History of Hubble Space Telescope (HST)

NASA Image and Video Library

1969-01-01

This image of the Egg Nebula, also known as CRL-2688 and located roughly 3,000 light-years from us, was taken in red light with the Wide Field Planetary Camera 2 (WF/PC2) aboard the Hubble Space Telescope (HST). The image shows a pair of mysterious searchlight beams emerging from a hidden star, crisscrossed by numerous bright arcs. This image sheds new light on the poorly understood ejection of stellar matter that accompanies the slow death of Sun-like stars. The image is shown in false color.

Parental Decisions regarding pre-hospital therapy and costing of the Emergency Department Visit.

PubMed

McGovern, M; Kernan, R; O'Neill, M B

2017-02-10

Paediatric patients represent a large percentage of Emergency Department (ED) visits and there is often a perception that the acuity of these presentations is low. The decision-making process that results in parents attending the ED is poorly understood. We designed a cross-sectional cohort study to explore the reasons for attendance, the treatment initiated at home and to assess parental perception of the economic cost of attendance. Data was collected on 200 patients using a survey administered to parents in ED with a follow-up phone call 4-6 weeks later. Our results suggest that attendances are often prompted by parental anxiety rather than clinical deterioration and that prior ED usage is common among those presenting for assessment. Many parents had attempted community therapy with 128/200 patients (64%) having been referred by a healthcare professional and medical therapy at home having been employed by 114/200 (57%) parents before attendance. Parental knowledge of the safety of over-the-counter medications was variable the economic cost of an ED visit was poorly understood by participants. The results of our study suggest that parental desire for control over worrisome symptoms drives much of their management strategy prior to hospital attendance. Strategies in the ED may need to focus more on managing parental expectations than on managing the illness itself and management strategies employed should focus not only on medical therapy of the child's illness but on educating and empowering the parent.

Exploring the Buruli Ulcer Incidence across a socio-ecological landscape in Ghana

NASA Astrophysics Data System (ADS)

Naithani, K. J.; Konzelman, C.; Tschakert, P.; Smithwick, E. A. H.

2016-12-01

The Buruli Ulcer (BU) disease is one of the most prevalent, but poorly understood mycobacterial infections in the world. Fundamental ecological aspects of the disease causing bacteria (Mycobacterium ulcerans) are not understood completely, but its emergence is attributed to unidentified thresholds in human and natural systems. We explored the network of these interactions across socio-ecological landscapes of Ghana to understand the movement of bacteria and the emergence of BU in response to climate, disturbance, social and economic factors. We chose five communities, three endemic and two control, and explored the correlations of disease incidence with climate, landscape disturbance, water quality and social factors using path analysis. Our results show that water quality is strongly linked to disease emergence with high alkalinity, PO43-, NH4+, F, Mn, S, Cd, Fe, Pb, and Se were associated with higher disease incidents and high Cu concentration was associated with low or healthy communities. Contrary to previous studies, arsenic concentration in water was not linked to higher disease incidence. Water quality was linked to climate, type of mining, and agricultural practices. Higher annual precipitation and lower air temperature were found linked to higher disease incidence across communities. Our exploratory work provides insight into how human land use, social practices, demographics, and climatic factors influence the BU disease spread.

Long non-coding RNAs in cancer metabolism.

PubMed

Xiao, Zhen-Dong; Zhuang, Li; Gan, Boyi

2016-10-01

Altered cellular metabolism is an emerging hallmark of cancer. Accumulating recent evidence links long non-coding RNAs (lncRNAs), a still poorly understood class of non-coding RNAs, to cancer metabolism. Here we review the emerging findings on the functions of lncRNAs in cancer metabolism, with particular emphasis on how lncRNAs regulate glucose and glutamine metabolism in cancer cells, discuss how lncRNAs regulate various aspects of cancer metabolism through their cross-talk with other macromolecules, explore the mechanistic conceptual framework of lncRNAs in reprogramming metabolism in cancers, and highlight the challenges in this field. A more in-depth understanding of lncRNAs in cancer metabolism may enable the development of novel and effective therapeutic strategies targeting cancer metabolism. © 2016 WILEY Periodicals, Inc.

Bordetella pertussis pathogenesis: current and future challenges.

PubMed

Melvin, Jeffrey A; Scheller, Erich V; Miller, Jeff F; Cotter, Peggy A

2014-04-01

Pertussis, also known as whooping cough, has recently re-emerged as a major public health threat despite high levels of vaccination against the aetiological agent Bordetella pertussis. In this Review, we describe the pathogenesis of this disease, with a focus on recent mechanistic insights into B. pertussis virulence-factor function. We also discuss the changing epidemiology of pertussis and the challenges facing vaccine development. Despite decades of research, many aspects of B. pertussis physiology and pathogenesis remain poorly understood. We highlight knowledge gaps that must be addressed to develop improved vaccines and therapeutic strategies.

Accelerated Gene Evolution and Subfunctionalization in thePseudotetraploid Frog Xenopus Laevis

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

Hellsten, Uffe; Khokha, Mustafa K.; Grammar, Timothy C.

2007-03-01

Ancient whole genome duplications have been implicated in the vertebrate and teleost radiations, and in the emergence of diverse angiosperm lineages, but the evolutionary response to such a perturbation is still poorly understood. The African clawed frog Xenopus laevis experienced a relatively recent tetraploidization {approx} 40 million years ago. Analysis of the considerable amount of EST sequence available for this species together with the genome sequence of the related diploid Xenopus tropicalis provides a unique opportunity to study the genomic response to whole genome duplication.

Neuropsychiatric conditions associated with anesthesia exposure.

PubMed

Gross, Anne F; Stern, Theodore A

2014-01-01

Although anesthetics have been used for more than a century, their mechanisms of action remain poorly understood. Given that a number of intraoperative and postoperative neuropsychiatric syndromes have been linked to the use of anesthetics, practitioners should familiarize themselves with these conditions. Basic concepts about anesthesia are reviewed and neuropsychiatric syndromes associated with anesthesia exposure described. Emergence delirium, postoperative delirium, postoperative cognitive dysfunction, and intraoperative awareness can develop in association with use of inhalation anesthetics and intravenously administered anesthetics. Copyright © 2014 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.

The basics of epithelial-mesenchymal transition.

PubMed

Kalluri, Raghu; Weinberg, Robert A

2009-06-01

The origins of the mesenchymal cells participating in tissue repair and pathological processes, notably tissue fibrosis, tumor invasiveness, and metastasis, are poorly understood. However, emerging evidence suggests that epithelial-mesenchymal transitions (EMTs) represent one important source of these cells. As we discuss here, processes similar to the EMTs associated with embryo implantation, embryogenesis, and organ development are appropriated and subverted by chronically inflamed tissues and neoplasias. The identification of the signaling pathways that lead to activation of EMT programs during these disease processes is providing new insights into the plasticity of cellular phenotypes and possible therapeutic interventions.

The emergence of spontaneous activity in neuronal cultures

NASA Astrophysics Data System (ADS)

Orlandi, J. G.; Alvarez-Lacalle, E.; Teller, S.; Soriano, J.; Casademunt, J.

2013-01-01

In vitro neuronal networks of dissociated hippocampal or cortical tissues are one of the most attractive model systems for the physics and neuroscience communities. Cultured neurons grow and mature, develop axons and dendrites, and quickly connect to their neighbors to establish a spontaneously active network within a week. The resulting neuronal network is characterized by a combination of excitatory and inhibitory neurons coupled through synaptic connections that interact in a highly nonlinear manner. The nonlinear behavior emerges from the dynamics of both the neurons' spiking activity and synaptic transmission, together with biological noise. These ingredients give rise to a rich repertoire of phenomena that are still poorly understood, including the emergence and maintenance of periodic spontaneous activity, avalanches, propagation of fronts and synchronization. In this work we present an overview on the rich activity of cultured neuronal networks, and detail the minimal theoretical considerations needed to describe experimental observations.

Neural correlations enable invariant coding and perception of natural stimuli in weakly electric fish

PubMed Central

Metzen, Michael G; Hofmann, Volker; Chacron, Maurice J

2016-01-01

Neural representations of behaviorally relevant stimulus features displaying invariance with respect to different contexts are essential for perception. However, the mechanisms mediating their emergence and subsequent refinement remain poorly understood in general. Here, we demonstrate that correlated neural activity allows for the emergence of an invariant representation of natural communication stimuli that is further refined across successive stages of processing in the weakly electric fish Apteronotus leptorhynchus. Importantly, different patterns of input resulting from the same natural communication stimulus occurring in different contexts all gave rise to similar behavioral responses. Our results thus reveal how a generic neural circuit performs an elegant computation that mediates the emergence and refinement of an invariant neural representation of natural stimuli that most likely constitutes a neural correlate of perception. DOI: http://dx.doi.org/10.7554/eLife.12993.001 PMID:27128376

Factors Influencing the Sahelian Paradox at the Local Watershed Scale: Causal Inference Insights

NASA Astrophysics Data System (ADS)

Van Gordon, M.; Groenke, A.; Larsen, L.

2017-12-01

While the existence of paradoxical rainfall-runoff and rainfall-groundwater correlations are well established in the West African Sahel, the hydrologic mechanisms involved are poorly understood. In pursuit of mechanistic explanations, we perform a causal inference analysis on hydrologic variables in three watersheds in Benin and Niger. Using an ensemble of techniques, we compute the strength of relationships between observational soil moisture, runoff, precipitation, and temperature data at seasonal and event timescales. Performing analysis over a range of time lags allows dominant time scales to emerge from the relationships between variables. By determining the time scales of hydrologic connectivity over vertical and lateral space, we show differences in the importance of overland and subsurface flow over the course of the rainy season and between watersheds. While previous work on the paradoxical hydrologic behavior in the Sahel focuses on surface processes and infiltration, our results point toward the importance of subsurface flow to rainfall-runoff relationships in these watersheds. The hypotheses generated from our ensemble approach suggest that subsequent explorations of mechanistic hydrologic processes in the region include subsurface flow. Further, this work highlights how an ensemble approach to causal analysis can reveal nuanced relationships between variables even in poorly understood hydrologic systems.

The Nutrient Density of Snacks

PubMed Central

Hess, Julie; Rao, Goutham; Slavin, Joanne

2017-01-01

Background: Although Americans receive almost a quarter of their daily energy from snacks, snacking remains a poorly defined and understood eating occasion. However, there is little dietary guidance about choosing snacks. Families, clinicians, and researchers need a comprehensive approach to assessing their nutritional value. Objective: To quantify and compare the nutrient density of commonly consumed snacks by their overall nutrient profiles using the Nutrient-Rich Foods (NRF) Index 10.3. Methods: NRF Index scores were calculated for the top 3 selling products (based on 2014 market research data) in different snack categories. These NRF scores were averaged to provide an overall nutrient-density score for each category. Results: Based on NRF scores, yogurt (55.3), milk (52.5), and fruit (30.1) emerged as the most nutrient-dense snacks. Ice cream (−4.4), pies and cakes (−11.1), and carbonated soft drinks (−17.2) emerged as the most nutrient-poor snacks. Conclusions: The NRF Index is a useful tool for assessing the overall nutritional value of snacks based on nutrients to limit and nutrients to encourage. PMID:28491924

The Nutrient Density of Snacks: A Comparison of Nutrient Profiles of Popular Snack Foods Using the Nutrient-Rich Foods Index.

PubMed

Hess, Julie; Rao, Goutham; Slavin, Joanne

2017-01-01

Background: Although Americans receive almost a quarter of their daily energy from snacks, snacking remains a poorly defined and understood eating occasion. However, there is little dietary guidance about choosing snacks. Families, clinicians, and researchers need a comprehensive approach to assessing their nutritional value. Objective: To quantify and compare the nutrient density of commonly consumed snacks by their overall nutrient profiles using the Nutrient-Rich Foods (NRF) Index 10.3. Methods: NRF Index scores were calculated for the top 3 selling products (based on 2014 market research data) in different snack categories. These NRF scores were averaged to provide an overall nutrient-density score for each category. Results: Based on NRF scores, yogurt (55.3), milk (52.5), and fruit (30.1) emerged as the most nutrient-dense snacks. Ice cream (-4.4), pies and cakes (-11.1), and carbonated soft drinks (-17.2) emerged as the most nutrient-poor snacks. Conclusions: The NRF Index is a useful tool for assessing the overall nutritional value of snacks based on nutrients to limit and nutrients to encourage.

The effects of perinatal testosterone exposure on the DNA methylome of the mouse brain are late-emerging

PubMed Central

2014-01-01

Background The biological basis for sex differences in brain function and disease susceptibility is poorly understood. Examining the role of gonadal hormones in brain sexual differentiation may provide important information about sex differences in neural health and development. Permanent masculinization of brain structure, function, and disease is induced by testosterone prenatally in males, but the possible mediation of these effects by long-term changes in the epigenome is poorly understood. Methods We investigated the organizational effects of testosterone on the DNA methylome and transcriptome in two sexually dimorphic forebrain regions—the bed nucleus of the stria terminalis/preoptic area and the striatum. To study the contribution of testosterone to both the establishment and persistence of sex differences in DNA methylation, we performed genome-wide surveys in male, female, and female mice given testosterone on the day of birth. Methylation was assessed during the perinatal window for testosterone's organizational effects and in adulthood. Results The short-term effect of testosterone exposure was relatively modest. However, in adult animals the number of genes whose methylation was altered had increased by 20-fold. Furthermore, we found that in adulthood, methylation at a substantial number of sexually dimorphic CpG sites was masculinized in response to neonatal testosterone exposure. Consistent with this, testosterone's effect on gene expression in the striatum was more apparent in adulthood. Conclusion Taken together, our data imply that the organizational effects of testosterone on the brain methylome and transcriptome are dramatic and late-emerging. Our findings offer important insights into the long-term molecular effects of early-life hormonal exposure. PMID:24976947

Neuronal correlates of decisions to speak and act: Spontaneous emergence and dynamic topographies in a computational model of frontal and temporal areas

PubMed Central

Garagnani, Max; Pulvermüller, Friedemann

2013-01-01

The neural mechanisms underlying the spontaneous, stimulus-independent emergence of intentions and decisions to act are poorly understood. Using a neurobiologically realistic model of frontal and temporal areas of the brain, we simulated the learning of perception–action circuits for speech and hand-related actions and subsequently observed their spontaneous behaviour. Noise-driven accumulation of reverberant activity in these circuits leads to their spontaneous ignition and partial-to-full activation, which we interpret, respectively, as model correlates of action intention emergence and action decision-and-execution. Importantly, activity emerged first in higher-association prefrontal and temporal cortices, subsequently spreading to secondary and finally primary sensorimotor model-areas, hence reproducing the dynamics of cortical correlates of voluntary action revealed by readiness-potential and verb-generation experiments. This model for the first time explains the cortical origins and topography of endogenous action decisions, and the natural emergence of functional specialisation in the cortex, as mechanistic consequences of neurobiological principles, anatomical structure and sensorimotor experience. PMID:23489583

Alternative splicing in plant immunity.

PubMed

Yang, Shengming; Tang, Fang; Zhu, Hongyan

2014-06-10

Alternative splicing (AS) occurs widely in plants and can provide the main source of transcriptome and proteome diversity in an organism. AS functions in a range of physiological processes, including plant disease resistance, but its biological roles and functional mechanisms remain poorly understood. Many plant disease resistance (R) genes undergo AS, and several R genes require alternatively spliced transcripts to produce R proteins that can specifically recognize pathogen invasion. In the finely-tuned process of R protein activation, the truncated isoforms generated by AS may participate in plant disease resistance either by suppressing the negative regulation of initiation of immunity, or by directly engaging in effector-triggered signaling. Although emerging research has shown the functional significance of AS in plant biotic stress responses, many aspects of this topic remain to be understood. Several interesting issues surrounding the AS of R genes, especially regarding its functional roles and regulation, will require innovative techniques and additional research to unravel.

Wound repair and regeneration: mechanisms, signaling, and translation.

PubMed

Eming, Sabine A; Martin, Paul; Tomic-Canic, Marjana

2014-12-03

The cellular and molecular mechanisms underpinning tissue repair and its failure to heal are still poorly understood, and current therapies are limited. Poor wound healing after trauma, surgery, acute illness, or chronic disease conditions affects millions of people worldwide each year and is the consequence of poorly regulated elements of the healthy tissue repair response, including inflammation, angiogenesis, matrix deposition, and cell recruitment. Failure of one or several of these cellular processes is generally linked to an underlying clinical condition, such as vascular disease, diabetes, or aging, which are all frequently associated with healing pathologies. The search for clinical strategies that might improve the body's natural repair mechanisms will need to be based on a thorough understanding of the basic biology of repair and regeneration. In this review, we highlight emerging concepts in tissue regeneration and repair, and provide some perspectives on how to translate current knowledge into viable clinical approaches for treating patients with wound-healing pathologies. Copyright © 2014, American Association for the Advancement of Science.

Wound repair and regeneration: Mechanisms, signaling, and translation

PubMed Central

Eming, Sabine A.; Martin, Paul; Tomic-Canic, Marjana

2015-01-01

The cellular and molecular mechanisms underpinning tissue repair and its failure to heal are still poorly understood, and current therapies are limited. Poor wound healing after trauma, surgery, acute illness, or chronic disease conditions affects millions of people worldwide each year and is the consequence of poorly regulated elements of the healthy tissue repair response, including inflammation, angiogenesis, matrix deposition, and cell recruitment. Failure of one or several of these cellular processes is generally linked to an underlying clinical condition, such as vascular disease, diabetes, or aging, which are all frequently associated with healing pathologies. The search for clinical strategies that might improve the body’s natural repair mechanisms will need to be based on a thorough understanding of the basic biology of repair and regeneration. In this review, we highlight emerging concepts in tissue regeneration and repair, and provide some perspectives on how to translate current knowledge into viable clinical approaches for treating patients with wound-healing pathologies. PMID:25473038

Hypertensive Emergencies in Pregnancy.

PubMed

Olson-Chen, Courtney; Seligman, Neil S

2016-01-01

The prevalence of hypertensive disorders in pregnancy is increasing. The etiology and pathophysiology of hypertensive disorders in pregnancy remain poorly understood. Hypertensive disorders are a major cause of maternal and perinatal morbidity and mortality. Treatment of hypertension decreases the incidence of severe hypertension, but it does not impact rates of preeclampsia or other pregnancy complications. Several antihypertensive medications are commonly used in pregnancy, although there is a lack of randomized controlled trials. Severe hypertension should be treated immediately to prevent maternal end-organ damage. Appropriate antepartum, intrapartum, and postpartum management is important in caring for patients with hypertensive disorders. Copyright © 2016 Elsevier Inc. All rights reserved.

Persistent RNA virus infections: do PAMPS drive chronic disease?

PubMed Central

McCarthy, Mary K.; Morrison, Thomas E.

2017-01-01

Chronic disease associated with persistent RNA virus infections represents a key public health concern. While human immunodeficiency virus-1 and hepatitis C virus are perhaps the most well-known examples of persistent RNA viruses that cause chronic disease, evidence suggests that many other RNA viruses, including re-emerging viruses such as chikungunya virus, Ebola virus and Zika virus, establish persistent infections. The mechanisms by which RNA viruses drive chronic disease are poorly understood. Here, we discuss how the persistence of viral RNA may drive chronic disease manifestations via the activation of RNA sensing pathways. PMID:28214732

A framework for the study of zoonotic disease emergence and its drivers: spillover of bat pathogens as a case study

PubMed Central

Wood, James L. N.; Leach, Melissa; Waldman, Linda; MacGregor, Hayley; Fooks, Anthony R.; Jones, Kate E.; Restif, Olivier; Dechmann, Dina; Hayman, David T. S.; Baker, Kate S.; Peel, Alison J.; Kamins, Alexandra O.; Fahr, Jakob; Ntiamoa-Baidu, Yaa; Suu-Ire, Richard; Breiman, Robert F.; Epstein, Jonathan H.; Field, Hume E.; Cunningham, Andrew A.

2012-01-01

Many serious emerging zoonotic infections have recently arisen from bats, including Ebola, Marburg, SARS-coronavirus, Hendra, Nipah, and a number of rabies and rabies-related viruses, consistent with the overall observation that wildlife are an important source of emerging zoonoses for the human population. Mechanisms underlying the recognized association between ecosystem health and human health remain poorly understood and responding appropriately to the ecological, social and economic conditions that facilitate disease emergence and transmission represents a substantial societal challenge. In the context of disease emergence from wildlife, wildlife and habitat should be conserved, which in turn will preserve vital ecosystem structure and function, which has broader implications for human wellbeing and environmental sustainability, while simultaneously minimizing the spillover of pathogens from wild animals into human beings. In this review, we propose a novel framework for the holistic and interdisciplinary investigation of zoonotic disease emergence and its drivers, using the spillover of bat pathogens as a case study. This study has been developed to gain a detailed interdisciplinary understanding, and it combines cutting-edge perspectives from both natural and social sciences, linked to policy impacts on public health, land use and conservation. PMID:22966143

The Emerging Importance of IgG Fab Glycosylation in Immunity.

