential landscape theory from steady state distribution of stochastic differential equations (SDEs), the Freidlin-Wentzell quasi-potential from the large deviation theory, and the construction through SDE decomposition and A-type integral. We revisit that the quasi-potential is the zero noise limit of the potential landscape, and the potential function in the third proposal coincides with the quasi-potential. We compare the difference between local and global quasi-potential through the viewpoint of exchange of limit order for time and noise amplitude. We argue that local quasi-potentials are responsible for getting transition rates between neighboring stable states, while the global quasi-potential mainly characterizes the residence time of the states as the system reaches stationarity. The difference between these two is prominent when the transitivity property is broken. The most probable transition path by minimizing the Onsager-Machlup or Freidlin-Wentzell action functional is also discussed. As a consequence of the established connections among different proposals, we arrive at the novel result which guarantees the existence of SDE decomposition while denies its uniqueness in general cases. It is, therefore, clarified that the A-type integral is more appropriate to be applied to the decomposed SDEs rather than its primitive form as believed by previous researchers. Our results contribute to a deeper understanding of landscape theories for biological systems.

Mitochondrial Effects of PGC-1alpha Silencing in MPP+ Treated Human SH-SY5Y Neuroblastoma Cells

PubMed Central

Ye, Qinyong; Chen, Chun; Si, Erwang; Cai, Yousheng; Wang, Juhua; Huang, Wanling; Li, Dongzhu; Wang, Yingqing; Chen, Xiaochun

2017-01-01

The dopaminergic neuron degeneration and loss that occurs in Parkinson’s disease (PD) has been tightly linked to mitochondrial dysfunction. Although the aged-related cause of the mitochondrial defect observed in PD patients remains unclear, nuclear genes are of potential importance to mitochondrial function. Human peroxisome proliferator-activated receptor γ coactivator-1alpha (PGC-1α) is a multi-functional transcription factor that tightly regulates mitochondrial biogenesis and oxidative capacity. The goal of the present study was to explore the potential pathogenic effects of interference by the PGC-1α gene on N-methyl-4-phenylpyridinium ion (MPP+)-induced SH-SY5Y cells. We utilized RNA interference (RNAi) technology to probe the pathogenic consequences of inhibiting PGC-1α in the SH-SY5Y cell line. Remarkably, a reduction in PGC-1α resulted in the reduction of mitochondrial membrane potential, intracellular ATP content and intracellular H2O2 generation, leading to the translocation of cytochrome c (cyt c) to the cytoplasm in the MPP+-induced PD cell model. The expression of related proteins in the signaling pathway (e.g., estrogen-related receptor α (ERRα), nuclear respiratory factor 1 (NRF-1), NRF-2 and Peroxisome proliferator-activated receptor γ (PPARγ)) also decreased. Our finding indicates that small interfering RNA (siRNA) interference targeting the PGC-1α gene could inhibit the function of mitochondria in several capacities and that the PGC-1α gene may modulate mitochondrial function by regulating the expression of ERRα, NRF-1, NRF-2 and PPARγ. Thus, PGC-1α can be considered a potential therapeutic target for PD. PMID:28611589

Consequences of Diffusion of Innovations.

ERIC Educational Resources Information Center

Goss, Kevin F.

1979-01-01

The article traces evolution of diffusion theory; illustrates undesirable consequences in a cross-cultural setting, reviews criticisms of several scholars; considers distributional effects and unanticipated consequences for potential ameliorative impact on diffusion theory; and codifies these factors into a framework for research into consequences…

Epithelial adhesion molecules and the regulation of intestinal homeostasis during neutrophil transepithelial migration

PubMed Central

Sumagin, Ronen; Parkos, Charles A

2014-01-01

Epithelial adhesion molecules play essential roles in regulating cellular function and maintaining mucosal tissue homeostasis. Some form epithelial junctional complexes to provide structural support for epithelial monolayers and act as a selectively permeable barrier separating luminal contents from the surrounding tissue. Others serve as docking structures for invading viruses and bacteria, while also regulating the immune response. They can either obstruct or serve as footholds for the immune cells recruited to mucosal surfaces. Currently, it is well appreciated that adhesion molecules collectively serve as environmental cue sensors and trigger signaling events to regulate epithelial function through their association with the cell cytoskeleton and various intracellular adapter proteins. Immune cells, particularly neutrophils (PMN) during transepithelial migration (TEM), can modulate adhesion molecule expression, conformation, and distribution, significantly impacting epithelial function and tissue homeostasis. This review discusses the roles of key intestinal epithelial adhesion molecules in regulating PMN trafficking and outlines the potential consequences on epithelial function. PMID:25838976

LSD1 activates a lethal prostate cancer gene network independently of its demethylase function.

PubMed

Sehrawat, Archana; Gao, Lina; Wang, Yuliang; Bankhead, Armand; McWeeney, Shannon K; King, Carly J; Schwartzman, Jacob; Urrutia, Joshua; Bisson, William H; Coleman, Daniel J; Joshi, Sunil K; Kim, Dae-Hwan; Sampson, David A; Weinmann, Sheila; Kallakury, Bhaskar V S; Berry, Deborah L; Haque, Reina; Van Den Eeden, Stephen K; Sharma, Sunil; Bearss, Jared; Beer, Tomasz M; Thomas, George V; Heiser, Laura M; Alumkal, Joshi J

2018-05-01

Medical castration that interferes with androgen receptor (AR) function is the principal treatment for advanced prostate cancer. However, clinical progression is universal, and tumors with AR-independent resistance mechanisms appear to be increasing in frequency. Consequently, there is an urgent need to develop new treatments targeting molecular pathways enriched in lethal prostate cancer. Lysine-specific demethylase 1 (LSD1) is a histone demethylase and an important regulator of gene expression. Here, we show that LSD1 promotes the survival of prostate cancer cells, including those that are castration-resistant, independently of its demethylase function and of the AR. Importantly, this effect is explained in part by activation of a lethal prostate cancer gene network in collaboration with LSD1's binding protein, ZNF217. Finally, that a small-molecule LSD1 inhibitor-SP-2509-blocks important demethylase-independent functions and suppresses castration-resistant prostate cancer cell viability demonstrates the potential of LSD1 inhibition in this disease.

The effect of a periodic absorptive strip arrangement on an interior sound field in a room.

PubMed

Park, Joo-Bae; Grosh, Karl; Kim, Yang-Hann

2005-02-01

In this paper we study the effect of periodically arranged sound absorptive strips on the mean acoustic potential energy density distribution of a room. The strips are assumed to be attached on the room's surface of interest. In order to determine their effect, the mean acoustic potential energy density variation is evaluated as the function of a ratio of the strip's arrangement period to wavelength. The evaluation demonstrates that the mean acoustic potential energy density tends to converge. In addition, a comparison with a case in which absorptive materials completely cover the selected absorptive plane shows that a periodic arrangement that uses only half of the absorptive material can be more efficient than a total covering, unless the frequency of interest does not coincide with the room's resonant frequencies. Consequently, the results prove that the ratio of the arrangement period to the wavelength plays an important role in the effectiveness of a periodic absorptive strip arrangement to minimize a room's mean acoustic potential energy density.

Differential Item Functioning: Its Consequences. Research Report. ETS RR-10-01

ERIC Educational Resources Information Center

Lee, Yi-Hsuan; Zhang, Jinming

2010-01-01

This report examines the consequences of differential item functioning (DIF) using simulated data. Its impact on total score, item response theory (IRT) ability estimate, and test reliability was evaluated in various testing scenarios created by manipulating the following four factors: test length, percentage of DIF items per form, sample sizes of…

Ventricular structure, function, and mechanics at high altitude: chronic remodeling in Sherpa vs. short-term lowlander adaptation.

PubMed

Stembridge, Mike; Ainslie, Philip N; Hughes, Michael G; Stöhr, Eric J; Cotter, James D; Nio, Amanda Q X; Shave, Rob

2014-08-01

Short-term, high-altitude (HA) exposure raises pulmonary artery systolic pressure (PASP) and decreases left-ventricular (LV) volumes. However, relatively little is known of the long-term cardiac consequences of prolonged exposure in Sherpa, a highly adapted HA population. To investigate short-term adaptation and potential long-term cardiac remodeling, we studied ventricular structure and function in Sherpa at 5,050 m (n = 11; 31 ± 13 yr; mass 68 ± 10 kg; height 169 ± 6 cm) and lowlanders at sea level (SL) and following 10 ± 3 days at 5,050 m (n = 9; 34 ± 7 yr; mass 82 ± 10 kg; height 177 ± 6 cm) using conventional and speckle-tracking echocardiography. At HA, PASP was higher in Sherpa and lowlanders compared with lowlanders at SL (both P < 0.05). Sherpa had smaller right-ventricular (RV) and LV stroke volumes than lowlanders at SL with lower RV systolic strain (P < 0.05) but similar LV systolic mechanics. In contrast to LV systolic mechanics, LV diastolic, untwisting velocity was significantly lower in Sherpa compared with lowlanders at both SL and HA. After partial acclimatization, lowlanders demonstrated no change in the RV end-diastolic area; however, both RV strain and LV end-diastolic volume were reduced. In conclusion, short-term hypoxia induced a reduction in RV systolic function that was also evident in Sherpa following chronic exposure. We propose that this was consequent to a persistently higher PASP. In contrast to the RV, remodeling of LV volumes and normalization of systolic mechanics indicate structural and functional adaptation to HA. However, altered LV diastolic relaxation after chronic hypoxic exposure may reflect differential remodeling of systolic and diastolic LV function. Copyright © 2014 the American Physiological Society.

The impact of ageing on natural killer cell function and potential consequences for health in older adults.

PubMed

Hazeldine, Jon; Lord, Janet M

2013-09-01

Forming the first line of defence against virally infected and malignant cells, natural killer (NK) cells are critical effector cells of the innate immune system. With age, significant impairments have been reported in the two main mechanisms by which NK cells confer host protection: direct cytotoxicity and the secretion of immunoregulatory cytokines and chemokines. In elderly subjects, decreased NK cell activity has been shown to be associated with an increased incidence and severity of viral infection, highlighting the clinical implications that age-associated changes in NK cell biology have on the health of older adults. However, is an increased susceptibility to viral infection the only consequence of these age-related changes in NK cell function? Recently, evidence has emerged that has shown that in addition to eliminating transformed cells, NK cells are involved in many other biological processes such as immune regulation, anti-microbial immune responses and the recognition and elimination of senescent cells, novel functions that involve NK-mediated cytotoxicity and/or cytokine production. Thus, the decrease in NK cell function that accompanies physiological ageing is likely to have wider implications for the health of older adults than originally thought. Here, we give a detailed description of the changes in NK cell biology that accompany human ageing and propose that certain features of the ageing process such as: (i) the increased reactivation rates of latent Mycobacterium tuberculosis, (ii) the slower resolution of inflammatory responses and (iii) the increased incidence of bacterial and fungal infection are attributable in part to an age-associated decline in NK cell function. Copyright © 2013 Elsevier B.V. All rights reserved.

Ventricular structure, function, and mechanics at high altitude: chronic remodeling in Sherpa vs. short-term lowlander adaptation

PubMed Central

Ainslie, Philip N.; Hughes, Michael G.; Stöhr, Eric J.; Cotter, James D.; Nio, Amanda Q. X.; Shave, Rob

2014-01-01

Short-term, high-altitude (HA) exposure raises pulmonary artery systolic pressure (PASP) and decreases left-ventricular (LV) volumes. However, relatively little is known of the long-term cardiac consequences of prolonged exposure in Sherpa, a highly adapted HA population. To investigate short-term adaptation and potential long-term cardiac remodeling, we studied ventricular structure and function in Sherpa at 5,050 m (n = 11; 31 ± 13 yr; mass 68 ± 10 kg; height 169 ± 6 cm) and lowlanders at sea level (SL) and following 10 ± 3 days at 5,050 m (n = 9; 34 ± 7 yr; mass 82 ± 10 kg; height 177 ± 6 cm) using conventional and speckle-tracking echocardiography. At HA, PASP was higher in Sherpa and lowlanders compared with lowlanders at SL (both P < 0.05). Sherpa had smaller right-ventricular (RV) and LV stroke volumes than lowlanders at SL with lower RV systolic strain (P < 0.05) but similar LV systolic mechanics. In contrast to LV systolic mechanics, LV diastolic, untwisting velocity was significantly lower in Sherpa compared with lowlanders at both SL and HA. After partial acclimatization, lowlanders demonstrated no change in the RV end-diastolic area; however, both RV strain and LV end-diastolic volume were reduced. In conclusion, short-term hypoxia induced a reduction in RV systolic function that was also evident in Sherpa following chronic exposure. We propose that this was consequent to a persistently higher PASP. In contrast to the RV, remodeling of LV volumes and normalization of systolic mechanics indicate structural and functional adaptation to HA. However, altered LV diastolic relaxation after chronic hypoxic exposure may reflect differential remodeling of systolic and diastolic LV function. PMID:24876358

Developmental changes in decision making under risk: The role of executive functions and reasoning abilities in 8- to 19-year-old decision makers.

PubMed

Schiebener, Johannes; García-Arias, María; García-Villamisar, Domingo; Cabanyes-Truffino, Javier; Brand, Matthias

2015-01-01

Previous studies have shown that children and adolescents often tend toward risky decisions despite explicit knowledge about the potential negative consequences. This phenomenon has been suggested to be associated with the immaturity of brain areas involved in cognitive control functions. Particularly, "frontal lobe functions," such as executive functions and reasoning, mature until young adulthood and are thought to be involved in age-related changes in decision making under explicit risk conditions. We investigated 112 participants, aged 8-19 years, with a frequently used task assessing decisions under risk, the Game of Dice Task (GDT). Additionally, we administered the Modified Card Sorting Test assessing executive functioning (categorization, cognitive flexibility, and strategy maintenance) as well as the Ravens Progressive Matrices assessing reasoning. The results showed that risk taking in the GDT decreased with increasing age and this effect was not moderated by reasoning but by executive functions: Particularly, young persons with weak executive functioning showed very risky decision making. Thus, the individual maturation of executive functions, associated with areas in the prefrontal cortex, seems to be an important factor in young peoples' behavior in risky decision-making situations.

A Postsecondary Transition Model for Low-Income, Minority Youth in Philadelphia

ERIC Educational Resources Information Center

Brown, Alexis Tolbert

2016-01-01

School administrators are in the best position, but often lack the knowledge, to help low-income, minority youth transition to college. Consequently, some youth are not meeting their full potential and there are long-term, deleterious consequences on local economies as wage earning potential stagnates. Using Aslanargun's, Farmer-Hinton's, and…

Social Bullying: Correlates, Consequences, and Prevention. In Brief

ERIC Educational Resources Information Center

Stuart-Cassel, Victoria; Terzian, Mary; Bradshaw, Catherine

2013-01-01

Bullying is considered one of the most prevalent and potentially damaging forms of school violence. Each year, more than a quarter of middle and high school students are subjected to some form of bullying in their school environments. Research has identified potentially harmful immediate and long-term consequences for bullying-involved youth and…

Dysregulation of chemokine receptor expression and function in leukocytes from ALS patients.

PubMed

Perner, Caroline; Perner, Florian; Stubendorff, Beatrice; Förster, Martin; Witte, Otto W; Heidel, Florian H; Prell, Tino; Grosskreutz, Julian

2018-03-28

Amyotrophic lateral sclerosis (ALS) is rapidly progressive adult-onset motor neuron disease characterized by the neurodegeneration of both upper and lower motor neurons in the cortex and the spinal cord; the majority of patients succumb to respiratory failure. Although the etiology is not yet fully understood, there is compelling evidence that ALS is a multi-systemic disorder, with peripheral inflammation critically contributing to the disease process. However, the full extent and nature of this immunological dysregulation remains to be established, particularly within circulating blood cells. Therefore, the aim of the present study was to identify dysregulated inflammatory molecules in peripheral blood cells of ALS patients and analyze for functional consequences of the observed findings. To this end, we employed flow cytometry-based screening to quantify the surface expression of major chemokine receptors and integrins. A significantly increased expression of CXCR3, CXCR4, CCL2, and CCL5 was observed on T cells in ALS patients compared to healthy controls. Intriguingly, the expression was even more pronounced in patients with a slow progressive phenotype. To further investigate the functional consequences of this altered surface expression, we used a modified Boyden chamber assay to measure chemotaxis in ALS patient-derived lymphocytes. Interestingly, chemoattraction with the CXCR3-Ligand IP10 led to upregulated migratory behavior of ALS lymphocytes compared to healthy controls. Taken together, our data provides evidence for a functional dysregulation of IP10-directed chemotaxis in peripheral blood cells in ALS patients. However, whether the chemokine itself or its receptor CXCR3, or both, could serve as potential therapeutic targets in ALS requires further investigations.

A Review of Prevention, Diagnosis and Treatment of Relative Energy Deficiency in Sport (RED-S) in Artistic (Synchronized) Swimming.

PubMed

Robertson, Sherry; Mountjoy, Margo

2018-05-03

The syndrome Relative Energy Deficiency in Sport (RED-S) is a clinical entity characterized by low energy availability (LEA), which can negatively affect the health and performance of both male and female athletes. The underlying mechanism of RED-S is an inadequacy of dietary energy to support optimal health and performance. This syndrome refers to impaired physiological function including metabolic rate, menstrual function, bone health, immunity, protein synthesis, and cardiovascular health, with psychological consequences which can either precede (through restrictive dietary habits) or result from RED-S. The term RED-S extends beyond the condition termed the "Female Athlete Triad". Formerly known as synchronized swimming, artistic swimming is an Olympic sport requiring a high level of fitness as well as technical skill and artistry. The risk of RED-S is high in artistic swimming as it is an aesthetic, judged sport with an emphasis on a lean physique. RED-S is of significant concern in the sport of artistic swimming because of the potential negative effects on physical and mental health as well as consequences on athletic performance. This paper reviews health and performance consequences associated with LEA resulting in RED-S in artistic swimming. Medical and nutritional considerations specific to artistic swimming are reviewed and methods to help detect and manage RED-S are discussed. Prevention and management of RED-S in this athlete population should be a priority for coaches and the sport medicine professionals working with artistic swimming athletes should utilize the RED-S CAT, a Clinical Assessment Tool for screening and managing RED-S.

Molecular Evolution of piRNA and Transposon Control Pathways in Drosophila

PubMed Central

Malone, C.D.; Hannon, G.J.

2011-01-01

The mere prevalence and potential mobilization of transposable elements in eukaryotic genomes present challenges at both the organismal and population levels. Not only is transposition able to alter gene function and chromosomal structure, but loss of control over even a single active element in the germline can create an evolutionary dead end. Despite the dangers of coexistence, transposons and their activity have been shown to drive the evolution of gene function, chromosomal organization, and even population dynamics (Kazazian 2004). This implies that organisms have adopted elaborate means to balance both the positive and detrimental consequences of transposon activity. In this chapter, we focus on the fruit fly to explore some of the molecular clues into the long- and short-term adaptation to transposon colonization and persistence within eukaryotic genomes. PMID:20453205

One-year clinical experience with a fully digitized nuclear medicine department: organizational and economical aspects

NASA Astrophysics Data System (ADS)

Anema, P. C.; de Graaf, C. N.; Wilmink, J. B.; Hall, David R.; Hoekstra, A. G.; van Rijk, P. P.; Van Isselt, J. W.; Viergever, Max A.

1991-07-01

At the department of nuclear medicine of the University Hospital Utrecht a single-modality PACS has been operational since mid-1990. After one year of operation the functionality, the organizational and economical consequences, and the acceptability of the PACS were evaluated. The functional aspects reviewed were: viewing facilities, patient data management, connectivity, reporting facilities, archiving, privacy, and security. It was concluded that the improved quality of diagnostic viewing and the potential integration with diagnosis, reporting, and archiving are highly appreciated. The many problems that have occurred during the transition period, however, greatly influence the appreciation and acceptability of the PACS. Overall, it is felt that in the long term there will be a positive effect on the quality and efficiency of the work.

SpliceSeq: a resource for analysis and visualization of RNA-Seq data on alternative splicing and its functional impacts.

PubMed

Ryan, Michael C; Cleland, James; Kim, RyangGuk; Wong, Wing Chung; Weinstein, John N

2012-09-15

SpliceSeq is a resource for RNA-Seq data that provides a clear view of alternative splicing and identifies potential functional changes that result from splice variation. It displays intuitive visualizations and prioritized lists of results that highlight splicing events and their biological consequences. SpliceSeq unambiguously aligns reads to gene splice graphs, facilitating accurate analysis of large, complex transcript variants that cannot be adequately represented in other formats. SpliceSeq is freely available at http://bioinformatics.mdanderson.org/main/SpliceSeq:Overview. The application is a Java program that can be launched via a browser or installed locally. Local installation requires MySQL and Bowtie. mryan@insilico.us.com Supplementary data are available at Bioinformatics online.

Importance of β-defensins in sperm function.

PubMed

Dorin, Julia R; Barratt, Christopher L R

2014-09-01

Recent work in humans and mouse has confirmed the involvement of the host defence β-defensin peptides in male fertility. We discuss here the work that has implicated β-defensins in sperm function including the identification of the epididymis as the predominant site of expression of the peptides and the in vivo consequences of mutation and deletion. The potential dual role of these peptides in the regulation of infection and control of sperm maturation is compelling and may combine their antimicrobial activity with the ability of these molecules to interact with cell membrane receptors and modulate ion transport. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Polymer Brushes as Functional, Patterned Surfaces for Nanobiotechnology.

PubMed

Welch, M Elizabeth; Xu, Youyong; Chen, Hongjun; Smith, Norah; Tague, Michele E; Abruña, Héctor D; Baird, Barbara; Ober, Christopher K

2013-01-01

Polymer brushes have many desirable characteristics such as the ability to tether molecules to a substrate or change the properties of a surface. Patterning of polymer films has been an area of great interest due to the broad range of applications including bio-related and medicinal research. Consequently, we have investigated patterning techniques for polymer brushes which allow for two different functionalities on the same surface. This method has been applied to a biosensor device which requires both polymer brushes and a photosensitizer to be polymerized on a patterned gold substrate. Additionally, the nature of patterned polymer brushes as removable thin films was explored. An etching process has enabled us to lift off very thin membranes for further characterization with the potential of using them as Janus membranes for biological applications.

Scaling up our understanding of non-consumptive effects in insect systems

DOE PAGES

Hermann, Sara L.; Landis, Douglas A.

2017-04-06

Here, non-consumptive effects (NCEs) of predators on prey is an important topic in insect ecology with potential applications for pest management. NCEs are changes in prey behavior and physiology that aid in predation avoidance. While NCEs can have positive outcomes for prey survival there may also be negative consequences including increased stress and reduced growth. These effects can cascade through trophic systems influencing ecosystem function. Most NCEs have been studied at small spatial and temporal scales. However, recent studies show promise for the potential to manipulate NCEs for pest management. We suggest the next frontier for NCE studies includes manipulatingmore » the landscape of fear to improve pest control, which requires scaling-up to field and landscape levels, over ecologically relevant time frames.« less

Scaling up our understanding of non-consumptive effects in insect systems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hermann, Sara L.; Landis, Douglas A.

Here, non-consumptive effects (NCEs) of predators on prey is an important topic in insect ecology with potential applications for pest management. NCEs are changes in prey behavior and physiology that aid in predation avoidance. While NCEs can have positive outcomes for prey survival there may also be negative consequences including increased stress and reduced growth. These effects can cascade through trophic systems influencing ecosystem function. Most NCEs have been studied at small spatial and temporal scales. However, recent studies show promise for the potential to manipulate NCEs for pest management. We suggest the next frontier for NCE studies includes manipulatingmore » the landscape of fear to improve pest control, which requires scaling-up to field and landscape levels, over ecologically relevant time frames.« less

Neuromodulation of hypoglossal motoneurons: cellular and developmental mechanisms.