PubMed

van de Bovenkamp, Fleur S; Hafkenscheid, Lise; Rispens, Theo; Rombouts, Yoann

2016-02-15

Human IgG is the most abundant glycoprotein in serum and is crucial for protective immunity. In addition to conserved IgG Fc glycans, ∼15-25% of serum IgG contains glycans within the variable domains. These so-called "Fab glycans" are primarily highly processed complex-type biantennary N-glycans linked to N-glycosylation sites that emerge during somatic hypermutation. Specific patterns of Fab glycosylation are concurrent with physiological and pathological conditions, such as pregnancy and rheumatoid arthritis. With respect to function, Fab glycosylation can significantly affect stability, half-life, and binding characteristics of Abs and BCRs. Moreover, Fab glycans are associated with the anti-inflammatory activity of IVIgs. Consequently, IgG Fab glycosylation appears to be an important, yet poorly understood, process that modulates immunity. Copyright © 2016 by The American Association of Immunologists, Inc.

Adenosine signaling promotes hematopoietic stem and progenitor cell emergence

PubMed Central

Jing, Lili; Tamplin, Owen J.; Chen, Michael J.; Deng, Qing; Patterson, Shenia; Kim, Peter G.; Durand, Ellen M.; McNeil, Ashley; Green, Julie M.; Matsuura, Shinobu; Ablain, Julien; Brandt, Margot K.; Schlaeger, Thorsten M.; Huttenlocher, Anna; Daley, George Q.; Ravid, Katya

2015-01-01

Hematopoietic stem cells (HSCs) emerge from aortic endothelium via the endothelial-to-hematopoietic transition (EHT). The molecular mechanisms that initiate and regulate EHT remain poorly understood. Here, we show that adenosine signaling regulates hematopoietic stem and progenitor cell (HSPC) development in zebrafish embryos. The adenosine receptor A2b is expressed in the vascular endothelium before HSPC emergence. Elevated adenosine levels increased runx1+/cmyb+ HSPCs in the dorsal aorta, whereas blocking the adenosine pathway decreased HSPCs. Knockdown of A2b adenosine receptor disrupted scl+ hemogenic vascular endothelium and the subsequent EHT process. A2b adenosine receptor activation induced CXCL8 via cAMP–protein kinase A (PKA) and mediated hematopoiesis. We further show that adenosine increased multipotent progenitors in a mouse embryonic stem cell colony-forming assay and in embryonic day 10.5 aorta-gonad-mesonephros explants. Our results demonstrate that adenosine signaling plays an evolutionary conserved role in the first steps of HSPC formation in vertebrates. PMID:25870200

REVIEWING HIV-RELATED RESEARCH IN EMERGING ECONOMIES: THE ROLE OF GOVERNMENT REVIEWING AGENCIES

PubMed Central

Klitzman, Robert; Sexton, Patrina; Hui, Katrina; Hanrahan, Donna; Barnes, Mark; Sugarman, Jeremy; London, Alex John

2015-01-01

Little research has explored the possible effects of government institutions in emerging economies on ethical reviews of multinational research. We conducted semi-structured, in-depth telephone interviews with 15 researchers, Research Ethics Committees (RECs) personnel, and a government agency member involved in multinational HIV Prevention Trials Network (HPTN) research in emerging economies. Ministries of Health (MOH) or other government agencies often play pivotal roles as facilitators or barriers in the research ethics approval process. Government agency RECs reviewing protocols may face particular challenges, as they can lack resources, be poorly organized, have inconsistent review processes and, limited expertise, use differing definitions of national interests, including upholding national reputation and avoiding potential exploitation and stigma of the country’s population. The MOH/governmental review body may be affected by power dynamics and politics in study reviews; may consider issues both related and unrelated to research ethics as understood elsewhere; and may prioritize particular diseases, treatments, or interventions over other topics/types of research. Poor communication and deeply-rooted tensions may exist between sponsor and host countries, impeding optimal interactions and reviews. Investigators must understand and plan for the potential effects of governmental agencies on multinational collaborative research, including preserving adequate time for agency review, and contacting these agencies beforehand to address issues that may arise. Better understanding of these issues can aid and advance appropriate global scientific collaboration. PMID:25388003

Reviewing HIV-Related Research in Emerging Economies: The Role of Government Reviewing Agencies.

PubMed

Sexton, Patrina; Hui, Katrina; Hanrahan, Donna; Barnes, Mark; Sugarman, Jeremy; London, Alex John; Klitzman, Robert

2016-04-01

Little research has explored the possible effects of government institutions in emerging economies on ethical reviews of multinational research. We conducted semi-structured, in-depth telephone interviews with 15 researchers, Research Ethics Committees (RECs) personnel, and a government agency member involved in multinational HIV Prevention Trials Network (HPTN) research in emerging economies. Ministries of Health (MOH) or other government agencies often play pivotal roles as facilitators or barriers in the research ethics approval process. Government agency RECs reviewing protocols may face particular challenges, as they can lack resources, be poorly organized, have inconsistent review processes and limited expertise, and use differing definitions of national interests, including upholding national reputation and avoiding potential exploitation and stigma of the country's population. The MOH/governmental review body may be affected by power dynamics and politics in study reviews; may consider issues both related and unrelated to research ethics as understood elsewhere; and may prioritize particular diseases, treatments, or interventions over other topics/types of research. Poor communication and deeply-rooted tensions may exist between sponsor and host countries, impeding optimal interactions and reviews. Investigators must understand and plan for the potential effects of governmental agencies on multinational collaborative research, including preserving adequate time for agency review, and contacting these agencies beforehand to address issues that may arise. Better understanding of these issues can aid and advance appropriate global scientific collaboration. © 2014 John Wiley & Sons Ltd.

Needs and fears of young people presenting at accident and emergency department following an act of self-harm: secondary analysis of qualitative data.

PubMed

Owens, Christabel; Hansford, Lorraine; Sharkey, Siobhan; Ford, Tamsin

2016-03-01

Presentation at an accident and emergency (A&E) department is a key opportunity to engage with a young person who self-harms. The needs of this vulnerable group and their fears about presenting to healthcare services, including A&E, are poorly understood. To examine young people's perceptions of A&E treatment following self-harm and their views on what constitutes a positive clinical encounter. Secondary analysis of qualitative data from an experimental online discussion forum. Threads selected for secondary analysis represent the views of 31 young people aged 16-25 with experience of self-harm. Participants reported avoiding A&E whenever possible, based on their own and others' previous poor experiences. When forced to seek emergency care, they did so with feelings of shame and unworthiness. These feelings were reinforced when they received what they perceived as punitive treatment from A&E staff, perpetuating a cycle of shame, avoidance and further self-harm. Positive encounters were those in which they received 'treatment as usual', i.e. non-discriminatory care, delivered with kindness, which had the potential to challenge negative self-evaluation and break the cycle. The clinical needs of young people who self-harm continue to demand urgent attention. Further hypothesis testing and trials of different models of care delivery for this vulnerable group are warranted. © The Royal College of Psychiatrists 2016.

Predictors of hopelessness among clinically depressed youth.

PubMed

Becker-Weidman, Emily G; Reinecke, Mark A; Jacobs, Rachel H; Martinovich, Zoran; Silva, Susan G; March, John S

2009-05-01

Factors that distinguish depressed individuals who become hopeless from those who do not are poorly understood. In this study, predictors of hopelessness were examined in a sample of 439 clinically depressed adolescents participating in the Treatment for Adolescents with Depression Study (TADS). The total score of the Beck Hopelessness Scale (BHS) was used to assess hopelessness at baseline. Multiple regression and logistic regression analyses were conducted to evaluate the extent to which variables were associated with hopelessness and determine which cluster of measures best predicted clinically significantly hopelessness. Hopelessness was associated with greater depression severity, poor social problem-solving, cognitive distortions, and family conflict. View of self, view of the world, internal attributional style, need for social approval, positive problem-solving orientation, and family problems consistently emerged as the best predictors of hopelessness in depressed youth. Cognitive and familial factors predict those depressed youth who have high levels of hopelessness.

Investigation of Nitride Morphology After Self-Aligned Contact Etch

NASA Technical Reports Server (NTRS)

Hwang, Helen H.; Keil, J.; Helmer, B. A.; Chien, T.; Gopaladasu, P.; Kim, J.; Shon, J.; Biegel, Bryan (Technical Monitor)

2001-01-01

Self-Aligned Contact (SAC) etch has emerged as a key enabling technology for the fabrication of very large-scale memory devices. However, this is also a very challenging technology to implement from an etch viewpoint. The issues that arise range from poor oxide etch selectivity to nitride to problems with post etch nitride surface morphology. Unfortunately, the mechanisms that drive nitride loss and surface behavior remain poorly understood. Using a simple langmuir site balance model, SAC nitride etch simulations have been performed and compared to actual etched results. This approach permits the study of various etch mechanisms that may play a role in determining nitride loss and surface morphology. Particle trajectories and fluxes are computed using Monte-Carlo techniques and initial data obtained from double Langmuir probe measurements. Etched surface advancement is implemented using a shock tracking algorithm. Sticking coefficients and etch yields are adjusted to obtain the best agreement between actual etched results and simulated profiles.

Early childhood growth failure and the developmental origins of adult disease: Do enteric infections and malnutrition increase risk for the metabolic syndrome?

PubMed Central

DeBoer, Mark D.; Lima, Aldo A. M.; Oría, Reinaldo B.; Scharf, Rebecca J.; Moore, Sean R.; Luna, Max A.; Guerrant, Richard L.

2012-01-01

Hypotheses regarding the developmental origins of health and disease postulate that developing fetuses–and potentially young children—undergo adaptive epigenetic changes with longstanding effects on metabolism and other processes. Ongoing research explores whether these adaptations occur during early life following malnutrition. In the developing world there remains a high degree of nutritional stunting—linear growth failure due to inadequate calories that may be exacerbated by inflammation from ongoing infections. In areas with poor sanitation children experience vicious cycles of enteric infections and malnutrition, resulting in poor nutrient absorption from intestinal mucosa changes now termed “environmental enteropathy.” Emerging evidence links early childhood diarrhea and/or growth failure with increased CVD risk factors in later life, including dyslipidemia, hypertension and glucose intolerance. The mechanisms for these associations remain poorly understood and may relate to epigenetic responses to poor nutrition, increased inflammation or both. Given increases in CVD in developing areas of the world, associations between childhood malnutrition, early life infections and increased CVD risk factors underscore further reasons to improve nutrition and infection-related outcomes for young children worldwide. PMID:23110643

Emergence of collective propulsion through cell-cell adhesion.

PubMed

Matsushita, Katsuyoshi

2018-04-01

The mechanisms driving the collective movement of cells remain poorly understood. To contribute toward resolving this mystery, a model was formulated to theoretically explore the possible functions of polarized cell-cell adhesion in collective cell migration. The model consists of an amoeba cell with polarized cell-cell adhesion, which is controlled by positive feedback with cell motion. This model cell has no persistent propulsion and therefore exhibits a simple random walk when in isolation. However, at high density, these cells acquire collective propulsion and form ordered movement. This result suggests that cell-cell adhesion has a potential function, which induces collective propulsion with persistence.

Mantle convection and plate tectonics: toward an integrated physical and chemical theory

PubMed

Tackley

2000-06-16

Plate tectonics and convection of the solid, rocky mantle are responsible for transporting heat out of Earth. However, the physics of plate tectonics is poorly understood; other planets do not exhibit it. Recent seismic evidence for convection and mixing throughout the mantle seems at odds with the chemical composition of erupted magmas requiring the presence of several chemically distinct reservoirs within the mantle. There has been rapid progress on these two problems, with the emergence of the first self-consistent models of plate tectonics and mantle convection, along with new geochemical models that may be consistent with seismic and dynamical constraints on mantle structure.

Emergence of collective propulsion through cell-cell adhesion

NASA Astrophysics Data System (ADS)

Matsushita, Katsuyoshi

2018-04-01

The mechanisms driving the collective movement of cells remain poorly understood. To contribute toward resolving this mystery, a model was formulated to theoretically explore the possible functions of polarized cell-cell adhesion in collective cell migration. The model consists of an amoeba cell with polarized cell-cell adhesion, which is controlled by positive feedback with cell motion. This model cell has no persistent propulsion and therefore exhibits a simple random walk when in isolation. However, at high density, these cells acquire collective propulsion and form ordered movement. This result suggests that cell-cell adhesion has a potential function, which induces collective propulsion with persistence.

'Maybe it was her fate and maybe she ran out of blood': final caregivers' perspectives on access to care in obstetric emergencies in rural Indonesia.

PubMed

D'Ambruoso, Lucia; Byass, Peter; Qomariyah, Siti Nurul

2010-03-01

Maternal mortality persists in low-income settings despite preventability with skilled birth attendance and emergency obstetric care. Poor access limits the effectiveness of life-saving interventions and is typical of maternal health care in low-income settings. This paper examines access to care in obstetric emergencies from the perspectives of service users, using established and contemporary theoretical frameworks of access and a routine health surveillance method. The implications for health planning are also considered. The final caregivers of 104 women who died during pregnancy or childbirth were interviewed in two rural districts in Indonesia using an adapted verbal autopsy. Qualitative analysis revealed social and economic barriers to access and barriers that arose from the health system itself. Health insurance for the poor was highly problematic. For providers, incomplete reimbursements, and low public pay, acted as disincentives to treat the poor. For users, the schemes were poorly socialized and understood, complicated to use and led to lower quality care. Services, staff, transport, equipment and supplies were also generally unavailable or unaffordable. The multiple barriers to access conferred a cumulative disadvantage that culminated in exclusion. This was reflected in expressions of powerlessness and fatalism regarding the deaths. The analysis suggests that conceiving of access as a structurally determined, complex and dynamic process, and as a reciprocally maintained phenomenon of disadvantaged groups, may provide useful explanatory concepts for health planning. Health planning from this perspective may help to avoid perpetuating exclusion on social and economic grounds, by health systems and services, and help foster a sense of control at the micro-level, among peoples' feelings and behaviours regarding their health. Verbal autopsy surveys provide an opportunity to routinely collect information on the exclusory mechanisms of health systems, important information for equitable health planning.

The influence of bacteria on multitrophic interactions among plants, psyllids, and pathogen.

PubMed

Tamborindeguy, Cecilia; Huot, Ordom Brian; Ibanez, Freddy; Levy, Julien

2017-12-01

The recent emergence of several plant diseases caused by psyllid-borne bacterial pathogens worldwide (Candidatus Liberibacter spp.) has created renewed interest on the interaction between psyllids and bacteria. In spite of these efforts to understand psyllid association with bacteria, many aspects of their interactions remain poorly understood. As more organisms are studied, subtleties on the molecular interactions as well as on the effects of the bacteria on the psyllid host are being uncovered. Additionally, psyllid-borne bacterial phytopathogens can also affect the host plant, which in turn can impact psyllid physiology and behavior. Here, we review the current literature on different aspects of the influence of bacteria on multitrophic interactions among plants, psyllids, and pathogens. We then highlight gaps that need to be addressed to advance this field, which can have significant implications for controlling these newly emergent and other plant diseases. © 2017 Institute of Zoology, Chinese Academy of Sciences.

Alpha-synuclein Toxicity in the Early Secretory Pathway: How It Drives Neurodegeneration in Parkinsons Disease

PubMed Central

Wang, Ting; Hay, Jesse C.

2015-01-01

Alpha-synuclein is a predominant player in the pathogenesis of Parkinson's Disease. However, despite extensive study for two decades, its physiological and pathological mechanisms remain poorly understood. Alpha-synuclein forms a perplexing web of interactions with lipids, trafficking machinery, and other regulatory factors. One emerging consensus is that synaptic vesicles are likely the functional site for alpha-synuclein, where it appears to facilitate vesicle docking and fusion. On the other hand, the dysfunctions of alpha-synuclein are more dispersed and numerous; when mutated or over-expressed, alpha-synuclein affects several membrane trafficking and stress pathways, including exocytosis, ER-to-Golgi transport, ER stress, Golgi homeostasis, endocytosis, autophagy, oxidative stress, and others. Here we examine recent developments in alpha-synuclein's toxicity in the early secretory pathway placed in the context of emerging themes from other affected pathways to help illuminate its underlying pathogenic mechanisms in neurodegeneration. PMID:26617485

Evolutionary interplay between sister cytochrome P450 genes shapes plasticity in plant metabolism.

PubMed

Liu, Zhenhua; Tavares, Raquel; Forsythe, Evan S; André, François; Lugan, Raphaël; Jonasson, Gabriella; Boutet-Mercey, Stéphanie; Tohge, Takayuki; Beilstein, Mark A; Werck-Reichhart, Danièle; Renault, Hugues

2016-10-07

Expansion of the cytochrome P450 gene family is often proposed to have a critical role in the evolution of metabolic complexity, in particular in microorganisms, insects and plants. However, the molecular mechanisms underlying the evolution of this complexity are poorly understood. Here we describe the evolutionary history of a plant P450 retrogene, which emerged and underwent fixation in the common ancestor of Brassicales, before undergoing tandem duplication in the ancestor of Brassicaceae. Duplication leads first to gain of dual functions in one of the copies. Both sister genes are retained through subsequent speciation but eventually return to a single copy in two of three diverging lineages. In the lineage in which both copies are maintained, the ancestral functions are split between paralogs and a novel function arises in the copy under relaxed selection. Our work illustrates how retrotransposition and gene duplication can favour the emergence of novel metabolic functions.

Microscale insights into pneumococcal antibiotic mutant selection windows

PubMed Central

Sorg, Robin A.; Veening, Jan-Willem

2015-01-01

The human pathogen Streptococcus pneumoniae shows alarming rates of antibiotic resistance emergence. The basic requirements for de novo resistance emergence are poorly understood in the pneumococcus. Here we systematically analyse the impact of antibiotics on S. pneumoniae at concentrations that inhibit wild type cells, that is, within the mutant selection window. We identify discrete growth-inhibition profiles for bacteriostatic and bactericidal compounds, providing a predictive framework for distinction between the two classifications. Cells treated with bacteriostatic agents show continued gene expression activity, and real-time mutation assays link this activity to the development of genotypic resistance. Time-lapse microscopy reveals that antibiotic-susceptible pneumococci display remarkable growth and death bistability patterns in response to many antibiotics. We furthermore capture the rise of subpopulations with decreased susceptibility towards cell wall synthesis inhibitors (heteroresisters). We show that this phenomenon is epigenetically inherited, and that heteroresistance potentiates the accumulation of genotypic resistance. PMID:26514094

Local Generation and Propagation of Ripples along the Septotemporal Axis of the Hippocampus

PubMed Central

Patel, Jagdish; Schomburg, Erik W.; Berényi, Antal; Fujisawa, Shigeyoshi

2013-01-01

A topographical relationship exists between the septotemporal segments of the hippocampus and their entorhinal–neocortical targets, but the physiological organization of activity along the septotemporal axis is poorly understood. We recorded sharp-wave ripple patterns in rats during sleep from the entire septotemporal axis of the CA1 pyramidal layer. Qualitatively similar ripples emerged at all levels. From the local seed, ripples traveled septally or temporally at a speed of ∼0.35 m/s, and the spatial spread depended on ripple magnitude. Ripples propagated smoothly across the septal and intermediate segments of the hippocampus, but ripples in the temporal segment often remained isolated. These findings show that ripples can combine information from the septal and intermediate hippocampus and transfer integrated signals downstream. In contrast, ripples that emerged in the temporal pole broadcast largely independent information to their cortical and subcortical targets. PMID:24155307

Genetics and epigenetics of rheumatoid arthritis

PubMed Central

Viatte, Sebastien; Plant, Darren; Raychaudhuri, Soumya

2013-01-01

Investigators have made key advances in rheumatoid arthritis (RA) genetics in the past 10 years. Although genetic studies have had limited influence on clinical practice and drug discovery, they are currently generating testable hypotheses to explain disease pathogenesis. Firstly, we review here the major advances in identifying RA genetic susceptibility markers both within and outside of the MHC. Understanding how genetic variants translate into pathogenic mechanisms and ultimately into phenotypes remains a mystery for most of the polymorphisms that confer susceptibility to RA, but functional data are emerging. Interplay between environmental and genetic factors is poorly understood and in need of further investigation. Secondly, we review current knowledge of the role of epigenetics in RA susceptibility. Differences in the epigenome could represent one of the ways in which environmental exposures translate into phenotypic outcomes. The best understood epigenetic phenomena include post-translational histone modifications and DNA methylation events, both of which have critical roles in gene regulation. Epigenetic studies in RA represent a new area of research with the potential to answer unsolved questions. PMID:23381558

Laboratory tests for mumps vaccines.

PubMed

Minor, P D

1997-03-01

The action of live attenuated vaccines against mumps is poorly understood although their clinical efficacy is beyond doubt. The attenuated character of the vaccine is assured by consistency of production related to clinical trials, and limited studies of vaccine seeds in primates. Potency is assessed by infectivity in vitro and is subject to poorly understood sources of variation. Molecular biological studies are at an early stage.

Emergence of a bacterial clone with enhanced virulence by acquisition of a phage encoding a secreted phospholipase A2.