PubMed

Bayliss, D A; Viana, F; Talley, E M; Berger, A J

1997-11-01

Hypoglossal motoneurons (HMs) in the caudal brainstem have a respiratory-related activity pattern and contribute to control of upper airway resistance. In this review, we focus primarily on signalling mechanisms utilized by neurotransmitters to enhance HM excitability. In particular, we consider: (1) the membrane depolarization induced by a number of different putative transmitters [thyrotropin-releasing hormone (TRH), serotonin (5-HT), norepinephrine (NE)]; and (2) the inhibition of a calcium-dependent spike after hyperpolarization (AHP) by 5-HT and its effect on firing behavior. Potential functional consequences on HM behavior of these different neurotransmitter effects is discussed. In addition, we describe postnatal changes in transmitter effects and suggest potential cellular mechanisms to explain those developmental changes. Most of the data discussed are derived from in vitro electrophysiological recordings performed in preparations from neonatal and adult rats.

Innate Lymphoid Cells: A Promising New Regulator in Fibrotic Diseases.

PubMed

Zhang, Yi; Tang, Jun; Tian, Zhiqiang; van Velkinburgh, Jennifer C; Song, Jianxun; Wu, Yuzhang; Ni, Bing

2016-09-02

Fibrosis is a consequence of chronic inflammation and the persistent accumulation of extracellular matrix, for which the cycle of tissue injury and repair becomes a predominant feature. Both the innate and adaptive immune systems play key roles in the progress of fibrosis. The recently identified subsets of innate lymphoid cells (ILCs), which are mainly localize to epithelial surfaces, have been characterized as regulators of chronic inflammation and tissue remodeling, representing a functional bridge between the innate and adaptive immunity. Moreover, recent research has implicated ILCs as potential contributing factors to several kinds of fibrosis diseases, such as hepatic fibrosis and pulmonary fibrosis. Here, we will summarize and discuss the key roles of ILCs and their related factors in fibrotic diseases and their potential for translation to the clinic.

Power-Law Dynamics of Membrane Conductances Increase Spiking Diversity in a Hodgkin-Huxley Model.

PubMed

Teka, Wondimu; Stockton, David; Santamaria, Fidel

2016-03-01

We studied the effects of non-Markovian power-law voltage dependent conductances on the generation of action potentials and spiking patterns in a Hodgkin-Huxley model. To implement slow-adapting power-law dynamics of the gating variables of the potassium, n, and sodium, m and h, conductances we used fractional derivatives of order η≤1. The fractional derivatives were used to solve the kinetic equations of each gate. We systematically classified the properties of each gate as a function of η. We then tested if the full model could generate action potentials with the different power-law behaving gates. Finally, we studied the patterns of action potential that emerged in each case. Our results show the model produces a wide range of action potential shapes and spiking patterns in response to constant current stimulation as a function of η. In comparison with the classical model, the action potential shapes for power-law behaving potassium conductance (n gate) showed a longer peak and shallow hyperpolarization; for power-law activation of the sodium conductance (m gate), the action potentials had a sharp rise time; and for power-law inactivation of the sodium conductance (h gate) the spikes had wider peak that for low values of η replicated pituitary- and cardiac-type action potentials. With all physiological parameters fixed a wide range of spiking patterns emerged as a function of the value of the constant input current and η, such as square wave bursting, mixed mode oscillations, and pseudo-plateau potentials. Our analyses show that the intrinsic memory trace of the fractional derivative provides a negative feedback mechanism between the voltage trace and the activity of the power-law behaving gate variable. As a consequence, power-law behaving conductances result in an increase in the number of spiking patterns a neuron can generate and, we propose, expand the computational capacity of the neuron.

Potential unintended consequences of smoke-free policies in public places on pregnant women in China.

PubMed

Yao, Tingting; Lee, Anita H; Mao, Zhengzhong

2009-08-01

Smoke-free policies in public places have become more common in China. Little is known, however, about the potential unintended consequences of such policies on pregnant women. The study was conducted in 2006 in Chengdu, China. Nonsmoking pregnant women (N=55) whose husband were smokers participated in a study of their knowledge about secondhand smoke and smoke-free policies, their exposure to secondhand smoke, and their husbands' smoking status at home. This study presents descriptive statistics, analyses based on family income and pregnant women's education level, and the findings of focus group discussions that examined the potential unintended consequences of the smoke-free policies on pregnant women. Exposure to secondhand smoke at home was reported by 69.1% of the pregnant women. Both family income and the education level of the pregnant women had a significant (p<0.05) association with exposure to secondhand smoke. The four main potential unintended consequences of the smoke-free policies were: (1) increased exposure of pregnant women to secondhand smoke at home; (2) reduced work efficiency; (3) adverse effect on family harmony; and (4) poor air quality at home. Education is needed to increase knowledge of secondhand smoke among smokers and nonsmokers alike. When the smoking location is shifted from public places and workplaces to home, women, and in particular pregnant women, become the victims. Policymakers should recognize such potential unintended consequences and take necessary measures to increase awareness about the harms of secondhand smoke.

Homeland Biological Warfare Consequence Management: Capabilities and Needs Assessment

DTIC Science & Technology

2001-04-01

AU/ACSC/105/2001-04 AIR COMMAND AND STAFF COLLEGE AIR UNIVERSITY HOMELAND BIOLOGICAL WARFARE CONSEQUENCE MANAGEMENT: CAPABILITIES AND NEEDS...Dates Covered (from... to) - Title and Subtitle Homeland biological Warfare Consequence Management: Capabilities and Needs Assessment Contract...FEMA, DoJ, DoD, HHS, etc.) make a comprehensive, organized solution to the problem difficult. Focusing on the consequence management functions

Initiatives and Challenges in Consequence Management after a WMD Attack

DTIC Science & Technology

2004-08-01

Challenges in Consequence Management people to seek shelter or other protection when possible, to avoid exposure to weapons of mass destruction effects . The...Potential Effects .........................................9 V. Methods for Managing the Consequences of WMD Use.................14 VI. Toward a...mass destruction (WMD). Consequence management1 is a process to mitigate the effects of the use of weapons of mass destruction, including

Measuring Engagement with the Potential Consequences of Climate Change

NASA Astrophysics Data System (ADS)

Young, N.; Danielson, R. W.; Lombardi, D.

2015-12-01

Across three studies, we investigated engagement with the consequences of climate change. We drew from the conceptual change and risk analysis literatures to find the factors that determine how much people will care about future risks. Questions derived from these factors were then asked about many hypothesized consequences of climate change. These consequences were drawn from an Intergovernmental Panel on Climate Change special report (IPCC, 2012) and, in the third study, additionally from the IPCC AR5 (IPCC, 2014). The first two studies, using undergraduate students, demonstrated that some consequences were indeed considerably more engaging than others. The third study used a more representative sample of American adults, drawn from Amazon Mechanical Turk and used the Global Warming's Six Americas Screening Tool (Maibach, Leiserowitz, Roser-Renouf, Mertz, & Akerlof, 2011) in a large screening survey to find 20 participants in each of the six audiences defined by this tool. These participants were then asked about the potential consequences of climate change. Results again showed that some consequences are considered more engaging than others, and also showed the ways in which members of these six audiences perceive the consequences of climate change differently.

Hidden addiction: Television

PubMed Central

Sussman, Steve; Moran, Meghan B.

2013-01-01

Background and aims: The most popular recreational pastime in the U.S. is television viewing. Some researchers have claimed that television may be addictive. We provide a review of the definition, etiology, prevention and treatment of the apparent phenomenon of television addiction. Methods: Selective review. Results: We provide a description of television (TV) addiction, including its negative consequences, assessment and potential etiology, considering neurobiological, cognitive and social/cultural factors. Next, we provide information on its prevention and treatment. Discussion and conclusions: We suggest that television addiction may function similarly to substance abuse disorders but a great deal more research is needed. PMID:25083294

Cardiac ion channels

PubMed Central

Priest, Birgit T; McDermott, Jeff S

2015-01-01

Ion channels are critical for all aspects of cardiac function, including rhythmicity and contractility. Consequently, ion channels are key targets for therapeutics aimed at cardiac pathophysiologies such as atrial fibrillation or angina. At the same time, off-target interactions of drugs with cardiac ion channels can be the cause of unwanted side effects. This manuscript aims to review the physiology and pharmacology of key cardiac ion channels. The intent is to highlight recent developments for therapeutic development, as well as elucidate potential mechanisms for drug-induced cardiac side effects, rather than present an in-depth review of each channel subtype. PMID:26556552

Contribution to the Understanding of Particle Motion Perception in Marine Invertebrates.

PubMed

André, Michel; Kaifu, Kenzo; Solé, Marta; van der Schaar, Mike; Akamatsu, Tomonari; Balastegui, Andreu; Sánchez, Antonio M; Castell, Joan V

2016-01-01

Marine invertebrates potentially represent a group of species whose ecology may be influenced by artificial noise. Exposure to anthropogenic sound sources could have a direct consequence on the functionality and sensitivity of their sensory organs, the statocysts, which are responsible for their equilibrium and movements in the water column. The availability of novel laser Doppler vibrometer techniques has recently opened the possibility of measuring whole body (distance, velocity, and acceleration) vibration as a direct stimulus eliciting statocyst response, offering the scientific community a new level of understanding of the marine invertebrate hearing mechanism.

Similarities and Differences in Psychology.

PubMed

Chen, Yu; Sun, Yan; Ai, Si-Zhi; Li, Jason J; Lu, Lin; Shi, Jie

2017-01-01

Addiction is marked by repeating a certain behavior while ignoring the potential physical or mental consequences. Non-substance addiction provides an ideal model for researching the emergence and development of addiction's basic mechanism. Comparative studies of substance and non-substance addiction are helpful to reveal the common basis of addiction development. This article explores this topic from a psychological angle, touching upon sensation seeking, inhibitory control, attentional bias, intertemporal choice and environment. A review of previous literature urges future research to propose a biopsychosocial model of addiction and consider addiction's effect on basic cognitive function alongside cognitive neuroscience technology.

Leptin and its potential interest in assisted reproduction cycles.

PubMed

Catteau, A; Caillon, H; Barrière, P; Denis, M G; Masson, D; Fréour, T

2016-04-01

Leptin, an adipose hormone, has been shown to control energy homeostasis and food intake, and exert many actions on female reproductive function. Consequently, this adipokine is a pivotal factor in studies conducted on animal models and humans to decipher the mechanisms behind the infertility often observed in obese women. A systematic PubMed search was conducted on all articles, published up to January 2015 and related to leptin and its actions on energy balance and reproduction, using the following key words: leptin, reproduction, infertility, IVF and controlled ovarian stimulation. The available literature was reviewed in order to provide an overview of the current knowledge on the physiological roles of leptin, its involvement in female reproductive function and its potential interest as a prognostic marker in IVF cycles. Animal and human studies show that leptin communicates nutritional status to the central nervous system and emerging evidence has demonstrated that leptin is involved in the control of reproductive functions by acting both directly on the ovaries and indirectly on the central nervous system. With respect to the clinical use of leptin as a biomarker in IVF cycles, a systematic review of the literature suggested its potential interest as a predictor of IVF outcome, as high serum and/or follicular fluid leptin concentrations have correlated negatively with cycle outcome. However, these preliminary results remain to be confirmed. Leptin regulates energy balance and female reproductive function, mainly through its action on hypothalamic-pituitary-ovarian function, whose molecular and cellular aspects are progressively being deciphered. Preliminary studies evaluating leptin as a biomarker in human IVF seem promising but need further confirmation. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Estradiol and the Relationship between Dendritic Spines, NR2B Containing NMDA Receptors, and the Magnitude of Long-Term Potentiation at Hippocampal CA3-CA1 Synapses

PubMed Central

Smith, Caroline C.; Vedder, Lindsey C.; McMahon, Lori L.

2009-01-01

Summary When circulating estrogen levels decline as a natural consequence of menopause and aging in women, there is an increased incidence of deficits in working memory. In many cases, these deficits are rescued by estrogen replacement therapy. These clinical data therefore highlight the importance of defining the biological pathways linking estrogen to the cellular substrates of learning and memory. It has been known for nearly two decades that estrogen enhances dendritic spine density on apical dendrites of CA1 pyramidal cells in hippocampus, a brain region required for learning. Interestingly, at synapses between CA3-CA1 pyramidal cells, estrogen has also been shown to enhance synaptic NMDA receptor current and the magnitude of long term potentiation, a cellular correlate of learning and memory. Given that synapse density, NMDAR function, and long term potentiation at CA3-CA1 synapses in hippocampus are associated with normal learning, it is likely that modulation of these parameters by estrogen facilitates the improvement in learning observed in rats, primates and humans following estrogen replacement. To facilitate the design of clinical strategies to potentially prevent or reverse the age-related decline in learning and memory during menopause, the relationship between the estrogen-induced morphological and functional changes in hippocampus must be defined and the role these changes play in facilitating learning must be elucidated. The aim of this report is to provide a summary of the proposed mechanisms by which this hormone increases synaptic function and in doing so, it briefly addresses potential mechanisms contributing to the estrogen-induced increase in synaptic morphology and plasticity, as well as important future directions. PMID:19596521

Systematic pharmacogenomics analysis of a Malay whole genome: proof of concept for personalized medicine.

PubMed

Salleh, Mohd Zaki; Teh, Lay Kek; Lee, Lian Shien; Ismet, Rose Iszati; Patowary, Ashok; Joshi, Kandarp; Pasha, Ayesha; Ahmed, Azni Zain; Janor, Roziah Mohd; Hamzah, Ahmad Sazali; Adam, Aishah; Yusoff, Khalid; Hoh, Boon Peng; Hatta, Fazleen Haslinda Mohd; Ismail, Mohamad Izwan; Scaria, Vinod; Sivasubbu, Sridhar

2013-01-01

With a higher throughput and lower cost in sequencing, second generation sequencing technology has immense potential for translation into clinical practice and in the realization of pharmacogenomics based patient care. The systematic analysis of whole genome sequences to assess patient to patient variability in pharmacokinetics and pharmacodynamics responses towards drugs would be the next step in future medicine in line with the vision of personalizing medicine. Genomic DNA obtained from a 55 years old, self-declared healthy, anonymous male of Malay descent was sequenced. The subject's mother died of lung cancer and the father had a history of schizophrenia and deceased at the age of 65 years old. A systematic, intuitive computational workflow/pipeline integrating custom algorithm in tandem with large datasets of variant annotations and gene functions for genetic variations with pharmacogenomics impact was developed. A comprehensive pathway map of drug transport, metabolism and action was used as a template to map non-synonymous variations with potential functional consequences. Over 3 million known variations and 100,898 novel variations in the Malay genome were identified. Further in-depth pharmacogenetics analysis revealed a total of 607 unique variants in 563 proteins, with the eventual identification of 4 drug transport genes, 2 drug metabolizing enzyme genes and 33 target genes harboring deleterious SNVs involved in pharmacological pathways, which could have a potential role in clinical settings. The current study successfully unravels the potential of personal genome sequencing in understanding the functionally relevant variations with potential influence on drug transport, metabolism and differential therapeutic outcomes. These will be essential for realizing personalized medicine through the use of comprehensive computational pipeline for systematic data mining and analysis.

Taking two to tango: a role for ghrelin receptor heterodimerization in stress and reward.

PubMed

Schellekens, Harriët; Dinan, Timothy G; Cryan, John F

2013-08-30

The gut hormone, ghrelin, is the only known peripherally derived orexigenic signal. It activates its centrally expressed receptor, the growth hormone secretagogue receptor (GHS-R1a), to stimulate food intake. The ghrelin signaling system has recently been suggested to play a key role at the interface of homeostatic control of appetite and the hedonic aspects of food intake, as a critical role for ghrelin in dopaminergic mesolimbic circuits involved in reward signaling has emerged. Moreover, enhanced plasma ghrelin levels are associated with conditions of physiological stress, which may underline the drive to eat calorie-dense "comfort-foods" and signifies a role for ghrelin in stress-induced food reward behaviors. These complex and diverse functionalities of the ghrelinergic system are not yet fully elucidated and likely involve crosstalk with additional signaling systems. Interestingly, accumulating data over the last few years has shown the GHS-R1a receptor to dimerize with several additional G-protein coupled receptors (GPCRs) involved in appetite signaling and reward, including the GHS-R1b receptor, the melanocortin 3 receptor (MC3), dopamine receptors (D1 and D2), and more recently, the serotonin 2C receptor (5-HT2C). GHS-R1a dimerization was shown to affect downstream signaling and receptor trafficking suggesting a potential novel mechanism for fine-tuning GHS-R1a receptor mediated activity. This review summarizes ghrelin's role in food reward and stress and outlines the GHS-R1a dimer pairs identified to date. In addition, the downstream signaling and potential functional consequences of dimerization of the GHS-R1a receptor in appetite and stress-induced food reward behavior are discussed. The existence of multiple GHS-R1a heterodimers has important consequences for future pharmacotherapies as it significantly increases the pharmacological diversity of the GHS-R1a receptor and has the potential to enhance specificity of novel ghrelin-targeted drugs.

Oxidative stress, thiols, and redox profiles.

PubMed

Harris, Craig; Hansen, Jason M

2012-01-01

Oxidative stress has been recognized as a contributing factor in the toxicity of a large number of developmental toxicants. Traditional definitions of oxidative stress state that a shift in the balance between reduced and oxidized biomolecules within cells, in favor of the latter, result in changes that are deleterious to vital cell functions and can culminate in malformations and death. The glutathione (GSH)/glutathione disulfide (GSSG) redox couple has been the traditional marker of choice for characterization of oxidative stress because of its high concentrations and direct roles as antioxidant and cellular protectant. Steady state depletion of GSH through conjugation, oxidation, or export has often been reported as the sole criteria for invoking oxidative stress and a myriad of associated deleterious consequences. Numerous other, mostly qualitative, observations have also been reported to suggest oxidative stress has occurred but it is not always clear how well they reflect the state of a cell or its functions. Our emerging understanding of redox signaling and the roles of reactive oxygen species (ROS), thiols, oxidant molecules, and cellular antioxidants, all acting as second messengers, has prompted a redefinition of oxidative stress based on changes in the real posttranslational protein thiol modifications that are central to redox regulation and control. Thiol-based redox couples such as GSH/GSSG, cysteine/cystine (cys/cySS), thioredoxin-reduced/thioredoxin-oxidized (TRX(red)/TRX(ox)) form independent signaling nodes that selectively regulate developmental events and are closely linked to changes in intracellular redox potentials. Accurate assessment of the consequences of increased free radicals in developing conceptuses should best be made using a battery of measurements including the quantitative assessment of intracellular redox potential, ROS, redox status of biomolecules, and induced changes in specific redox signaling nodes. Methods are presented for a determination of ROS production, soluble thiol oxidation, redox potential, and a proteomic approach to evaluate the thiol oxidation state of specific proteins.

Taking two to tango: a role for ghrelin receptor heterodimerization in stress and reward

PubMed Central

Schellekens, Harriët; Dinan, Timothy G.; Cryan, John F.

2013-01-01

The gut hormone, ghrelin, is the only known peripherally derived orexigenic signal. It activates its centrally expressed receptor, the growth hormone secretagogue receptor (GHS-R1a), to stimulate food intake. The ghrelin signaling system has recently been suggested to play a key role at the interface of homeostatic control of appetite and the hedonic aspects of food intake, as a critical role for ghrelin in dopaminergic mesolimbic circuits involved in reward signaling has emerged. Moreover, enhanced plasma ghrelin levels are associated with conditions of physiological stress, which may underline the drive to eat calorie-dense “comfort-foods” and signifies a role for ghrelin in stress-induced food reward behaviors. These complex and diverse functionalities of the ghrelinergic system are not yet fully elucidated and likely involve crosstalk with additional signaling systems. Interestingly, accumulating data over the last few years has shown the GHS-R1a receptor to dimerize with several additional G-protein coupled receptors (GPCRs) involved in appetite signaling and reward, including the GHS-R1b receptor, the melanocortin 3 receptor (MC3), dopamine receptors (D1 and D2), and more recently, the serotonin 2C receptor (5-HT2C). GHS-R1a dimerization was shown to affect downstream signaling and receptor trafficking suggesting a potential novel mechanism for fine-tuning GHS-R1a receptor mediated activity. This review summarizes ghrelin's role in food reward and stress and outlines the GHS-R1a dimer pairs identified to date. In addition, the downstream signaling and potential functional consequences of dimerization of the GHS-R1a receptor in appetite and stress-induced food reward behavior are discussed. The existence of multiple GHS-R1a heterodimers has important consequences for future pharmacotherapies as it significantly increases the pharmacological diversity of the GHS-R1a receptor and has the potential to enhance specificity of novel ghrelin-targeted drugs. PMID:24009547

Quantum threshold reflection is not a consequence of a region of the long-range attractive potential with rapidly varying de Broglie wavelength

NASA Astrophysics Data System (ADS)

Petersen, Jakob; Pollak, Eli; Miret-Artes, Salvador

2018-04-01

Quantum threshold reflection is a well-known quantum phenomenon which prescribes that at threshold, except for special circumstances, a quantum particle scattering from any potential, even if attractive at long range, will be reflected with unit probability. In the past, this property had been associated with the so-called badlands region of the potential, where the semiclassical description of the scattering fails due to a rapid spatial variation of the de Broglie wavelength. This badlands region occurs far from the strong interaction region of the potential and has therefore been used to "explain" the quantum reflection phenomenon. In this paper we show that the badlands region of the interaction potential is immaterial. The extremely long wavelength of the scattered particle at threshold is much longer than the spatial extension of the badlands region, which therefore does not affect the scattering. For this purpose, we review and generalize the proof for the existence of quantum threshold reflection to stress that it is only a consequence of continuity and boundary conditions. The nonlocal character of the scattering implies that the whole interaction potential is involved in the phenomenon. We then provide a detailed numerical study of the threshold scattering of a particle by a Morse potential and an Eckart potential, especially in the time domain. We compare exact quantum computations with incoherent results obtained from a classical Wigner approximation. This study shows that close to threshold the time-dependent amplitude of the scattered particle is negligible in the badlands region and is the same whether the potential has a reflecting wall as in the Morse potential or a steplike structure as in the Eckart smooth step potential. The mean flight time of the particle is not shortened due to a local reflection from the badlands region or due to the lower density of the wave function at short distances. This study should serve to definitely rule out the badlands region as a qualitative guide to the properties of quantum threshold reflection.

Cardiac Atrophy and Diastolic Dysfunction During and After Long Duration Spaceflight: Functional Consequences for Orthostatic Intolerance, Exercise Capability and Risk for Cardiac Arrhythmias

NASA Technical Reports Server (NTRS)

Levine, Benjamin D.; Bungo, Michael W.; Platts, Steven H.; Hamilton, Douglas R.; Johnston, Smith L.

2009-01-01

Cardiac Atrophy and Diastolic Dysfunction During and After Long Duration Spaceflight: Functional Consequences for Orthostatic Intolerance, Exercise Capability and Risk for Cardiac Arrhythmias (Integrated Cardiovascular) will quantify the extent of long-duration space flightassociated cardiac atrophy (deterioration) on the International Space Station crewmembers.

Development of a Conceptual Model for Smoking Cessation: Physical Activity, Neurocognition, and Executive Functioning.

PubMed

Loprinzi, Paul D; Herod, Skyla M; Walker, Jerome F; Cardinal, Bradley J; Mahoney, Sara E; Kane, Christy

2015-01-01

Considerable research has shown adverse neurobiological effects of chronic alcohol use, including long-term and potentially permanent changes in the structure and function of the brain; however, much less is known about the neurobiological consequences of chronic smoking, as it has largely been ignored until recently. In this article, we present a conceptual model proposing the effects of smoking on neurocognition and the role that physical activity may play in this relationship as well as its role in smoking cessation. Pertinent published peer-reviewed articles deposited in PubMed delineating the pathways in the proposed model were reviewed. The proposed model, which is supported by emerging research, demonstrates a bidirectional relationship between smoking and executive functioning. In support of our conceptual model, physical activity may moderate this relationship and indirectly influence smoking behavior through physical activity-induced changes in executive functioning. Our model may have implications for aiding smoking cessation efforts through the promotion of physical activity as a mechanism for preventing smoking-induced deficits in neurocognition and executive function.

Temporal recalibration of motor and visual potentials in lag adaptation in voluntary movement.

PubMed

Cai, Chang; Ogawa, Kenji; Kochiyama, Takanori; Tanaka, Hirokazu; Imamizu, Hiroshi

2018-05-15

Adaptively recalibrating motor-sensory asynchrony is critical for animals to perceive self-produced action consequences. It is controversial whether motor- or sensory-related neural circuits recalibrate this asynchrony. By combining magnetoencephalography (MEG) and functional MRI (fMRI), we investigate the temporal changes in brain activities caused by repeated exposure to a 150-ms delay inserted between a button-press action and a subsequent flash. We found that readiness potentials significantly shift later in the motor system, especially in parietal regions (average: 219.9 ms), while visually evoked potentials significantly shift earlier in occipital regions (average: 49.7 ms) in the delay condition compared to the no-delay condition. Moreover, the shift in readiness potentials, but not in visually evoked potentials, was significantly correlated with the psychophysical measure of motor-sensory adaptation. These results suggest that although both motor and sensory processes contribute to the recalibration, the motor process plays the major role, given the magnitudes of shift and the correlation with the psychophysical measure. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

A temporal interestingness measure for drug interaction signal detection in post-marketing surveillance.

PubMed

Ji, Yanqing; Ying, Hao; Tran, John; Dews, Peter; Mansour, Ayman; Massanari, R Michael

2014-01-01

Drug-drug interactions (DDIs) can result in serious consequences, including death. Existing methods for identifying potential DDIs in post-marketing surveillance primarily rely on the FDA's (Food and Drug Administration) spontaneous reporting system. However, this system suffers from severe underreporting, which makes it difficult to timely collect enough valid cases for statistical analysis. In this paper, we study how to signal potential DDIs using patient electronic health data. Specifically, we focus on discovery of potential DDIs by analyzing the temporal relationships between the concurrent use of two drugs of interest and the occurrences of various symptoms using novel temporal association mining techniques we developed. A new interestingness measure called functional temporal interest was proposed to assess the degrees of temporal association between two drugs of interest and each symptom. The measure was employed to screen potential DDIs from 21,405 electronic patient cases retrieved from the Veterans Affairs Medical Center in Detroit, Michigan. The preliminary results indicate the usefulness of our method in finding potential DDIs for further analysis (e.g., epidemiology study) and investigation (e.g., case review) by drug safety professionals.

Metabolites from invasive pests inhibit mitochondrial complex II: A potential strategy for the treatment of human ovarian carcinoma?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ferramosca, Alessandra, E-mail: alessandra.ferramosca@unisalento.it; Conte, Annalea; Guerra, Flora

The red pigment caulerpin, a secondary metabolite from the marine invasive green algae Caulerpa cylindracea can be accumulated and transferred along the trophic chain, with detrimental consequences on biodiversity and ecosystem functioning. Despite increasing research efforts to understand how caulerpin modifies fish physiology, little is known on the effects of algal metabolites on mammalian cells. Here we report for the first time the mitochondrial targeting activity of both caulerpin, and its closely related derivative caulerpinic acid, by using as experimental model rat liver mitochondria, a system in which bioenergetics mechanisms are not altered. Mitochondrial function was tested by polarographic andmore » spectrophotometric methods. Both compounds were found to selectively inhibit respiratory complex II activity, while complexes I, III, and IV remained functional. These results led us to hypothesize that both algal metabolites could be used as antitumor agents in cell lines with defects in mitochondrial complex I. Ovarian cancer cisplatin-resistant cells are a good example of cell lines with a defective complex I function on which these molecules seem to have a toxic effect on proliferation. This provided novel insight toward the potential use of metabolites from invasive Caulerpa species for the treatment of human ovarian carcinoma cisplatin-resistant cells. -- Highlights: •Novel insight toward the potential use of the algal metabolites for the treatment of human diseases. •Caulerpin and caulerpinic acid inhibit respiratory complex II activity. •Both algal metabolites could be used as antitumor agents in ovarian cancer cisplatin-resistant cells.« less

Responses of the functional structure of soil microbial community to livestock grazing in the Tibetan alpine grassland.

PubMed

Yang, Yunfeng; Wu, Linwei; Lin, Qiaoyan; Yuan, Mengting; Xu, Depeng; Yu, Hao; Hu, Yigang; Duan, Jichuang; Li, Xiangzhen; He, Zhili; Xue, Kai; van Nostrand, Joy; Wang, Shiping; Zhou, Jizhong

2013-02-01

Microbes play key roles in various biogeochemical processes, including carbon (C) and nitrogen (N) cycling. However, changes of microbial community at the functional gene level by livestock grazing, which is a global land-use activity, remain unclear. Here we use a functional gene array, GeoChip 4.0, to examine the effects of free livestock grazing on the microbial community at an experimental site of Tibet, a region known to be very sensitive to anthropogenic perturbation and global warming. Our results showed that grazing changed microbial community functional structure, in addition to aboveground vegetation and soil geochemical properties. Further statistical tests showed that microbial community functional structures were closely correlated with environmental variables, and variations in microbial community functional structures were mainly controlled by aboveground vegetation, soil C/N ratio, and NH4 (+) -N. In-depth examination of N cycling genes showed that abundances of N mineralization and nitrification genes were increased at grazed sites, but denitrification and N-reduction genes were decreased, suggesting that functional potentials of relevant bioprocesses were changed. Meanwhile, abundances of genes involved in methane cycling, C fixation, and degradation were decreased, which might be caused by vegetation removal and hence decrease in litter accumulation at grazed sites. In contrast, abundances of virulence, stress, and antibiotics resistance genes were increased because of the presence of livestock. In conclusion, these results indicated that soil microbial community functional structure was very sensitive to the impact of livestock grazing and revealed microbial functional potentials in regulating soil N and C cycling, supporting the necessity to include microbial components in evaluating the consequence of land-use and/or climate changes. © 2012 Blackwell Publishing Ltd.

Male fertility potential alteration in rheumatic diseases: a systematic review

PubMed Central

Tiseo, Bruno Camargo; Cocuzza, Marcello; Bonfá, Eloisa; Srougi, Miguel; Clovis, A

2016-01-01

ABSTRACT Background Improved targeted therapies for rheumatic diseases were developed recently resulting in a better prognosis for affected patients. Nowadays, patients are living longer and with improved quality of life, including fertility potential. These patients are affected by impaired reproductive function and the causes are often multifactorial related to particularities of each disease. This review highlights how rheumatic diseases and their management affect testicular function and male fertility. Materials and Methods A systematic review of literature of all published data after 1970 was conducted. Data was collected about fertility abnormalities in male patients with systemic lupus erythematosus, rheumatoid arthritis, dermatomyositis, ankylosing spondylitis, Behçet disease and gout. Two independent researchers carried out the search in online databases. Results A total of 19 articles were included addressing the following diseases: 7 systemic lupus erythematosus, 6 Behçet disease, 4 ankylosing spondylitis, 2 rheumatoid arthritis, 2 dermatomyositis and one gout. Systemic lupus erythematosus clearly affects gonadal function impairing spermatogenesis mainly due to antisperm antibodies and cyclophosphamide therapy. Behçet disease, gout and ankylosing spondylitis patients, including those under anti-TNF therapy in the latter disease, do not seem to have reduced fertility whereas in dermatomyositis, the fertility potential is hampered by disease activity and by alkylating agents. Data regarding rheumatoid arthritis is scarce, gonadal dysfunction observed as consequence of disease activity and antisperm antibodies. Conclusions Reduced fertility potential is not uncommon. Its frequency and severity vary among the different rheumatic diseases. Permanent infertility is rare and often associated with alkylating agent therapy. PMID:27120778

Systematic literature review of the risk factors, comorbidities, and consequences of hypogonadism in men.

PubMed

Zarotsky, V; Huang, M-Y; Carman, W; Morgentaler, A; Singhal, P K; Coffin, D; Jones, T H

2014-11-01

The objective of this review was to summarize the literature on the risk factors, comorbidities, and consequences of male hypogonadism, which is defined as a syndrome complex that includes biochemical confirmation of low testosterone (T) and the consistent symptoms and signs associated with low T. A systematic literature search was performed in PubMed/MEDLINE, EMBASE, Cochrane Library for articles published in the last 10 years on risk factors, comorbidities, and consequences of male hypogonadism. Of the 53 relevant studies identified, nine examined potential risk factors, 14 examined potential comorbidities, and 30 examined potential consequences of male hypogonadism. Based on studies conducted in Asia, Australia, Europe, and North & South America, the important factors that predicted and correlated with hypogonadism were advanced age, obesity, a diagnosis of metabolic syndrome (MetS), and a poor general health status. Diabetes mellitus was correlated with hypogonadism in most studies, but was not established as a risk factor. Although diseases, such as coronary heart disease, hypertension, stroke, and peripheral arterial disease did not predict hypogonadism, they did correlate with incident low T. The data reviewed on potential consequences suggest that low T levels may be linked to earlier all-cause and cardiovascular related mortality among men. This literature review suggests that men with certain factors, such as advanced age, obesity, MetS, and poor general health, are more likely to have and develop hypogonadism. Low levels of T may have important long-term negative health consequences. © 2014 American Society of Andrology and European Academy of Andrology.

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

Perceptual consequences of normal and abnormal peripheral compression: Potential links between psychoacoustics and speech perception

NASA Astrophysics Data System (ADS)

Oxenham, Andrew J.; Rosengard, Peninah S.; Braida, Louis D.

2004-05-01

Cochlear damage can lead to a reduction in the overall amount of peripheral auditory compression, presumably due to outer hair cell (OHC) loss or dysfunction. The perceptual consequences of functional OHC loss include loudness recruitment and reduced dynamic range, poorer frequency selectivity, and poorer effective temporal resolution. These in turn may lead to a reduced ability to make use of spectral and temporal fluctuations in background noise when listening to a target sound, such as speech. We tested the effect of OHC function on speech reception in hearing-impaired listeners by comparing psychoacoustic measures of cochlear compression and sentence recognition in a variety of noise backgrounds. In line with earlier studies, we found weak (nonsignificant) correlations between the psychoacoustic tasks and speech reception thresholds in quiet or in steady-state noise. However, when spectral and temporal fluctuations were introduced in the masker, speech reception improved to an extent that was well predicted by the psychoacoustic measures. Thus, our initial results suggest a strong relationship between measures of cochlear compression and the ability of listeners to take advantage of spectral and temporal masker fluctuations in recognizing speech. [Work supported by NIH Grants Nos. R01DC03909, T32DC00038, and R01DC00117.

High-intensity interval exercise and cerebrovascular health: curiosity, cause, and consequence

PubMed Central

Lucas, Samuel J E; Cotter, James D; Brassard, Patrice; Bailey, Damian M

2015-01-01

Exercise is a uniquely effective and pluripotent medicine against several noncommunicable diseases of westernised lifestyles, including protection against neurodegenerative disorders. High-intensity interval exercise training (HIT) is emerging as an effective alternative to current health-related exercise guidelines. Compared with traditional moderate-intensity continuous exercise training, HIT confers equivalent if not indeed superior metabolic, cardiac, and systemic vascular adaptation. Consequently, HIT is being promoted as a more time-efficient and practical approach to optimize health thereby reducing the burden of disease associated with physical inactivity. However, no studies to date have examined the impact of HIT on the cerebrovasculature and corresponding implications for cognitive function. This review critiques the implications of HIT for cerebrovascular function, with a focus on the mechanisms and translational impact for patient health and well-being. It also introduces similarly novel interventions currently under investigation as alternative means of accelerating exercise-induced cerebrovascular adaptation. We highlight a need for studies of the mechanisms and thereby also the optimal dose-response strategies to guide exercise prescription, and for studies to explore alternative approaches to optimize exercise outcomes in brain-related health and disease prevention. From a clinical perspective, interventions that selectively target the aging brain have the potential to prevent stroke and associated neurovascular diseases. PMID:25833341

High-intensity interval exercise and cerebrovascular health: curiosity, cause, and consequence.

PubMed

Lucas, Samuel J E; Cotter, James D; Brassard, Patrice; Bailey, Damian M

2015-06-01

Exercise is a uniquely effective and pluripotent medicine against several noncommunicable diseases of westernised lifestyles, including protection against neurodegenerative disorders. High-intensity interval exercise training (HIT) is emerging as an effective alternative to current health-related exercise guidelines. Compared with traditional moderate-intensity continuous exercise training, HIT confers equivalent if not indeed superior metabolic, cardiac, and systemic vascular adaptation. Consequently, HIT is being promoted as a more time-efficient and practical approach to optimize health thereby reducing the burden of disease associated with physical inactivity. However, no studies to date have examined the impact of HIT on the cerebrovasculature and corresponding implications for cognitive function. This review critiques the implications of HIT for cerebrovascular function, with a focus on the mechanisms and translational impact for patient health and well-being. It also introduces similarly novel interventions currently under investigation as alternative means of accelerating exercise-induced cerebrovascular adaptation. We highlight a need for studies of the mechanisms and thereby also the optimal dose-response strategies to guide exercise prescription, and for studies to explore alternative approaches to optimize exercise outcomes in brain-related health and disease prevention. From a clinical perspective, interventions that selectively target the aging brain have the potential to prevent stroke and associated neurovascular diseases.

Heavy browsing affects the hydraulic capacity of Ceanothus rigidus (Rhamnaceae).

PubMed

Pittermann, Jarmila; Lance, Jonathan; Poster, Lauren; Baer, Alex; Fox, Laurel R

2014-07-01

Defoliation by herbivores can reduce carbon assimilation, change plant water relations, and even shift the biotic structure of plant communities. In this study, we took advantage of a long-term deer exclosure experiment to examine the consequences of persistent deer herbivory on plant water relations and the xylem structure-function relationships in Ceanothus rigidus, a maritime chaparral shrub in coastal California. Browsed plants had thicker stems with many intertwined short distal twigs, and significantly higher sapwood-to-leaf area ratios than their non-browsed counterparts. Leaf area-specific hydraulic conductivity was similar in both browsed and non-browsed plants, but xylem area-specific conductivity was significantly lower in the browsed plants. Vessel diameters were equivalent in both plant groups, but the number of vessels on a transverse area basis was nearly 40% lower in the browsed plants, accounting for their lower transport efficiency. Mid-day in situ water potentials and losses of hydraulic conductivity due to embolism were similar in both groups of plants but stomatal conductance was higher in the browsed shrubs in the early part of the growing season. We discuss our findings in the context of whole-plant ecophysiology, and explore the consequences of herbivory on hormonal signals, wood anatomy, and xylem function.

Single-center experience of N-linked Congenital Disorders of Glycosylation with a Summary of Molecularly Characterized Cases in Arabs.

PubMed

Bastaki, Fatma; Bizzari, Sami; Hamici, Sana; Nair, Pratibha; Mohamed, Madiha; Saif, Fatima; Malik, Ethar Mustafa; Al-Ali, Mahmoud Taleb; Hamzeh, Abdul Rezzak

2018-01-01

Congenital disorders of glycosylation (CDG) represent an expanding group of conditions that result from defects in protein and lipid glycosylation. Different subgroups of CDG display considerable clinical and genetic heterogeneity due to the highly complex nature of cellular glycosylation. This is further complicated by ethno-geographic differences in the mutational landscape of each of these subgroups. Ten Arab CDG patients from Latifa Hospital in Dubai, United Arab Emirates, were assessed using biochemical (glycosylation status of transferrin) and molecular approaches (next-generation sequencing [NGS] and Sanger sequencing). In silico tools including CADD and PolyPhen-2 were used to predict the functional consequences of uncovered mutations. In our sample of patients, five novel mutations were uncovered in the genes: MPDU1, PMM2, MAN1B1, and RFT1. In total, 9 mutations were harbored by the 10 patients in 7 genes. These are missense and nonsense mutations with deleterious functional consequences. This article integrates a single-center experience within a list of reported CDG mutations in the Arab world, accompanied by full molecular and clinical details pertaining to the studied cases. It also sheds light on potential ethnic differences that were not noted before in regards to CDG in the Arab world. © 2017 John Wiley & Sons Ltd/University College London.

Changes in the location of biodiversity-ecosystem function hot spots across the seafloor landscape with increasing sediment nutrient loading.

PubMed

Thrush, Simon F; Hewitt, Judi E; Kraan, Casper; Lohrer, A M; Pilditch, Conrad A; Douglas, Emily

2017-04-12

Declining biodiversity and loss of ecosystem function threatens the ability of habitats to contribute ecosystem services. However, the form of the relationship between biodiversity and ecosystem function (BEF) and how relationships change with environmental change is poorly understood. This limits our ability to predict the consequences of biodiversity loss on ecosystem function, particularly in real-world marine ecosystems that are species rich, and where multiple ecosystem functions are represented by multiple indicators. We investigated spatial variation in BEF relationships across a 300 000 m 2 intertidal sandflat by nesting experimental manipulations of sediment pore water nitrogen concentration into sites with contrasting macrobenthic community composition. Our results highlight the significance of many different elements of biodiversity associated with environmental characteristics, community structure, functional diversity, ecological traits or particular species (ecosystem engineers) to important functions of coastal marine sediments (benthic oxygen consumption, ammonium pore water concentrations and flux across the sediment-water interface). Using the BEF relationships developed from our experiment, we demonstrate patchiness across a landscape in functional performance and the potential for changes in the location of functional hot and cold spots with increasing nutrient loading that have important implications for mapping and predicating change in functionality and the concomitant delivery of ecosystem services. © 2017 The Author(s).

The effect of sex on the repeatability of evolution in different environments.

PubMed

Lachapelle, Josianne; Colegrave, Nick

2017-04-01

The adaptive function of sex has been extensively studied, while less consideration has been given to the potential downstream consequences of sex on evolution. Here, we investigate one such potential consequence, the effect of sex on the repeatability of evolution. By affecting the repeatability of evolution, sex could have important implications for biodiversity, and for our ability to make predictions about the outcome of environmental change. We allowed asexual and sexual populations of Chlamydomonas reinhardtii to evolve in novel environments and monitored both their change in fitness and variance in fitness after evolution. Sex affected the repeatability of evolution by changing the importance of the effect of selection, chance, and ancestral constraints on the outcome of the evolutionary process. In particular, the effects of sex were highly dependent on the initial genetic composition of the population and on the environment. Given the lack of a consistent effect of sex on repeatability across the environments used here, further studies to dissect in more detail the underlying reasons for these differences as well as studies in additional environments are required if we are to have a general understanding of the effects of sex on the repeatability of evolution. © 2017 The Author(s). Evolution © 2017 The Society for the Study of Evolution.

The renal consequences of maternal obesity in offspring are overwhelmed by postnatal high fat diet

PubMed Central

Glastras, Sarah J.; Chen, Hui; Tsang, Michael; Teh, Rachel; McGrath, Rachel T.; Zaky, Amgad; Chen, Jason; Wong, Muh Geot; Pollock, Carol A.; Saad, Sonia

2017-01-01

Aims/Hypothesis Developmental programming induced by maternal obesity influences the development of chronic disease in offspring. In the present study, we aimed to determine whether maternal obesity exaggerates obesity-related kidney disease. Methods Female C57BL/6 mice were fed high-fat diet (HFD) for six weeks prior to mating, during gestation and lactation. Male offspring were weaned to normal chow or HFD. At postnatal Week 8, HFD-fed offspring were administered one dose streptozotocin (STZ, 100 mg/kg i.p.) or vehicle control. Metabolic parameters and renal functional and structural changes were observed at postnatal Week 32. Results HFD-fed offspring had increased adiposity, glucose intolerance and hyperlipidaemia, associated with increased albuminuria and serum creatinine levels. Their kidneys displayed structural changes with increased levels of fibrotic, inflammatory and oxidative stress markers. STZ administration did not potentiate the renal effects of HFD. Though maternal obesity had a sustained effect on serum creatinine and oxidative stress markers in lean offspring, the renal consequences of maternal obesity were overwhelmed by the powerful effect of diet-induced obesity. Conclusion Maternal obesity portends significant risks for metabolic and renal health in adult offspring. However, diet-induced obesity is an overwhelming and potent stimulus for the development of CKD that is not potentiated by maternal obesity. PMID:28225809

Umyuangcaryaraq "Reflecting": multidimensional assessment of reflective processes on the consequences of alcohol use among rural Yup'ik Alaska Native youth.

PubMed

Allen, James; Fok, Carlotta Ching Ting; Henry, David; Skewes, Monica

2012-09-01

Concerns in some settings regarding the accuracy and ethics of employing direct questions about alcohol use suggest need for alternative assessment approaches with youth. Umyuangcaryaraq is a Yup'ik Alaska Native word meaning "Reflecting." The Reflective Processes Scale was developed as a youth measure tapping awareness and thinking over potential negative consequences of alcohol misuse as a protective factor that includes cultural elements often shared by many other Alaska Native and American Indian cultures. This study assessed multidimensional structure, item functioning, and validity. Responses from 284 rural Alaska Native youth allowed bifactor analysis to assess structure, estimates of location and discrimination parameters, and convergent and discriminant validity. A bifactor model of the scale items with three content factors provided excellent fit to observed data. Item response theory analysis suggested a binary response format as optimal. Evidence of convergent and discriminant validity was established. The measure provides an assessment of reflective processes about alcohol that Alaska Native youth engage in when thinking about reasons not to drink. The concept of reflective processes has potential to extend understandings of cultural variation in mindfulness, alcohol expectancies research, and culturally mediated protective factors in Alaska Native and American Indian youth.

Voltage and pH sensing by the voltage-gated proton channel, HV1.

PubMed

DeCoursey, Thomas E

2018-04-01

Voltage-gated proton channels are unique ion channels, membrane proteins that allow protons but no other ions to cross cell membranes. They are found in diverse species, from unicellular marine life to humans. In all cells, their function requires that they open and conduct current only under certain conditions, typically when the electrochemical gradient for protons is outwards. Consequently, these proteins behave like rectifiers, conducting protons out of cells. Their activity has electrical consequences and also changes the pH on both sides of the membrane. Here we summarize what is known about the way these proteins sense the membrane potential and the pH inside and outside the cell. Currently, it is hypothesized that membrane potential is sensed by permanently charged arginines (with very high p K a ) within the protein, which results in parts of the protein moving to produce a conduction pathway. The mechanism of pH sensing appears to involve titratable side chains of particular amino acids. For this purpose their p K a needs to be within the operational pH range. We propose a 'counter-charge' model for pH sensing in which electrostatic interactions within the protein are selectively disrupted by protonation of internally or externally accessible groups. © 2018 The Author.

The renal consequences of maternal obesity in offspring are overwhelmed by postnatal high fat diet.

PubMed

Glastras, Sarah J; Chen, Hui; Tsang, Michael; Teh, Rachel; McGrath, Rachel T; Zaky, Amgad; Chen, Jason; Wong, Muh Geot; Pollock, Carol A; Saad, Sonia

2017-01-01

Developmental programming induced by maternal obesity influences the development of chronic disease in offspring. In the present study, we aimed to determine whether maternal obesity exaggerates obesity-related kidney disease. Female C57BL/6 mice were fed high-fat diet (HFD) for six weeks prior to mating, during gestation and lactation. Male offspring were weaned to normal chow or HFD. At postnatal Week 8, HFD-fed offspring were administered one dose streptozotocin (STZ, 100 mg/kg i.p.) or vehicle control. Metabolic parameters and renal functional and structural changes were observed at postnatal Week 32. HFD-fed offspring had increased adiposity, glucose intolerance and hyperlipidaemia, associated with increased albuminuria and serum creatinine levels. Their kidneys displayed structural changes with increased levels of fibrotic, inflammatory and oxidative stress markers. STZ administration did not potentiate the renal effects of HFD. Though maternal obesity had a sustained effect on serum creatinine and oxidative stress markers in lean offspring, the renal consequences of maternal obesity were overwhelmed by the powerful effect of diet-induced obesity. Maternal obesity portends significant risks for metabolic and renal health in adult offspring. However, diet-induced obesity is an overwhelming and potent stimulus for the development of CKD that is not potentiated by maternal obesity.