PubMed

Sitkiewicz, Izabela; Nagiec, Michal J; Sumby, Paul; Butler, Stephanie D; Cywes-Bentley, Colette; Musser, James M

2006-10-24

The molecular basis of pathogen clone emergence is relatively poorly understood. Acquisition of a bacteriophage encoding a previously unknown secreted phospholipase A(2) (designated SlaA) has been implicated in the rapid emergence in the mid-1980s of a new hypervirulent clone of serotype M3 group A Streptococcus. Although several lines of circumstantial evidence suggest that SlaA is a virulence factor, this issue has not been addressed experimentally. We found that an isogenic DeltaslaA mutant strain was significantly impaired in ability to adhere to and kill human epithelial cells compared with the wild-type parental strain. The mutant strain was less virulent for mice than the wild-type strain, and immunization with purified SlaA significantly protected mice from invasive disease. Importantly, the mutant strain was significantly attenuated for colonization in a monkey model of pharyngitis. We conclude that transductional acquisition of the ability of a GAS strain to produce SlaA enhanced the spread and virulence of the serotype M3 precursor strain. Hence, these studies identified a crucial molecular event underlying the evolution, rapid emergence, and widespread dissemination of unusually severe human infections caused by a distinct bacterial clone.

Cross-ecosystem impacts of stream pollution reduce resource and contaminant flux to riparian food webs

USGS Publications Warehouse

Kraus, Johanna M.; Schmidt, Travis S.; Walters, David; Wanty, Richard B.; Zuellig, Robert E.; Wolf, Ruth E.

2014-01-01

The effects of aquatic contaminants are propagated across ecosystem boundaries by aquatic insects that export resources and contaminants to terrestrial food webs; however, the mechanisms driving these effects are poorly understood. We examined how emergence, contaminant concentration, and total contaminant flux by adult aquatic insects changed over a gradient of bioavailable metals in streams and how these changes affected riparian web-building spiders. Insect emergence decreased 97% over the metal gradient, whereas metal concentrations in adult insects changed relatively little. As a result, total metal exported by insects (flux) was lowest at the most contaminated streams, declining 96% among sites. Spiders were affected by the decrease in prey biomass, but not by metal exposure or metal flux to land in aquatic prey. Aquatic insects are increasingly thought to increase exposure of terrestrial consumers to aquatic contaminants, but stream metals reduce contaminant flux to riparian consumers by strongly impacting the resource linkage. Our results demonstrate the importance of understanding the contaminant-specific effects of aquatic pollutants on adult insect emergence and contaminant accumulation in adults to predict impacts on terrestrial food webs.

Acute, Nontraumatic Spontaneous Spinal Subdural Hematoma: A Case Report and Systematic Review of the Literature

PubMed Central

Abel, Taylor J.

2017-01-01

Spontaneous spinal subdural hematoma (sSDH) is a rare condition outright. Moreover, cases that occur spontaneously in the absence of an identifiable etiology are considerably less common and remain poorly understood. Here, we present the case of a 43-year-old man with spontaneous sSDH presenting with acute onset low back pain and paraplegia. Urgent magnetic resonance imaging identified a dorsal SDH from T8 to T11 with compression of the spinal cord. Emergent T8–T10 laminectomies with intradural exploration and hematoma evacuation were performed. However, despite prompt identification and appropriate action, the patient's recovery was modest and significant disability remained at discharge. This unique and unusual case demonstrates that spontaneous sSDH requires prompt surgical treatment to minimize associated morbidity and supports the association between the presence of severe neurological deficits upon initial presentation with less favorable outcomes. We performed a comprehensive systematic review of spontaneous sSDH of unknown etiology, which demonstrates that emergent surgical intervention is indicated for patients presenting with severe neurological deficits and the presence of these deficits is predictive of poor neurological outcome. Furthermore, conservative management should be considered in patients presenting with mild neurological deficits as spontaneous resolution followed by favorable neurological outcomes is often observed in these patients. PMID:29441210

Metabolic and Demographic Feedbacks Shape the Emergent Spatial Structure and Function of Microbial Communities

PubMed Central

Estrela, Sylvie; Brown, Sam P.

2013-01-01

Microbes are predominantly found in surface-attached and spatially structured polymicrobial communities. Within these communities, microbial cells excrete a wide range of metabolites, setting the stage for interspecific metabolic interactions. The links, however, between metabolic and ecological interactions (functional relationships), and species spatial organization (structural relationships) are still poorly understood. Here, we use an individual-based modelling framework to simulate the growth of a two-species surface-attached community where food (resource) is traded for detoxification (service) and investigate how metabolic constraints of individual species shape the emergent structural and functional relationships of the community. We show that strong metabolic interdependence drives the emergence of mutualism, robust interspecific mixing, and increased community productivity. Specifically, we observed a striking and highly stable emergent lineage branching pattern, generating a persistent lineage mixing that was absent when the metabolic exchange was removed. These emergent community properties are driven by demographic feedbacks, such that aid from neighbouring cells directly enhances focal cell growth, which in turn feeds back to neighbour fecundity. In contrast, weak metabolic interdependence drives conflict (exploitation or competition), and in turn greater interspecific segregation. Together, these results support the idea that species structural and functional relationships represent the net balance of metabolic interdependencies. PMID:24385891

Women and men with intellectual disabilities who sell or trade sex: voices from the professionals.

PubMed

Kuosmanen, Jari; Starke, Mikaela

2011-01-01

The phenomenon of women and men with intellectual disabilities (ID) selling or exchanging sexual services is poorly understood. In this study, the authors explored the knowledge and perceptions of this phenomenon shared by professionals working in the field. Focus group discussions demonstrated broad familiarity with the phenomenon. Different motives and contributing factors were identified for the behavior, blurring the boundary line between free choice and exploitation. Two distinct discourses emerged from the interviews based on the assumed "rationality" of the sex transaction and its rewards: Those with ID who traded sexual favors were presented as either conscious and autonomous agents or unaware and exploited victims.

Clostridium difficile infection: Evolution, phylogeny and molecular epidemiology.

PubMed

Elliott, Briony; Androga, Grace O; Knight, Daniel R; Riley, Thomas V

2017-04-01

Over the recent decades, Clostridium difficile infection (CDI) has emerged as a global public health threat. Despite growing attention, C. difficile remains a poorly understood pathogen, however, the exquisite sensitivity offered by next generation sequencing (NGS) technology has enabled analysis of the genome of C. difficile, giving us access to massive genomic data on factors such as virulence, evolution, and genetic relatedness within C. difficile groups. NGS has also demonstrated excellence in investigations of outbreaks and disease transmission, in both small and large-scale applications. This review summarizes the molecular epidemiology, evolution, and phylogeny of C. difficile, one of the most important pathogens worldwide in the current antibiotic resistance era. Copyright © 2016 Elsevier B.V. All rights reserved.

Interplay of DNA repair with transcription: from structures to mechanisms.

PubMed

Deaconescu, Alexandra M; Artsimovitch, Irina; Grigorieff, Nikolaus

2012-12-01

Many DNA transactions are crucial for maintaining genomic integrity and faithful transfer of genetic information but remain poorly understood. An example is the interplay between nucleotide excision repair (NER) and transcription, also known as transcription-coupled DNA repair (TCR). Discovered decades ago, the mechanisms for TCR have remained elusive, not in small part due to the scarcity of structural studies of key players. Here we summarize recent structural information on NER/TCR factors, focusing on bacterial systems, and integrate it with existing genetic, biochemical, and biophysical data to delineate the mechanisms at play. We also review emerging, alternative modalities for recruitment of NER proteins to DNA lesions. Copyright © 2012 Elsevier Ltd. All rights reserved.

Motor and somatosensory conversion disorder: a functional unawareness syndrome?

PubMed

Perez, David L; Barsky, Arthur J; Daffner, Kirk; Silbersweig, David A

2012-01-01

Although conversion disorder is closely connected to the origins of neurology and psychiatry, it remains poorly understood. In this article, the authors discuss neural and clinical parallels between lesional unawareness disorders and unilateral motor and somatosensory conversion disorder, emphasizing functional neuroimaging/disease correlates. Authors suggest that a functional-unawareness neurobiological framework, mediated by right hemisphere-lateralized, large-scale brain network dysfunction, may play a significant role in the neurobiology of conversion disorder. The perigenual anterior cingulate and the posterior parietal cortices are detailed as important in disease pathophysiology. Further investigations will refine the functional-unawareness concept, clarify the role of affective circuits, and delineate the process through which functional neurologic symptoms emerge.

[Pulmonary hypertension in patients infected with human immunodeficiency virus: current situation].

PubMed

Soto-Abánades, Clara Itzíar; Alcolea-Batres, Sergio; Ríos-Blanco, Juan José

2013-01-01

The increase in survival that has been achieved with the new treatments in the era of highly active antiretroviral therapy, has enabled clinicians and researchers to analyze issues that emerge in the long term in patients with HIV infection. Although the majority of cardiovascular complications have been widely described, the pathogenesis of pulmonary arterial hypertension is still poorly understood, and is one of the more complex and feared complications as it worsens the prognosis and quality of life of these patients This article reviews newer aspects related to the aetiology, symptoms, diagnosis and treatment of this disease. Copyright © 2011 Elsevier España, S.L. All rights reserved.

Agricultural intensification, priming for persistence and the emergence of Nipah virus: a lethal bat-borne zoonosis

PubMed Central

Pulliam, Juliet R. C.; Epstein, Jonathan H.; Dushoff, Jonathan; Rahman, Sohayati A.; Bunning, Michel; Jamaluddin, Aziz A.; Hyatt, Alex D.; Field, Hume E.; Dobson, Andrew P.; Daszak, Peter

2012-01-01

Emerging zoonoses threaten global health, yet the processes by which they emerge are complex and poorly understood. Nipah virus (NiV) is an important threat owing to its broad host and geographical range, high case fatality, potential for human-to-human transmission and lack of effective prevention or therapies. Here, we investigate the origin of the first identified outbreak of NiV encephalitis in Malaysia and Singapore. We analyse data on livestock production from the index site (a commercial pig farm in Malaysia) prior to and during the outbreak, on Malaysian agricultural production, and from surveys of NiV's wildlife reservoir (flying foxes). Our analyses suggest that repeated introduction of NiV from wildlife changed infection dynamics in pigs. Initial viral introduction produced an explosive epizootic that drove itself to extinction but primed the population for enzootic persistence upon reintroduction of the virus. The resultant within-farm persistence permitted regional spread and increased the number of human infections. This study refutes an earlier hypothesis that anomalous El Niño Southern Oscillation-related climatic conditions drove emergence and suggests that priming for persistence drove the emergence of a novel zoonotic pathogen. Thus, we provide empirical evidence for a causative mechanism previously proposed as a precursor to widespread infection with H5N1 avian influenza and other emerging pathogens. PMID:21632614

Agricultural intensification, priming for persistence and the emergence of Nipah virus: a lethal bat-borne zoonosis.

PubMed

Pulliam, Juliet R C; Epstein, Jonathan H; Dushoff, Jonathan; Rahman, Sohayati A; Bunning, Michel; Jamaluddin, Aziz A; Hyatt, Alex D; Field, Hume E; Dobson, Andrew P; Daszak, Peter

2012-01-07

Emerging zoonoses threaten global health, yet the processes by which they emerge are complex and poorly understood. Nipah virus (NiV) is an important threat owing to its broad host and geographical range, high case fatality, potential for human-to-human transmission and lack of effective prevention or therapies. Here, we investigate the origin of the first identified outbreak of NiV encephalitis in Malaysia and Singapore. We analyse data on livestock production from the index site (a commercial pig farm in Malaysia) prior to and during the outbreak, on Malaysian agricultural production, and from surveys of NiV's wildlife reservoir (flying foxes). Our analyses suggest that repeated introduction of NiV from wildlife changed infection dynamics in pigs. Initial viral introduction produced an explosive epizootic that drove itself to extinction but primed the population for enzootic persistence upon reintroduction of the virus. The resultant within-farm persistence permitted regional spread and increased the number of human infections. This study refutes an earlier hypothesis that anomalous El Niño Southern Oscillation-related climatic conditions drove emergence and suggests that priming for persistence drove the emergence of a novel zoonotic pathogen. Thus, we provide empirical evidence for a causative mechanism previously proposed as a precursor to widespread infection with H5N1 avian influenza and other emerging pathogens.

Multifaceted role of EZH2 in breast and prostate tumorigenesis: epigenetics and beyond.

PubMed

Deb, Gauri; Thakur, Vijay S; Gupta, Sanjay

2013-05-01

Overexpression of EZH2 and other PRC2 subunits, such as SUZ12, is associated with tumor progression and poor prognosis in several human malignancies. Nevertheless, the underlying mechanisms driving aberrant EZH2 expression are poorly understood. This review provides molecular insights into the essential role of EZH2 in breast and prostate tumorigenesis. We addressed the current understanding on the oncogenic role of EZH2, with an emphasis on: (1) the less known PRC2-independent role of EZH2 in gene activation, in addition to its canonical role in transcriptional silencing as a histone methyltransferase catalyzing the trimethylation of histone H3 at lysine 27; (2) causes and consequences of its deregulation in tumor cells and; (3) collaboration of EZH2 with other epigenetic and hormone receptor-mediated oncogenic signaling pathways. We also summarize how EZH2 has emerged as a promising therapeutic target in hormone-refractory cancers and the prospects for integrating EZH2 blockade with available pharmacological inhibitors.

Chronic Wound Repair and Healing in Older Adults: Current Status and Future Research

PubMed Central

Gould, Lisa; Abadir, Peter; Brem, Harold; Carter, Marissa; Conner-Kerr, Teresa; Davidson, Jeff; DiPietro, Luisa; Falanga, Vincent; Fife, Caroline; Gardner, Sue; Grice, Elizabeth; Harmon, John; Hazzard, William R.; High, Kevin P.; Houghton, Pamela; Jacobson, Nasreen; Kirsner, Robert S.; Kovacs, Elizabeth J.; Margolish, David; McFarland Horne, Frances; Reed, May J.; Sullivan, Dennis H.; Thom, Stephen; Tomic-Canic, Marjana; Walston, Jeremy; Whitney, JoAnne; Williams, John; Zieman, Susan; Schmader, Kenneth

2014-01-01

The incidence of chronic wounds is increased among older adults, and the impact of chronic wounds on quality of life is particularly profound in this population. It is well established that wound healing slows with age. However, the basic biology underlying chronic wounds and the influence of age-associated changes on wound healing are poorly understood. Most studies have used in vitro approaches and various animal models, but observed changes translate poorly to human healing conditions. The impact of age and accompanying multi-morbidity on the effectiveness of existing and emerging treatment approaches for chronic wounds is also unknown, and older adults tend to be excluded from randomized clinical trials. Poorly defined outcomes and variables, lack of standardization in data collection, and variations in the definition, measurement, and treatment of wounds also hamper clinical studies. The Association of Specialty Professors, in conjunction with the National Institute on Aging and the Wound Healing Society, held a workshop, summarized in this paper, to explore the current state of knowledge and research challenges, engage investigators across disciplines, and identify key research questions to guide future study of age-associated changes in chronic wound healing. PMID:25486905

Chronic Wound Repair and Healing in Older Adults: Current Status and Future Research

PubMed Central

Gould, Lisa; Abadir, Peter; Brem, Harold; Carter, Marissa; Conner-Kerr, Teresa; Davidson, Jeff; DiPietro, Luisa; Falanga, Vincent; Fife, Caroline; Gardner, Sue; Grice, Elizabeth; Harmon, John; Hazzard, William R.; High, Kevin P.; Houghton, Pamela; Jacobson, Nasreen; Kirsner, Robert S.; Kovacs, Elizabeth J.; Margolis, David; Horne, Frances McFarland; Reed, May J.; Sullivan, Dennis H.; Thom, Stephen; Tomic-Canic, Marjana; Walston, Jeremy; Whitney, Jo Anne; Williams, John; Zieman, Susan; Schmader, Kenneth

2015-01-01

Older adults are more likely to have chronic wounds than younger people, and the effect of chronic wounds on quality of life is particularly profound in this population. Wound healing slows with age, but the basic biology underlying chronic wounds and the influence of age-associated changes on wound healing are poorly understood. Most studies have used in vitro approaches and various animal models, but observed changes translate poorly to human healing conditions. The effect of age and accompanying multimorbidity on the effectiveness of existing and emerging treatment approaches for chronic wounds is also unknown, and older adults tend to be excluded from randomized clinical trials. Poorly defined outcomes and variables; lack of standardization in data collection; and variations in the definition, measurement, and treatment of wounds also hamper clinical studies. The Association of Specialty Professors, in conjunction with the National Institute on Aging and the Wound Healing Society, held a workshop, summarized in this article, to explore the current state of knowledge and research challenges, engage investigators across disciplines, and identify research questions to guide future study of age-associated changes in chronic wound healing. PMID:25753048

Interoception, contemplative practice, and health

PubMed Central

Farb, Norman; Daubenmier, Jennifer; Price, Cynthia J.; Gard, Tim; Kerr, Catherine; Dunn, Barnaby D.; Klein, Anne Carolyn; Paulus, Martin P.; Mehling, Wolf E.

2015-01-01

Interoception can be broadly defined as the sense of signals originating within the body. As such, interoception is critical for our sense of embodiment, motivation, and well-being. And yet, despite its importance, interoception remains poorly understood within modern science. This paper reviews interdisciplinary perspectives on interoception, with the goal of presenting a unified perspective from diverse fields such as neuroscience, clinical practice, and contemplative studies. It is hoped that this integrative effort will advance our understanding of how interoception determines well-being, and identify the central challenges to such understanding. To this end, we introduce an expanded taxonomy of interoceptive processes, arguing that many of these processes can be understood through an emerging predictive coding model for mind–body integration. The model, which describes the tension between expected and felt body sensation, parallels contemplative theories, and implicates interoception in a variety of affective and psychosomatic disorders. We conclude that maladaptive construal of bodily sensations may lie at the heart of many contemporary maladies, and that contemplative practices may attenuate these interpretative biases, restoring a person’s sense of presence and agency in the world. PMID:26106345

Attend or defend? Sex differences in behavioral, autonomic, and respiratory response patterns to emotion-eliciting films.

PubMed

Wilhelm, Frank H; Rattel, Julina A; Wegerer, Melanie; Liedlgruber, Michael; Schweighofer, Simon; Kreibig, Sylvia D; Kolodyazhniy, Vitaliy; Blechert, Jens

2017-12-01

Sex differences in emotional reactivity have been studied primarily for negative but less so for positive stimuli; likewise, sex differences in the psychophysiological response-patterning during such stimuli are poorly understood. Thus, the present study examined sex differences in response to negative/positive and high/low arousing films (classified as threat-, loss-, achievement-, and recreation-related, vs. neutral films), while measuring 18 muscular, autonomic, and respiratory parameters. Sex differences emerged for all films, but were most prominent for threat-related films: Despite equivalent valence and arousal ratings, women displayed more facial-muscular and respiratory responding than men and pronounced sympathetic activation (preejection period, other cardiovascular and electrodermal measures), while men showed coactivated sympathetic/parasympathetic responding (including increased respiratory sinus arrhythmia). This indicates a prototypical threat-related defense response in women, while men showed a pattern of sustained orienting, which can be understood as a shift toward less threat proximity in the defense cascade model. Clinical implications are discussed within a socio-evolutionary framework. Copyright © 2017 Elsevier B.V. All rights reserved.

Life history linked to immune investment in developing amphibians.

PubMed

Woodhams, Douglas C; Bell, Sara C; Bigler, Laurent; Caprioli, Richard M; Chaurand, Pierre; Lam, Brianna A; Reinert, Laura K; Stalder, Urs; Vazquez, Victoria M; Schliep, Klaus; Hertz, Andreas; Rollins-Smith, Louise A

2016-01-01

The broad diversity of amphibian developmental strategies has been shaped, in part, by pathogen pressure, yet trade-offs between the rate of larval development and immune investment remain poorly understood. The expression of antimicrobial peptides (AMPs) in skin secretions is a crucial defense against emerging amphibian pathogens and can also indirectly affect host defense by influencing the composition of skin microbiota. We examined the constitutive or induced expression of AMPs in 17 species at multiple life-history stages. We found that AMP defenses in tadpoles of species with short larval periods (fast pace of life) were reduced in comparison with species that overwinter as tadpoles and grow to a large size. A complete set of defensive peptides emerged soon after metamorphosis. These findings support the hypothesis that species with a slow pace of life invest energy in AMP production to resist potential pathogens encountered during the long larval period, whereas species with a fast pace of life trade this investment in defense for more rapid growth and development.

Emergent dynamics of spatio-temporal chaos in a heterogeneous excitable medium.

PubMed

Bittihn, Philip; Berg, Sebastian; Parlitz, Ulrich; Luther, Stefan

2017-09-01

Self-organized activation patterns in excitable media such as spiral waves and spatio-temporal chaos underlie dangerous cardiac arrhythmias. While the interaction of single spiral waves with different types of heterogeneity has been studied extensively, the effect of heterogeneity on fully developed spatio-temporal chaos remains poorly understood. We investigate how the complexity and stability properties of spatio-temporal chaos in the Bär-Eiswirth model of excitable media depend on the heterogeneity of the underlying medium. We employ different measures characterizing the chaoticity of the system and find that the spatial arrangement of multiple discrete lower excitability regions has a strong impact on the complexity of the dynamics. Varying the number, shape, and spatial arrangement of the heterogeneities, we observe strong emergent effects ranging from increases in chaoticity to the complete cessation of chaos, contrasting the expectation from the homogeneous behavior. The implications of our findings for the development and treatment of arrhythmias in the heterogeneous cardiac muscle are discussed.