Voltage and pH sensing by the voltage-gated proton channel, HV1

PubMed Central

2018-01-01

Voltage-gated proton channels are unique ion channels, membrane proteins that allow protons but no other ions to cross cell membranes. They are found in diverse species, from unicellular marine life to humans. In all cells, their function requires that they open and conduct current only under certain conditions, typically when the electrochemical gradient for protons is outwards. Consequently, these proteins behave like rectifiers, conducting protons out of cells. Their activity has electrical consequences and also changes the pH on both sides of the membrane. Here we summarize what is known about the way these proteins sense the membrane potential and the pH inside and outside the cell. Currently, it is hypothesized that membrane potential is sensed by permanently charged arginines (with very high pKa) within the protein, which results in parts of the protein moving to produce a conduction pathway. The mechanism of pH sensing appears to involve titratable side chains of particular amino acids. For this purpose their pKa needs to be within the operational pH range. We propose a ‘counter-charge’ model for pH sensing in which electrostatic interactions within the protein are selectively disrupted by protonation of internally or externally accessible groups. PMID:29643227

The consequence of spatial visual processing dysfunction caused by traumatic brain injury (TBI).

PubMed

Padula, William V; Capo-Aponte, Jose E; Padula, William V; Singman, Eric L; Jenness, Jonathan

2017-01-01

A bi-modal visual processing model is supported by research to affect dysfunction following a traumatic brain injury (TBI). TBI causes dysfunction of visual processing affecting binocularity, spatial orientation, posture and balance. Research demonstrates that prescription of prisms influence the plasticity between spatial visual processing and motor-sensory systems improving visual processing and reducing symptoms following a TBI. The rationale demonstrates that visual processing underlies the functional aspects of binocularity, balance and posture. The bi-modal visual process maintains plasticity for efficiency. Compromise causes Post Trauma Vision Syndrome (PTVS) and Visual Midline Shift Syndrome (VMSS). Rehabilitation through use of lenses, prisms and sectoral occlusion has inter-professional implications in rehabilitation affecting the plasticity of the bi-modal visual process, thereby improving binocularity, spatial orientation, posture and balance Main outcomes: This review provides an opportunity to create a new perspective of the consequences of TBI on visual processing and the symptoms that are often caused by trauma. It also serves to provide a perspective of visual processing dysfunction that has potential for developing new approaches of rehabilitation. Understanding vision as a bi-modal process facilitates a new perspective of visual processing and the potentials for rehabilitation following a concussion, brain injury or other neurological events.

Fourth-Order Vibrational Transition State Theory and Chemical Kinetics

NASA Astrophysics Data System (ADS)

Stanton, John F.; Matthews, Devin A.; Gong, Justin Z.

2015-06-01

Second-order vibrational perturbation theory (VPT2) is an enormously successful and well-established theory for treating anharmonic effects on the vibrational levels of semi-rigid molecules. Partially as a consequence of the fact that the theory is exact for the Morse potential (which provides an appropriate qualitative model for stretching anharmonicity), VPT2 calculations for such systems with appropriate ab initio potential functions tend to give fundamental and overtone levels that fall within a handful of wavenumbers of experimentally measured positions. As a consequence, the next non-vanishing level of perturbation theory -- VPT4 -- offers only slight improvements over VPT2 and is not practical for most calculations since it requires information about force constants up through sextic. However, VPT4 (as well as VPT2) can be used for other applications such as the next vibrational correction to rotational constants (the ``gammas'') and other spectroscopic parameters. In addition, the marriage of VPT with the semi-classical transition state theory of Miller (SCTST) has recently proven to be a powerful and accurate treatment for chemical kinetics. In this talk, VPT4-based SCTST tunneling probabilities and cumulative reaction probabilities are give for the first time for selected low-dimensional model systems. The prospects for VPT4, both practical and intrinsic, will also be discussed.

Volatile substance misuse : clinical considerations, neuropsychopharmacology and potential role of pharmacotherapy in management.

PubMed

Garland, Eric L; Howard, Matthew O

2012-11-01

Volatile substance misuse is among the most prevalent and toxic forms of psychoactive drug use, and often results in highly deleterious social, psychological and medical consequences. The prevalence of this pernicious form of substance misuse owes in part to the fact that volatile substances of misuse are ubiquitous in the natural environment. Commonly misused commercial products include glue, shoe polish, nail polish remover, butane lighter fluid, gasoline and computer duster spray. National samples of volatile substance misusers tend to exhibit high rates of psychiatric problems and antisocial behaviour. In addition, cognitive impairments and affective dysregulation are often observed among these individuals. Volatile substances exert their complex neuropharmacological effects on dopaminergic, glutamatergic, GABAergic and serotoninergic receptor systems, as well as on cell membranes and ion channels. Concomitantly, pharmacotherapies for volatile substance abuse might profitably target a number of mechanisms, including reward circuitry in the brain, symptoms of craving and withdrawal, neuropsychiatric and emotional impairments that promote volatile substance abuse, and cognitive enhancement to rectify deficits in executive function. This review details the modes of use, subjective effects, epidemiology, adverse consequences, neuropsychopharmacology and drug treatment of volatile substance misuse, and discusses the potential role of novel forms of pharmacological intervention for this oft-overlooked public health threat of epidemic proportions.

Female guppies agree to differ: phenotypic and genetic variation in mate-choice behavior and the consequences for sexual selection.

PubMed

Brooks, R; Endler, J A

2001-08-01

Variation among females in mate choice may influence evolution by sexual selection. The genetic basis of this variation is of interest because the elaboration of mating preferences requires additive genetic variation in these traits. Here we measure the repeatability and heritability of two components of female choosiness (responsiveness and discrimination) and of female preference functions for the multiple ornaments borne by male guppies (Poecilia reticulata). We show that there is significant repeatable variation in both components of choosiness and in some preference functions but not in others. There appear to be several male ornaments that females find uniformly attractive and others for which females differ in preference. One consequence is that there is no universally attractive male phenotype. Only responsiveness shows significant additive genetic variation. Variation in responsiveness appears to mask variation in discrimination and some preference functions and may be the most biologically relevant source of phenotypic and genetic variation in mate-choice behavior. To test the potential evolutionary importance of the phenotypic variation in mate choice that we report, we estimated the opportunity for and the intensity of sexual selection under models of mate choice that excluded and that incorporated individual female variation. We then compared these estimates with estimates based on measured mating success. Incorporating individual variation in mate choice generally did not predict the outcome of sexual selection any better than models that ignored such variation.

An Overview of Nitrogen Cycling in a Semiarid Savanna: Some Implications for Management and Conservation in a Large African Park

NASA Astrophysics Data System (ADS)

Coetsee, Corli; Jacobs, Shayne; Govender, Navashni

2012-02-01

Nitrogen (N) is a major control on primary productivity and hence on the productivity and diversity of secondary producers and consumers. As such, ecosystem structure and function cannot be understood without a comprehensive understanding of N cycling and dynamics. This overview describes the factors that govern N distribution and dynamics and the consequences that variable N dynamics have for structure, function and thresholds of potential concern (TPCs) for management of a semiarid southern African savanna. We focus on the Kruger National Park (KNP), a relatively intact savanna, noted for its wide array of animal and plant species and a prized tourist destination. KNP's large size ensures integrity of most ecosystem processes and much can be learned about drivers of ecosystem structure and function using this park as a baseline. Our overview shows that large scale variability in substrates exists, but do not necessarily have predictable consequences for N cycling. The impact of major drivers such as fire is complex; at a landscape scale little differences in stocks and cycling were found, though at a smaller scale changes in woody cover can lead to concomitant changes in total N. Contrasting impacts of browsers and grazers on N turnover has been recorded. Due to the complexity of this ecosystem, we conclude that it will be complicated to draw up TPCs for most transformations and pools involved with the N cycle. However, we highlight in which cases the development of TPCs will be possible.

Protein lipoxidation: Detection strategies and challenges

PubMed Central

Aldini, Giancarlo; Domingues, M. Rosário; Spickett, Corinne M.; Domingues, Pedro; Altomare, Alessandra; Sánchez-Gómez, Francisco J.; Oeste, Clara L.; Pérez-Sala, Dolores

2015-01-01

Enzymatic and non-enzymatic lipid metabolism can give rise to reactive species that may covalently modify cellular or plasma proteins through a process known as lipoxidation. Under basal conditions, protein lipoxidation can contribute to normal cell homeostasis and participate in signaling or adaptive mechanisms, as exemplified by lipoxidation of Ras proteins or of the cytoskeletal protein vimentin, both of which behave as sensors of electrophilic species. Nevertheless, increased lipoxidation under pathological conditions may lead to deleterious effects on protein structure or aggregation. This can result in impaired degradation and accumulation of abnormally folded proteins contributing to pathophysiology, as may occur in neurodegenerative diseases. Identification of the protein targets of lipoxidation and its functional consequences under pathophysiological situations can unveil the modification patterns associated with the various outcomes, as well as preventive strategies or potential therapeutic targets. Given the wide structural variability of lipid moieties involved in lipoxidation, highly sensitive and specific methods for its detection are required. Derivatization of reactive carbonyl species is instrumental in the detection of adducts retaining carbonyl groups. In addition, use of tagged derivatives of electrophilic lipids enables enrichment of lipoxidized proteins or peptides. Ultimate confirmation of lipoxidation requires high resolution mass spectrometry approaches to unequivocally identify the adduct and the targeted residue. Moreover, rigorous validation of the targets identified and assessment of the functional consequences of these modifications are essential. Here we present an update on methods to approach the complex field of lipoxidation along with validation strategies and functional assays illustrated with well-studied lipoxidation targets. PMID:26072467

Renal denervation and hypertension - The need to investigate unintended effects and neural control of the human kidney.

PubMed

Grisk, Olaf

2017-05-01

Increased renal sympathetic nerve activity (RSNA) is present in human and experimental forms of arterial hypertension. Experimental denervation studies showed that renal nerves contribute to the development of hypertension. Clinical trials provided equivocal results on the antihypertensive efficacy of renal denervation in patients spurring discussions on technical aspects of renal denervation and further research on the role of renal nerves for the regulation of kidney function as well as the pathophysiology of hypertension. This review summarizes recent findings on adrenoceptor expression and function in the human kidney, adrenoceptor-dependent regulation of sodium chloride transport in the distal nephron, experimental data on chronic RSNA and the development of high arterial pressure and consequences of renal denervation that may limit its antihypertensive efficacy. Future research needs to reduce the gap between our knowledge on neural control of renal function in animals vs. humans to facilitate translation of experimental animal data to humans. More experimental studies on the temporal relationship between RSNA and arterial pressure in the chronic setting are needed to better define the pathogenetic role of heightened RSNA in different forms of arterial hypertension in order to improve the rational basis for renal denervation in antihypertensive therapy. Finally, research on unintended consequences of renal denervation including but not limited to reinnervation and denervation supersensitivity needs to be intensified to further assess the potential of renal denervation to slow the progression of renal disease and hypertension. Copyright © 2016 Elsevier B.V. All rights reserved.

A Field Investigation of the Effects of Drinking Consequences on Young Adults’ Readiness to Change

PubMed Central

Usala, Julie M.; Celio, Mark A.; Lisman, Stephen A.; Day, Anne M.; Spear, Linda P.

2014-01-01

In the research on readiness to change (RTC) one’s drinking, there has been little assessment of the influence of positive drinking consequences or other potential moderating variables. To address these limitations, we examined how young adults’ RTC their alcohol consumption shortly following a drinking episode was associated with self-reported drinking consequences, as well as any potential moderating effects of gender and Breath Alcohol Concentration (BrAC). In street interviews outside bars, 238 young adults were administered questionnaires about their drinking, including a measure examining participants’ current readiness to reduce their alcohol consumption. Within 72 hours of their drinking episode, 67 participants (36 males; Entire Sample Mage = 20.90 years, Range = 18–26 years) completed an online survey, once again measuring RTC as well as positive and negative drinking consequences. Consistent with our hypothesis, positive drinking consequences were negatively associated with participants’ changes in RTC. Additionally, a three-way interaction of gender x BrAC x Positive Drinking Consequences on RTC showed that females with low BrACs reported higher RTC scores when they had endorsed fewer positive drinking consequences. Interestingly, negative drinking consequences alone did not impact individuals’ RTC. Because positive drinking consequences were a significantly better predictor of RTC than were negative drinking consequences, researchers are advised to examine both types of consequences in future studies. Finally, effective alcohol education programs for those who have never consumed alcohol as well as social drinkers should include consideration of the experience of positive outcomes. PMID:25452061

Consequences of germline variation disrupting the constitutional translational initiation codon start sites of MLH1 and BRCA2: use of potential alternative start sites and implications for predicting variant pathogenicity

PubMed Central

Parsons, Michael T.; Whiley, Phillip J.; Beesley, Jonathan; Drost, Mark; de Wind, Niels; Thompson, Bryony A.; Marquart, Louise; Hopper, John L.; Jenkins, Mark A.; Brown, Melissa A.; Tucker, Kathy; Warwick, Linda; Buchanan, Daniel D.; Spurdle, Amanda B.

2014-01-01

Variants that disrupt the translation initiation sequences in cancer predisposition genes are generally assumed to be deleterious. However few studies have validated these assumptions with functional and clinical data. Two cancer syndrome gene variants likely to affect native translation initiation were identified by clinical genetic testing: MLH1:c.1A>G p.(Met1?) and BRCA2:c.67+3A>G. In vitro GFP-reporter assays were conducted to assess the consequences of translation initiation disruption on alternative downstream initiation codon usage. Analysis of MLH1:c.1A>G p.(Met1?) showed that translation was mostly initiated at an in-frame position 103 nucleotides downstream, but also at two ATG sequences downstream. The protein product encoded by the in-frame transcript initiating from position c.103 showed loss of in vitro mismatch repair activity comparable to known pathogenic mutations. BRCA2:c.67+3A>G was shown by mRNA analysis to result in an aberrantly spliced transcript deleting exon 2 and the consensus ATG site. In the absence of exon 2, translation initiated mostly at an out-of-frame ATG 323 nucleotides downstream, and to a lesser extent at an in-frame ATG 370 nucleotides downstream. Initiation from any of the downstream alternative sites tested in both genes would lead to loss of protein function, but further clinical data is required to confirm if these variants are associated with a high cancer risk. Importantly, our results highlight the need for caution in interpreting the functional and clinical consequences of variation that leads to disruption of the initiation codon, since translation may not necessarily occur from the first downstream alternative start site, or from a single alternative start site. PMID:24302565

Loss of tumor suppressor KDM6A amplifies PRC2-regulated transcriptional repression in bladder cancer and can be targeted through inhibition of EZH2.

PubMed

Ler, Lian Dee; Ghosh, Sujoy; Chai, Xiaoran; Thike, Aye Aye; Heng, Hong Lee; Siew, Ee Yan; Dey, Sucharita; Koh, Liang Kai; Lim, Jing Quan; Lim, Weng Khong; Myint, Swe Swe; Loh, Jia Liang; Ong, Pauline; Sam, Xin Xiu; Huang, Dachuan; Lim, Tony; Tan, Puay Hoon; Nagarajan, Sanjanaa; Cheng, Christopher Wai Sam; Ho, Henry; Ng, Lay Guat; Yuen, John; Lin, Po-Hung; Chuang, Cheng-Keng; Chang, Ying-Hsu; Weng, Wen-Hui; Rozen, Steven G; Tan, Patrick; Creasy, Caretha L; Pang, See-Tong; McCabe, Michael T; Poon, Song Ling; Teh, Bin Tean

2017-02-22

Trithorax-like group complex containing KDM6A acts antagonistically to Polycomb-repressive complex 2 (PRC2) containing EZH2 in maintaining the dynamics of the repression and activation of gene expression through H3K27 methylation. In urothelial bladder carcinoma, KDM6A (a H3K27 demethylase) is frequently mutated, but its functional consequences and therapeutic targetability remain unknown. About 70% of KDM6A mutations resulted in a total loss of expression and a consequent loss of demethylase function in this cancer type. Further transcriptome analysis found multiple deregulated pathways, especially PRC2/EZH2, in KDM6A -mutated urothelial bladder carcinoma. Chromatin immunoprecipitation sequencing analysis revealed enrichment of H3K27me3 at specific loci in KDM6A -null cells, including PRC2/EZH2 and their downstream targets. Consequently, we targeted EZH2 (an H3K27 methylase) and demonstrated that KDM6A -null urothelial bladder carcinoma cell lines were sensitive to EZH2 inhibition. Loss- and gain-of-function assays confirmed that cells with loss of KDM6A are vulnerable to EZH2. IGFBP3, a direct KDM6A/EZH2/H3K27me3 target, was up-regulated by EZH2 inhibition and contributed to the observed EZH2-dependent growth suppression in KDM6A -null cell lines. EZH2 inhibition delayed tumor onset in KDM6A -null cells and caused regression of KDM6A -null bladder tumors in both patient-derived and cell line xenograft models. In summary, our study demonstrates that inactivating mutations of KDM6A , which are common in urothelial bladder carcinoma, are potentially targetable by inhibiting EZH2. Copyright © 2017, American Association for the Advancement of Science.

Rodents as potential couriers for bioterrorism agents.

PubMed

Lõhmus, Mare; Janse, Ingmar; van de Goot, Frank; van Rotterdam, Bart J

2013-09-01

Many pathogens that can cause major public health, economic, and social damage are relatively easily accessible and could be used as biological weapons. Wildlife is a natural reservoir for many potential bioterrorism agents, and, as history has shown, eliminating a pathogen that has dispersed among wild fauna can be extremely challenging. Since a number of wild rodent species live close to humans, rodents constitute a vector for pathogens to circulate among wildlife, domestic animals, and humans. This article reviews the possible consequences of a deliberate spread of rodentborne pathogens. It is relatively easy to infect wild rodents with certain pathogens or to release infected rodents, and the action would be difficult to trace. Rodents can also function as reservoirs for diseases that have been spread during a bioterrorism attack and cause recurring disease outbreaks. As rats and mice are common in both urban and rural settlements, deliberately released rodentborne infections have the capacity to spread very rapidly. The majority of pathogens that are listed as potential agents of bioterrorism by the Centers for Disease Control and Prevention and the National Institute of Allergy and Infectious Diseases exploit rodents as vectors or reservoirs. In addition to zoonotic diseases, deliberately released rodentborne epizootics can have serious economic consequences for society, for example, in the area of international trade restrictions. The ability to rapidly detect introduced diseases and effectively communicate with the public in crisis situations enables a quick response and is essential for successful and cost-effective disease control.

Role of oxidative stress in cardiovascular disease outcomes following exposure to ambient air pollution.

PubMed

Kelly, Frank J; Fussell, Julia C

2017-09-01

Exposure to ambient air pollution is associated with adverse cardiovascular outcomes. These are manifested through several, likely overlapping, pathways including at the functional level, endothelial dysfunction, atherosclerosis, pro-coagulation and alterations in autonomic nervous system balance and blood pressure. At numerous points within each of these pathways, there is potential for cellular oxidative imbalances to occur. The current review examines epidemiological, occupational and controlled exposure studies and research employing healthy and diseased animal models, isolated organs and cell cultures in assessing the importance of the pro-oxidant potential of air pollution in the development of cardiovascular disease outcomes. The collective body of data provides evidence that oxidative stress (OS) is not only central to eliciting specific cardiac endpoints, but is also implicated in modulating the risk of succumbing to cardiovascular disease, sensitivity to ischemia/reperfusion injury and the onset and progression of metabolic disease following ambient pollution exposure. To add to this large research effort conducted to date, further work is required to provide greater insight into areas such as (a) whether an oxidative imbalance triggers and/or worsens the effect and/or is representative of the consequence of disease progression, (b) OS pathways and cardiac outcomes caused by individual pollutants within air pollution mixtures, or as a consequence of inter-pollutant interactions and (c) potential protection provided by nutritional supplements and/or pharmacological agents with antioxidant properties, in susceptible populations residing in polluted urban cities. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Antistress and antioxidant effects of virgin coconut oil in vivo.

PubMed

Yeap, Swee Keong; Beh, Boon Kee; Ali, Norlaily Mohd; Yusof, Hamidah Mohd; Ho, Wan Yong; Koh, Soo Peng; Alitheen, Noorjahan Banu; Long, Kamariah

2015-01-01

Virgin coconut oil (VCO) has been consumed worldwide for various health-related reasons and some of its benefits have been scientifically evaluated. Medium-chain fatty acids were found to be a potential antidepressant functional food; however, this effect had not been evaluated in VCO, which is rich in polyphenols and medium-chain fatty acids. The aim of this study was to evaluate the antistress and antioxidant effects of VCO in vivo , using mice with stress-induced injury. The antistress effect of VCO (administered per os , at a dose of 10 ml/kg body weight) was evaluated using the forced swim test and chronic cold restraint stress models. VCO was able to reduce immobility time and restore oxidative stress in mice post-swim test. Furthermore, mice treated with VCO were found to exhibit higher levels of brain antioxidants, lower levels of brain 5-hydroxytryptamine and reduced weight of the adrenal glands. Consequently, the serum cholesterol, triglyceride, glucose and corticosterone levels were also lower in VCO-treated mice. These results suggest the potential value of VCO as an antistress functional oil.

Antistress and antioxidant effects of virgin coconut oil in vivo

PubMed Central

YEAP, SWEE KEONG; BEH, BOON KEE; ALI, NORLAILY MOHD; YUSOF, HAMIDAH MOHD; HO, WAN YONG; KOH, SOO PENG; ALITHEEN, NOORJAHAN BANU; LONG, KAMARIAH

2015-01-01

Virgin coconut oil (VCO) has been consumed worldwide for various health-related reasons and some of its benefits have been scientifically evaluated. Medium-chain fatty acids were found to be a potential antidepressant functional food; however, this effect had not been evaluated in VCO, which is rich in polyphenols and medium-chain fatty acids. The aim of this study was to evaluate the antistress and antioxidant effects of VCO in vivo, using mice with stress-induced injury. The antistress effect of VCO (administered per os, at a dose of 10 ml/kg body weight) was evaluated using the forced swim test and chronic cold restraint stress models. VCO was able to reduce immobility time and restore oxidative stress in mice post-swim test. Furthermore, mice treated with VCO were found to exhibit higher levels of brain antioxidants, lower levels of brain 5-hydroxytryptamine and reduced weight of the adrenal glands. Consequently, the serum cholesterol, triglyceride, glucose and corticosterone levels were also lower in VCO-treated mice. These results suggest the potential value of VCO as an antistress functional oil. PMID:25452773

Neurobiological and neurocognitive effects of chronic cigarette smoking and alcoholism.

PubMed

Durazzo, Timothy C; Meyerhoff, Dieter J

2007-05-01

Chronic cigarette smoking is associated with adverse effects on cardiac, pulmonary, and vascular function as well as the increased risk for various forms of cancer. However, little is known about the effects of chronic smoking on human brain function. Although smoking rates have decreased in the developed world, they remain high in individuals with alcohol use disorders (AUD) and other neuropsychiatric conditions. Despite the high prevalence of chronic smoking in AUD, few studies have addressed the potential neurobiological or neurocognitive consequences of chronic smoking in alcohol use disorders. Here, we review the the neurobiological and neurocognitive findings in both AUD and chronic cigarette smoking, followed by a review of the effects of comorbid cigarette smoking on neurobiology and neurocognition in AUD. Recent research suggests that comorbid chronic cigarette smoking modulates magnetic resonance-detectable brain injury and neurocognition in alcohol use disorders and adversely affects neurobiological and neurocognitive recovery in abstinent alcoholics.. Consideration of the potential separate and interactive effects of chronic smoking and alcohol use disorders may have significant implications for pharmacological and behavioral treatment interventions.

HIF Activation Against CVD in CKD: Novel Treatment Opportunities.

PubMed

Tanaka, Tetsuhiro; Eckardt, Kai-Uwe

2018-05-01

Cardiovascular disease is a common and serious complication in patients with chronic kidney disease (CKD). One of the fundamental functions of the cardiovascular system is oxygen delivery, therefore cardiovascular disease inherently is linked to insufficient tissue oxygenation. Advances in our knowledge of cellular oxygen sensing by a family of prolyl hydroxylases (PHDs) and their role in regulating hypoxia-inducible factors (HIFs) have led to the discovery of PHD inhibitors as HIF stabilizers. Several small-molecule PHD inhibitors are currently in clinical trials for the treatment of anemia in CKD. An additional advantage of PHD inhibition may be found in the potential impact on cardiovascular consequences associated with CKD. Several preclinical studies have suggested a potential benefit of HIF activation in myocardial infarction, cardiac remodeling, atherosclerosis, and peripheral artery disease. Ameliorating glucose and lipid metabolism and lowering blood pressure may also contribute to cardiovascular protection. On the other hand, the broad spectrum of HIF-dependent functions also may include unwanted side effects. Clinical application of PHD inhibitors therefore necessitates careful evaluation of the net systemic effect of HIF activation. Copyright © 2018 Elsevier Inc. All rights reserved.

Aging and brain rejuvenation as systemic events

PubMed Central

Bouchard, Jill; Villeda, Saul A

2015-01-01

The effects of aging were traditionally thought to be immutable, particularly evident in the loss of plasticity and cognitive abilities occurring in the aged central nervous system (CNS). However, it is becoming increasingly apparent that extrinsic systemic manipulations such as exercise, caloric restriction, and changing blood composition by heterochronic parabiosis or young plasma administration can partially counteract this age-related loss of plasticity in the aged brain. In this review, we discuss the process of aging and rejuvenation as systemic events. We summarize genetic studies that demonstrate a surprising level of malleability in organismal lifespan, and highlight the potential for systemic manipulations to functionally reverse the effects of aging in the CNS. Based on mounting evidence, we propose that rejuvenating effects of systemic manipulations are mediated, in part, by blood-borne ‘pro-youthful’ factors. Thus, systemic manipulations promoting a younger blood composition provide effective strategies to rejuvenate the aged brain. As a consequence, we can now consider reactivating latent plasticity dormant in the aged CNS as a means to rejuvenate regenerative, synaptic, and cognitive functions late in life, with potential implications even for extending lifespan. PMID:25327899

Cytoskeletal Regulation of Dermal Regeneration

PubMed Central

Strudwick, Xanthe L.; Cowin, Allison J.

2012-01-01

Wound healing results in the repair of injured tissues however fibrosis and scar formation are, more often than not the unfortunate consequence of this process. The ability of lower order vertebrates and invertebrates to regenerate limbs and tissues has been all but lost in mammals; however, there are some instances where glimpses of mammalian regenerative capacity do exist. Here we describe the unlocked potential that exists in mammals that may help us understand the process of regeneration post-injury and highlight the potential role of the actin cytoskeleton in this process. The precise function and regulation of the cytoskeleton is critical to the success of the healing process and its manipulation may therefore facilitate regenerative healing. The gelsolin family of actin remodelling proteins in particular has been shown to have important functions in wound healing and family member Flightless I (Flii) is involved in both regeneration and repair. Understanding the interactions between different cytoskeletal proteins and their dynamic control of processes including cellular adhesion, contraction and motility may assist the development of therapeutics that will stimulate regeneration rather than repair. PMID:24710556

Perceptions of Sexual Harassment as a Function of Sex of Rater and Incident Form and Consequence.

ERIC Educational Resources Information Center

Popovich, Paula M.; And Others

1992-01-01

Examined perceptions of verbal versus physical sexual harassment incidents and consequences among 99 male and 99 female white undergraduates. Found significant "consequence" and "sex" effects. Males rated verbal incidents less negatively than did females, especially when the statement described "physical" behavior…

Use of cognitive behavior therapy for functional hypothalamic amenorrhea.

PubMed

Berga, Sarah L; Loucks, Tammy L

2006-12-01

Behaviors that chronically activate the hypothalamic-pituitary-adrenal (HPA) axis and/or suppress the hypothalamic-pituitary-thyroidal (HPT) axis disrupt the hypothalamic-pituitary-gonadal axis in women and men. Individuals with functional hypothalamic hypogonadism typically engage in a combination of behaviors that concomitantly heighten psychogenic stress and increase energy demand. Although it is not widely recognized clinically, functional forms of hypothalamic hypogonadism are more than an isolated disruption of gonadotropin-releasing hormone (GnRH) drive and reproductive compromise. Indeed, women with functional hypothalamic amenorrhea display a constellation of neuroendocrine aberrations that reflect allostatic adjustments to chronic stress. Given these considerations, we have suggested that complete neuroendocrine recovery would involve more than reproductive recovery. Hormone replacement strategies have limited benefit because they do not ameliorate allostatic endocrine adjustments, particularly the activation of the adrenal and the suppression of the thyroidal axes. Indeed, the rationale for the use of sex steroid replacement is based on the erroneous assumption that functional forms of hypothalamic hypogonadism represent only or primarily an alteration in the hypothalamic-pituitary-gonadal axis. Potential health consequences of functional hypothalamic amenorrhea, often termed stress-induced anovulation, may include an increased risk of cardiovascular disease, osteoporosis, depression, other psychiatric conditions, and dementia. Although fertility can be restored with exogenous administration of gonadotropins or pulsatile GnRH, fertility management alone will not permit recovery of the adrenal and thyroidal axes. Initiating pregnancy with exogenous means without reversing the hormonal milieu induced by chronic stress may increase the likelihood of poor obstetrical, fetal, or neonatal outcomes. In contrast, behavioral and psychological interventions that address problematic behaviors and attitudes, such as cognitive behavior therapy (CBT), have the potential to permit resumption of full ovarian function along with recovery of the adrenal, thyroidal, and other neuroendocrine aberrations. Full endocrine recovery potentially offers better individual, maternal, and child health.

The human spermatozoon--not waving but drowning.

PubMed

Aitken, R John; Sawyer, Dennis

2003-01-01

The poor quality of the human ejaculate sets man apart from all other mammalian species. Even in normal fertile men the ejaculate may contain up to 85% abnormal forms according to the World Heath Organization (1999). In the wake of this poor semen quality comes extremely poor fertility (Hull et al, 1985) and the highest rates of aneuploidy, pregnancy loss and birth defects in viviparous vertebrates. Thus, the poor quality of human spermatozoa is reflected in both their capacity for fertilization and their genetic integrity. The ultimate cause of defective sperm function is unknown. In certain patients a genetic basis for male infertility has been identified involving DNA deletions on the long arm of the Y chromosome. Such deletions might explain the impoverished semen quality seen in about 10-14% of men with severely impaired spermatogenesis, but fail to explain the infertility seen in most (>85%) cases of male infertility. One of the key attributes and probable causes of defective sperm function is oxidative stress created by excessive ROS generation by the spermatozoa and/or the disruption of antioxidant defence systems in the male reproductive tract. Excess free radical generation frequently involves an error in spermiogenesis resulting in the release of spermatozoa from the germinal epithelium exhibiting abnormally high levels of cytoplasmic retention. The excess cytoplasm contains enzymes that fuel the generation of ROS by the spermatozoa's plasma membrane redox systems. The consequences of such oxidative stress include a loss of motility and fertilizing potential and the induction of DNA damage in the sperm nucleus. The loss of sperm function is due to the peroxidation of unsaturated fatty acids in the sperm plasma membrane as a consequence of which the latter loses its fluidity and the cells lose their function. The causes and consequences of oxidative damage to the DNA in the sperm nucleus are still not known with certainty. The available evidence suggests that early pregnancy loss and morbidity in the offspring, including childhood cancer, are associated with such damage. Developing animal models with which to establish the validity of these relationships and identifying the environmental factors associated with the proposed 'testicular dysgenesis syndrome' will clearly be important tasks for the future.

The Consequences of Unintended Childbearing: A White Paper

ERIC Educational Resources Information Center

Logan, Cassandra; Holcombe, Emily; Manlove, Jennifer; Ryan, Suzanne

2007-01-01

This report provides a critical review of the current research literature on the consequences of unintended childbearing for families and children. The review addresses the following potential consequences: prenatal and perinatal risks (e.g., inadequate or delayed initiation of prenatal care, smoking/drinking/substance use during pregnancy,…

Multi-period response management to contaminated water distribution networks: dynamic programming versus genetic algorithms

NASA Astrophysics Data System (ADS)

Bashi-Azghadi, Seyyed Nasser; Afshar, Abbas; Afshar, Mohammad Hadi

2018-03-01

Previous studies on consequence management assume that the selected response action including valve closure and/or hydrant opening remains unchanged during the entire management period. This study presents a new embedded simulation-optimization methodology for deriving time-varying operational response actions in which the network topology may change from one stage to another. Dynamic programming (DP) and genetic algorithm (GA) are used in order to minimize selected objective functions. Two networks of small and large sizes are used in order to illustrate the performance of the proposed modelling schemes if a time-dependent consequence management strategy is to be implemented. The results show that for a small number of decision variables even in large-scale networks, DP is superior in terms of accuracy and computer runtime. However, as the number of potential actions grows, DP loses its merit over the GA approach. This study clearly proves the priority of the proposed dynamic operation strategy over the commonly used static strategy.

Extreme Magnitude Earthquakes and their Economical Consequences

NASA Astrophysics Data System (ADS)

Chavez, M.; Cabrera, E.; Ashworth, M.; Perea, N.; Emerson, D.; Salazar, A.; Moulinec, C.

2011-12-01

The frequency of occurrence of extreme magnitude earthquakes varies from tens to thousands of years, depending on the considered seismotectonic region of the world. However, the human and economic losses when their hypocenters are located in the neighborhood of heavily populated and/or industrialized regions, can be very large, as recently observed for the 1985 Mw 8.01 Michoacan, Mexico and the 2011 Mw 9 Tohoku, Japan, earthquakes. Herewith, a methodology is proposed in order to estimate the probability of exceedance of: the intensities of extreme magnitude earthquakes, PEI and of their direct economical consequences PEDEC. The PEI are obtained by using supercomputing facilities to generate samples of the 3D propagation of extreme earthquake plausible scenarios, and enlarge those samples by Monte Carlo simulation. The PEDEC are computed by using appropriate vulnerability functions combined with the scenario intensity samples, and Monte Carlo simulation. An example of the application of the methodology due to the potential occurrence of extreme Mw 8.5 subduction earthquakes on Mexico City is presented.

Ecohydrological consequences of vegetation interactions within the critical zone in the tropical Andes: multi-scale assessment of vegetation change consequences

NASA Astrophysics Data System (ADS)

Villegas, J. C.; Salazar, J. F.; Arias, P. A.; León, J. D.

2017-12-01

Land cover transformation is currently one of the most important challenges in tropical South America. These transformations occur both because of climate-related ecological perturbations, as well as in response to ongoing socio-economic processes. A fundamental difference between those two drivers is the spatial and temporal scale at which they operate. However, when considered in a larger context, both drivers affect the ability of ecosystems to provide fundamental services to society. In this work, we use a multi-scale approach to identify key-mechanisms through which land cover transformation significantly affects ecological, hydrological and ecoclimatological dynamics, potentially leading to loss of societally-critical regulation services. We propose a suite of examples spanning multiple spatial and temporal scales that illustrate the effects of land cover trnasformations in ecological, hydrological, biogeochemical and climatic functions in tropical South America. These examples highlight important global-change-effects management challenges, as well as the need to consider the feedbacks and interactions between multi-scale processes.

Risks endemic to long-haul trucking in North America: strategies to protect and promote driver well-being.

PubMed

Apostolopoulos, Yorghos; Lemke, Michael; Sönmez, Sevil

2014-01-01

Long-haul truck drivers in North America function in a work context marked by excess physical and psychological workload, erratic schedules, disrupted sleep patterns, extreme time pressures, and these factors' far-reaching consequences. These work-induced stressors are connected with excess risk for cardiometabolic disease, certain cancers, and musculoskeletal and sleep disorders, as well as highway crashes, which in turn exert enormous financial burdens on trucking and warehousing companies, governments and healthcare systems, along with working people within the sector. This article: 1) delineates the unique work environment of long-haul truckers, describing their work characteristics and duties; (2) discusses the health hazards of long-haul trucking that impact drivers, the general population, and trucking enterprises, examining how this work context induces, sustains, and exacerbates these hazards; and (3) proposes comprehensive, multi-level strategies with potential to protect and promote the health, safety, and well-being of truckers, while reducing adverse consequences for companies and highway safety.

A systems engineering approach to AIS accreditation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Harris, L.M.; Hunteman, W.J.

1994-04-01

The systems engineering model provides the vehicle for communication between the developer and the customer by presenting system facts and demonstrating the system in an organized form. The same model provides implementors with views of the system`s function and capability. The authors contend that the process of obtaining accreditation for a classified Automated Information System (AIS) adheres to the typical systems engineering model. The accreditation process is modeled as a ``roadmap`` with the customer represented by the Designed Accrediting Authority. The ``roadmap`` model reduces the amount of accreditation knowledge required of an AIS developer and maximizes the effectiveness of participationmore » in the accreditation process by making the understanding of accreditation a natural consequence of applying the model. This paper identifies ten ``destinations`` on the ``road`` to accreditation. The significance of each ``destination`` is explained, as are the potential consequences of its exclusion. The ``roadmap,`` which has been applied to a range of information systems throughout the DOE community, establishes a paradigm for the certification and accreditation of classified AISs.« less

Physical consequences of the mitochondrial targeting of single-walled carbon nanotubes probed computationally

NASA Astrophysics Data System (ADS)

Chistyakov, V. A.; Zolotukhin, P. V.; Prazdnova, E. V.; Alperovich, I.; Soldatov, A. V.

2015-06-01

Experiments by F. Zhou and coworkers (2010) [16] showed that mitochondria are the main target of the cellular accumulation of single-walled carbon nanotubes (SWCNTs). Our in silico experiments, based on geometrical optimization of the system consisting of SWCNT+proton within Density Functional Theory, revealed that protons can bind to the outer side of SWCNT so generating a positive charge. Calculation results allow one to propose the following mechanism of SWCNTs mitochondrial targeting. SWCNTs enter the space between inner and outer membranes of mitochondria, where the excess of protons has been formed by diffusion. In this compartment SWCNTs are loaded with protons and acquire positive charges distributed over their surface. Protonation of hydrophobic SWCNTs can also be carried out within the mitochondrial membrane through interaction with the protonated ubiquinone. Such "charge loaded" particles can be transferred as "Sculachev ions" through the inner membrane of the mitochondria due to the potential difference generated by the inner membrane. Physiological consequences of the described mechanism are discussed.

Protective Effect of Bendavia (SS-31) Against Oxygen/Glucose-Deprivation Stress-Induced Mitochondrial Damage in Human Brain Microvascular Endothelial Cells.

PubMed

Imai, Takahiko; Mishiro, Keisuke; Takagi, Toshinori; Isono, Aoi; Nagasawa, Hideko; Tsuruma, Kazuhiro; Shimazawa, Masamitsu; Hara, Hideaki

2017-01-01

Mitochondria play a key role in cell survival by perfoming functions such as adenosine tri-phosphate (ATP) synthesis, regulation of apoptotic cell death, calcium storage. Hypoxic conditions induce mitochondrial dysfunction, which leads to endothelial injury in cerebral ischemia. Functional disorders include the following: collapse of mitochondrial membrane potential, reduction of ATP synthesis, and generation of reactive oxygen species (ROS). Bendavia, a novel tetra-peptide, has been reported to restrict the uncoupling of the mitochondrial membrane chain, protect the synthesis of ATP, and inhibit ROS generation. In the present study, we investigated whether bendavia protects mitochondria under hypoxic and starved conditions by using human brain microvascular endothelial cells (HBMVECs). After pre-treatment with bendavia, we exposed HBMVECs to oxygen glucose deprivation (OGD) for 6 h. We then assessed cell viability, the level of caspase-3/7 activity, ROS generation, mitochondrial membrane potential, ATP contents, and the number of mitochondria. Bendavia recovered cell viability and reduced the caspase-3/7 activity induced by OGDinduced damage. Bendavia also recovered mitochondrial functions. These results suggest that bendavia protects mitochondrial function against OGD-induced injury and inhibits apoptosis in HBMVECs. Consequently, our findings indicate that bendavia might become the new therapeutic drug of choice to target mitochondria in case of cerebral ischemia. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Analysis of the functional consequences of targeted exon deletion in COL7A1 reveals prospects for dystrophic epidermolysis bullosa therapy

PubMed Central

Bornert, Olivier; Kühl, Tobias; Bremer, Jeroen; van den Akker, Peter C; Pasmooij, Anna MG; Nyström, Alexander

2016-01-01

Genetically evoked deficiency of collagen VII causes dystrophic epidermolysis bullosa (DEB)—a debilitating disease characterized by chronic skin fragility and progressive fibrosis. Removal of exons carrying frame-disrupting mutations can reinstate protein expression in genetic diseases. The therapeutic potential of this approach is critically dependent on gene, protein, and disease intrinsic factors. Naturally occurring exon skipping in COL7A1, translating collagen VII, suggests that skipping of exons containing disease-causing mutations may be feasible for the treatment of DEB. However, despite a primarily in-frame arrangement of exons in the COL7A1 gene, no general conclusion of the aptitude of exon skipping for DEB can be drawn, since regulation of collagen VII functionality is complex involving folding, intra- and intermolecular interactions. To directly address this, we deleted two conceptually important exons located at both ends of COL7A1, exon 13, containing recurrent mutations, and exon 105, predicted to impact folding. The resulting recombinantly expressed proteins showed conserved functionality in biochemical and in vitro assays. Injected into DEB mice, the proteins promoted skin stability. By demonstrating functionality of internally deleted collagen VII variants, our study provides support of targeted exon deletion or skipping as a potential therapy to treat a large number of individuals with DEB. PMID:27157667

Why personality differences matter for social functioning and social structure.

PubMed

Wolf, Max; Krause, Jens

2014-06-01

We outline three main ways how personality differences can affect social functioning and social structure. By highlighting the broad and significant consequences that personality differences can have for social processes, our article might serve as a starting point for a research focus that aims at a systematic understanding of these consequences. Copyright © 2014. Published by Elsevier Ltd.

Dana-Farber Cancer Institute | Office of Cancer Genomics

Cancer.gov

Functional Annotation of Cancer Genomes Principal Investigator: William C. Hahn, M.D., Ph.D. The comprehensive characterization of cancer genomes has and will continue to provide an increasingly complete catalog of genetic alterations in specific cancers. However, most epithelial cancers harbor hundreds of genetic alterations as a consequence of genomic instability. Therefore, the functional consequences of the majority of mutations remain unclear.

Deconstructing multivariate decoding for the study of brain function.

PubMed

Hebart, Martin N; Baker, Chris I

2017-08-04

Multivariate decoding methods were developed originally as tools to enable accurate predictions in real-world applications. The realization that these methods can also be employed to study brain function has led to their widespread adoption in the neurosciences. However, prior to the rise of multivariate decoding, the study of brain function was firmly embedded in a statistical philosophy grounded on univariate methods of data analysis. In this way, multivariate decoding for brain interpretation grew out of two established frameworks: multivariate decoding for predictions in real-world applications, and classical univariate analysis based on the study and interpretation of brain activation. We argue that this led to two confusions, one reflecting a mixture of multivariate decoding for prediction or interpretation, and the other a mixture of the conceptual and statistical philosophies underlying multivariate decoding and classical univariate analysis. Here we attempt to systematically disambiguate multivariate decoding for the study of brain function from the frameworks it grew out of. After elaborating these confusions and their consequences, we describe six, often unappreciated, differences between classical univariate analysis and multivariate decoding. We then focus on how the common interpretation of what is signal and noise changes in multivariate decoding. Finally, we use four examples to illustrate where these confusions may impact the interpretation of neuroimaging data. We conclude with a discussion of potential strategies to help resolve these confusions in interpreting multivariate decoding results, including the potential departure from multivariate decoding methods for the study of brain function. Copyright © 2017. Published by Elsevier Inc.

CLHM-1 is a functionally conserved and conditionally toxic Ca2+-permeable ion channel in Caenorhabditis elegans.

PubMed

Tanis, Jessica E; Ma, Zhongming; Krajacic, Predrag; He, Liping; Foskett, J Kevin; Lamitina, Todd

2013-07-24

Disruption of neuronal Ca(2+) homeostasis contributes to neurodegenerative diseases through mechanisms that are not fully understood. A polymorphism in CALHM1, a recently described ion channel that regulates intracellular Ca(2+) levels, is a possible risk factor for late-onset Alzheimer's disease. Since there are six potentially redundant CALHM family members in humans, the physiological and pathophysiological consequences of CALHM1 function in vivo remain unclear. The nematode Caenorhabditis elegans expresses a single CALHM1 homolog, CLHM-1. Here we find that CLHM-1 is expressed at the plasma membrane of sensory neurons and muscles. Like human CALHM1, C. elegans CLHM-1 is a Ca(2+)-permeable ion channel regulated by voltage and extracellular Ca(2+). Loss of clhm-1 in the body-wall muscles disrupts locomotory kinematics and biomechanics, demonstrating that CLHM-1 has a physiologically significant role in vivo. The motility defects observed in clhm-1 mutant animals can be rescued by muscle-specific expression of either C. elegans CLHM-1 or human CALHM1, suggesting that the function of these proteins is conserved in vivo. Overexpression of either C. elegans CLHM-1 or human CALHM1 in neurons is toxic, causing degeneration through a necrotic-like mechanism that is partially Ca(2+) dependent. Our data show that CLHM-1 is a functionally conserved ion channel that plays an important but potentially toxic role in excitable cell function.

Overcoming Potential Negative Consequences of Customer Orientation in Higher Education: Closing the Ideological Gap

ERIC Educational Resources Information Center

Nguyen, Adam; Rosetti, Joseph

2013-01-01

Substantial discussion has been going on surrounding the potential negative consequences of a customer orientation in college education. A major concern stems from the ideological gap--the perceived differentiation between what the students want and the educators' view of what is in the best interests of the students. A key aspect of the…

Perspectives on Adolescent Alcohol Use and Consideration of Future Consequences: Results from a Qualitative Study

ERIC Educational Resources Information Center

Harvey, Séamus A.; McKay, Michael T.

2017-01-01

Consideration of future consequences (CFC) is described as the attention that individuals pay to the potential outcomes of their behaviour, and how their behaviour is affected as a result of attention to these outcomes. Greater CFC has been associated with less alcohol use, thus indicating its potential utility in health-promotion initiatives. A…

["Handle with care": about the potential unintended consequences of oracular artificial intelligence systems in medicine.

PubMed

Cabitza, Federico; Alderighi, Camilla; Rasoini, Raffaele; Gensini, Gian Franco

2017-10-01

Decisional support systems based on machine learning (ML) in medicine are gaining a growing interest as some recent articles have highlighted the high diagnostic accuracy exhibited by these systems in specific medical contexts. However, it is implausible that any potential advantage can be obtained without some potential drawbacks. In light of the current gaps in medical research about the side effects of the application of these new AI systems in medical practice, in this article we summarize the main unexpected consequences that may result from the widespread application of "oracular" systems, that is highly accurate systems that cannot give reasonable explanations of their advice as those endowed with predictive models developed with ML techniques usually are. These consequences range from the intrinsic uncertainty in the data that are used to train and feed these systems, to the inadequate explainability of their output; through the risk of overreliance, deskilling and context desensitization of their end-users. Although some of these issues may be currently hard to evaluate due to the still scarce adoption of these decisional systems in medical practice, we advocate the study of these potential consequences also for a more informed policy of approval beyond hype and disenchantment.