Ethical perspectives on emerging assistive technologies: insights from focus groups with stakeholders in long-term care facilities.

PubMed

Dorsten, Aimee-Marie; Sifford, K Susan; Bharucha, Ashok; Mecca, Laurel Person; Wactlar, Howard

2009-03-01

ASSISTIVE TECHNOLOGIES ARE RELATIVELY novel tools for research and daily care in long-term care (LTC) facilities that are faced with the burgeoning of the older adult population and dwindling staffing resources. The degree to which stakeholders in LTC facilities are receptive to the use of these technologies is poorly understood. Eighteen semi-structured focus groups and one interview were conducted with relevant groups of stakeholders at seven LTC facilities in southwestern Pennsylvania. Common themes identified across all focus groups centered on concerns for privacy, autonomy, cost, and safety associated with implementation of novel technologies. The relative importance of each theme varied by stakeholder group as well as the perceived severity of cognitive and/or physical disability. Our findings suggest that ethical issues are critical to acceptance of novel technologies by their end users, and that stakeholder groups are interdependent and require shared communication about the acceptance of these emerging technologies.

Protein and DNA Modifications: Evolutionary Imprints of Bacterial Biochemical Diversification and Geochemistry on the Provenance of Eukaryotic Epigenetics

PubMed Central

Aravind, L.; Burroughs, A. Maxwell; Zhang, Dapeng; Iyer, Lakshminarayan M.

2014-01-01

Epigenetic information, which plays a major role in eukaryotic biology, is transmitted by covalent modifications of nuclear proteins (e.g., histones) and DNA, along with poorly understood processes involving cytoplasmic/secreted proteins and RNAs. The origin of eukaryotes was accompanied by emergence of a highly developed biochemical apparatus for encoding, resetting, and reading covalent epigenetic marks in proteins such as histones and tubulins. The provenance of this apparatus remained unclear until recently. Developments in comparative genomics show that key components of eukaryotic epigenetics emerged as part of the extensive biochemical innovation of secondary metabolism and intergenomic/interorganismal conflict systems in prokaryotes, particularly bacteria. These supplied not only enzymatic components for encoding and removing epigenetic modifications, but also readers of some of these marks. Diversification of these prokaryotic systems and subsequently eukaryotic epigenetics appear to have been considerably influenced by the great oxygenation event in the Earth’s history. PMID:24984775

Protein and DNA modifications: evolutionary imprints of bacterial biochemical diversification and geochemistry on the provenance of eukaryotic epigenetics.

PubMed

Aravind, L; Burroughs, A Maxwell; Zhang, Dapeng; Iyer, Lakshminarayan M

2014-07-01

Epigenetic information, which plays a major role in eukaryotic biology, is transmitted by covalent modifications of nuclear proteins (e.g., histones) and DNA, along with poorly understood processes involving cytoplasmic/secreted proteins and RNAs. The origin of eukaryotes was accompanied by emergence of a highly developed biochemical apparatus for encoding, resetting, and reading covalent epigenetic marks in proteins such as histones and tubulins. The provenance of this apparatus remained unclear until recently. Developments in comparative genomics show that key components of eukaryotic epigenetics emerged as part of the extensive biochemical innovation of secondary metabolism and intergenomic/interorganismal conflict systems in prokaryotes, particularly bacteria. These supplied not only enzymatic components for encoding and removing epigenetic modifications, but also readers of some of these marks. Diversification of these prokaryotic systems and subsequently eukaryotic epigenetics appear to have been considerably influenced by the great oxygenation event in the Earth's history. Copyright © 2014 Cold Spring Harbor Laboratory Press; all rights reserved.

Emergent dynamics of spatio-temporal chaos in a heterogeneous excitable medium

NASA Astrophysics Data System (ADS)

Bittihn, Philip; Berg, Sebastian; Parlitz, Ulrich; Luther, Stefan

2017-09-01

Self-organized activation patterns in excitable media such as spiral waves and spatio-temporal chaos underlie dangerous cardiac arrhythmias. While the interaction of single spiral waves with different types of heterogeneity has been studied extensively, the effect of heterogeneity on fully developed spatio-temporal chaos remains poorly understood. We investigate how the complexity and stability properties of spatio-temporal chaos in the Bär-Eiswirth model of excitable media depend on the heterogeneity of the underlying medium. We employ different measures characterizing the chaoticity of the system and find that the spatial arrangement of multiple discrete lower excitability regions has a strong impact on the complexity of the dynamics. Varying the number, shape, and spatial arrangement of the heterogeneities, we observe strong emergent effects ranging from increases in chaoticity to the complete cessation of chaos, contrasting the expectation from the homogeneous behavior. The implications of our findings for the development and treatment of arrhythmias in the heterogeneous cardiac muscle are discussed.

Emerging roles for the BAI1 protein family in the regulation of phagocytosis, synaptogenesis, neurovasculature, and tumor development

PubMed Central

Cork, Sarah M.

2011-01-01

While G-protein-coupled receptors (GPCRs) have received considerable attention for their biological activity in a diversity of physiological functions and have become targets for therapeutic intervention in many diseases, the function of the cell adhesion subfamily of GPCRs remains poorly understood. Within this group, the family of brain angiogenesis inhibitor molecules (BAI1-3) has become increasingly appreciated for their diverse roles in biology and disease. In particular, recent findings suggest emerging roles for BAI1 in the regulation of phenomena including phagocytosis, synaptogenesis, and the inhibition of tumor growth and angiogenesis via the processing of its extracellular domain into secreted vasculostatins. Here we summarize the known biological features of the BAI proteins, including their structure, proteolysis events, and interacting partners, and their recently identified ability to regulate certain signaling pathways. Finally, we discuss the potential of the BAIs as therapeutics or targets for diseases as varied as cancer, stroke, and schizophrenia. PMID:21509575

Sea-ice floe-size distribution in the context of spontaneous scaling emergence in stochastic systems.

PubMed

Herman, Agnieszka

2010-06-01

Sea-ice floe-size distribution (FSD) in ice-pack covered seas influences many aspects of ocean-atmosphere interactions. However, data concerning FSD in the polar oceans are still sparse and processes shaping the observed FSD properties are poorly understood. Typically, power-law FSDs are assumed although no feasible explanation has been provided neither for this one nor for other properties of the observed distributions. Consequently, no model exists capable of predicting FSD parameters in any particular situation. Here I show that the observed FSDs can be well represented by a truncated Pareto distribution P(x)=x(-1-α) exp[(1-α)/x] , which is an emergent property of a certain group of multiplicative stochastic systems, described by the generalized Lotka-Volterra (GLV) equation. Building upon this recognition, a possibility of developing a simple agent-based GLV-type sea-ice model is considered. Contrary to simple power-law FSDs, GLV gives consistent estimates of the total floe perimeter, as well as floe-area distribution in agreement with observations.

Sea-ice floe-size distribution in the context of spontaneous scaling emergence in stochastic systems

NASA Astrophysics Data System (ADS)

Herman, Agnieszka

2010-06-01

Sea-ice floe-size distribution (FSD) in ice-pack covered seas influences many aspects of ocean-atmosphere interactions. However, data concerning FSD in the polar oceans are still sparse and processes shaping the observed FSD properties are poorly understood. Typically, power-law FSDs are assumed although no feasible explanation has been provided neither for this one nor for other properties of the observed distributions. Consequently, no model exists capable of predicting FSD parameters in any particular situation. Here I show that the observed FSDs can be well represented by a truncated Pareto distribution P(x)=x-1-αexp[(1-α)/x] , which is an emergent property of a certain group of multiplicative stochastic systems, described by the generalized Lotka-Volterra (GLV) equation. Building upon this recognition, a possibility of developing a simple agent-based GLV-type sea-ice model is considered. Contrary to simple power-law FSDs, GLV gives consistent estimates of the total floe perimeter, as well as floe-area distribution in agreement with observations.

Persistent and emerging micro-organic contaminants in Chalk groundwater of England and France.

PubMed

Lapworth, D J; Baran, N; Stuart, M E; Manamsa, K; Talbot, J

2015-08-01

The Chalk aquifer of Northern Europe is an internationally important source of drinking water and sustains baseflow for surface water ecosystems. The areal distribution of microorganic (MO) contaminants, particularly non-regulated emerging MOs, in this aquifer is poorly understood. This study presents results from a reconnaissance survey of MOs in Chalk groundwater, including pharmaceuticals, personal care products and pesticides and their transformation products, conducted across the major Chalk aquifers of England and France. Data from a total of 345 sites collected during 2011 were included in this study to provide a representative baseline assessment of MO occurrence in groundwater. A suite of 42 MOs were analysed for at each site including industrial compounds (n=16), pesticides (n=14) and pharmaceuticals, personal care and lifestyle products (n=12). Occurrence data is evaluated in relation to land use, aquifer exposure, well depth and depth to groundwater to provide an understanding of vulnerable groundwater settings. Copyright © 2015 Natural Environment Research Council. Published by Elsevier Ltd.. All rights reserved.

Metabolic Complementation in Bacterial Communities: Necessary Conditions and Optimality

PubMed Central

Mori, Matteo; Ponce-de-León, Miguel; Peretó, Juli; Montero, Francisco

2016-01-01

Bacterial communities may display metabolic complementation, in which different members of the association partially contribute to the same biosynthetic pathway. In this way, the end product of the pathway is synthesized by the community as a whole. However, the emergence and the benefits of such complementation are poorly understood. Herein, we present a simple model to analyze the metabolic interactions among bacteria, including the host in the case of endosymbiotic bacteria. The model considers two cell populations, with both cell types encoding for the same linear biosynthetic pathway. We have found that, for metabolic complementation to emerge as an optimal strategy, both product inhibition and large permeabilities are needed. In the light of these results, we then consider the patterns found in the case of tryptophan biosynthesis in the endosymbiont consortium hosted by the aphid Cinara cedri. Using in-silico computed physicochemical properties of metabolites of this and other biosynthetic pathways, we verified that the splitting point of the pathway corresponds to the most permeable intermediate. PMID:27774085

Paradigm shift in plant growth control.

PubMed

Körner, Christian

2015-06-01

For plants to grow they need resources and appropriate conditions that these resources are converted into biomass. While acknowledging the importance of co-drivers, the classical view is still that carbon, that is, photosynthetic CO2 uptake, ranks above any other drivers of plant growth. Hence, theory and modelling of growth traditionally is carbon centric. Here, I suggest that this view is not reflecting reality, but emerged from the availability of methods and process understanding at leaf level. In most cases, poorly understood processes of tissue formation and cell growth are governing carbon demand, and thus, CO2 uptake. Carbon can only be converted into biomass to the extent chemical elements other than carbon, temperature or cell turgor permit. Copyright © 2015. Published by Elsevier Ltd.

Exploring the Influence of Social Determinants, Social Capital, and Health Expertise on Health and the Rural Church.

PubMed

Plunkett, Robyn; Leipert, Beverly; Olson, Joanne

2016-09-01

In rural communities, religious places can significantly shape health for individuals, families, and communities. Rural churches are prominent community centers in rural communities and are deeply woven into rural culture. Thus, health influences arising from the rural church likely have health implications for the greater community. This article explores health influences emerging from rural churches using social determinants of health, social capital, and health expertise. Although nurses are important health resources for all populations, their value in rural areas may be exceedingly significant. The contribution of nurses to church-based health capital in rural communities may be quite significant and underestimated, although it remains poorly understood. © The Author(s) 2015.

Human casualties in earthquakes: Modelling and mitigation

USGS Publications Warehouse

Spence, R.J.S.; So, E.K.M.

2011-01-01

Earthquake risk modelling is needed for the planning of post-event emergency operations, for the development of insurance schemes, for the planning of mitigation measures in the existing building stock, and for the development of appropriate building regulations; in all of these applications estimates of casualty numbers are essential. But there are many questions about casualty estimation which are still poorly understood. These questions relate to the causes and nature of the injuries and deaths, and the extent to which they can be quantified. This paper looks at the evidence on these questions from recent studies. It then reviews casualty estimation models available, and finally compares the performance of some casualty models in making rapid post-event casualty estimates in recent earthquakes.

Biologically Inspired Micro-Flight Research

NASA Technical Reports Server (NTRS)

Raney, David L.; Waszak, Martin R.

2003-01-01

Natural fliers demonstrate a diverse array of flight capabilities, many of which are poorly understood. NASA has established a research project to explore and exploit flight technologies inspired by biological systems. One part of this project focuses on dynamic modeling and control of micro aerial vehicles that incorporate flexible wing structures inspired by natural fliers such as insects, hummingbirds and bats. With a vast number of potential civil and military applications, micro aerial vehicles represent an emerging sector of the aerospace market. This paper describes an ongoing research activity in which mechanization and control concepts for biologically inspired micro aerial vehicles are being explored. Research activities focusing on a flexible fixed- wing micro aerial vehicle design and a flapping-based micro aerial vehicle concept are presented.

The Molecular Biology of Adenoid Cystic Carcinoma

PubMed Central

Liu, Jia; Shao, Chunbo; Tan, Marietta L.; Mu, David; Ferris, Robert L.; Ha, Patrick K.

2011-01-01

Background Adenoid cystic carcinoma (ACC) is an unusual salivary gland malignancy that remains poorly understood. Standard treatment, including surgery with postoperative radiation therapy have attained reasonable local control rates, but the propensity for distant metastases has limited any improvement in survival over time. Our understanding of the molecular mechanisms driving adenoid cystic carcinoma is quite rudimentary, due to the infrequent nature of its occurrence. Methods An extensive literature review was performed on salivary gland adenoid cystic carcinoma and basic science research findings. Results This review highlights many findings that are emerging about the carcinogenesis of ACC including cytogenetics, tumor suppressor genes, oncogenes, epigenetic alterations, mitochondrial alterations, and biomarker studies. Conclusions While there have been many discoveries, much still remains unknown about this rare malignancy. PMID:22006498

Expected utility violations evolve under status-based selection mechanisms.

PubMed

Dickson, Eric S

2008-10-07

The expected utility theory of decision making under uncertainty, a cornerstone of modern economics, assumes that humans linearly weight "utilities" for different possible outcomes by the probabilities with which these outcomes occur. Despite the theory's intuitive appeal, both from normative and from evolutionary perspectives, many experiments demonstrate systematic, though poorly understood, patterns of deviation from EU predictions. This paper offers a novel theoretical account of such patterns of deviation by demonstrating that EU violations can emerge from evolutionary selection when individual "status" affects inclusive fitness. In humans, battles for resources and social standing involve high-stakes decision making, and assortative mating ensures that status matters for fitness outcomes. The paper therefore proposes grounding the study of decision making under uncertainty in an evolutionary game-theoretic framework.

Exploring the Chemistry and Biology of Vanadium-dependent Haloperoxidases*

PubMed Central

Winter, Jaclyn M.; Moore, Bradley S.

2009-01-01

Nature has developed an exquisite array of methods to introduce halogen atoms into organic compounds. Most of these enzymes are oxidative and require either hydrogen peroxide or molecular oxygen as a cosubstrate to generate a reactive halogen atom for catalysis. Vanadium-dependent haloperoxidases contain a vanadate prosthetic group and utilize hydrogen peroxide to oxidize a halide ion into a reactive electrophilic intermediate. These metalloenzymes have a large distribution in nature, where they are present in macroalgae, fungi, and bacteria, but have been exclusively characterized in eukaryotes. In this minireview, we highlight the chemistry and biology of vanadium-dependent haloperoxidases from fungi and marine algae and the emergence of new bacterial members that extend the biological function of these poorly understood halogenating enzymes. PMID:19363038

Emerging Synaptic Molecules as Candidates in the Etiology of Neurological Disorders

PubMed Central

Torres, Viviana I.; Vallejo, Daniela

2017-01-01

Synapses are complex structures that allow communication between neurons in the central nervous system. Studies conducted in vertebrate and invertebrate models have contributed to the knowledge of the function of synaptic proteins. The functional synapse requires numerous protein complexes with specialized functions that are regulated in space and time to allow synaptic plasticity. However, their interplay during neuronal development, learning, and memory is poorly understood. Accumulating evidence links synapse proteins to neurodevelopmental, neuropsychiatric, and neurodegenerative diseases. In this review, we describe the way in which several proteins that participate in cell adhesion, scaffolding, exocytosis, and neurotransmitter reception from presynaptic and postsynaptic compartments, mainly from excitatory synapses, have been associated with several synaptopathies, and we relate their functions to the disease phenotype. PMID:28331639

Language, embodiment, and the cognitive niche.

PubMed

Clark, Andy

2006-08-01

Embodied agents use bodily actions and environmental interventions to make the world a better place to think in. Where does language fit into this emerging picture of the embodied, ecologically efficient agent? One useful way to approach this question is to consider language itself as a cognition-enhancing animal-built structure. To take this perspective is to view language as a kind of self-constructed cognitive niche: a persisting but never stationary material scaffolding whose crucial role in promoting thought and reason remains surprisingly poorly understood. It is the very materiality of this linguistic scaffolding, I suggest, that gives it some key benefits. By materializing thought in words, we create structures that are themselves proper objects of perception, manipulation, and (further) thought.

The effect of wind mixing on the vertical distribution of buoyant plastic debris

NASA Astrophysics Data System (ADS)

Kukulka, T.; Proskurowski, G.; Morét-Ferguson, S.; Meyer, D. W.; Law, K. L.

2012-04-01

Micro-plastic marine debris is widely distributed in vast regions of the subtropical gyres and has emerged as a major open ocean pollutant. The fate and transport of plastic marine debris is governed by poorly understood geophysical processes, such as ocean mixing within the surface boundary layer. Based on profile observations and a one-dimensional column model, we demonstrate that plastic debris is vertically distributed within the upper water column due to wind-driven mixing. These results suggest that total oceanic plastics concentrations are significantly underestimated by traditional surface measurements, requiring a reinterpretation of existing plastic marine debris data sets. A geophysical approach must be taken in order to properly quantify and manage this form of marine pollution.

Engineering education as a complex system

NASA Astrophysics Data System (ADS)

Gattie, David K.; Kellam, Nadia N.; Schramski, John R.; Walther, Joachim

2011-12-01

This paper presents a theoretical basis for cultivating engineering education as a complex system that will prepare students to think critically and make decisions with regard to poorly understood, ill-structured issues. Integral to this theoretical basis is a solution space construct developed and presented as a benchmark for evaluating problem-solving orientations that emerge within students' thinking as they progress through an engineering curriculum. It is proposed that the traditional engineering education model, while analytically rigorous, is characterised by properties that, although necessary, are insufficient for preparing students to address complex issues of the twenty-first century. A Synthesis and Design Studio model for engineering education is proposed, which maintains the necessary rigor of analysis within a uniquely complex yet sufficiently structured learning environment.

Triage and the Lost Art of Decoding Vital Signs: Restoring Physiologically Based Triage Skills in Complex Humanitarian Emergencies.

PubMed

Burkle, Frederick M

2018-02-01

Triage management remains a major challenge, especially in resource-poor settings such as war, complex humanitarian emergencies, and public health emergencies in developing countries. In triage it is often the disruption of physiology, not anatomy, that is critical, supporting triage methodology based on clinician-assessed physiological parameters as well as anatomy and mechanism of injury. In recent times, too many clinicians from developed countries have deployed to humanitarian emergencies without the physical exam skills needed to assess patients without the benefit of remotely fed electronic monitoring, laboratory, and imaging studies. In triage, inclusion of the once-widely accepted and collectively taught "art of decoding vital signs" with attention to their character and meaning may provide clues to a patient's physiological state, improving triage sensitivity. Attention to decoding vital signs is not a triage methodology of its own or a scoring system, but rather a skill set that supports existing triage methodologies. With unique triage management challenges being raised by an ever-changing variety of humanitarian crises, these once useful skill sets need to be revisited, understood, taught, and utilized by triage planners, triage officers, and teams as a necessary adjunct to physiologically based triage decision-making. (Disaster Med Public Health Preparedness. 2018;12:76-85).

Increased Cell Proliferation and Gene Expression of Genes Related to Bone Remodeling, Cell Adhesion and Collagen Metabolism in the Periodontal Ligament of Unopposed Molars in Growing Rats

PubMed Central

Dorotheou, Domna; Farsadaki, Vassiliki; Bochaton-Piallat, Marie-Luce; Giannopoulou, Catherine; Halazonetis, Thanos D.; Kiliaridis, Stavros

2017-01-01

Tooth eruption, the process by which teeth emerge from within the alveolar bone into the oral cavity, is poorly understood. The post-emergent phase of tooth eruption continues throughout life, in particular, if teeth are not opposed by antagonists. The aim of the present study was to better understand the molecular processes underlying post-emergent tooth eruption. Toward this goal, we removed the crowns of the maxillary molars on one side of the mouth of 14 young rats and examined gene expression patterns in the periodontal ligaments (PDLs) of the ipsilateral and contralateral mandibular molars, 3 and 15 days later. Nine untreated rats served as controls. Expression of six genes, Adamts18, Ostn, P4ha3, Panx3, Pth1r, and Tnmd, was upregulated in unopposed molars relative to molars with antagonists. These genes function in osteoblast differentiation and proliferation, cell adhesion and collagen metabolism. Proliferation of PDL cells also increased following loss of the antagonist teeth. Interestingly, mutations in PTH1R have been linked to defects in the post-emergent phase of tooth eruption in humans. We conclude that post-emergent eruption of unopposed teeth is associated with gene expression patterns conducive to alveolar bone formation and PDL remodeling. PMID:28239357

The puzzle of Buruli ulcer transmission, ethno-ecological history and the end of "love" in the Akonolinga district, Cameroon.

PubMed

Giles-Vernick, Tamara; Owona-Ntsama, Joseph; Landier, Jordi; Eyangoh, Sara

2015-03-01

The "One World One Health Initiative" has attended little to the priorities, concepts and practices of resource-poor communities confronting disease and the implications of these concerns for its biomedical, ecological and institutional approach to disease surveillance and control. Using the example of Buruli ulcer (BU) and its bacterial etiology, Mycobacterium ulcerans, in south-central Cameroon, we build on debates about the contributions of "local knowledge" and "alternative models" to biomedical knowledge of disease transmission. BU's mode of transmission remains poorly understood. Our approach employs ethno-ecological histories - local understandings of the putative emergence and expansion of a locally important, neglected disease. We develop these histories from 52 individual and small group interviews, group discussions, and participant-observation of daily and seasonal activities, conducted in 2013-2013. These histories offer important clues about past environmental and social change that should guide further ecological, epidemiological research. They highlight a key historical moment (the late 1980s and 1990s); specific ecological transformations; new cultivation practices in unexploited zones that potentially increased exposure to M. ulcerans; and ecological degradation that may have lowered nutritional standards and heightened susceptibility to BU. They also recast transmission, broadening insight into BU and its local analog, atom, by emphasizing the role of social change and economic crisis in its emergence and expansion. Copyright © 2014 Elsevier Ltd. All rights reserved.

Atmospheric Research at BNL

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

Peter Daum

2008-10-06

Brookhaven researcher Peter Daum discusses an international field experiment designed to make observations of critical components of the climate system of the southeastern Pacific. Because elements of this system are poorly understood and poorly represent

Atmospheric Research at BNL

ScienceCinema

Peter Daum

2017-12-09

Brookhaven researcher Peter Daum discusses an international field experiment designed to make observations of critical components of the climate system of the southeastern Pacific. Because elements of this system are poorly understood and poorly represent

Long-term priority effects among insects and fungi colonizing decaying wood.

PubMed

Weslien, Jan; Djupström, Line B; Schroeder, Martin; Widenfalk, Olof

2011-11-01

1. Priority effects have been hypothesized to have long-lasting impact on community structure in natural ecosystems. Long-term studies of priority effects in natural ecosystems are however sparse, especially in terrestrial ecosystems. 2. Wood decay is a slow process involving a high diversity of insect and fungus species. Species interactions that drive change in communities of insects and fungi during wood decay are poorly understood because of a lack of sufficient long-term studies. 3. In this paper, we followed the colonization and succession of wood-living insects and fungi on cut trees during 15 years, from tree death and onwards, in a boreal forest landscape. We test the long-term priority effects hypothesis that the identity and abundance of species that colonize first affect the colonization success of later-arriving species. We also hypothesize that species interact in both facilitative and inhibitory ways, which ultimately affect habitat quality for a red-listed late-succession beetle species. 4. Possible causal associations between species were explored by path analysis. The results indicate that one bark beetle species, Hylurgops palliatus, and one wood-borer species, Monochamus sutor, which colonized the wood during the first year after cutting, influenced the occurrence of a rare, wood-living beetle, Peltis grossa, that started to emerge from the stumps about 10 years later. The positive effects of Hylurgops palliatus and negative effects of M. sutor were largely mediated through the wood-decaying fungus species Fomitopsis pinicola. 5. The study shows that variable priority effects may have long-lasting impact on community assembly in decaying wood. The study also exemplifies new possibilities for managing populations of threatened species by exploring links between early, well-understood species guilds and late, more poorly understood species guilds. © 2011 The Authors. Journal of Animal Ecology © 2011 British Ecological Society.

Advances in IBS 2016: A Review of Current and Emerging Data.

PubMed

Schoenfeld, Philip S

2016-08-01

Irritable bowel syndrome (IBS) is characterized by chronic intermittent abdominal pain and associated diarrhea (IBS-D), constipation (IBS-C), or both. IBS can significantly impact patient function and quality of life. The diagnosis of IBS is based on the presence of characteristic symptoms, the exclusion of concerning features, and selected tests to exclude organic diseases that can mimic IBS. The pathophysiology of IBS remains incompletely understood, and new contributing factors have been identified over the past decade. Altered gut immune activation, intestinal permeability, and the intestinal and colonic microbiome may be important factors. Poorly absorbed carbohydrates have been implicated in triggering IBS symptoms. Increasing evidence supports the benefit of a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs). Although there are several randomized controlled trials of probiotics in IBS, they are typically poorly designed and have not consistently demonstrated efficacy. Until recently, there were few effective treatments for IBS-D. Data from recent clinical trials support the use of rifaximin, eluxadoline, and peppermint oil. Options for the treatment of IBS-C include lubiprostone and linaclotide.

Advances in IBS 2016: A Review of Current and Emerging Data

PubMed Central

Schoenfeld, Philip S.

2016-01-01

Irritable bowel syndrome (IBS) is characterized by chronic intermittent abdominal pain and associated diarrhea (IBS-D), constipation (IBS-C), or both. IBS can significantly impact patient function and quality of life. The diagnosis of IBS is based on the presence of characteristic symptoms, the exclusion of concerning features, and selected tests to exclude organic diseases that can mimic IBS. The pathophysiology of IBS remains incompletely understood, and new contributing factors have been identified over the past decade. Altered gut immune activation, intestinal permeability, and the intestinal and colonic microbiome may be important factors. Poorly absorbed carbohydrates have been implicated in triggering IBS symptoms. Increasing evidence supports the benefit of a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs). Although there are several randomized controlled trials of probiotics in IBS, they are typically poorly designed and have not consistently demonstrated efficacy. Until recently, there were few effective treatments for IBS-D. Data from recent clinical trials support the use of rifaximin, eluxadoline, and peppermint oil. Options for the treatment of IBS-C include lubiprostone and linaclotide. PMID:28070176

Munchausen Syndrome by Proxy: An Alarming Face of Child Abuse

PubMed Central

Gehlawat, Pratibha; Gehlawat, Virender Kumar; Singh, Priti; Gupta, Rajiv

2015-01-01

Munchausen syndrome by proxy (MSBP) is emerging as a serious form of child abuse. It is an intentional production of illness in another, usually children by mothers, to assume sick role by proxy. It is poorly understood and a controversial diagnosis. Treatment is very difficult. We present a case of 9-year-old boy brought to Pt. B. D. Sharma, PGIMS, Rohtak, a tertiary care hospital in northern India by his father and paternal uncle with complaints of hematemesis since July 2012. He underwent many invasive procedures until the diagnosis of MSBP was finally considered. The examination of the blood sample confirmed the diagnosis. The child was placed under custody of his mother. The case was reported to social services, which incorporated whole family in the management. PMID:25722520

Munchausen syndrome by proxy: an alarming face of child abuse.

PubMed

Gehlawat, Pratibha; Gehlawat, Virender Kumar; Singh, Priti; Gupta, Rajiv

2015-01-01

Munchausen syndrome by proxy (MSBP) is emerging as a serious form of child abuse. It is an intentional production of illness in another, usually children by mothers, to assume sick role by proxy. It is poorly understood and a controversial diagnosis. Treatment is very difficult. We present a case of 9-year-old boy brought to Pt. B. D. Sharma, PGIMS, Rohtak, a tertiary care hospital in northern India by his father and paternal uncle with complaints of hematemesis since July 2012. He underwent many invasive procedures until the diagnosis of MSBP was finally considered. The examination of the blood sample confirmed the diagnosis. The child was placed under custody of his mother. The case was reported to social services, which incorporated whole family in the management.

Microbial community assembly and metabolic function during mammalian corpse decomposition

USGS Publications Warehouse

Metcalf, Jessica L; Xu, Zhenjiang Zech; Weiss, Sophie; Lax, Simon; Van Treuren, Will; Hyde, Embriette R.; Song, Se Jin; Amir, Amnon; Larsen, Peter; Sangwan, Naseer; Haarmann, Daniel; Humphrey, Greg C; Ackermann, Gail; Thompson, Luke R; Lauber, Christian; Bibat, Alexander; Nicholas, Catherine; Gebert, Matthew J; Petrosino, Joseph F; Reed, Sasha C.; Gilbert, Jack A; Lynne, Aaron M; Bucheli, Sibyl R; Carter, David O; Knight, Rob

2016-01-01

Vertebrate corpse decomposition provides an important stage in nutrient cycling in most terrestrial habitats, yet microbially mediated processes are poorly understood. Here we combine deep microbial community characterization, community-level metabolic reconstruction, and soil biogeochemical assessment to understand the principles governing microbial community assembly during decomposition of mouse and human corpses on different soil substrates. We find a suite of bacterial and fungal groups that contribute to nitrogen cycling and a reproducible network of decomposers that emerge on predictable time scales. Our results show that this decomposer community is derived primarily from bulk soil, but key decomposers are ubiquitous in low abundance. Soil type was not a dominant factor driving community development, and the process of decomposition is sufficiently reproducible to offer new opportunities for forensic investigations.

Anxiety and nicotine dependence: Emerging role of the habenulo-interpeduncular axis

PubMed Central

Molas, Susanna; DeGroot, Steven; Zhao-Shea, Rubing; Tapper, Andrew R.

2016-01-01

While innovative modern neuroscience approaches have aided in discerning brain circuitry underlying negative emotional behaviors including fear and anxiety responses, how these circuits are recruited in normal and pathological conditions remains poorly understood. Recently, genetic tools that selectively manipulate single neuronal populations have uncovered an understudied circuit, the medial habenula (mHb)-interpeduncular (IPN) axis, that modulates basal negative emotional responses. Interestingly, the mHb-IPN pathway also represents an essential circuit that signals heightened anxiety induced by nicotine withdrawal. Insights into how this circuit inter-connects with regions more classically associated with anxiety and how chronic nicotine exposure induces neuroadaptations resulting in an anxiogenic state, may thereby provide novel strategies and molecular targets for therapies that facilitate smoking cessation, as well as, anxiety relief. PMID:27890353

Detection of quasars in the time domain

NASA Astrophysics Data System (ADS)

Graham, Matthew J.; Djorgovski, S. G.; Stern, Daniel J.; Drake, Andrew; Mahabal, Ashish

2017-06-01

The time domain is the emerging forefront of astronomical research with new facilities and instruments providing unprecedented amounts of data on the temporal behavior of astrophysical populations. Dealing with the size and complexity of this requires new techniques and methodologies. Quasars are an ideal work set for developing and applying these: they vary in a detectable but not easily quantifiable manner whose physical origins are poorly understood. In this paper, we will review how quasars are identified by their variability and how these techniques can be improved, what physical insights into their variability can be gained from studying extreme examples of variability, and what approaches can be taken to increase the number of quasars known. These will demonstrate how astroinformatics is essential to discovering and understanding this important population.

Genes, molecules and patients—Emerging topics to guide clinical pain research

PubMed Central

Sikandar, Shafaq; Patel, Ryan; Patel, Sital; Sikander, Sanam; Bennett, David L.H.; Dickenson, Anthony H.

2013-01-01

This review selectively explores some areas of pain research that, until recently, have been poorly understood. We have chosen four topics that relate to clinical pain and we discuss the underlying mechanisms and related pathophysiologies contributing to these pain states. A key issue in pain medicine involves crucial events and mediators that contribute to normal and abnormal pain signaling, but remain unseen without genetic, biomarker or imaging analysis. Here we consider how the altered genetic make-up of familial pains reveals the human importance of channels discovered by preclinical research, followed by the contribution of receptors as stimulus transducers in cold sensing and cold pain. Finally we review recent data on the neuro-immune interactions in chronic pain and the potential targets for treatment in cancer-induced bone pain. PMID:23500200

Microbial community assembly and metabolic function during mammalian corpse decomposition

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

Metcalf, J. L.; Xu, Z. Z.; Weiss, S.

2015-12-10

Vertebrate corpse decomposition provides an important stage in nutrient cycling in most terrestrial habitats, yet microbially mediated processes are poorly understood. Here we combine deep microbial community characterization, community-level metabolic reconstruction, and soil biogeochemical assessment to understand the principles governing microbial community assembly during decomposition of mouse and human corpses on different soil substrates. We find a suite of bacterial and fungal groups that contribute to nitrogen cycling and a reproducible network of decomposers that emerge on predictable time scales. Our results show that this decomposer community is derived primarily from bulk soil, but key decomposers are ubiquitous in lowmore » abundance. Soil type was not a dominant factor driving community development, and the process of decomposition is sufficiently reproducible to offer new opportunities for forensic investigations.« less

Air Pollution: Mechanisms of Neuroinflammation & CNS Disease

PubMed Central

Block, Michelle L.; Calderón-Garcidueñas, Lilian

2009-01-01

Emerging evidence implicates air pollution as a chronic source of neuroinflammation, reactive oxygen species (ROS), and neuropathology instigating central nervous system (CNS) disease. Stroke incidence, and Alzheimer’s and Parkinson’s disease pathology are linked to air pollution. Recent reports reveal that air pollution components reach the brain. Further, systemic effects known to impact lung and cardiovascular disease also impinge upon CNS health. While mechanisms driving air pollution-induced CNS pathology are poorly understood, new evidence suggests that activation of microglia and changes in the blood brain barrier may be key to this process. Here, we summarize recent findings detailing the mechanisms through which air pollution reaches the brain and activates the resident innate immune response to become a chronic source of pro-inflammatory factors and ROS culpable in CNS disease. PMID:19716187

Optimal chemotactic responses in stochastic environments

PubMed Central

Godány, Martin

2017-01-01

Although the “adaptive” strategy used by Escherichia coli has dominated our understanding of bacterial chemotaxis, the environmental conditions under which this strategy emerged is still poorly understood. In this work, we study the performance of various chemotactic strategies under a range of stochastic time- and space-varying attractant distributions in silico. We describe a novel “speculator” response in which the bacterium compare the current attractant concentration to the long-term average; if it is higher then they tumble persistently, while if it is lower than the average, bacteria swim away in search of more favorable conditions. We demonstrate how this response explains the experimental behavior of aerobically-grown Rhodobacter sphaeroides and that under spatially complex but slowly-changing nutrient conditions the speculator response is as effective as the adaptive strategy of E. coli. PMID:28644830

The pillars of land plants: new insights into stem development.

PubMed

Serrano-Mislata, Antonio; Sablowski, Robert

2018-05-12

In spite of its central importance in evolution, plant architecture and crop improvement, stem development remains poorly understood relative to other plant organs. Here, we summarise current knowledge of stem ontogenesis and its regulation, including insights from new image analysis and biophysical approaches. The stem initiates in the rib zone (RZ) of the shoot apical meristem, under transcriptional control by DELLA and BLH proteins. Links have emerged between these regulators and cell proliferation, patterning and oriented growth in the RZ. During subsequent internode elongation, cell wall properties and mechanics have been analysed in detail, revealing pectin modification as a prominent control point. Recent work has also highlighted signalling to coordinate growth of stem tissues with different mechanical properties. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Mixtures of macrophyte growth forms promote nitrogen cycling in wetlands.

PubMed

Choudhury, Maidul I; McKie, Brendan G; Hallin, Sara; Ecke, Frauke

2018-09-01

The importance of aquatic plant diversity in regulating nutrient cycling in wetlands remains poorly understood. We investigated how variation in macrophyte growth form (emerging, submerged and bryophyte) combinations and species mixtures affect nitrogen (N) removal from the water and N accumulation in plant biomass. We conducted a wetland mesocosm experiment for 100 days during July-September 2015. Twelve species were grown in mono- and in two-species mixed cultures for a total of 32 single and two-growth form combinations. Nitrogen removal from the water was quantified on three occasions during the experiment, while N accumulation in plant biomass was determined following termination of the experiment. The number of species and growth forms present increased N removal and accumulation. The growth form combinations of emerging and bryophyte species showed the highest N accumulation and N removal from water, followed by combinations of emerging species. By contrast, submerged species growing in the presence of emerging or other submerged species showed the lowest levels of N accumulation and N removal. Temporal variation in N removal also differed among growth form combinations: N removal was highest for emerging-bryophyte combinations in July, but peaked for the emerging-submerged and emerging-bryophyte combinations in August. Indeed, the occurrence of complementarity among macrophyte species, particularly in combinations of bryophyte and emerging species, enhanced N removal and uptake during the entire growing season. Our study highlights the importance of bryophytes, which have been neglected in research on nutrient cycling in wetlands, for aquatic N cycling, especially given their worldwide distribution across biomes. Overall, our findings point towards the potential important role of the diversity of macrophyte growth forms in regulating key ecosystem processes related to N cycling in wetlands. Copyright © 2018 Elsevier B.V. All rights reserved.

Deconstructing and Reconstructing Cognitive Performance in Sleep Deprivation

PubMed Central

Jackson, Melinda L.; Gunzelmann, Glenn; Whitney, Paul; Hinson, John M.; Belenky, Gregory; Rabat, Arnaud; Van Dongen, Hans P. A.

2012-01-01

Summary Mitigation of cognitive impairment due to sleep deprivation in operational settings is critical for safety and productivity. Achievements in this area are hampered by limited knowledge about the effects of sleep loss on actual job tasks. Sleep deprivation has different effects on different cognitive performance tasks, but the mechanisms behind this task-specificity are poorly understood. In this context it is important to recognize that cognitive performance is not a unitary process, but involves a number of component processes. There is emerging evidence that these component processes are differentially affected by sleep loss. Experiments have been conducted to decompose sleep-deprived performance into underlying cognitive processes using cognitive-behavioral, neuroimaging and cognitive modeling techniques. Furthermore, computational modeling in cognitive architectures has been employed to simulate sleep-deprived cognitive performance on the basis of the constituent cognitive processes. These efforts are beginning to enable quantitative prediction of the effects of sleep deprivation across different task contexts. This paper reviews a rapidly evolving area of research, and outlines a theoretical framework in which the effects of sleep loss on cognition may be understood from the deficits in the underlying neurobiology to the applied consequences in real-world job tasks. PMID:22884948

Deconstructing and reconstructing cognitive performance in sleep deprivation.

PubMed

Jackson, Melinda L; Gunzelmann, Glenn; Whitney, Paul; Hinson, John M; Belenky, Gregory; Rabat, Arnaud; Van Dongen, Hans P A

2013-06-01

Mitigation of cognitive impairment due to sleep deprivation in operational settings is critical for safety and productivity. Achievements in this area are hampered by limited knowledge about the effects of sleep loss on actual job tasks. Sleep deprivation has different effects on different cognitive performance tasks, but the mechanisms behind this task-specificity are poorly understood. In this context it is important to recognize that cognitive performance is not a unitary process, but involves a number of component processes. There is emerging evidence that these component processes are differentially affected by sleep loss. Experiments have been conducted to decompose sleep-deprived performance into underlying cognitive processes using cognitive-behavioral, neuroimaging and cognitive modeling techniques. Furthermore, computational modeling in cognitive architectures has been employed to simulate sleep-deprived cognitive performance on the basis of the constituent cognitive processes. These efforts are beginning to enable quantitative prediction of the effects of sleep deprivation across different task contexts. This paper reviews a rapidly evolving area of research, and outlines a theoretical framework in which the effects of sleep loss on cognition may be understood from the deficits in the underlying neurobiology to the applied consequences in real-world job tasks. Copyright © 2012 Elsevier Ltd. All rights reserved.

An assessment of emergency medicine residents' ability to perform in a multitasking environment.

PubMed

Ledrick, David; Fisher, Susan; Thompson, Justin; Sniadanko, Mark

2009-09-01

Multitasking (MT) is a term often applied to emergency medicine (EM), but it is still poorly understood. In an effort to facilitate MT research in EM, the authors conducted this pilot study to describe EM residents' scores on a Multi-Tasking Assessment Tool (MTAT) and compare these scores with the residents' work efficiency in the emergency department. The authors administered a previously developed test of MT ability to EM residents. They performed a multiple regression analysis to determine the effect of MT ability on resident work efficiency, defining efficiency as the number of relative value units billed per hour. They controlled the analysis for year of training and medical knowledge using as a standard the in-service exam administered by the American Board of Emergency Medicine. Complete data for 35 residents were available for analysis. Work efficiency was multivariately correlated with MTAT scores and year of training (P < .05). Whereas year of training explained the majority of the variance, a resident's MT ability accounted for a smaller but still significant portion. This pilot study further validates the MTAT and lays the groundwork for further research in MT in EM. Resident year of training and MTAT scores explain the variability in resident work efficiency significantly more than medical knowledge. Understanding MT ability may ultimately help in resident selection, education, and remediation as well as career counseling and improvement of practice systems in EM.

Mammalian gastrointestinal parasites in rainforest remnants of Anamalai Hills, Western Ghats, India.