The relation between the Gross Pitaevskii and Bogoliubov descriptions of a dilute Bose gas

NASA Astrophysics Data System (ADS)

Leggett, A. J.

2003-07-01

I formulate a 'pseudo-paradox' in the theory of a dilute Bose gas with repulsive interactions: the standard expression for the ground state energy within the Gross-Pitaevskii (GP) approximation is lower than that in the Bogoliubov approximation, and hence, by the standard variational argument, the former should prima facie be a better approximation than the latter to the true ground state—a conclusion which is of course opposite to the established wisdom concerning this problem. It is shown that the pseudo-paradox is (unsurprisingly) resolved by a correct transcription of the two-body scattering theory to the many-body case; however, contrary to what appears to be a widespread belief, the resolution has nothing to do with any spurious ultraviolet divergences which result from the replacement of the true interatomic potential by a delta-function pseudopotential. Rather, it relates to an infrared divergence which has the consequence that (a) the most obvious form of the GP 'approximation' actually does not correspond to any well-defined ansatz for the many-body wavefunction, and (b) that the 'best shot' at such a wavefunction always produces an energy which exceeds, or at best equals, that calculated in the Bogoliubov approximation. In fact, the necessity of the latter may be seen as a consequence of the need to reduce the Fock term in the energy, which is absent in the two-particle problem but dominant in the many-body case; it does this by increasing the density correlations, at distances less than or approximately equal to the correlation length \\xi , above the value extrapolated from the two-body case. As a by-product I devise an alternative formulation of the Bogoliubov approximation which does not require the explicit replacement of the true interatomic potential by a delta-function pseudopotential.

Brain structural connectivity increases concurrent with functional improvement: evidence from diffusion tensor MRI in children with cerebral palsy during therapy.

PubMed

Englander, Zoë A; Sun, Jessica; Laura Case; Mikati, Mohamad A; Kurtzberg, Joanne; Song, Allen W

2015-01-01

Cerebral Palsy (CP) refers to a heterogeneous group of permanent but non-progressive movement disorders caused by injury to the developing fetal or infant brain (Bax et al., 2005). Because of its serious long-term consequences, effective interventions that can help improve motor function, independence, and quality of life are critically needed. Our ongoing longitudinal clinical trial to treat children with CP is specifically designed to meet this challenge. To maximize the potential for functional improvement, all children in this trial received autologous cord blood transfusions (with order randomized with a placebo administration over 2 years) in conjunction with more standard physical and occupational therapies. As a part of this trial, magnetic resonance imaging (MRI) is used to improve our understanding of how these interventions affect brain development, and to develop biomarkers of treatment efficacy. In this report, diffusion tensor imaging (DTI) and subsequent brain connectome analyses were performed in a subset of children enrolled in the clinical trial (n = 17), who all exhibited positive but varying degrees of functional improvement over the first 2-year period of the study. Strong correlations between increases in white matter (WM) connectivity and functional improvement were demonstrated; however no significant relationships between either of these factors with the age of the child at time of enrollment were identified. Thus, our data indicate that increases in brain connectivity reflect improved functional abilities in children with CP. In future work, this potential biomarker can be used to help differentiate the underlying mechanisms of functional improvement, as well as to identify treatments that can best facilitate functional improvement upon un-blinding of the timing of autologous cord blood transfusions at the completion of this study.

ROLE OF THE RENAL MICROCIRCULATION IN PROGRESSION OF CHRONIC KIDNEY INJURY IN OBESITY

PubMed Central

Chade, Alejandro R.; Hall, John E.

2016-01-01

Background Obesity is largely responsible for the growing incidence and prevalence of diabetes, cardiovascular, and renal disease. Current strategies to prevent and treat obesity and its consequences have been insufficient to reverse the ongoing trends. Lifestyle modification or pharmacological therapies often produce modest weight loss which is not sustained and recurrence of obesity is frequently observed, leading to progression of target organ damage in many obese subjects. Therefore, research efforts have focused not only on the factors that regulate energy balance, but also on understanding mechanisms of target organ injury in obesity. Summary and Key message Microvascular disease plays a pivotal role in progressive kidney injury from different etiologies such as hypertension, diabetes, and atherosclerosis, which are all important consequences of chronic obesity. The microvascular networks are anatomical units that are closely adapted to specific functions of nutrition and removal of waste in every organ. Damage of the small vessels in several tissues and organs has been reported in obesity and may increase cardio-renal risk. However, the mechanisms by which obesity and its attendant cardiovascular and metabolic consequences interact to cause renal microvascular injury and chronic kidney disease are still unclear, although substantial progress has been made in recent years. This review addresses potential mechanisms and consequences of obesity-induced renal microvascular injury as well as current treatments that may provide protection of the renal microcirculation and slow progressive kidney injury in obesity. PMID:27771702

Functions of TET Proteins in Hematopoietic Transformation.

PubMed

Han, Jae-A; An, Jungeun; Ko, Myunggon

2015-11-01

DNA methylation is a well-characterized epigenetic modification that plays central roles in mammalian development, genomic imprinting, X-chromosome inactivation and silencing of retrotransposon elements. Aberrant DNA methylation pattern is a characteristic feature of cancers and associated with abnormal expression of oncogenes, tumor suppressor genes or repair genes. Ten-eleven-translocation (TET) proteins are recently characterized dioxygenases that catalyze progressive oxidation of 5-methylcytosine to produce 5-hydroxymethylcytosine and further oxidized derivatives. These oxidized methylcytosines not only potentiate DNA demethylation but also behave as independent epigenetic modifications per se. The expression or activity of TET proteins and DNA hydroxymethylation are highly dysregulated in a wide range of cancers including hematologic and non-hematologic malignancies, and accumulating evidence points TET proteins as a novel tumor suppressor in cancers. Here we review DNA demethylation-dependent and -independent functions of TET proteins. We also describe diverse TET loss-of-function mutations that are recurrently found in myeloid and lymphoid malignancies and their potential roles in hematopoietic transformation. We discuss consequences of the deficiency of individual Tet genes and potential compensation between different Tet members in mice. Possible mechanisms underlying facilitated oncogenic transformation of TET-deficient hematopoietic cells are also described. Lastly, we address non-mutational mechanisms that lead to suppression or inactivation of TET proteins in cancers. Strategies to restore normal 5mC oxidation status in cancers by targeting TET proteins may provide new avenues to expedite the development of promising anti-cancer agents.

[Review: executive functioning and cannabis use].

PubMed

Almeida, Priscila Previato; Novaes, Maria Alice Fontes Pinto; Bressan, Rodrigo Affonseca; Lacerda, Acioly Luiz Tavares de

2008-03-01

Cannabis is the most used illicit drug worldwide, however only a few studies have examined cognitive deficits related to its use. Clinical manifestations associated with those deficits include a motivational syndrome, impairment in cognitive flexibility, inattention, deficits in abstract reasoning and concept formation, aspects intimately related to the executive functions, which potentially exert a central role in substance dependence. The objective was to make a review about consequences of cannabis use in executive functioning. This review was carried out on reports drawn from MedLine, SciELO, and Lilacs. In studies investigating acute use effects, higher doses of tetrahydrocannabinol are associated to impairments in performance of nonsevere users in planning and control impulse tasks. However, chronic cannabis users do not show those impairments. Although demonstration of residual effects of cannabis in the executive functioning is controversial, persistent deficits seem to be present at least in a subgroup of chronic users after 28 days of abstinence. The neuropsychological studies found did not have as a main aim the evaluation of executive functioning. A criterial selection of standardized neuropsychological tests, more appropriate study designs as well as concomitant investigations with structural and functional neuroimaging techniques may improve the understanding of eventual neurotoxicity associated with cannabis use.

Listening to music and physiological and psychological functioning: the mediating role of emotion regulation and stress reactivity.

PubMed

Thoma, M V; Scholz, U; Ehlert, U; Nater, U M

2012-01-01

Music listening has been suggested to have short-term beneficial effects. The aim of this study was to investigate the association and potential mediating mechanisms between various aspects of habitual music-listening behaviour and physiological and psychological functioning. An internet-based survey was conducted in university students, measuring habitual music-listening behaviour, emotion regulation, stress reactivity, as well as physiological and psychological functioning. A total of 1230 individuals (mean = 24.89 ± 5.34 years, 55.3% women) completed the questionnaire. Quantitative aspects of habitual music-listening behaviour, i.e. average duration of music listening and subjective relevance of music, were not associated with physiological and psychological functioning. In contrast, qualitative aspects, i.e. reasons for listening (especially 'reducing loneliness and aggression', and 'arousing or intensifying specific emotions') were significantly related to physiological and psychological functioning (all p = 0.001). These direct effects were mediated by distress-augmenting emotion regulation and individual stress reactivity. The habitual music-listening behaviour appears to be a multifaceted behaviour that is further influenced by dispositions that are usually not related to music listening. Consequently, habitual music-listening behaviour is not obviously linked to physiological and psychological functioning.

Long-time behavior of the momentum distribution during the sudden expansion of a spin-imbalanced Fermi gas in one dimension.

PubMed

Bolech, C J; Heidrich-Meisner, F; Langer, S; McCulloch, I P; Orso, G; Rigol, M

2012-09-14

We study the sudden expansion of spin-imbalanced ultracold lattice fermions with attractive interactions in one dimension after turning off the longitudinal confining potential. We show that the momentum distribution functions of majority and minority fermions quickly approach stationary values due to a quantum distillation mechanism that results in a spatial separation of pairs and majority fermions. As a consequence, Fulde-Ferrell-Larkin-Ovchinnikov (FFLO) correlations are lost during the expansion. Furthermore, we argue that the shape of the stationary momentum distribution functions can be understood by relating them to the integrals of motion in this integrable quantum system. We discuss our results in the context of proposals to observe FFLO correlations, related to recent experiments by Liao et al., Nature (London) 467, 567 (2010).

Does the IMF vary with galaxy mass? The X-ray binary population of a key galaxy, NGC7457

NASA Astrophysics Data System (ADS)

Peacock, Mark

2014-09-01

We propose a 100ksec observation of NGC7457. The primary goal of this observation is to test for variations in the initial mass function (IMF). Many recent studies have proposed that the IMF varies systematically as a function of early-type galaxy mass. This has potentially dramatic consequences and must to be confirmed. The number of LMXBs in a galaxy (per stellar luminosity) can be used to provide an independent test of this hypothesis (see Peacock et al. 2014). Unfortunately, only galaxies with intermediate to high masses currently have the data needed to perform this test. The proposed observation of the elliptical galaxy NGC7457 will detect an order of magnitude more LMXBs in a low mass galaxy - hence providing the crucial constraint needed to significantly test for a variable IMF.

Evolutionary rewiring of bacterial regulatory networks

PubMed Central

Taylor, Tiffany B.; Mulley, Geraldine; McGuffin, Liam J.; Johnson, Louise J.; Brockhurst, Michael A.; Arseneault, Tanya; Silby, Mark W.; Jackson, Robert W.

2015-01-01

Bacteria have evolved complex regulatory networks that enable integration of multiple intracellular and extracellular signals to coordinate responses to environmental changes. However, our knowledge of how regulatory systems function and evolve is still relatively limited. There is often extensive homology between components of different networks, due to past cycles of gene duplication, divergence, and horizontal gene transfer, raising the possibility of cross-talk or redundancy. Consequently, evolutionary resilience is built into gene networks - homology between regulators can potentially allow rapid rescue of lost regulatory function across distant regions of the genome. In our recent study [Taylor, et al. Science (2015), 347(6225)] we find that mutations that facilitate cross-talk between pathways can contribute to gene network evolution, but that such mutations come with severe pleiotropic costs. Arising from this work are a number of questions surrounding how this phenomenon occurs. PMID:28357301

SpliceSeq: a resource for analysis and visualization of RNA-Seq data on alternative splicing and its functional impacts

PubMed Central

Ryan, Michael C.; Cleland, James; Kim, RyangGuk; Wong, Wing Chung; Weinstein, John N.

2012-01-01

Summary: SpliceSeq is a resource for RNA-Seq data that provides a clear view of alternative splicing and identifies potential functional changes that result from splice variation. It displays intuitive visualizations and prioritized lists of results that highlight splicing events and their biological consequences. SpliceSeq unambiguously aligns reads to gene splice graphs, facilitating accurate analysis of large, complex transcript variants that cannot be adequately represented in other formats. Availability and implementation: SpliceSeq is freely available at http://bioinformatics.mdanderson.org/main/SpliceSeq:Overview. The application is a Java program that can be launched via a browser or installed locally. Local installation requires MySQL and Bowtie. Contact: mryan@insilico.us.com Supplementary Information: Supplementary data are available at Bioinformatics online. PMID:22820202

Tai Chi Chuan: an ancient wisdom on exercise and health promotion.

PubMed

Lan, Ching; Lai, Jin-Shin; Chen, Ssu-Yuan

2002-01-01

Tai Chi Chuan (TCC) is a Chinese conditioning exercise and is well known for its slow and graceful movements. Recent investigations have found that TCC is beneficial to cardiorespiratory function, strength, balance, flexibility, microcirculation and psychological profile. The long-term practice of TCC can attenuate the age decline in physical function, and consequently it is a suitable exercise for the middle-aged and elderly individuals. TCC can be prescribed as an alternative exercise programme for selected patients with cardiovascular, orthopaedic, or neurological diseases, and can reduce the risk of falls in elderly individuals. The exercise intensity of TCC depends on training style, posture and duration. Participants can choose to perform a complete set of TCC or selected movements according to their needs. In conclusion, TCC has potential benefits in health promotion, and is appropriate for implementation in the community.

Using social media to facilitate knowledge transfer in complex engineering environments: a primer for educators

NASA Astrophysics Data System (ADS)

Murphy, Glen; Salomone, Sonia

2013-03-01

While highly cohesive groups are potentially advantageous they are also often correlated with the emergence of knowledge and information silos based around those same functional or occupational clusters. Consequently, an essential challenge for engineering organisations wishing to overcome informational silos is to implement mechanisms that facilitate, encourage and sustain interactions between otherwise disconnected groups. This paper acts as a primer for those seeking to gain an understanding of the design, functionality and utility of a suite of software tools generically termed social media technologies in the context of optimising the management of tacit engineering knowledge. Underpinned by knowledge management theory and using detailed case examples, this paper explores how social media technologies achieve such goals, allowing for the transfer of knowledge by tapping into the tacit and explicit knowledge of disparate groups in complex engineering environments.

Glial response to polyglutamine-mediated stress

PubMed Central

Vig, Parminder J.S.; Shao, Qingmei; Lopez, Maripar E

2009-01-01

Neurodegenerative trinucleotide (CAG) repeat disorders are caused by the expansion of polyglutamine tracts within the disease proteins. Some of these proteins have an unknown function. How does expanded polyglutamine cause target neurons to degenerate, is not clear. Recent evidence suggests that intercellular miscommunication may contribute to polyglutamine pathogenesis in CAG repeat disorders. Polyglutamine induced degeneration of the target neuron can be mediated via glia-neuron interactions. Here we hypothesize during neurodegenerative process the failure of cell: cell interactions have more severe consequences than alterations in intracellular neuron biology. We further believe that bidirectional communication between neurons and glia are prerequisite for the normal development and function of either cell-type. Understanding intercellular signaling mechanisms such as glial trophic factors and their receptors, cell adhesion or other well-defined signaling molecules provide opportunities for developing potential therapies. PMID:20046986

Selenoprotein K form an intermolecular diselenide bond with unusually high redox potential

PubMed Central

Liu, Jun; Zhang, Zhengqi; Rozovsky, Sharon

2014-01-01

Selenoprotein K (SelK) is a membrane protein involved in antioxidant defense, calcium regulation and the ER-associated protein degradation pathway. We found that SelK exhibits a peroxidase activity with a rate that is low but within the range of other peroxidases. Notably, SelK reduced hydrophobic substrates, such as phospholipid hydroperoxides, which damage membranes. Thus, SelK might be involved in membrane repair or related pathways. SelK was also found to contain a diselenide bond — the first intramolecular bond of that kind reported for a selenoprotein. The redox potential of SelK was −257 mV, significantly higher than that of diselenide bonds in small molecules or proteins. Consequently, SelK can be reduced by thioredoxin reductase. These finding are essential for understanding SelK activity and function. PMID:25117454

Combining network analysis with Cognitive Work Analysis: insights into social organisational and cooperation analysis.

PubMed

Houghton, Robert J; Baber, Chris; Stanton, Neville A; Jenkins, Daniel P; Revell, Kirsten

2015-01-01

Cognitive Work Analysis (CWA) allows complex, sociotechnical systems to be explored in terms of their potential configurations. However, CWA does not explicitly analyse the manner in which person-to-person communication is performed in these configurations. Consequently, the combination of CWA with Social Network Analysis provides a means by which CWA output can be analysed to consider communication structure. The approach is illustrated through a case study of a military planning team. The case study shows how actor-to-actor and actor-to-function mapping can be analysed, in terms of centrality, to produce metrics of system structure under different operating conditions. In this paper, a technique for building social network diagrams from CWA is demonstrated.The approach allows analysts to appreciate the potential impact of organisational structure on a command system.

Stress reactivity speeds basic encoding processes in infants.

PubMed

de Barbaro, Kaya; Clackson, Kaili; Wass, Sam

2016-07-01

Acute stress attenuates frontal lobe functioning and increases distractibility while enhancing subcortical processes in both human and nonhuman animals (reviewed by Arnsten [2009] Nature Reviews Neuroscience, 10(6):410-422). To date however these relations have not been examined for their potential effects in developing populations. Here, we examined the relationship between stress reactivity (infants' heart rate response to watching videos of another child crying) and infant performance on measures of looking duration and visual recognition memory. Our findings indicate that infants with increased stress reactivity showed shorter look durations and more novelty preference. Thus, stress appears to lead to a faster, more stimulus-ready attentional profile in infants. Additional work is required to assess potential negative consequences of stimulus-responsivity, such as decreased focus or distractibility. © 2016 Wiley Periodicals, Inc. Dev Psychobiol 58: 546-555, 2016. © 2016 Wiley Periodicals, Inc.

On the Definition of Surface Potentials for Finite-Difference Operators

NASA Technical Reports Server (NTRS)

Tsynkov, S. V.; Bushnell, Dennis M. (Technical Monitor)

2001-01-01

For a class of linear constant-coefficient finite-difference operators of the second order, we introduce the concepts similar to those of conventional single- and double-layer potentials for differential operators. The discrete potentials are defined completely independently of any notion related to the approximation of the continuous potentials on the grid. We rather use all approach based on differentiating, and then inverting the differentiation of a function with surface discontinuity of a particular kind, which is the most general way of introducing surface potentials in the theory of distributions. The resulting finite-difference "surface" potentials appear to be solutions of the corresponding continuous potentials. Primarily, this pertains to the possibility of representing a given solution to the homogeneous equation on the domain as a variety of surface potentials, with the density defined on the domain's boundary. At the same time the discrete surface potentials can be interpreted as one specific realization of the generalized potentials of Calderon's type, and consequently, their approximation properties can be studied independently in the framework of the difference potentials method by Ryaben'kii. The motivation for introducing and analyzing the discrete surface potentials was provided by the problems of active shielding and control of sound, in which the aforementioned source terms that drive the potentials are interpreted as the acoustic control sources that cancel out the unwanted noise on a predetermined region of interest.

Reduced dopamine function within the medial shell of the nucleus accumbens enhances latent inhibition.

PubMed

Nelson, A J D; Thur, K E; Horsley, R R; Spicer, C; Marsden, C A; Cassaday, H J

2011-03-01

Latent inhibition (LI) manifests as poorer conditioning to a CS that has previously been presented without consequence. There is some evidence that LI can be potentiated by reduced mesoaccumbal dopamine (DA) function but the locus within the nucleus accumbens of this effect is as yet not firmly established. Experiment 1 tested whether 6-hydroxydopamine (6-OHDA)-induced lesions of DA terminals within the core and medial shell subregions of the nucleus accumbens (NAc) would enhance LI under conditions that normally disrupt LI in controls (weak pre-exposure). LI was measured in a thirst motivated conditioned emotional response procedure with 10 pre-exposures (to a noise CS) and 2 conditioning trials. The vehicle-injected and core-lesioned animals did not show LI and conditioned to the pre-exposed CS at comparable levels to the non-pre-exposed controls. 6-OHDA lesions to the medial shell, however, produced potentiation of LI, demonstrated across two extinction tests. In a subsequent experiment, haloperidol microinjected into the medial shell prior to conditioning similarly enhanced LI. These results underscore the dissociable roles of core and shell subregions of the NAc in mediating the expression of LI and indicate that reduced DA function within the medial shell leads to enhanced LI. Copyright © 2010 Elsevier Inc. All rights reserved.

Systemic evaluation of cellular reprogramming processes exploiting a novel R-tool: eegc.

PubMed

Zhou, Xiaoyuan; Meng, Guofeng; Nardini, Christine; Mei, Hongkang

2017-08-15

Cells derived by cellular engineering, i.e. differentiation of induced pluripotent stem cells and direct lineage reprogramming, carry a tremendous potential for medical applications and in particular for regenerative therapies. These approaches consist in the definition of lineage-specific experimental protocols that, by manipulation of a limited number of biological cues-niche mimicking factors, (in)activation of transcription factors, to name a few-enforce the final expression of cell-specific (marker) molecules. To date, given the intricate complexity of biological pathways, these approaches still present imperfect reprogramming fidelity, with uncertain consequences on the functional properties of the resulting cells. We propose a novel tool eegc to evaluate cellular engineering processes, in a systemic rather than marker-based fashion, by integrating transcriptome profiling and functional analysis. Our method clusters genes into categories representing different states of (trans)differentiation and further performs functional and gene regulatory network analyses for each of the categories of the engineered cells, thus offering practical indications on the potential lack of the reprogramming protocol. eegc R package is released under the GNU General Public License within the Bioconductor project, freely available at https://bioconductor.org/packages/eegc/. christine.nardini.rsrc@gmail.com or hongkang.k.mei@gsk.com. Supplementary data are available at Bioinformatics online. © The Author(s) 2017. Published by Oxford University Press.

Systemic evaluation of cellular reprogramming processes exploiting a novel R-tool: eegc

PubMed Central

Zhou, Xiaoyuan; Meng, Guofeng; Nardini, Christine; Mei, Hongkang

2017-01-01

Abstract Motivation Cells derived by cellular engineering, i.e. differentiation of induced pluripotent stem cells and direct lineage reprogramming, carry a tremendous potential for medical applications and in particular for regenerative therapies. These approaches consist in the definition of lineage-specific experimental protocols that, by manipulation of a limited number of biological cues—niche mimicking factors, (in)activation of transcription factors, to name a few—enforce the final expression of cell-specific (marker) molecules. To date, given the intricate complexity of biological pathways, these approaches still present imperfect reprogramming fidelity, with uncertain consequences on the functional properties of the resulting cells. Results We propose a novel tool eegc to evaluate cellular engineering processes, in a systemic rather than marker-based fashion, by integrating transcriptome profiling and functional analysis. Our method clusters genes into categories representing different states of (trans)differentiation and further performs functional and gene regulatory network analyses for each of the categories of the engineered cells, thus offering practical indications on the potential lack of the reprogramming protocol. Availability and Implementation eegc R package is released under the GNU General Public License within the Bioconductor project, freely available at https://bioconductor.org/packages/eegc/. Contact christine.nardini.rsrc@gmail.com or hongkang.k.mei@gsk.com Supplementary information Supplementary data are available at Bioinformatics online. PMID:28398503

Branched-chain amino acids alter neurobehavioral function in rats

PubMed Central

Coppola, Anna; Wenner, Brett R.; Ilkayeva, Olga; Stevens, Robert D.; Maggioni, Mauro; Slotkin, Theodore A.; Levin, Edward D.