PubMed

Chakraborty, Debapriyo; Hussain, Shaik; Reddy, D Mahendar; Raut, Sachin; Tiwari, Sunil; Kumar, Vinod; Umapathy, Govindhaswamy

2015-06-01

Habitat fragmentation is postulated to be a major factor influencing infectious disease dynamics in wildlife populations and may also be responsible, at least in part, for the recent spurt in the emergence, or re-emergence, of infectious diseases in humans. The mechanism behind these relationships are poorly understood due to the lack of insights into the interacting local factors and insufficient baseline data in ecological parasitology of wildlife. Here, we studied the gastrointestinal parasites of nonhuman mammalian hosts living in 10 rainforest patches of the Anamalai Tiger Reserve, India. We examined 349 faecal samples of 17 mammalian species and successfully identified 24 gastrointestinal parasite taxa including 1 protozoan, 2 trematode, 3 cestode and 18 nematode taxa. Twenty of these parasites are known parasites of humans. We also found that as much as 73% of all infected samples were infected by multiple parasites. In addition, the smallest and most fragmented forest patches recorded the highest parasite richness; the pattern across fragments, however, seemed to be less straightforward, suggesting potential interplay of local factors.

Praziquantel Treatment in Trematode and Cestode Infections: An Update

PubMed Central

2013-01-01

Status and emerging issues in the use of praziquantel for treatment of human trematode and cestode infections are briefly reviewed. Since praziquantel was first introduced as a broadspectrum anthelmintic in 1975, innumerable articles describing its successful use in the treatment of the majority of human-infecting trematodes and cestodes have been published. The target trematode and cestode diseases include schistosomiasis, clonorchiasis and opisthorchiasis, paragonimiasis, heterophyidiasis, echinostomiasis, fasciolopsiasis, neodiplostomiasis, gymnophalloidiasis, taeniases, diphyllobothriasis, hymenolepiasis, and cysticercosis. However, Fasciola hepatica and Fasciola gigantica infections are refractory to praziquantel, for which triclabendazole, an alternative drug, is necessary. In addition, larval cestode infections, particularly hydatid disease and sparganosis, are not successfully treated by praziquantel. The precise mechanism of action of praziquantel is still poorly understood. There are also emerging problems with praziquantel treatment, which include the appearance of drug resistance in the treatment of Schistosoma mansoni and possibly Schistosoma japonicum, along with allergic or hypersensitivity reactions against praziquantel treatment. To cope with and overcome these problems, combined use of drugs, i.e., praziquantel and other newly introduced compounds such as triclabendazole, artemisinins, and tribendimidine, is being tried. PMID:24265948

Reach-scale predictions of the transport and fate of contaminants of emerging concern using a multi-tracer injection at Fourmile Creek (Ankeny, Iowa)

NASA Astrophysics Data System (ADS)

Cullin, J. A.; Ward, A. S.; Cwiertny, D. M.; Barber, L. B.; Kolpin, D. W.; Bradley, P. M.; Keefe, S. H.; Hubbard, L. E.

2013-12-01

Contaminants of emerging concern (CECs) are an unregulated suite of constituents possessing the potential to cause a host of reproductive and developmental problems in humans and wildlife. CECs are frequently detected in environmental waters. Degradation pathways of several CECs are well-characterized in idealized laboratory settings, but CEC fate and transport in complex field settings is poorly understood. In the present study we used a multi-tracer solute injection study to quantify physical transport, photodegradation, and sorption in a wastewater effluent-impacted stream. Conservative tracers were used to quantify physical transport processes in the stream. Use of reactive fluorescent tracers allows for isolation of the relative contribution of photodegradation and sorption within the system. Field data was used to calibrate a one-dimensional transport model allowing us to use forward modeling to predict the transport of sulfamethoxazole, an antibiotic documented to be present in the wastewater effluent and in Fourmile Creek which is susceptible to both sorption and photolysis. Forward modeling will predict both temporal persistence and spatial extent of sulfamethoxazole in Fourmile Creek

Supporting an emerging workforce: characteristics of rural and remote therapy assistants in Western Australia.

PubMed

Lin, Ivan; Goodale, Belinda; Villanueva, Karen; Spitz, Suzanne

2007-10-01

Multidisciplinary therapy assistants (TAs) are an emerging but poorly understood rural and remote allied health workforce. As an aid to planning and support of TA programs in rural and remote Western Australia (WA), the number, locality and a range of practice variables of rural and remote TAs in WA were determined. Survey questionnaire. Rural and remote regions of WA. Allied health professionals, TAs, TA coordinators and managers of allied health in country regions of WA. Information was gathered on TA location, qualifications, employing organisation, allied health disciplines TAs work with, supervision practices, role and work scenarios. Ninety-eight TAs were identified in rural and remote WA with a further 23 vacant TA positions. Most TAs work across multiple allied health disciplines, half are located at a distance to their supervisors, and very few have a recognised qualification for their TA work. A substantial rural and remote TA workforce was found. A range of TA characteristics were identified that have considerable relevance to the future planning of TA initiatives in rural and remote WA.

Complexity of low-frequency blood oxygen level-dependent fluctuations covaries with local connectivity.

PubMed

Anderson, Jeffrey S; Zielinski, Brandon A; Nielsen, Jared A; Ferguson, Michael A

2014-04-01

Very low-frequency blood oxygen level-dependent (BOLD) fluctuations have emerged as a valuable tool for describing brain anatomy, neuropathology, and development. Such fluctuations exhibit power law frequency dynamics, with largest amplitude at lowest frequencies. The biophysical mechanisms generating such fluctuations are poorly understood. Using publicly available data from 1,019 subjects of age 7-30, we show that BOLD fluctuations exhibit temporal complexity that is linearly related to local connectivity (regional homogeneity), consistently and significantly covarying across subjects and across gray matter regions. This relationship persisted independently of covariance with gray matter density or standard deviation of BOLD signal. During late neurodevelopment, BOLD fluctuations were unchanged with age in association cortex while becoming more random throughout the rest of the brain. These data suggest that local interconnectivity may play a key role in establishing the complexity of low-frequency BOLD fluctuations underlying functional magnetic resonance imaging connectivity. Stable low-frequency power dynamics may emerge through segmentation and integration of connectivity during development of distributed large-scale brain networks. Copyright © 2013 Wiley Periodicals, Inc.

Scheduling terminology for oral and maxillofacial surgery. Are we speaking a universal language?

PubMed

Howe, T E; Varley, I; Allen, J E; Glossop, A; McKechnie, A

2017-05-01

Use of a universal vocabulary to assist with the scheduling of operations has been shown to considerably reduce delays and improve the use of theatre resources. Within the UK the National Confidential Enquiry into Patient Outcome and Death (NCEPOD) has established a classification to assist with the triage of both emergency and non-emergency operating lists. We completed a survey to assess the uptake and understanding of this classification when scheduling maxillofacial operations. From a list of eight scheduling terms, respondents had to choose one each for 20 different clinical situations (that represented equally) immediate, urgent, expedited, and elective operations as defined by them. A total of 50 surveys were collated. Only 65% of answers selected represented NCPOD terms. 25% of answers represented a term higher and 18% a term lower, on the scale of intervention for the same category of situation. Current NCEPOD terms do not seem to be used universally and are poorly understood. Considerable variation in terminology exists when scheduling maxillofacial operations. Copyright © 2016 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Multifocal small bowel stromal tumours presenting with peritonitis in an HIV positive patient.

PubMed

Mansoor, Ebrahim

2014-01-01

The most common mesenchymal tumour of the gastrointestinal tract is stromal tumours (GISTs). Symptomatic GISTs can present with complications such as haemorrhage, obstruction and perforation. Complete surgical resection with negative margins is the mainstay of treatment but may be imprudent on emergent occasion. Tyrosine-kinase inhibitors (TKIs) have been revolutionary in the treatment of GISTs and have resulted in improved outcomes. A 41 year old HIV positive male presented with an acute history of abdominal pain and obstructive symptoms. Clinical examination revealed sepsis and peritonitis. One of the several small bowel tumours discovered at exploratory laparotomy was necrotic and perforated. The perforated tumour alone was resected and a small bowel internal hernia reduced. The patient made an uneventful recovery and will be considered for TKI therapy with a view to later re-operation. GISTs very rarely perforate. The pathophysiology of stromal tumour necrosis is poorly understood. Multifocality and small bowel location are poor prognosticators and may occur in the setting of familial GISTs, specific syndromes and sporadic cases. There is no established association between HIV and GISTs. Perforation occurs infrequently in ≤8% of symptomatic cases and poses increased risk of local recurrence. The surgical management of perforation takes precedence in an emergency. The surgeon must however take cognisance of the adherence to ideal oncologic principles where feasible. TKI therapy is invaluable if a re-exploration is to be later considered. Copyright © 2014 The Author. Published by Elsevier Ltd.. All rights reserved.

CYP2D6 predicted metabolizer status and safety in adult patients with attention-deficit hyperactivity disorder participating in a large placebo-controlled atomoxetine maintenance of response clinical trial.

PubMed

Fijal, Bonnie A; Guo, Yingying; Li, Si G; Ahl, Jonna; Goto, Taro; Tanaka, Yoko; Nisenbaum, Laura K; Upadhyaya, Himanshu P

2015-10-01

Atomoxetine, which is indicated for treatment of attention-deficit hyperactivity disorder (ADHD), is predominantly metabolized by genetically polymorphic cytochrome P450 2D6 (CYP2D6). Based on identified CYP2D6 genotypes, individuals can be categorized into 4 phenotypic metabolizer groups as ultrarapid, extensive, intermediate, and poor. Previous studies have focused on observed differences between poor and extensive metabolizers, but it is not well understood whether the safety profile of intermediate metabolizers differs from that of ultrarapid and extensive metabolizers. This study compared safety and tolerability among the different CYP2D6 metabolizer groups in the 12-week open-label phase of an atomoxetine study in adult patients with ADHD. Genotyping identified 1039 patients as extensive/ultrarapid metabolizers, 780 patients as intermediate metabolizers, and 117 patients as poor metabolizers. Common (≥5% frequency) treatment-emergent adverse events did not significantly differ between extensive/ultrarapid and intermediate metabolizers (odds ratios were <2.0 or >0.5). Poor metabolizers had higher frequencies of dry mouth, erectile dysfunction, hyperhidrosis, insomnia, and urinary retention compared with the other metabolizer groups. There were no significant differences between extensive/ultrarapid and intermediate metabolizers in changes from baseline in vital signs. These results suggest that data from CYP2D6 intermediate and extensive/ultrarapid metabolizers can be combined when considering safety analyses related to atomoxetine. © 2015, The American College of Clinical Pharmacology.

Implications of newborn amygdala connectivity for fear and cognitive development at 6-months-of-age

PubMed Central

Graham, Alice M.; Buss, Claudia; Rasmussen, Jerod M.; Rudolph, Marc D.; Demeter, Damion V.; Gilmore, John H.; Styner, Martin; Entringer, Sonja; Wadhwa, Pathik D.; Fair, Damien A.

2015-01-01

The first year of life is an important period for emergence of fear in humans. While animal models have revealed developmental changes in amygdala circuitry accompanying emerging fear, human neural systems involved in early fear development remain poorly understood. To increase understanding of the neural foundations of human fear, it is important to consider parallel cognitive development, which may modulate associations between typical development of early fear and subsequent risk for fear-related psychopathology. We, therefore, examined amygdala functional connectivity with rs-fcMRI in 48 neonates (M=3.65 weeks, SD=1.72), and measured fear and cognitive development at 6-months-of-age. Stronger, positive neonatal amygdala connectivity to several regions, including bilateral anterior insula and ventral striatum, was prospectively associated with higher fear at 6-months. Stronger amygdala connectivity to ventral anterior cingulate/anterior medial prefrontal cortex predicted a specific phenotype of higher fear combined with more advanced cognitive development. Overall, findings demonstrate unique profiles of neonatal amygdala functional connectivity related to emerging fear and cognitive development, which may have implications for normative and pathological fear in later years. Consideration of infant fear in the context of cognitive development will likely contribute to a more nuanced understanding of fear, its neural bases, and its implications for future mental health. PMID:26499255

Honey bees consider larval nutritional status rather than genetic relatedness when selecting larvae for emergency queen rearing.

PubMed

Sagili, Ramesh R; Metz, Bradley N; Lucas, Hannah M; Chakrabarti, Priyadarshini; Breece, Carolyn R

2018-05-16

In honey bees and many other social insects, production of queens is a vital task, as colony fitness is dependent on queens. The factors considered by honey bee workers in selecting larvae to rear new queens during emergency queen rearing are poorly understood. Identifying these parameters is critical, both in an evolutionary and apicultural context. As female caste development in honey bees is dependent on larval diet (i.e. nutrition), we hypothesized that larval nutritional state is meticulously assessed and used by workers in selection of larvae for queen rearing. To test this hypothesis, we conducted a series of experiments manipulating the nutritional status of one day old larvae by depriving them of brood food for a four-hour period, and then allowing workers to choose larvae for rearing queens from nutritionally deprived and non-deprived larvae. We simultaneously investigated the role of genetic relatedness in selection of larvae for queen rearing. In all the experiments, significantly greater numbers of non-deprived larvae than deprived larvae were selected for queen rearing irrespective of genetic relatedness. Our results demonstrate that honey bees perceive the nutritional state of larvae and use that information when selecting larvae for rearing queens in the natural emergency queen replacement process.

Complementary uses of small angle X-ray scattering and X-ray crystallography.

PubMed

Pillon, Monica C; Guarné, Alba

2017-11-01

Most proteins function within networks and, therefore, protein interactions are central to protein function. Although stable macromolecular machines have been extensively studied, dynamic protein interactions remain poorly understood. Small-angle X-ray scattering probes the size, shape and dynamics of proteins in solution at low resolution and can be used to study samples in a large range of molecular weights. Therefore, it has emerged as a powerful technique to study the structure and dynamics of biomolecular systems and bridge fragmented information obtained using high-resolution techniques. Here we review how small-angle X-ray scattering can be combined with other structural biology techniques to study protein dynamics. This article is part of a Special Issue entitled: Biophysics in Canada, edited by Lewis Kay, John Baenziger, Albert Berghuis and Peter Tieleman. Copyright © 2017 Elsevier B.V. All rights reserved.

Anxiety and Nicotine Dependence: Emerging Role of the Habenulo-Interpeduncular Axis.

PubMed

Molas, Susanna; DeGroot, Steven R; Zhao-Shea, Rubing; Tapper, Andrew R

2017-02-01

While innovative modern neuroscience approaches have aided in discerning brain circuitry underlying negative emotional behaviors including fear and anxiety responses, how these circuits are recruited in normal and pathological conditions remains poorly understood. Recently, genetic tools that selectively manipulate single neuronal populations have uncovered an understudied circuit, the medial habenula (mHb)-interpeduncular (IPN) axis, that modulates basal negative emotional responses. Interestingly, the mHb-IPN pathway also represents an essential circuit that signals heightened anxiety induced by nicotine withdrawal. Insights into how this circuit interconnects with regions more classically associated with anxiety, and how chronic nicotine exposure induces neuroadaptations resulting in an anxiogenic state, may thereby provide novel strategies and molecular targets for therapies that facilitate smoking cessation, as well as for anxiety relief. Copyright © 2016 Elsevier Ltd. All rights reserved.

Semen Anxiety: Materiality, Agency and the Internet.

PubMed

Shand, Alex

2007-12-01

Semen is a potent cultural symbol of masculinity. The social life of semen is poorly understood because of the intensely personal nature of its being. But the Internet has opened up new avenues for people to explore sensitive issues without disclosing their identity. This paper examines a set of questions submitted anonymously for answering by a medical team over a three month period to a UK-based consumer health website. The questions are analysed for emergent themes and these are divided into three groups: those concerning the material quality of semen; semen relating to masturbation; and those that concern semen and potency. It argues that far from being a phenomenon isolated to non-western cultures, semen anxiety is present in the UK in the twenty-first century and is the expression of anxieties surrounding shifting gender roles and masculine identities.

GABAergic interneurons: The orchestra or the conductor in fear learning and memory?

PubMed

Lucas, Elizabeth K; Clem, Roger L

2017-12-02

Fear conditioning is a form of associative learning that is fundamental to survival and involves potentiation of activity in excitatory projection neurons (PNs). Current models stipulate that the mechanisms underlying this process involve plasticity of PN synapses, which exhibit strengthening in response to fear conditioning. However, excitatory PNs are extensively modulated by a diverse array of GABAergic interneurons whose contributions to acquisition, storage, and expression of fear memory remain poorly understood. Here we review emerging evidence that genetically-defined interneurons play important subtype-specific roles in processing of fear-related stimuli and that these dynamics shape PN firing through both inhibition and disinhibition. Furthermore, interneurons exhibit structural, molecular, and electrophysiological evidence of fear learning-induced synaptic plasticity. These studies warrant discarding the notion of interneurons as passive bystanders in long-term memory. Copyright © 2017. Published by Elsevier Inc.

[Dieffenbachia poisoning in an infant].

PubMed

Mocking, Roel J T; Schene, Kiry M; Maingay-Visser, Dianne A P G F

2015-01-01

Plant poisoning is becoming an increasingly common reason to consult a doctor. A 7-month-old infant was sent to the emergency room by her general practitioner with a suspected apparent life-threatening event (ALTE). Her parents reported the sudden development of fluctuating restlessness and listlessness, superficial breathing, vomiting, drowsiness and episodes of loss of consciousness. On physical examination we saw a pale, listless and variably responsive girl. During admission for observation, she improved within a few hours, although she had one episode of blood admixture with the stool. After discharge from hospital, the infant's grandmother suggested that the symptoms could be due to poisoning from a Dieffenbachia plant. The literature supports this explanation. Young parents and doctors appear to know little about plant toxicity in general and Dieffenbachia in particular. In small children with poorly-understood symptoms, the possibility plant poisoning should be considered.

Microbial community assembly and metabolic function during mammalian corpse decomposition.

PubMed

Metcalf, Jessica L; Xu, Zhenjiang Zech; Weiss, Sophie; Lax, Simon; Van Treuren, Will; Hyde, Embriette R; Song, Se Jin; Amir, Amnon; Larsen, Peter; Sangwan, Naseer; Haarmann, Daniel; Humphrey, Greg C; Ackermann, Gail; Thompson, Luke R; Lauber, Christian; Bibat, Alexander; Nicholas, Catherine; Gebert, Matthew J; Petrosino, Joseph F; Reed, Sasha C; Gilbert, Jack A; Lynne, Aaron M; Bucheli, Sibyl R; Carter, David O; Knight, Rob

2016-01-08

Vertebrate corpse decomposition provides an important stage in nutrient cycling in most terrestrial habitats, yet microbially mediated processes are poorly understood. Here we combine deep microbial community characterization, community-level metabolic reconstruction, and soil biogeochemical assessment to understand the principles governing microbial community assembly during decomposition of mouse and human corpses on different soil substrates. We find a suite of bacterial and fungal groups that contribute to nitrogen cycling and a reproducible network of decomposers that emerge on predictable time scales. Our results show that this decomposer community is derived primarily from bulk soil, but key decomposers are ubiquitous in low abundance. Soil type was not a dominant factor driving community development, and the process of decomposition is sufficiently reproducible to offer new opportunities for forensic investigations. Copyright © 2016, American Association for the Advancement of Science.

Prevalence and Nature of Late-Emerging Poor Readers.

PubMed

Catts, Hugh W; Compton, Donald; Tomblin, J Bruce; Bridges, Mindy Sittner

2012-02-01

Some children demonstrate adequate or better reading achievement in early school grades, but fall significantly behind their peers in later grades. These children are often referred to as late-emerging poor readers. In this study, we investigated the prevalence and heterogeneity of these poor readers. We also examined the early language and nonverbal cognitive abilities of late-emerging poor readers. Participants were 493 children who were a subsample from an epidemiological study of language impairments in school-age children. In kindergarten, children were administered a battery of language, early literacy, and nonverbal cognitive measures. Word reading and reading comprehension achievement was assessed in second, fourth, eighth, and tenth grades. Latent transition analysis was used to model changes in reading classification (good vs. poor reader) across grades. Population estimates revealed that 13.4% percent of children could be classified as late-emerging poor readers. These children could be divided into those with problems in comprehension alone (52%), word reading alone (36%), or both (12%). Further results indicated that late-emerging poor readers often had a history of language and/or nonverbal cognitive impairments in kindergarten. Subtypes of poor readers also differed significantly in their profiles of language, early literacy, and nonverbal cognitive abilities in kindergarten. Results are discussed in terms of causal factors and implications for early identification.

Research Review: The Neurobiology and Genetics of Maltreatment and Adversity

ERIC Educational Resources Information Center

McCrory, Eamon; De Brito, Stephane A.; Viding, Essi

2010-01-01

The neurobiological mechanisms by which childhood maltreatment heightens vulnerability to psychopathology remain poorly understood. It is likely that a complex interaction between environmental experiences (including poor caregiving) and an individual's genetic make-up influence neurobiological development across infancy and childhood, which in…

Ancient DNA Investigation of a Medieval German Cemetery Confirms Long-Term Stability of CCR5-Δ32 Allele Frequencies in Central Europe.

PubMed

Bouwman, Abigail; Shved, Natallia; Akgül, Gülfirde; Rühli, Frank; Warinner, Christina

2017-04-01

The CCR5-Δ32 mutation present in European populations is among the most prominently debated cases of recent positive selection in humans. This allele, a 32-bp deletion that renders the T-cell CCR5 receptor nonfunctional, has important epidemiological and public health significance, as homozygous carriers are resistant to several HIV strains. However, although the function of this allele in preventing HIV infection is now well described, its human evolutionary origin is poorly understood. Initial attempts to determine the emergence of the CCR5-Δ32 allele pointed to selection during the 14th-century Black Death pandemic; however, subsequent analyses suggest that the allele rose in frequency more than 5,000 years ago, possibly through drift. Recently, three studies have identified populations predating the 14th century CE that are positive for the CCR5-Δ32 allele, supporting the claim for a more ancient origin. However, these studies also suggest poorly understood regional differences in the recent evolutionary history of the CCR5-Δ32 allele. Here a new hydrolysis-probe-based real-time PCR assay was designed to ascertain CCR5 allele frequency in 53 individuals from a 10th- to 12th-century CE church and convent complex in central Germany that predates outbreaks of the Black Death pandemic. High-confidence genotypes were obtained for 32 individuals, and results show that CCR5-Δ32 allele frequency has remained unchanged in this region of Central Europe over the last millennium, suggesting that there has been no strong positive selective pressure over this time period and confirming a more ancient origin for the allele.

What the drivers do and do not tell you: using verbal protocol analysis to investigate driver behaviour in emergency situations.

PubMed

Banks, Victoria A; Stanton, Neville A; Harvey, Catherine

2014-01-01

Although task analysis of pedestrian detection can provide us with useful insights into how a driver may behave in emergency situations, the cognitive elements of driver decision-making are less well understood. To assist in the design of future Advanced Driver Assistance Systems, such as Autonomous Emergency Brake systems, it is essential that the cognitive elements of the driving task are better understood. This paper uses verbal protocol analysis in an exploratory fashion to uncover the thought processes underlying behavioural outcomes represented by hard data collected using the Southampton University Driving Simulator.

NASA Aims to Create First-Ever Space-Based Sodium Lidar to Study Poorly Understood Mesosphere

NASA Image and Video Library

2017-12-08

Caption: Mike Krainak (left) and Diego Janches recently won NASA follow-on funding to advance a spaceborne sodium lidar needed to probe Earth’s poorly understood mesosphere. Credits: NASA/W. Hrybyk More: A team of NASA scientists and engineers now believes it can leverage recent advances in a greenhouse-detecting instrument to build the world’s first space-based sodium lidar to study Earth’s poorly understood mesosphere. Scientist Diego Janches and laser experts Mike Krainak and Tony Yu, all of whom work at NASA’s Goddard Space Flight Center in Greenbelt, Maryland, are leading a research-and-development effort to further advance the sodium lidar, which the group plans to deploy on the International Space Station if it succeeds in proving its flightworthiness. Read more: go.nasa.gov/2rcGpSM NASA image use policy. NASA Goddard Space Flight Center enables NASA’s mission through four scientific endeavors: Earth Science, Heliophysics, Solar System Exploration, and Astrophysics. Goddard plays a leading role in NASA’s accomplishments by contributing compelling scientific knowledge to advance the Agency’s mission. Follow us on Twitter Like us on Facebook Find us on Instagram

Auditory Processing Disorders: Acquisition and Treatment

ERIC Educational Resources Information Center

Moore, David R.

2007-01-01

Auditory processing disorder (APD) describes a mixed and poorly understood listening problem characterised by poor speech perception, especially in challenging environments. APD may include an inherited component, and this may be major, but studies reviewed here of children with long-term otitis media with effusion (OME) provide strong evidence…

'Why didn't you write a not-for-cardiopulmonary resuscitation order?' Unexpected death or failure of process?

PubMed

Levinson, Michele; Mills, Amber; Barrett, Jonathan; Sritharan, Gaya; Gellie, Anthea

2018-02-01

Objective The aim of the present study was to understand the reasons for the delivery of non-beneficial cardiopulmonary resuscitation (CPR) attempts in a tertiary private hospital over 12 months. We determined doctors' expectations of survival after CPR for their patient, whether they had considered a not-for-resuscitation (NFR) order and the barriers to completion of NFR orders. Methods Anonymous questionnaires were sent to the doctors primarily responsible for a given patient's care in the hospital within 2 weeks of the unsuccessful CPR attempt. The data were analysed quantitatively where appropriate and qualitatively for themes for open-text responses Results Most doctors surveyed in the present study understood the poor outcome after CPR in the older person. Most doctors had an expectation that their own patient had a poor prognosis and a poor likely predicted outcome after CPR. This implied that the patient's death was neither unexpected nor likely to be reversible. Some doctors considered NFR orders, but multiple barriers to completion were cited, including the family's wishes, being time poor and diffusion or deferral of responsibility. Conclusions It is likely that futile CPR is provided contrary to policy and legal documents relating to end-of-life care, with the potential for harms relating to both patient and family, and members of resuscitation teams. The failure appears to relate to process rather than recognition of poor patient outcome. What is known about the topic? Mandatory CPR has been established in Australian hospitals on the premise that it will save lives. The outcome from in-hospital cardiac arrest has not improved despite significant training and resources. The outcome for those acutely hospitalised patients aged over 80 years has been repeatedly demonstrated to be poor with significant morbidity in the survivors. There is emerging literature on the extent of the delivery of non-beneficial treatments at the end of life, including futile CPR, the recognition of harms incurred by patients, families and members of the resuscitation teams and on the opportunity cost of the inappropriate use of resources. What does this paper add? This is the first study, to our knowledge, that has demonstrated that doctors understood the outcomes for CPR, particularly in those aged 80 years and older, and that failure to recognise poor outcome and prognosis in their own patients is not a barrier to writing NFR orders. What are the implications for practitioners? Recognition of the poor outcomes from CPR for the elderly patient for whom the doctor has a duty of care should result in a discussion with the patients, allowing an exploration of values and expectations of treatment. This would promote shared decision making, which includes the use of CPR. Facilitation of these discussions should be the focus of health service review.

Similar and contrasting dimensions of social cognition in schizophrenia and healthy subjects.

PubMed

Mehta, Urvakhsh Meherwan; Thirthalli, Jagadisha; Bhagyavathi, H D; Keshav Kumar, J; Subbakrishna, D K; Gangadhar, Bangalore N; Eack, Shaun M; Keshavan, Matcheri S

2014-08-01

Schizophrenia patients experience substantial impairments in social cognition (SC) and these deficits are associated with their poor functional outcome. Though SC is consistently shown to emerge as a cognitive dimension distinct from neurocognition, the dimensionality of SC is poorly understood. Moreover, comparing the components of SC between schizophrenia patients and healthy comparison subjects would provide specific insights on the construct validity of SC. We conducted principal component analyses of eight SC test scores (representing four domains of SC, namely, theory of mind, emotion processing, social perception and attributional bias) independently in 170 remitted schizophrenia patients and 111 matched healthy comparison subjects. We also conducted regression analyses to evaluate the relative contribution of individual SC components to other symptom dimensions, which are important clinical determinants of functional outcome (i.e., neurocognition, negative symptoms, motivational deficits and insight) in schizophrenia. A three-factor solution representing socio-emotional processing, social-inferential ability and external attribution components emerged in the patient group that accounted for 64.43% of the variance. In contrast, a two-factor solution representing socio-emotional processing and social-inferential ability was derived in the healthy comparison group that explained 56.5% of the variance. In the patient group, the social-inferential component predicted negative symptoms and motivational deficits. Our results suggest the presence of a multidimensional SC construct. The dimensionality of SC observed across the two groups, though not identical, displayed important parallels. Individual components also demonstrated distinct patterns of association with other symptom dimensions, thus supporting their external validity. Copyright © 2014 Elsevier B.V. All rights reserved.

"Candidatus anaplasma camelii" in one-humped camels (Camelus dromedarius) in Morocco: a novel and emerging anaplasma species?

PubMed

Ait Lbacha, Hicham; Zouagui, Zaid; Alali, Said; Rhalem, Abdelkbir; Petit, Elisabeth; Ducrotoy, Marie Julie; Boulouis, Henri-Jean; Maillard, Renaud

2017-02-05

There has been a growing interest in camel anaplasmosis due to its recent emergence in this reservoir species and concerns for its zoonotic potential. The epidemiology of anaplasmosis in camels therefore remains poorly understood mostly because camels belong to marginalised poor and often transhumant populations whose interests are largely neglected. Most studies of anaplasmosis in camels have relied on microscopy and serology for diagnosis and only three studies, undertaken in Tunisia, Saudia Arabia and China, have used molecular diagnostics. The present work characterises Anaplasmataceae strains circulating in the Camelus dromedarius reservoir in Morocco using PCR. Camels (n = 106) were randomly sampled from 6 regions representing different agro-ecological areas in southern Morocco. Whole blood was collected and screened using PCR methods targeting the gene groEL. Anaplasmataceae strains were characterised by sequence analysis of the gene groEL. A total of 39.62% (42/106) camels screened were positive for Anaplasmataceae spp. GenBank BLAST analysis of five positive sequenced samples revealed that all strains were 100% identical to "Candidatus Anaplasma camelii". Phylogenetic investigation and genetic characterisation of the aligned segment (650 bp) of the gene groEL confirmed high similarity with A. platys. This study demonstrates the circulation of a previously unidentified species of the genus Anaplasma in Morocco which is genetically close to the agent causing canine anaplasmosis but whose main reservoir is thought to be Camelus dromedarius. This study is not a clinical trial and therefore a trial registration number does not apply.

Identification of the Intragenomic Promoter Controlling Hepatitis E Virus Subgenomic RNA Transcription.

PubMed

Ding, Qiang; Nimgaonkar, Ila; Archer, Nicholas F; Bram, Yaron; Heller, Brigitte; Schwartz, Robert E; Ploss, Alexander

2018-05-08

Approximately 20 million hepatitis E virus (HEV) infections occur annually in both developing and industrialized countries. Most infections are self-limiting, but they can lead to chronic infections and cirrhosis in immunocompromised patients, and death in pregnant women. The mechanisms of HEV replication remain incompletely understood due to scarcity of adequate experimental platforms. HEV undergoes asymmetric genome replication, but it produces an additional subgenomic (SG) RNA encoding the viral capsid and a viroporin in partially overlapping open reading frames. Using a novel transcomplementation system, we mapped the intragenomic subgenomic promoter regulating SG RNA synthesis. This cis -acting element is highly conserved across all eight HEV genotypes, and when the element is mutated, it abrogates particle assembly and release. Our work defines previously unappreciated viral regulatory elements and provides the first in-depth view of the intracellular genome dynamics of this emerging human pathogen. IMPORTANCE HEV is an emerging pathogen causing severe liver disease. The genetic information of HEV is encoded in RNA. The genomic RNA is initially copied into a complementary, antigenomic RNA that is a template for synthesis of more genomic RNA and for so-called subgenomic RNA. In this study, we identified the precise region within the HEV genome at which the synthesis of the subgenomic RNA is initiated. The nucleotides within this region are conserved across genetically distinct variants of HEV, highlighting the general importance of this segment for the virus. To identify this regulatory element, we developed a new experimental system that is a powerful tool with broad utility to mechanistically dissect many other poorly understood functional elements of HEV. Copyright © 2018 Ding et al.

Central and peripheral clocks are coupled by a neuropeptide pathway in Drosophila

PubMed Central

Selcho, Mareike; Millán, Carola; Palacios-Muñoz, Angelina; Ruf, Franziska; Ubillo, Lilian; Chen, Jiangtian; Bergmann, Gregor; Ito, Chihiro; Silva, Valeria; Wegener, Christian; Ewer, John

2017-01-01

Animal circadian clocks consist of central and peripheral pacemakers, which are coordinated to produce daily rhythms in physiology and behaviour. Despite its importance for optimal performance and health, the mechanism of clock coordination is poorly understood. Here we dissect the pathway through which the circadian clock of Drosophila imposes daily rhythmicity to the pattern of adult emergence. Rhythmicity depends on the coupling between the brain clock and a peripheral clock in the prothoracic gland (PG), which produces the steroid hormone, ecdysone. Time information from the central clock is transmitted via the neuropeptide, sNPF, to non-clock neurons that produce the neuropeptide, PTTH. These secretory neurons then forward time information to the PG clock. We also show that the central clock exerts a dominant role on the peripheral clock. This use of two coupled clocks could serve as a paradigm to understand how daily steroid hormone rhythms are generated in animals. PMID:28555616

Population Pulsation Resonances of Excitons in Monolayer MoSe 2 with Sub-1 μeV Linewidths

DOE PAGES

Schaibley, John R.; Karin, Todd; Yu, Hongyi; ...

2015-04-01

Monolayer transition metal dichalcogenides, a new class of atomically thin semiconductors, possess optically coupled 2D valley excitons. The nature of exciton relaxation in these systems is currently poorly understood. In this paper, we investigate exciton relaxation in monolayer MoSe 2 using polarization-resolved coherent nonlinear optical spectroscopy with high spectral resolution. We report strikingly narrow population pulsation resonances with two different characteristic linewidths of 1 and <0.2 μeV at low temperature. These linewidths are more than 3 orders of magnitude narrower than the photoluminescence and absorption linewidth, and indicate that a component of the exciton relaxation dynamics occurs on time scalesmore » longer than 1 ns. Finally, the ultranarrow resonance (<0.2 μeV) emerges with increasing excitation intensity, and implies the existence of a long-lived state whose lifetime exceeds 6 ns.« less

Recent Advances in Biosensor Development for Foodborne Virus Detection

PubMed Central

Neethirajan, Suresh; Ahmed, Syed Rahin; Chand, Rohit; Buozis, John; Nagy, Éva

2017-01-01

Outbreaks of foodborne diseases related to fresh produce have been increasing in North America and Europe. Viral foodborne pathogens are poorly understood, suffering from insufficient awareness and surveillance due to the limits on knowledge, availability, and costs of related technologies and devices. Current foodborne viruses are emphasized and newly emerging foodborne viruses are beginning to attract interest. To face current challenges regarding foodborne pathogens, a point-of-care (POC) concept has been introduced to food testing technology and device. POC device development involves technologies such as microfluidics, nanomaterials, biosensors and other advanced techniques. These advanced technologies, together with the challenges in developing foodborne virus detection assays and devices, are described and analysed in this critical review. Advanced technologies provide a path forward for foodborne virus detection, but more research and development will be needed to provide the level of manufacturing capacity required. PMID:29071193

Intercellular and systemic spread of RNA and RNAi in plants.

PubMed

Nazim Uddin, Mohammad; Kim, Jae-Yean

2013-01-01

Plants possess dynamic networks of intercellular communication that are crucial for plant development and physiology. In plants, intercellular communication involves a combination of ligand-receptor-based apoplasmic signaling, and plasmodesmata and phloem-mediated symplasmic signaling. The intercellular trafficking of macromolecules, including RNAs and proteins, has emerged as a novel mechanism of intercellular communication in plants. Various forms of regulatory RNAs move over distinct cellular boundaries through plasmodesmata and phloem. This plant-specific, non-cell-autonomous RNA trafficking network is also involved in development, nutrient homeostasis, gene silencing, pathogen defense, and many other physiological processes. However, the mechanism underlying macromolecular trafficking in plants remains poorly understood. Current progress made in RNA trafficking research and its biological relevance to plant development will be summarized. Diverse plant regulatory mechanisms of cell-to-cell and systemic long-distance transport of RNAs, including mRNAs, viral RNAs, and small RNAs, will also be discussed. Copyright © 2013 John Wiley & Sons, Ltd.

Early but not late blindness leads to enhanced arithmetic and working memory abilities.

PubMed

Dormal, Valérie; Crollen, Virginie; Baumans, Christine; Lepore, Franco; Collignon, Olivier

2016-10-01

Behavioural and neurophysiological evidence suggest that vision plays an important role in the emergence and development of arithmetic abilities. However, how visual deprivation impacts on the development of arithmetic processing remains poorly understood. We compared the performances of early (EB), late blind (LB) and sighted control (SC) individuals during various arithmetic tasks involving addition, subtraction and multiplication of various complexities. We also assessed working memory (WM) performances to determine if they relate to a blind person's arithmetic capacities. Results showed that EB participants performed better than LB and SC in arithmetic tasks, especially in conditions in which verbal routines and WM abilities are needed. Moreover, EB participants also showed higher WM abilities. Together, our findings demonstrate that the absence of developmental vision does not prevent the development of refined arithmetic skills and can even trigger the refinement of these abilities in specific tasks. Copyright © 2016 Elsevier Ltd. All rights reserved.

Linking acute kidney injury to chronic kidney disease: the missing links.

PubMed

Kaballo, Mohammed A; Elsayed, Mohamed E; Stack, Austin G

2017-08-01

Acute kidney injury (AKI) is considered to be a major public health problem around the globe, and it is associated with major adverse clinical outcomes and significant health care costs. There is growing evidence suggesting that AKI is associated with the subsequent development of chronic kidney disease (CKD). While recovery of kidney function occurs in the majority of patients surviving an AKI episode, a large number of patients do not recover completely. Similarly, CKD is a well-known risk factor for the development of AKI. Recent studies suggest that both AKI and CKD are not separate disease entities but are in fact components of a far more closely interconnected disease continuum. However, the true nature of this relationship is complex and poorly understood. This review explores potential relationships between AKI and CKD, and seeks to uncover a number of "missing links" in this tentative emerging relationship.

Cascade of neural processing orchestrates cognitive control in human frontal cortex

PubMed Central

Tang, Hanlin; Yu, Hsiang-Yu; Chou, Chien-Chen; Crone, Nathan E; Madsen, Joseph R; Anderson, William S; Kreiman, Gabriel

2016-01-01

Rapid and flexible interpretation of conflicting sensory inputs in the context of current goals is a critical component of cognitive control that is orchestrated by frontal cortex. The relative roles of distinct subregions within frontal cortex are poorly understood. To examine the dynamics underlying cognitive control across frontal regions, we took advantage of the spatiotemporal resolution of intracranial recordings in epilepsy patients while subjects resolved color-word conflict. We observed differential activity preceding the behavioral responses to conflict trials throughout frontal cortex; this activity was correlated with behavioral reaction times. These signals emerged first in anterior cingulate cortex (ACC) before dorsolateral prefrontal cortex (dlPFC), followed by medial frontal cortex (mFC) and then by orbitofrontal cortex (OFC). These results disassociate the frontal subregions based on their dynamics, and suggest a temporal hierarchy for cognitive control in human cortex. DOI: http://dx.doi.org/10.7554/eLife.12352.001 PMID:26888070

Relevance of Chronic Lyme Disease to Family Medicine as a Complex Multidimensional Chronic Disease Construct: A Systematic Review

PubMed Central

Goderis, Geert

2014-01-01

Lyme disease has become a global public health problem and a prototype of an emerging infection. Both treatment-refractory infection and symptoms that are related to Borrelia burgdorferi infection remain subject to controversy. Because of the absence of solid evidence on prevalence, causes, diagnostic criteria, tools and treatment options, the role of autoimmunity to residual or persisting antigens, and the role of a toxin or other bacterial-associated products that are responsible for the symptoms and signs, chronic Lyme disease (CLD) remains a relatively poorly understood chronic disease construct. The role and performance of family medicine in the detection, integrative treatment, and follow-up of CLD are not well studied either. The purpose of this paper is to describe insights into the complexity of CLD as a multidimensional chronic disease construct and its relevance to family medicine by means of a systematic literature review. PMID:25506429

Resource allocation and compensation during development in holometabolous insects.

PubMed

Nestel, David; Papadopoulos, Nikos T; Pascacio-Villafán, Carlos; Righini, Nicoletta; Altuzar-Molina, Alma R; Aluja, Martín

2016-12-01

We provide an extensive review on current knowledge and future research paths on the topic of resource allocation and compensation during development in holometabolous insects, emphasizing the role of resource management during development, and how compensatory mechanisms may be acting to remediate nutritional deficiencies carried over from earlier stages of development. We first review resource allocation in "open" and "closed" developmental stages and then move on to the topic of modelling resource allocation and its trade-offs. In doing so, we review novel methodological developments such as response-surface methods and mixture experiments as well as nutritional geometry. We also dwell on the fascinating topic of compensatory physiology and behavior. We finish by discussing future research paths, among them the emerging field of nutrigenomics and gut microbiome, which will shed light into the yet poorly understood role of the symbiotic microbiota in nutrient compensation or assimilation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Prominin-1-containing membrane vesicles: origins, formation, and utility.

PubMed

Marzesco, Anne-Marie

2013-01-01

The stem cell antigen prominin-1 (CD133) is associated with two major types (small and large) of extracellular membrane vesicles in addition to its selective concentration in various kinds of plasma membrane protrusion. During development of the mammalian central nervous system, differentiating neuroepithelial stem cells release these vesicles into the embryonic cerebrospinal fluid. In glioblastoma patients, an increase of such vesicles, particularly the smaller ones, have been also observed in cerebrospinal fluid. Similarly, hematopoietic stem and progenitor cells release small ones concomitantly with their differentiation. Although the functional significance of these prominin-1-containing membrane vesicles is poorly understood, a link between differentiation of stem (and cancer stem) cells and their release is emerging. In this chapter, I will summarize our knowledge about prominin-1-containing membrane vesicles including a potential role in cell-cell communication and highlight their prospective value as a new biomarker for tumorigenesis diagnostics.