2013-01-01

Recently, we have described a strong association of branched-chain amino acids (BCAA) and aromatic amino acids (AAA) with obesity and insulin resistance. In the current study, we have investigated the potential impact of BCAA on behavioral functions. We demonstrate that supplementation of either a high-sucrose or a high-fat diet with BCAA induces anxiety-like behavior in rats compared with control groups fed on unsupplemented diets. These behavioral changes are associated with a significant decrease in the concentration of tryptophan (Trp) in brain tissues and a consequent decrease in serotonin but no difference in indices of serotonin synaptic function. The anxiety-like behaviors and decreased levels of Trp in the brain of BCAA-fed rats were reversed by supplementation of Trp in the drinking water but not by administration of fluoxetine, a selective serotonin reuptake inhibitor, suggesting that the behavioral changes are independent of the serotonergic pathway of Trp metabolism. Instead, BCAA supplementation lowers the brain levels of another Trp-derived metabolite, kynurenic acid, and these levels are normalized by Trp supplementation. We conclude that supplementation of high-energy diets with BCAA causes neurobehavioral impairment. Since BCAA are elevated spontaneously in human obesity, our studies suggest a potential mechanism for explaining the strong association of obesity and mood disorders. PMID:23249694

Cardiac and renal function in patients with type 2 diabetes who have chronic kidney disease: potential effects of bardoxolone methyl.

PubMed

McCullough, Peter A; Ali, Sajid

2012-01-01

The intracellular and tissue balance of oxidant and antioxidant forces is a potential therapeutic target for a variety of agents in the treatment of complications due to chronic disease including diabetes mellitus and hypertension. There are a myriad of processes controlled at the level of genes, transcription factors, and protein messages that work to control the normal use of oxidative reactions within cells. Loss of control of these processes may lead to reversible dysfunction in many cell lines including the podocyte, renal tubular cells, and cardiac myocytes. Bardoxolone methyl is a novel nuclear regulator factor (Nrf-2) activator which works to tip the balance of effects towards antioxidation and as an observation made serendipitously, improves renal filtration function in humans after approximately 12 weeks of therapy. The improvement in estimated glomerular filtration can be up to 30% in those with stage 3 and 4 chronic kidney disease. However, experimental evidence suggests there may be a consequence of relative hyperfiltration in diseased kidneys as well as potential adverse effects on skeletal and cardiac myocytes. Only large, prospective randomized trials with carefully collected and adjudicated clinical outcomes will inform the research community on the therapeutic risks and benefits of this important new agent.

Cardiac and renal function in patients with type 2 diabetes who have chronic kidney disease: potential effects of bardoxolone methyl

PubMed Central

McCullough, Peter A; Ali, Sajid

2012-01-01

The intracellular and tissue balance of oxidant and antioxidant forces is a potential therapeutic target for a variety of agents in the treatment of complications due to chronic disease including diabetes mellitus and hypertension. There are a myriad of processes controlled at the level of genes, transcription factors, and protein messages that work to control the normal use of oxidative reactions within cells. Loss of control of these processes may lead to reversible dysfunction in many cell lines including the podocyte, renal tubular cells, and cardiac myocytes. Bardoxolone methyl is a novel nuclear regulator factor (Nrf-2) activator which works to tip the balance of effects towards antioxidation and as an observation made serendipitously, improves renal filtration function in humans after approximately 12 weeks of therapy. The improvement in estimated glomerular filtration can be up to 30% in those with stage 3 and 4 chronic kidney disease. However, experimental evidence suggests there may be a consequence of relative hyperfiltration in diseased kidneys as well as potential adverse effects on skeletal and cardiac myocytes. Only large, prospective randomized trials with carefully collected and adjudicated clinical outcomes will inform the research community on the therapeutic risks and benefits of this important new agent. PMID:22787387

Social Cognition Dysfunctions in Neurodegenerative Diseases: Neuroanatomical Correlates and Clinical Implications.

PubMed

Christidi, Foteini; Migliaccio, Raffaella; Santamaría-García, Hernando; Santangelo, Gabriella; Trojsi, Francesca

2018-01-01

Social cognitive function, involved in the perception, processing, and interpretation of social information, has been shown to be crucial for successful communication and interpersonal relationships, thereby significantly impacting mental health, well-being, and quality of life. In this regard, assessment of social cognition, mainly focusing on four key domains, such as theory of mind (ToM), emotional empathy, and social perception and behavior, has been increasingly evaluated in clinical settings, given the potential implications of impairments of these skills for therapeutic decision-making. With regard to neurodegenerative diseases (NDs), most disorders, characterized by variable disease phenotypes and progression, although similar for the unfavorable prognosis, are associated to impairments of social cognitive function, with consequent negative effects on patients' management. Specifically, in some NDs these deficits may represent core diagnostic criteria, such as for behavioral variant frontotemporal dementia (bvFTD), or may emerge during the disease course as critical aspects, such as for Parkinson's and Alzheimer's diseases. On this background, we aimed to revise the most updated evidence on the neurobiological hypotheses derived from network-based approaches, clinical manifestations, and assessment tools of social cognitive dysfunctions in NDs, also prospecting potential benefits on patients' well-being, quality of life, and outcome derived from potential therapeutic perspectives of these deficits.

The potential for dams to impact lowland meandering river floodplain geomorphology.

PubMed

Marren, Philip M; Grove, James R; Webb, J Angus; Stewardson, Michael J

2014-01-01

The majority of the world's floodplains are dammed. Although some implications of dams for riverine ecology and for river channel morphology are well understood, there is less research on the impacts of dams on floodplain geomorphology. We review studies from dammed and undammed rivers and include influences on vertical and lateral accretion, meander migration and cutoff formation, avulsion, and interactions with floodplain vegetation. The results are synthesized into a conceptual model of the effects of dams on the major geomorphic influences on floodplain development. This model is used to assess the likely consequences of eight dam and flow regulation scenarios for floodplain geomorphology. Sediment starvation downstream of dams has perhaps the greatest potential to impact on floodplain development. Such effects will persist further downstream where tributary sediment inputs are relatively low and there is minimal buffering by alluvial sediment stores. We can identify several ways in which floodplains might potentially be affected by dams, with varying degrees of confidence, including a distinction between passive impacts (floodplain disconnection) and active impacts (changes in geomorphological processes and functioning). These active processes are likely to have more serious implications for floodplain function and emphasize both the need for future research and the need for an "environmental sediment regime" to operate alongside environmental flows.

The Potential for Dams to Impact Lowland Meandering River Floodplain Geomorphology

PubMed Central

Marren, Philip M.; Grove, James R.; Webb, J. Angus; Stewardson, Michael J.

2014-01-01

The majority of the world's floodplains are dammed. Although some implications of dams for riverine ecology and for river channel morphology are well understood, there is less research on the impacts of dams on floodplain geomorphology. We review studies from dammed and undammed rivers and include influences on vertical and lateral accretion, meander migration and cutoff formation, avulsion, and interactions with floodplain vegetation. The results are synthesized into a conceptual model of the effects of dams on the major geomorphic influences on floodplain development. This model is used to assess the likely consequences of eight dam and flow regulation scenarios for floodplain geomorphology. Sediment starvation downstream of dams has perhaps the greatest potential to impact on floodplain development. Such effects will persist further downstream where tributary sediment inputs are relatively low and there is minimal buffering by alluvial sediment stores. We can identify several ways in which floodplains might potentially be affected by dams, with varying degrees of confidence, including a distinction between passive impacts (floodplain disconnection) and active impacts (changes in geomorphological processes and functioning). These active processes are likely to have more serious implications for floodplain function and emphasize both the need for future research and the need for an “environmental sediment regime” to operate alongside environmental flows. PMID:24587718

Point defect reduction in MOCVD (Al)GaN by chemical potential control and a comprehensive model of C incorporation in GaN

NASA Astrophysics Data System (ADS)

Reddy, Pramod; Washiyama, Shun; Kaess, Felix; Kirste, Ronny; Mita, Seiji; Collazo, Ramon; Sitar, Zlatko

2017-12-01

A theoretical framework that provides a quantitative relationship between point defect formation energies and growth process parameters is presented. It enables systematic point defect reduction by chemical potential control in metalorganic chemical vapor deposition (MOCVD) of III-nitrides. Experimental corroboration is provided by a case study of C incorporation in GaN. The theoretical model is shown to be successful in providing quantitative predictions of CN defect incorporation in GaN as a function of growth parameters and provides valuable insights into boundary phases and other impurity chemical reactions. The metal supersaturation is found to be the primary factor in determining the chemical potential of III/N and consequently incorporation or formation of point defects which involves exchange of III or N atoms with the reservoir. The framework is general and may be extended to other defect systems in (Al)GaN. The utility of equilibrium formalism typically employed in density functional theory in predicting defect incorporation in non-equilibrium and high temperature MOCVD growth is confirmed. Furthermore, the proposed theoretical framework may be used to determine optimal growth conditions to achieve minimum compensation within any given constraints such as growth rate, crystal quality, and other practical system limitations.

Elucidation of the Ebola virus VP24 cellular interactome and disruption of virus biology through targeted inhibition of host-cell protein function.

PubMed

García-Dorival, Isabel; Wu, Weining; Dowall, Stuart; Armstrong, Stuart; Touzelet, Olivier; Wastling, Jonathan; Barr, John N; Matthews, David; Carroll, Miles; Hewson, Roger; Hiscox, Julian A

2014-11-07

Viral pathogenesis in the infected cell is a balance between antiviral responses and subversion of host-cell processes. Many viral proteins specifically interact with host-cell proteins to promote virus biology. Understanding these interactions can lead to knowledge gains about infection and provide potential targets for antiviral therapy. One such virus is Ebola, which has profound consequences for human health and causes viral hemorrhagic fever where case fatality rates can approach 90%. The Ebola virus VP24 protein plays a critical role in the evasion of the host immune response and is likely to interact with multiple cellular proteins. To map these interactions and better understand the potential functions of VP24, label-free quantitative proteomics was used to identify cellular proteins that had a high probability of forming the VP24 cellular interactome. Several known interactions were confirmed, thus placing confidence in the technique, but new interactions were also discovered including one with ATP1A1, which is involved in osmoregulation and cell signaling. Disrupting the activity of ATP1A1 in Ebola-virus-infected cells with a small molecule inhibitor resulted in a decrease in progeny virus, thus illustrating how quantitative proteomics can be used to identify potential therapeutic targets.

Protein kinase and phosphatase modulation of quail brain GABA(A) and non-NMDA receptors co-expressed in Xenopus oocytes.

PubMed

Moon, C; Fraser, S P; Djamgoz, M B

2000-02-01

The GABA(A) receptor and the non-NMDA subtype of the ionotropic glutamate receptor were co-expressed in Xenopus oocytes by injection of quail brain mRNA. The oocytes were treated with various protein kinase (PK) and protein phosphatase (PP) activators and inhibitors and the effects on receptor functioning were monitored. Two phorbol esters, 4-beta-phorbol 12-myristate-13-acetate (PMA) and 4-beta-phorbol 12,13-dibutyrate (PDBu); the cGMP-dependent PK activators sodium nitroprusside (SNP) and S-nitrosoglutathione (SNOG); and the PP inhibitor okadaic acid (OA) reduced the amplitude of the GABA-induced currents, whilst the PK inhibitor staurosporine potentiated it. In addition, PMA, PDBu, SNP, and OA reduced the desensitization of the GABA-induced response. Identical treatments generally had similar but less pronounced effects on responses generated by kainate (KA) but the desensitization characteristic of the non-NMDA receptor was not affected. None of the treatments had any effect on the reversal potentials of the induced currents. Immunoblots revealed that the oocytes express endogenous PKG and guanylate cyclase. The results are discussed in terms of the molecular structures of GABA(A) and non-NMDA receptors and the potential functional consequences of phosphorylation/dephosphorylation.

Social Cognition Dysfunctions in Neurodegenerative Diseases: Neuroanatomical Correlates and Clinical Implications

PubMed Central

Santamaría-García, Hernando; Santangelo, Gabriella

2018-01-01

Social cognitive function, involved in the perception, processing, and interpretation of social information, has been shown to be crucial for successful communication and interpersonal relationships, thereby significantly impacting mental health, well-being, and quality of life. In this regard, assessment of social cognition, mainly focusing on four key domains, such as theory of mind (ToM), emotional empathy, and social perception and behavior, has been increasingly evaluated in clinical settings, given the potential implications of impairments of these skills for therapeutic decision-making. With regard to neurodegenerative diseases (NDs), most disorders, characterized by variable disease phenotypes and progression, although similar for the unfavorable prognosis, are associated to impairments of social cognitive function, with consequent negative effects on patients' management. Specifically, in some NDs these deficits may represent core diagnostic criteria, such as for behavioral variant frontotemporal dementia (bvFTD), or may emerge during the disease course as critical aspects, such as for Parkinson's and Alzheimer's diseases. On this background, we aimed to revise the most updated evidence on the neurobiological hypotheses derived from network-based approaches, clinical manifestations, and assessment tools of social cognitive dysfunctions in NDs, also prospecting potential benefits on patients' well-being, quality of life, and outcome derived from potential therapeutic perspectives of these deficits. PMID:29854017

Falls and Fear of Falling After Stroke: A Case-Control Study.

PubMed

Goh, Hui-Ting; Nadarajah, Mohanasuntharaam; Hamzah, Norhamizan Binti; Varadan, Parimalaganthi; Tan, Maw Pin

2016-12-01

Falls are common after stroke, with potentially serious consequences. Few investigations have included age-matched control participants to directly compare fall characteristics between older adults with and without stroke. Further, fear of falling, a significant psychological consequence of falls, has only been examined to a limited degree as a risk factor for future falls in a stroke population. To compare the fall history between older adults with and without a previous stroke and to identify the determinants of falls and fear of falling in older stroke survivors. Case-control observational study. Primary teaching hospital. Seventy-five patients with stroke (mean age ± standard deviation, 66 ± 7 years) and 50 age-matched control participants with no previous stroke were tested. Fall history, fear of falling, and physical, cognitive, and psychological function were assessed. A χ 2 test was performed to compare characteristics between groups, and logistic regression was performed to determine the risk factors for falls and fear of falling. Fall events in the past 12 months, Fall Efficacy Scale-International, Berg Balance Scale, Functional Ambulation Category, Fatigue Severity Scale, Montreal Cognitive Assessment, and Patient Healthy Questionnaire-9 were measured for all participants. Fugl-Meyer Motor Assessment was used to quantify severity of stroke motor impairments. Twenty-three patients and 13 control participants reported at least one fall in the past 12 months (P = .58). Nine participants with stroke had recurrent falls (≥2 falls) compared with none of the control participants (P < .01). Participants with stroke reported greater concern for falling than did nonstroke control participants (P < .01). Female gender was associated with falls in the nonstroke group, whereas falls in the stroke group were not significantly associated with any measured outcomes. Fear of falling in the stroke group was associated with functional ambulation level and balance. Functional ambulation level alone explained 22% of variance in fear of falling in the stroke group. Compared with persons without a stroke, patients with stroke were significantly more likely to experience recurrent falls and fear of falling. Falls in patients with stroke were not explained by any of the outcome measures used, whereas fear of falling was predicted by functional ambulation level. This study has identified potentially modifiable risk factors with which to devise future prevention strategies for falls in patients with stroke. III. Copyright © 2016. Published by Elsevier Inc.

Primary and Secondary Consequences of Rotator Cuff Injury on Joint Stabilizing Tissues in the Shoulder.

PubMed

Rahman, Hafizur; Currier, Eric; Johnson, Marshall; Goding, Rick; Johnson, Amy Wagoner; Kersh, Mariana E

2017-11-01

Rotator cuff tears (RCTs) are one of the primary causes of shoulder pain and dysfunction in the upper extremity accounting over 4.5 million physician visits per year with 250,000 rotator cuff repairs being performed annually in the U.S. While the tear is often considered an injury to a specific tendon/tendons and consequently treated as such, there are secondary effects of RCTs that may have significant consequences for shoulder function. Specifically, RCTs have been shown to affect the joint cartilage, bone, the ligaments, as well as the remaining intact tendons of the shoulder joint. Injuries associated with the upper extremities account for the largest percent of workplace injuries. Unfortunately, the variable success rate related to RCTs motivates the need for a better understanding of the biomechanical consequences associated with the shoulder injuries. Understanding the timing of the injury and the secondary anatomic consequences that are likely to have occurred are also of great importance in treatment planning because the approach to the treatment algorithm is influenced by the functional and anatomic state of the rotator cuff and the shoulder complex in general. In this review, we summarized the contribution of RCTs to joint stability in terms of both primary (injured tendon) and secondary (remaining tissues) consequences including anatomic changes in the tissues surrounding the affected tendon/tendons. The mechanical basis of normal shoulder joint function depends on the balance between active muscle forces and passive stabilization from the joint surfaces, capsular ligaments, and labrum. Evaluating the role of all tissues working together as a system for maintaining joint stability during function is important to understand the effects of RCT, specifically in the working population, and may provide insight into root causes of shoulder injury.

Screening for Alcohol Risk in Predominantly Hispanic Youths: Positive Rates and Behavioral Consequences

ERIC Educational Resources Information Center

Tomaka, Joe; Salaiz, Rebekah A.; Morales-Monks, Stormy; Thompson, Sharon; McKinnon, Sarah; O'Rourke, Kathleen

2012-01-01

The present study examined relationships between CAGE alcohol risk scores and predisposing factors for alcohol use, current alcohol use, and behavioral consequences in a large sample of secondary students. Students completed the CAGE, measures of demographics, potential predisposing factors, and consequences of alcohol use. More than 18% of…

24 CFR 401.313 - Consequences of PAE violations; finality of HUD determination.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 24 Housing and Urban Development 2 2010-04-01 2010-04-01 false Consequences of PAE violations... Portfolio Restructuring Agreement (PRA) § 401.313 Consequences of PAE violations; finality of HUD determination. (a) Effect on PRA. If a PAE, potential PAE or other restricted person (as defined in § 401.310...

Lower body functioning and correlates among older American Indians: The Cerebrovascular Disease and Its Consequences in American Indians Study.

PubMed

Goins, R Turner; Schure, Mark; Jensen, Paul N; Suchy-Dicey, Astrid; Nelson, Lonnie; Verney, Steven P; Howard, Barbara V; Buchwald, Dedra

2018-01-05

More than six million American Indians live in the United States, and an estimated 1.6 million will be aged ≥65 years old by 2050 tripling in numbers since 2012. Physical functioning and related factors in this population are poorly understood. Our study aimed to assess lower body functioning and identify the prevalence and correlates of "good" functioning in a multi-tribe, community-based sample of older American Indians. Assessments used the Short Physical Performance Battery (SPPB). "Good" lower body functioning was defined as a total SPPB score of ≥10. Potential correlates included demographic characteristics, study site, anthropometrics, cognitive functioning, depressive symptomatology, grip strength, hypertension, diabetes mellitus, heart disease, prior stroke, smoking, alcohol use, and over-the-counter medication use for arthritis or pain. Data were collected between 2010 and 2013 by the Cerebrovascular Disease and Its Consequences in American Indians Study from community-dwelling adults aged ≥60 years (n = 818). The sample's mean age was 73 ± 5.9 years. After adjustment for age and study site, average SPPB scores were 7.0 (95% CI, 6.8, 7.3) in women and 7.8 (95% CI, 7.5, 8.2) in men. Only 25% of the sample were classified with "good" lower body functioning. When treating lower body functioning as a continuous measure and adjusting for age, gender, and study site, the correlates of better functioning that we identified were younger age, male gender, married status, higher levels of education, higher annual household income, Southern Plains study site, lower waist-hip ratio, better cognitive functioning, stronger grip strength, lower levels of depressive symptomatology, alcohol consumption, and the absence of hypertension, diabetes mellitus, and heart disease. In our fully adjusted models, correlates of "good" lower body functioning were younger age, higher annual household income, better cognitive functioning, stronger grip, and the absence of diabetes mellitus and heart disease. These results suggest that "good" lower body functioning is uncommon in this population, whereas its correlates are similar to those found in studies of other older adult populations. Future efforts should include the development or cultural tailoring of interventions to improve lower body functioning in older American Indians.

Supported self-management for cancer survivors to address long-term biopsychosocial consequences of cancer and treatment to optimize living well.

PubMed

Howell, Doris D

2018-03-01

As individuals are living longer with cancer as a chronic disease, they face new health challenges that require the application of self-management behaviors and skills that may not be in their usual repertoire of self-regulatory health behaviors. Increasing attention is focused on supported self-management (SSM) programs to enable survivors in managing the long-term biopsychosocial consequences and health challenges of survivorship. This review explores current directions and evidence for SSM programs that enable survivors to manage these consequences and optimize health. Cancer survivors face complex health challenges that affect daily functioning and well being. Multiple systematic reviews show that SSM programs have positive effects on health outcomes in typical chronic diseases. However, the efficacy of these approaches in cancer survivors are in their infancy; and the 'one-size' fits all approach for chronic disease self-management may not be adequate for cancer as a complex chronic illness. This review suggests that SSM has promising potential for improving health and well being of cancer survivors, but there is a need for standardizing SSM for future research. Although there is increasing enthusiasm for SSM programs tailored to cancer survivors, there is a need for further research of their efficacy on long-term health outcomes.

Investigating the consequences of urban volcanism using a scenario approach I: Development and application of a hypothetical eruption in the Auckland Volcanic Field, New Zealand

NASA Astrophysics Data System (ADS)

Deligne, Natalia I.; Fitzgerald, Rebecca H.; Blake, Daniel M.; Davies, Alistair J.; Hayes, Josh L.; Stewart, Carol; Wilson, Grant; Wilson, Thomas M.; Castelino, Renella; Kennedy, Ben M.; Muspratt, Scott; Woods, Richard

2017-04-01

What happens when a city has a volcanic eruption within its boundaries? To explore the consequences of this rare but potentially catastrophic combination, we develop a detailed multi-hazard scenario of an Auckland Volcanic Field (AVF) eruption; the AVF underlies New Zealand's largest city, Auckland. We start with an existing AVF unrest scenario sequence and develop it through a month-long hypothetical eruption based on geologic investigations of the AVF and historic similar eruptions from around the world. We devise a credible eruption sequence and include all volcanic hazards that could occur in an AVF eruption. In consultation with Civil Defence and Emergency Management staff, we create a series of evacuation maps for before, during, and after the hypothetical eruption sequence. Our result is a versatile scenario with many possible applications, developed further in companion papers that explore eruption consequences on transportation and water networks. However, here we illustrate one application: evaluating the consequences of an eruption on electricity service provision. In a collaborative approach between scientists and electricity service providers, we evaluate the impact of the hypothetical eruption to electricity generation, transmission, and distribution infrastructure. We then evaluate how the impacted network functions, accounting for network adaptations (e.g., diverting power away from evacuated areas), site access, and restoration factors. We present a series of regional maps showing areas with full service, rolling outages, and no power as a result of the eruption. This illustrative example demonstrates how a detailed scenario can be used to further understand the ramifications of urban volcanism on local and regional populations, and highlights the importance of looking beyond damage to explore the consequences of volcanism.

A field investigation of the effects of drinking consequences on young adults' readiness to change.

PubMed

Usala, Julie M; Celio, Mark A; Lisman, Stephen A; Day, Anne M; Spear, Linda P

2015-02-01

In the research on readiness to change (RTC) one's drinking, there has been little assessment of the influence of positive drinking consequences or other potential moderating variables. To address these limitations, we examined how young adults' RTC their alcohol consumption shortly following a drinking episode was associated with self-reported drinking consequences, as well as any potential moderating effects of gender and Breath Alcohol Concentration (BrAC). In street interviews outside bars, 238 young adults were administered questionnaires about their drinking, including a measure examining participants' current readiness to reduce their alcohol consumption. Within 72h of their drinking episode, 67 participants (36 males; entire sample Mage=20.90years, Range=18-26years) completed an online survey, once again measuring RTC as well as positive and negative drinking consequences. Consistent with our hypothesis, positive drinking consequences were negatively associated with participants' changes in RTC. Additionally, a three-way interaction of gender×BrAC×positive drinking consequences on RTC showed that females with low BrACs reported higher RTC scores when they had endorsed fewer positive drinking consequences. Interestingly, negative drinking consequences alone did not impact individuals' RTC. Because positive drinking consequences were a significantly better predictor of RTC than were negative drinking consequences, researchers are advised to examine both types of consequences in future studies. Finally, effective alcohol education programs for those who have never consumed alcohol as well as social drinkers should include consideration of the experience of positive outcomes. Copyright © 2014 Elsevier Ltd. All rights reserved.

Correlation of Factor IXa Subsite Modulations with Effects on Substrate Discrimination

PubMed Central

Neuenschwander, Pierre F.; Deadmond, Kimberly J.; Zepeda, Karla; Rutland, Joshua

2012-01-01

Summary Background A key feature of factor IXa (fIXa) is its allosteric transformation from an enzymatically latent form into a potent procoagulant. Whilst several small molecules have been found capable of partially effecting fIXa function (i.e. ethylene glycol, calcium ion and LMWH), the resulting modest changes in peptidolytic activity have made the study of their mechanisms of action challenging. Since these effects yield hints into potential regulatory forces that may be operational in full expression of fIXa coagulant activity, their description remains of high interest. Studies of crystal structures have yielded insight into structural changes induced by these effectors, but there remains a paucity of information to correlate any given structural change with specific consequences on fIXa function. Objectives To correlate structural changes induced by these modulators with defined consequences in fIXa substrate discrimination and function. Methods A peptidomics-based MS approach was used to examine patterns of hydrolysis of four combinatorial chemistry-derived pentapeptide libraries by fIXa under various conditions in a soluble, active enzyme system. Results Ethylene glycol specifically alters the S3 subsite of fIXa to render it more tolerant to side chains at the P3 substrate position, while calcium enhances tolerance at the S2 subsite. In contrast, LMWH alters both S2 and S1' subsites. Conclusions These results demonstrate the role of plasticity in regulating fIXa function with respect to discrimination of extended substrate sequences, as well as provide crucial insight into active site modulations that may be capitalized upon by various physiological cofactors of fIXa and in future drug design. PMID:22212890

Perspectives of “Functional Failure”

PubMed Central

Sussman, Steve

2014-01-01

The present dialogue piece briefly examines six perspectives of functional failure (individual-level, societal-level, life spheres impacted, number of severe consequences, attribution of consequences to drug misuse, and socio-environmental generalizability) as they might apply to seven degrees of drug misuse (constant, dependence, heavy, binging, controlled use, “dry,” sober). Variation in judgments of failure is posited across the perspectives and across degrees of drug misuse. PMID:23186439

Long-term neuropsychological effects of opioid use in children: a descriptive literature review.

PubMed

Jain, Gaurav; Mahendra, Vijaita; Singhal, Sarita; Dzara, Kristina; Pilla, Trinadha R; Manworren, Renee; Kaye, Alan D

2014-01-01

Use of opioids in the management of pain and its consequences in children presents a substantial challenge. A significant concern in pediatric pain management is the long-term neuropsychological consequences of opioids. The authors aim to provide a descriptive review of the current literature surrounding the neuropsychological impact of opioid use in children, along with possible extrapolations from their use in adults and animal models. Systematic review of published literature. Various universities in the United States. The electronic review for papers published between January 1992 and December 2012 was conducted using Medline/Pubmed, PsychInfo, CINAHL, the Cochrane Library database, and Google Scholar. Findings assessing pediatric pain patients treated with opioids demonstrated no significant differences in intelligence, behavior, vocabulary, or motor skills. One study reported a decrease in a visuo-constructional ability, which measured higher order executive function. Studies from prenatal illicit opioid exposure found poorer performance on measures of language, verbal ability, mathematics, reading, impulse control, and school readiness skills. The literature from adult prescribed opioid users has mixed results. Some showed impairment in the neuropsychological domains of memory, decision-making, attention, concentration, information processing, psychomotor speed, visual special skills, and hand-eye coordination, while others found no differences or revealed improved perceptual-cognitive status, possibly due to the removal of pain as a stressor. Very few studies looked into the long term neuropsychological and cognitive effects of the opioids in pediatric population. In an attempt to extrapolate from other groups, this review also included literature from adult patients, prenatal opioid exposure, and animal studies. Opioid medications have the potential to produce long-lasting neuropsychological side effects. However, given the negative consequences of untreated pain, the potential benefit may offset their risk. More studies are needed to clarify this complex interaction.

Expeditionary Readiness Training (ExpeRT) Course Expansion Final Environmental Assessment Creech Air Force Base

DTIC Science & Technology

2006-07-01

potential environmental consequences of the proposed action and no-action alternative and are addressed for: air quality, soils and water resources...evaluated in detail to identify potential environmental consequences: air quality; soils and water resources; biological resources; and cultural resources...significance. Therefore, this proposed action would not constitute a significant impact and would conform to regional standards. Soils and Water Resources

Risk Management of Jettisoned Objects in LEO

NASA Technical Reports Server (NTRS)

Bacon, John B.; Gray, Charles

2011-01-01

The construction and maintenance of the International Space Station (ISS) has led to the release of many objects into its orbital plane, usually during the course of an extra-vehicular activity (EVA). Such releases are often unintentional, but in a growing number of cases, the jettison has been intentional, conducted after a careful assessment of the net risk to the partnership and to other objects in space. Since its launch in 1998 the ISS has contributed on average at least one additional debris object that is simultaneously in orbit with the station, although the number varies widely from zero to eight at any one moment. All of these objects present potential risks to other objects in orbit. Whether it comes from known and tracked orbiting objects or from unknown or untrackable objects, collision with orbital debris can have disastrous consequences. Objects greater than 10cm are generally well documented and tracked, allowing orbiting spacecraft or satellites opportunities to perform evasive maneuvers (commonly known as Debris Avoidance Maneuvers, or DAMs) in the event that imminent collision is predicted. The issue with smaller debris; however, is that it is too numerous to be tracked effectively and yet still poses disastrous consequences if it intercepts a larger object. Due to the immense kinetic energy of any item in orbit, collision with debris as small as 1cm can have catastrophic consequences for many orbiting satellites or spacecraft. Faced with the growing orbital debris threat and the potentially catastrophic consequences of a collision-generated debris shower originating in an orbit crossing the ISS altitude band, in 2007 the ISS program manger asked program specialists to coordinate a multilateral jettison policy amongst the ISS partners. This policy would define the acceptable risk trade rationale for intentional release of a debris object, and other mandatory constraints on such jettisons to minimize the residual risks whenever a jettison was accepted. Although ISS-related debris often presents untenable risks to the EVA crew, IVA crew, or to a departing cargo vehicle for a controlled disposal, such released objects also present a ballistic nuisance to the visiting vehicle traffic, and a potential fragmentation threat to the hundreds of other functional and debris objects whose perigees lie below the ISS orbital altitude. Thus, every such jettison decision is a conscious risk trade.

Supportive Non-Parental Adults and Adolescent Psychosocial Functioning: Using Social Support as a Theoretical Framework

PubMed Central

Sterrett, E. M.; Jones, D. J.; McKee, L. G.; Kincaid, C.

2014-01-01

Supportive Non-Parental Adults (SNPAs), or non-parental adults who provide social support to youth, are present in the lives of many adolescents; yet to date, a guiding framework for organizing the existing literature on the provision of support provided by multiple types of SNPAS, such as teachers, natural mentors, and extended family members, as well as to inform future research efforts, is lacking. The aim of the current paper is to utilize the well-established lens of social support to integrate, across this broad range of literatures, recent findings regarding associations between SNPAs and four indices of adolescent psychosocial adjustment: academic functioning, self-esteem, and behavioral and emotional problems. Beyond offering an integrative framework for understanding the link between SNPAs and adolescent functioning, the issues reviewed here have potentially far-reaching consequences for adolescents and their families, as well as the professionals working with adolescents and their families in the health care, school, and community settings. PMID:21384233

Emerging Role and Characterization of Immunometabolism: Relevance to HIV Pathogenesis, Serious Non-AIDS Events, and a Cure.

PubMed

Palmer, Clovis S; Henstridge, Darren C; Yu, Di; Singh, Amit; Balderson, Brad; Duette, Gabriel; Cherry, Catherine L; Anzinger, Joshua J; Ostrowski, Matias; Crowe, Suzanne M

2016-06-01

Immune cells cycle between a resting and an activated state. Their metabolism is tightly linked to their activation status and, consequently, functions. Ag recognition induces T lymphocyte activation and proliferation and acquisition of effector functions that require and depend on cellular metabolic reprogramming. Likewise, recognition of pathogen-associated molecular patterns by monocytes and macrophages induces changes in cellular metabolism. As obligate intracellular parasites, viruses manipulate the metabolism of infected cells to meet their structural and functional requirements. For example, HIV-induced changes in immune cell metabolism and redox state are associated with CD4(+) T cell depletion, immune activation, and inflammation. In this review, we highlight how HIV modifies immunometabolism with potential implications for cure research and pathogenesis of comorbidities observed in HIV-infected patients, including those with virologic suppression. In addition, we highlight recently described key methods that can be applied to study the metabolic dysregulation of immune cells in disease states. Copyright © 2016 by The American Association of Immunologists, Inc.

Transient protein-protein interactions perturb E. coli metabolome and cause gene dosage toxicity

PubMed Central

Bhattacharyya, Sanchari; Bershtein, Shimon; Yan, Jin; Argun, Tijda; Gilson, Amy I; Trauger, Sunia A; Shakhnovich, Eugene I

2016-01-01

Gene dosage toxicity (GDT) is an important factor that determines optimal levels of protein abundances, yet its molecular underpinnings remain unknown. Here, we demonstrate that overexpression of DHFR in E. coli causes a toxic metabolic imbalance triggered by interactions with several functionally related enzymes. Though deleterious in the overexpression regime, surprisingly, these interactions are beneficial at physiological concentrations, implying their functional significance in vivo. Moreover, we found that overexpression of orthologous DHFR proteins had minimal effect on all levels of cellular organization – molecular, systems, and phenotypic, in sharp contrast to E. coli DHFR. Dramatic difference of GDT between ‘E. coli’s self’ and ‘foreign’ proteins suggests the crucial role of evolutionary selection in shaping protein-protein interaction (PPI) networks at the whole proteome level. This study shows how protein overexpression perturbs a dynamic metabolon of weak yet potentially functional PPI, with consequences for the metabolic state of cells and their fitness. DOI: http://dx.doi.org/10.7554/eLife.20309.001 PMID:27938662

Liver cell therapy and tissue engineering for transplantation.

PubMed

Vacanti, Joseph P; Kulig, Katherine M

2014-06-01

Liver transplantation remains the only definitive treatment for liver failure and is available to only a tiny fraction of patients with end-stage liver diseases. Major limitations for the procedure include donor organ shortage, high cost, high level of required expertise, and long-term consequences of immune suppression. Alternative cell-based liver therapies could potentially greatly expand the number of patients provided with effective treatment. Investigative research into augmenting or replacing liver function extends into three general strategies. Bioartificial livers (BALs) are extracorporeal devices that utilize cartridges of primary hepatocytes or cell lines to process patient plasma. Injection of liver cell suspensions aims to foster organ regeneration or provide a missing metabolic function arising from a genetic defect. Tissue engineering recreates the organ in vitro for subsequent implantation to augment or replace patient liver function. Translational models and clinical trials have highlighted both the immense challenges involved and some striking examples of success. Copyright © 2014. Published by Elsevier Inc.

Pediatric traumatic brain injury: language outcomes and their relationship to the arcuate fasciculus.

PubMed

Liégeois, Frédérique J; Mahony, Kate; Connelly, Alan; Pigdon, Lauren; Tournier, Jacques-Donald; Morgan, Angela T

2013-12-01

Pediatric traumatic brain injury (TBI) may result in long-lasting language impairments alongside dysarthria, a motor-speech disorder. Whether this co-morbidity is due to the functional links between speech and language networks, or to widespread damage affecting both motor and language tracts, remains unknown. Here we investigated language function and diffusion metrics (using diffusion-weighted tractography) within the arcuate fasciculus, the uncinate fasciculus, and the corpus callosum in 32 young people after TBI (approximately half with dysarthria) and age-matched healthy controls (n=17). Only participants with dysarthria showed impairments in language, affecting sentence formulation and semantic association. In the whole TBI group, sentence formulation was best predicted by combined corpus callosum and left arcuate volumes, suggesting this "dual blow" seriously reduces the potential for functional reorganisation. Word comprehension was predicted by fractional anisotropy in the right arcuate. The co-morbidity between dysarthria and language deficits therefore seems to be the consequence of multiple tract damage. Copyright © 2013 Elsevier Inc. All rights reserved.

Cytoplasmic ASPP1 inhibits apoptosis through the control of YAP

PubMed Central

Vigneron, Arnaud M.; Ludwig, Robert L.; Vousden, Karen H.

2010-01-01

The ASPP (apoptosis-stimulating protein of p53) family of proteins can function in the nucleus to modulate the transcriptional activity of p53, with ASPP1 and ASPP2 contributing to the expression of apoptotic target genes. In this study, we describe a new function for cytoplasmic ASPP1 in controlling YAP (Yes-associated protein)/TAZ. ASPP1 can inhibit the interaction of YAP with LATS1 (large tumor suppressor 1), a kinase that phosphorylates YAP/TAZ and promotes cytoplasmic sequestration and protein degradation. This function of ASPP1 therefore enhances nuclear accumulation of YAP/TAZ and YAP/TAZ-dependent transcriptional regulation. The consequence of YAP/TAZ activation by ASPP1 is to inhibit apoptosis, in part through the down-regulation of Bim expression, leading to resistance to anoikis and enhanced cell migration. These results reveal a potential oncogenic role for cytoplasmic ASPP1, in contrast to the tumor-suppressive activity described previously for nuclear ASPP1. PMID:21041411

Imitation, mirror neurons and autism.

PubMed

Williams, J H; Whiten, A; Suddendorf, T; Perrett, D I

2001-06-01

Various deficits in the cognitive functioning of people with autism have been documented in recent years but these provide only partial explanations for the condition. We focus instead on an imitative disturbance involving difficulties both in copying actions and in inhibiting more stereotyped mimicking, such as echolalia. A candidate for the neural basis of this disturbance may be found in a recently discovered class of neurons in frontal cortex, 'mirror neurons' (MNs). These neurons show activity in relation both to specific actions performed by self and matching actions performed by others, providing a potential bridge between minds. MN systems exist in primates without imitative and 'theory of mind' abilities and we suggest that in order for them to have become utilized to perform social cognitive functions, sophisticated cortical neuronal systems have evolved in which MNs function as key elements. Early developmental failures of MN systems are likely to result in a consequent cascade of developmental impairments characterised by the clinical syndrome of autism.

Explorative solid-phase extraction (E-SPE) for accelerated microbial natural product discovery, dereplication, and purification.

PubMed

Månsson, Maria; Phipps, Richard K; Gram, Lone; Munro, Murray H G; Larsen, Thomas O; Nielsen, Kristian F

2010-06-25

Microbial natural products (NP) cover a high chemical diversity, and in consequence extracts from microorganisms are often complex to analyze and purify. A distribution analysis of calculated pK(a) values from the 34390 records in Antibase2008 revealed that within pH 2-11, 44% of all included compounds had an acidic functionality, 17% a basic functionality, and 9% both. This showed a great potential for using ion-exchange chromatography as an integral part of the separation procedure, orthogonal to the classic reversed-phase strategy. Thus, we investigated the use of an "explorative solid-phase extraction" (E-SPE) protocol using SAX, Oasis MAX, SCX, and LH-20 columns for targeted exploitation of chemical functionalities. E-SPE provides a minimum of fractions (15) for chemical and biological analyses and implicates development into a preparative scale methodology. Overall, this allows fast extract prioritization, easier dereplication, mapping of biological activities, and formulation of a purification strategy.

Quantum gravity fluctuations flatten the Planck-scale Higgs potential

NASA Astrophysics Data System (ADS)

Eichhorn, Astrid; Hamada, Yuta; Lumma, Johannes; Yamada, Masatoshi

2018-04-01

We investigate asymptotic safety of a toy model of a singlet-scalar extension of the Higgs sector including two real scalar fields under the impact of quantum-gravity fluctuations. Employing functional renormalization group techniques, we search for fixed points of the system which provide a tentative ultraviolet completion of the system. We find that in a particular regime of the gravitational parameter space the canonically marginal and relevant couplings in the scalar sector—including the mass parameters—become irrelevant at the ultraviolet fixed point. The infrared potential for the two scalars that can be reached from that fixed point is fully predicted and features no free parameters. In the remainder of the gravitational parameter space, the values of the quartic couplings in our model are predicted. In light of these results, we discuss whether the singlet-scalar could be a dark-matter candidate. Furthermore, we highlight how "classical scale invariance" in the sense of a flat potential of the scalar sector at the Planck scale could arise as a consequence of asymptotic safety.

Functional metagenomic profiling of intestinal microbiome in extreme ageing.

PubMed

Rampelli, Simone; Candela, Marco; Turroni, Silvia; Biagi, Elena; Collino, Sebastiano; Franceschi, Claudio; O'Toole, Paul W; Brigidi, Patrizia

2013-12-01

Age-related alterations in human gut microbiota composition have been thoroughly described, but a detailed functional description of the intestinal bacterial coding capacity is still missing. In order to elucidate the contribution of the gut metagenome to the complex mosaic of human longevity, we applied shotgun sequencing to total fecal bacterial DNA in a selection of samples belonging to a well-characterized human ageing cohort. The age-related trajectory of the human gut microbiome was characterized by loss of genes for shortchain fatty acid production and an overall decrease in the saccharolytic potential, while proteolytic functions were more abundant than in the intestinal metagenome of younger adults. This altered functional profile was associated with a relevant enrichment in "pathobionts", i.e. opportunistic pro-inflammatory bacteria generally present in the adult gut ecosystem in low numbers. Finally, as a signature for long life we identified 116 microbial genes that significantly correlated with ageing. Collectively, our data emphasize the relationship between intestinal bacteria and human metabolism, by detailing the modifications in the gut microbiota as a consequence of and/or promoter of the physiological changes occurring in the human host upon ageing.

Repeated daclizumab administration to delay the introduction of calcineurin inhibitors in heart transplant patients with postoperative renal dysfunction.

PubMed

Sánchez Lázaro, Ignacio J; Almenar Bonet, Luis; Martínez Dolz, Luis; Buendía Fuentes, Francisco; Navarro Manchón, Josep; Agüero Ramón-Llin, Jaime; Vicente Sánchez, José Luis; Salvador Sanz, Antonio

2011-03-01

Daclizumab is an interleukin-2 receptor antagonist which is used for induction therapy in heart transplant patients. It has few side effects and is associated with a low infection rate. Postoperative renal failure after heart transplantation is common and potentially fatal. The administration of calcineurin inhibitors in the postoperative period can aggravate the situation. We report the cases of six patients who underwent heart transplantation and developed acute renal failure in the immediate postoperative period. All were administered daclizumab weekly to avoid the introduction of calcineurin inhibitors and to facilitate recovery of renal function. Calcineurin inhibitors were introduced only once renal function had improved. Renal function recovered in all cases and there was a low complication rate. The administration of repeated doses of daclizumab to patients who experience acute postoperative renal failure after heart transplantation may provide an alternative therapeutic approach that enables calcineurin inhibitors to be avoided and, consequently, renal function to recover. Copyright © 2010 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.

The caudate: a key node in the neuronal network imbalance of insomnia?

PubMed Central

Altena, Ellemarije; van der Werf, Ysbrand D.; Sanz-Arigita, Ernesto J.; Voorn, Thom A.; Astill, Rebecca G.; Strijers, Rob L. M.; Waterman, Dé; Van Someren, Eus J. W.

2014-01-01

Insomnia is prevalent, severe and partially heritable. Unfortunately, its neuronal correlates remain enigmatic, hampering the development of mechanistic models and rational treatments. Consistently reported impairments concern fragmented sleep, hyper-arousal and executive dysfunction. Because fronto-striatal networks could well play a role in sleep, arousal regulation and executive functioning, the present series of studies used an executive task to evaluate fronto-striatal functioning in disturbed sleep. Patients with insomnia showed reduced recruitment of the head of the left caudate nucleus during executive functioning, which was not secondary to altered performance or baseline perfusion. Individual differences in caudate recruitment were associated with hyper-arousal severity. Seed-based functional connectivity analysis suggested that attenuated input from a projecting orbitofrontal area with reduced grey matter density contributes to altered caudate recruitment in patients with insomnia. Attenuated caudate recruitment persisted after successful treatment of insomnia, warranting evaluation as a potential vulnerability trait. A similar selective reduction in caudate recruitment could be elicited in participants without sleep complaints by slow-wave sleep fragmentation, providing a model to facilitate investigation of the causes and consequences of insomnia. PMID:24285642

Proteomics in investigation of cancer metastasis: functional and clinical consequences and methodological challenges.

PubMed

Maryáš, Josef; Faktor, Jakub; Dvořáková, Monika; Struhárová, Iva; Grell, Peter; Bouchal, Pavel

2014-03-01

Metastases are responsible for most of the cases of death in patients with solid tumors. There is thus an urgent clinical need of better understanding the exact molecular mechanisms and finding novel therapeutics targets and biomarkers of metastatic disease of various tumors. Metastases are formed in a complicated biological process called metastatic cascade. Up to now, proteomics has enabled the identification of number of metastasis-associated proteins and potential biomarkers in cancer tissues, microdissected cells, model systems, and secretomes. Expression profiles and biological role of key proteins were confirmed in verification and functional experiments. This communication reviews these observations and analyses the methodological aspects of the proteomics approaches used. Moreover, it reviews contribution of current proteomics in the field of functional characterization and interactome analysis of proteins involved in various events in metastatic cascade. It is evident that ongoing technical progress will further increase proteome coverage and sample capacity of proteomics technologies, giving complex answers to clinical and functional questions asked. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A well-refined in vitro model derived from human embryonic stem cell for screening phytochemicals with midbrain dopaminergic differentiation-boosting potential for improving Parkinson's disease.

PubMed

Hsieh, Wen-Ting; Chiang, Been-Huang

2014-07-09

Stimulation of endogenous neurogenesis is a potential approach to compensate for loss of dopaminergic neurons of substantia nigra compacta nigra (SNpc) in patients with Parkinson's disease (PD). This objective was to establish an in vitro model by differentiating pluripotent human embryonic stem cells (hESCs) into midbrain dopaminergic (mDA) neurons for screening phytochemicals with mDA neurogenesis-boosting potentials. Consequently, a five-stage differentiation process was developed. The derived cells expressed many mDA markers including tyrosine hydroxylase (TH), β-III tubulin, and dopamine transporter (DAT). The voltage-gated ion channels and dopamine release were also examined for verifying neuron function, and the dopamine receptor agonists bromocriptine and 7-hydroxy-2-(dipropylamino)tetralin (7-OH-DPAT) were used to validate our model. Then, several potential phytochemicals including green tea catechins and ginsenosides were tested using the model. Finally, ginsenoside Rb1 was identified as the most potent phytochemical which is capable of upregulating neurotrophin expression and inducing mDA differentiation.

[Liver and sport].

PubMed

Watelet, J

2008-11-01

The liver is a vital organ and plays a central role in energy exchange, protein synthesis as well as the elimination of waste products from the body. Acute and chronic injury may disturb a variety of liver functions to different degrees. Over the last three decades, the effects of physical activity and competitive sport on the liver have been described by various investigators. These include viral hepatitis and drug-induced liver disorders. Herein, we review acute and chronic liver diseases potentially caused by sport. Team physicians, trainers and others, responsible for the health of athletes, should be familiar with the risk factors, clinical features, and consequences of liver diseases that occur in sports.