Time-specific ecological niche modeling predicts spatial dynamics of vector insects and human dengue cases.

PubMed

Peterson, A Townsend; Martínez-Campos, Carmen; Nakazawa, Yoshinori; Martínez-Meyer, Enrique

2005-09-01

Numerous human diseases-malaria, dengue, yellow fever and leishmaniasis, to name a few-are transmitted by insect vectors with brief life cycles and biting activity that varies in both space and time. Although the general geographic distributions of these epidemiologically important species are known, the spatiotemporal variation in their emergence and activity remains poorly understood. We used ecological niche modeling via a genetic algorithm to produce time-specific predictive models of monthly distributions of Aedes aegypti in Mexico in 1995. Significant predictions of monthly mosquito activity and distributions indicate that predicting spatiotemporal dynamics of disease vector species is feasible; significant coincidence with human cases of dengue indicate that these dynamics probably translate directly into transmission of dengue virus to humans. This approach provides new potential for optimizing use of resources for disease prevention and remediation via automated forecasting of disease transmission risk.

Neural Correlates of Lyrical Improvisation: An fMRI Study of Freestyle Rap

PubMed Central

Liu, Siyuan; Chow, Ho Ming; Xu, Yisheng; Erkkinen, Michael G.; Swett, Katherine E.; Eagle, Michael W.; Rizik-Baer, Daniel A.; Braun, Allen R.

2012-01-01

The neural correlates of creativity are poorly understood. Freestyle rap provides a unique opportunity to study spontaneous lyrical improvisation, a multidimensional form of creativity at the interface of music and language. Here we use functional magnetic resonance imaging to characterize this process. Task contrast analyses indicate that improvised performance is characterized by dissociated activity in medial and dorsolateral prefrontal cortices, providing a context in which stimulus-independent behaviors may unfold in the absence of conscious monitoring and volitional control. Connectivity analyses reveal widespread improvisation-related correlations between medial prefrontal, cingulate motor, perisylvian cortices and amygdala, suggesting the emergence of a network linking motivation, language, affect and movement. Lyrical improvisation appears to be characterized by altered relationships between regions coupling intention and action, in which conventional executive control may be bypassed and motor control directed by cingulate motor mechanisms. These functional reorganizations may facilitate the initial improvisatory phase of creative behavior. PMID:23155479

Neural correlates of lyrical improvisation: an FMRI study of freestyle rap.

PubMed

Liu, Siyuan; Chow, Ho Ming; Xu, Yisheng; Erkkinen, Michael G; Swett, Katherine E; Eagle, Michael W; Rizik-Baer, Daniel A; Braun, Allen R

2012-01-01

The neural correlates of creativity are poorly understood. Freestyle rap provides a unique opportunity to study spontaneous lyrical improvisation, a multidimensional form of creativity at the interface of music and language. Here we use functional magnetic resonance imaging to characterize this process. Task contrast analyses indicate that improvised performance is characterized by dissociated activity in medial and dorsolateral prefrontal cortices, providing a context in which stimulus-independent behaviors may unfold in the absence of conscious monitoring and volitional control. Connectivity analyses reveal widespread improvisation-related correlations between medial prefrontal, cingulate motor, perisylvian cortices and amygdala, suggesting the emergence of a network linking motivation, language, affect and movement. Lyrical improvisation appears to be characterized by altered relationships between regions coupling intention and action, in which conventional executive control may be bypassed and motor control directed by cingulate motor mechanisms. These functional reorganizations may facilitate the initial improvisatory phase of creative behavior.

Integrative analyses of human reprogramming reveal dynamic nature of induced pluripotency

PubMed Central

Cacchiarelli, Davide; Trapnell, Cole; Ziller, Michael J.; Soumillon, Magali; Cesana, Marcella; Karnik, Rahul; Donaghey, Julie; Smith, Zachary D.; Ratanasirintrawoot, Sutheera; Zhang, Xiaolan; Ho Sui, Shannan J.; Wu, Zhaoting; Akopian, Veronika; Gifford, Casey A.; Doench, John; Rinn, John L.; Daley, George Q.; Meissner, Alexander; Lander, Eric S.; Mikkelsen, Tarjei S.

2015-01-01

Summary Induced pluripotency is a promising avenue for disease modeling and therapy, but the molecular principles underlying this process, particularly in human cells, remain poorly understood due to donor-to-donor variability and intercellular heterogeneity. Here we constructed and characterized a clonal, inducible human reprogramming system that provides a reliable source of cells at any stage of the process. This system enabled integrative transcriptional and epigenomic analysis across the human reprogramming timeline at high resolution. We observed distinct waves of gene network activation, including the ordered reactivation of broad developmental regulators followed by early embryonic patterning genes and culminating in the emergence of a signature reminiscent of pre-implantation stages. Moreover, complementary functional analyses allowed us to identify and validate novel regulators of the reprogramming process. Altogether, this study sheds light on the molecular underpinnings of induced pluripotency in human cells and provides a robust cell platform for further studies. PMID:26186193

Natural gold particles in Eucalyptus leaves and their relevance to exploration for buried gold deposits

PubMed Central

Lintern, Melvyn; Anand, Ravi; Ryan, Chris; Paterson, David

2013-01-01

Eucalyptus trees may translocate Au from mineral deposits and support the use of vegetation (biogeochemical) sampling in mineral exploration, particularly where thick sediments dominate. However, biogeochemistry has not been routinely adopted partly because biotic mechanisms of Au migration are poorly understood. For example, although Au has been previously measured in plant samples, there has been doubt as to whether it was truly absorbed rather than merely adsorbed on the plant surface as aeolian contamination. Here we show the first evidence of particulate Au within natural specimens of living biological tissue (not from laboratory experimentation). This observation conclusively demonstrates active biogeochemical adsorption of Au and provides insight into its behaviour in natural samples. The confirmation of biogeochemical adsorption of Au, and of a link with abiotic processes, promotes confidence in an emerging technique that may lead to future exploration success and maintain continuity of supply. PMID:24149278

Developmental neurogenetics of sexual dimorphism in Aedes aegypti

PubMed Central

Duman-Scheel, Molly; Syed, Zainulabeuddin

2015-01-01

Sexual dimorphism, a poorly understood but crucial aspect of vector mosquito biology, encompasses sex-specific physical, physiological, and behavioral traits related to mosquito reproduction. The study of mosquito sexual dimorphism has largely focused on analysis of the differences between adult female and male mosquitoes, particularly with respect to sex-specific behaviors related to disease transmission. However, sexually dimorphic behaviors are the products of differential gene expression that initiates during development and therefore must also be studied during development. Recent technical advancements are facilitating functional genetic studies in the dengue vector Aedes aegypti, an emerging model for mosquito development. These methodologies, many of which could be extended to other non-model insect species, are facilitating analysis of the development of sexual dimorphism in neural tissues, particularly the olfactory system. These studies are providing insight into the neurodevelopmental genetic basis for sexual dimorphism in vector mosquitoes. PMID:26949699

Inflammatory Bowel Disease: Influence and Implications in Reproduction

PubMed Central

Glover, Louise E.; Fennimore, Blair; Wingfield, Mary

2016-01-01

The incidence and prevalence of inflammatory bowel disease (IBD) continues to rise with time, signifying its emergence as a global disease. Clinical onset of IBD, comprising Crohn’s disease and ulcerative colitis, typically occurs prior to or at peak reproductive age. Although active disease in female patients is associated with reduced fertility and adverse obstetric outcomes in pregnancy, the molecular mechanisms underlying this altered reproductive course, as well as its impact on IBD transmission to offspring, remain poorly understood. Clinical and experimental studies have now begun to elucidate the hormonal, environmental and microbial factors that modulate immune-reproductive crosstalk in IBD, and define their impact on maternal health, fetal development and heritability of disease risk. Evolving insight into maternal-fetal imprinting in IBD has important implications for patient counseling and disease management during pregnancy, and may help predict clinical outcomes for both mother and child. PMID:27537054

A novel perivascular cell population in the zebrafish brain.

PubMed

Venero Galanternik, Marina; Castranova, Daniel; Gore, Aniket V; Blewett, Nathan H; Jung, Hyun Min; Stratman, Amber N; Kirby, Martha R; Iben, James; Miller, Mayumi F; Kawakami, Koichi; Maraia, Richard J; Weinstein, Brant M

2017-04-11

The blood-brain barrier is essential for the proper homeostasis and function of the CNS, but its mechanism of function is poorly understood. Perivascular cells surrounding brain blood vessels are thought to be important for blood-brain barrier establishment, but their roles are not well defined. Here, we describe a novel perivascular cell population closely associated with blood vessels on the zebrafish brain. Based on similarities in their morphology, location, and scavenger behavior, these cells appear to be the zebrafish equivalent of cells variably characterized as Fluorescent Granular Perithelial cells (FGPs), perivascular macrophages, or 'Mato Cells' in mammals. Despite their macrophage-like morphology and perivascular location, zebrafish FGPs appear molecularly most similar to lymphatic endothelium, and our imaging studies suggest that these cells emerge by differentiation from endothelium of the optic choroidal vascular plexus. Our findings provide the first report of a perivascular cell population in the brain derived from vascular endothelium.

Creating lenticular galaxies with mergers

NASA Astrophysics Data System (ADS)

Querejeta, Miguel; Eliche-Moral, M. Carmen; Tapia, Trinidad; Borlaff, Alejandro; van de Ven, Glenn; Lyubenova, Mariya; Martig, Marie; Falcón-Barroso, Jesús; Méndez-Abreu, Jairo; Zamorano, Jaime; Gallego, Jesús

2017-03-01

Lenticular galaxies (S0s) represent the majority of early-type galaxies in the local Universe, but their formation channels are still poorly understood. While galaxy mergers are obvious pathways to suppress star formation and increase bulge sizes, the marked parallelism between spiral and lenticular galaxies (e.g. photometric bulge-disc coupling) seemed to rule out a potential merger origin. Here, we summarise our recent work in which we have shown, through N-body numerical simulations, that disc-dominated lenticulars can emerge from major mergers of spiral galaxies, in good agreement with observational photometric scaling relations. Moreover, we show that mergers simultaneously increase the light concentration and reduce the angular momentum relative to their spiral progenitors. This explains the mismatch in angular momentum and concentration between spirals and lenticulars recently revealed by CALIFA observations, which is hard to reconcile with simple fading mechanisms (e.g. ram-pressure stripping).

Depression, Stress, and Anhedonia: Toward a Synthesis and Integrated Model

PubMed Central

Pizzagalli, Diego A.

2014-01-01

Depression is a significant public health problem, but its etiology and pathophysiology remain poorly understood. Such incomplete understanding likely arises from the fact that depression encompasses a heterogeneous set of disorders. To overcome these limitations, renewed interest in intermediate phenotypes (endophenotypes) has resurfaced, and anhedonia has emerged as one of the most promising endophenotypes of depression. Here, a heuristic model is presented postulating that anhedonia arises from dysfunctional interactions between stress and brain reward systems. To this end, we review and integrate three bodies of independent literature investigating the role of (1) anhedonia, (2) dopamine, and (3) stress in depression. In a fourth section, we summarize animal data indicating that stress negatively affect mesocorticolimbic dopaminergic pathways critically implicated in incentive motivation and reinforcement learning. In the last section, we provide a synthesis of these four literatures, present initial evidence consistent with our model, and discuss directions for future research. PMID:24471371

The contribution of group A streptococcal virulence determinants to the pathogenesis of sepsis

PubMed Central

Reglinski, Mark; Sriskandan, Shiranee

2014-01-01

Streptococcus pyogenes (group A streptococcus, GAS) is responsible for a wide range of pathologies ranging from mild pharyngitis and impetigo to severe invasive soft tissue infections. Despite the continuing susceptibility of the bacterium to β-lactam antibiotics there has been an unexplained resurgence in the prevalence of invasive GAS infection over the past 30 years. Of particular importance was the emergence of a GAS-associated sepsis syndrome that is analogous to the systemic toxicosis associated with TSST-1 producing strains of Staphylococcus aureus. Despite being recognized for over 20 years, the etiology of GAS associated sepsis and the streptococcal toxic shock syndrome remains poorly understood. Here we review the virulence factors that contribute to the etiology of GAS associated sepsis with a particular focus on coagulation system interactions and the role of the superantigens in the development of streptococcal toxic shock syndrome. PMID:24157731

Synergy between cellulolytic enzymes during the biodegradation of cellulose microfibrils measured using angle-scanning surface plasmon resonance (SPR) imaging

NASA Astrophysics Data System (ADS)

Raegen, Adam; Dion, Alexander; Reiter, Kyle; Clarke, Anthony; Lipkowski, Jacek; Dutcher, John

2014-03-01

The use of cellulosic ethanol, a promising emerging energy source, is limited by the energy intensive and costly step of first converting the cellulose fibers into their constituent glucose monomers. Industrial processes mimic those that occur in nature, using mixtures or ``cocktails'' of different classes of cellulolytic enzymes derived from fungi. Despite several decades of investigation, the molecular mechanisms for enzyme synergy remain poorly understood. To gain additional insight, we have used a custom angle-scanning surface plasmon resonance (SPR) imaging apparatus to obtain a sensitive measure of enzymatic degradation. By implementing a novel SPR data analysis procedure, we have been able to track the thickness and roughness of laterally heterogeneous cellulose microfibril-coated substrates as enzymatic degradation proceeds. This has allowed us to measure the synergistic actions of the different enzymes, providing data that are directly relevant to the cellulosic ethanol industry.

Testosterone-mediated sex differences in the face shape during adolescence: subjective impressions and objective features.

PubMed

Marečková, Klára; Weinbrand, Zohar; Chakravarty, M Mallar; Lawrence, Claire; Aleong, Rosanne; Leonard, Gabriel; Perron, Michel; Pike, G Bruce; Richer, Louis; Veillette, Suzanne; Pausova, Zdenka; Paus, Tomáš

2011-11-01

Sex identification of a face is essential for social cognition. Still, perceptual cues indicating the sex of a face, and mechanisms underlying their development, remain poorly understood. Previously, our group described objective age- and sex-related differences in faces of healthy male and female adolescents (12-18 years of age), as derived from magnetic resonance images (MRIs) of the adolescents' heads. In this study, we presented these adolescent faces to 60 female raters to determine which facial features most reliably predicted subjective sex identification. Identification accuracy correlated highly with specific MRI-derived facial features (e.g. broader forehead, chin, jaw, and nose). Facial features that most reliably cued male identity were associated with plasma levels of testosterone (above and beyond age). Perceptible sex differences in face shape are thus associated with specific facial features whose emergence may be, in part, driven by testosterone. Copyright © 2011 Elsevier Inc. All rights reserved.

Epidemiological and ecological determinants of Zika virus transmission in an urban setting.

PubMed

Lourenço, José; Maia de Lima, Maricelia; Faria, Nuno Rodrigues; Walker, Andrew; Kraemer, Moritz Ug; Villabona-Arenas, Christian Julian; Lambert, Ben; Marques de Cerqueira, Erenilde; Pybus, Oliver G; Alcantara, Luiz Cj; Recker, Mario

2017-09-09

The Zika virus has emerged as a global public health concern. Its rapid geographic expansion is attributed to the success of Aedes mosquito vectors, but local epidemiological drivers are still poorly understood. Feira de Santana played a pivotal role in the Chikungunya epidemic in Brazil and was one of the first urban centres to report Zika infections. Using a climate-driven transmission model and notified Zika case data, we show that a low observation rate and high vectorial capacity translated into a significant attack rate during the 2015 outbreak, with a subsequent decline in 2016 and fade-out in 2017 due to herd-immunity. We find a potential Zika-related, low risk for microcephaly per pregnancy, but with significant public health impact given high attack rates. The balance between the loss of herd-immunity and viral re-importation will dictate future transmission potential of Zika in this urban setting.

Meaning-making in the aftermath of sudden infant death syndrome.

PubMed

Krueger, Guenther

2006-09-01

The reconstruction of meaning in the aftermath of sudden infant death syndrome (SIDS) is part of the grieving process but has to date been poorly understood. Earlier theorists including Freud, Bowlby and Kübler-Ross provided a foundation for what occurs during this time using stage theories. More recent researchers, often using qualitative techniques, have provided a more complex and expanded view that enhances our knowledge of meaning reconstruction following infant loss. This overview of representative contemporary authors compares and contrasts them with the longstanding models that are being supplanted within the emerging field of thanatology. Understanding parental reactions within this new framework can help healthcare professionals in dealing with those affected by SIDS and provide a more empathic and sensitive approach to individual differences. Parents' own accounts of their post-SIDS experience are consistent with these newer theories. Comprehending how parents cope and reconstruct their lives is an important element in providing appropriate psychological support services.

Early dynamic fate changes in haemogenic endothelium characterized at the single-cell level

NASA Astrophysics Data System (ADS)

Swiers, Gemma; Baumann, Claudia; O'Rourke, John; Giannoulatou, Eleni; Taylor, Stephen; Joshi, Anagha; Moignard, Victoria; Pina, Cristina; Bee, Thomas; Kokkaliaris, Konstantinos D.; Yoshimoto, Momoko; Yoder, Mervin C.; Frampton, Jon; Schroeder, Timm; Enver, Tariq; Göttgens, Berthold; de Bruijn, Marella F. T. R.

2013-12-01

Haematopoietic stem cells (HSCs) are the founding cells of the adult haematopoietic system, born during ontogeny from a specialized subset of endothelium, the haemogenic endothelium (HE) via an endothelial-to-haematopoietic transition (EHT). Although recently imaged in real time, the underlying mechanism of EHT is still poorly understood. We have generated a Runx1 +23 enhancer-reporter transgenic mouse (23GFP) for the prospective isolation of HE throughout embryonic development. Here we perform functional analysis of over 1,800 and transcriptional analysis of 268 single 23GFP+ HE cells to explore the onset of EHT at the single-cell level. We show that initiation of the haematopoietic programme occurs in cells still embedded in the endothelial layer, and is accompanied by a previously unrecognized early loss of endothelial potential before HSCs emerge. Our data therefore provide important insights on the timeline of early haematopoietic commitment.

Dominant phonon polarization conversion across dimensionally mismatched interfaces: Carbon-nanotube-graphene junction

NASA Astrophysics Data System (ADS)

Shi, Jingjing; Lee, Jonghoon; Dong, Yalin; Roy, Ajit; Fisher, Timothy S.; Ruan, Xiulin

2018-04-01

Dimensionally mismatched interfaces are emerging for thermal management applications, but thermal transport physics remains poorly understood. Here we consider the carbon-nanotube-graphene junction, which is a dimensionally mismatched interface between one- and two-dimensional materials and is the building block for carbon-nanotube (CNT)-graphene three-dimensional networks. We predict the transmission function of individual phonon modes using the wave packet method; surprisingly, most incident phonon modes show predominantly polarization conversion behavior. For instance, longitudinal acoustic (LA) polarizations incident from CNTs transmit mainly into flexural transverse (ZA) polarizations in graphene. The frequency stays the same as the incident mode, indicating elastic transmission. Polarization conversion is more significant as the phonon wavelength increases. We attribute such unique phonon polarization conversion behavior to the dimensional mismatch across the interface, and it opens significantly new phonon transport channels as compared to existing theories where polarization conversion is neglected.

Epidemiological and ecological determinants of Zika virus transmission in an urban setting

PubMed Central

Maia de Lima, Maricelia; Faria, Nuno Rodrigues; Walker, Andrew; Kraemer, Moritz UG; Villabona-Arenas, Christian Julian; Lambert, Ben; Marques de Cerqueira, Erenilde; Pybus, Oliver G; Alcantara, Luiz CJ; Recker, Mario

2017-01-01

The Zika virus has emerged as a global public health concern. Its rapid geographic expansion is attributed to the success of Aedes mosquito vectors, but local epidemiological drivers are still poorly understood. Feira de Santana played a pivotal role in the Chikungunya epidemic in Brazil and was one of the first urban centres to report Zika infections. Using a climate-driven transmission model and notified Zika case data, we show that a low observation rate and high vectorial capacity translated into a significant attack rate during the 2015 outbreak, with a subsequent decline in 2016 and fade-out in 2017 due to herd-immunity. We find a potential Zika-related, low risk for microcephaly per pregnancy, but with significant public health impact given high attack rates. The balance between the loss of herd-immunity and viral re-importation will dictate future transmission potential of Zika in this urban setting. PMID:28887877

Distinct lateral inhibitory circuits drive parallel processing of sensory information in the mammalian olfactory bulb

PubMed Central

Geramita, Matthew A; Burton, Shawn D; Urban, Nathan N

2016-01-01

Splitting sensory information into parallel pathways is a common strategy in sensory systems. Yet, how circuits in these parallel pathways are composed to maintain or even enhance the encoding of specific stimulus features is poorly understood. Here, we have investigated the parallel pathways formed by mitral and tufted cells of the olfactory system in mice and characterized the emergence of feature selectivity in these cell types via distinct lateral inhibitory circuits. We find differences in activity-dependent lateral inhibition between mitral and tufted cells that likely reflect newly described differences in the activation of deep and superficial granule cells. Simulations show that these circuit-level differences allow mitral and tufted cells to best discriminate odors in separate concentration ranges, indicating that segregating information about different ranges of stimulus intensity may be an important function of these parallel sensory pathways. DOI: http://dx.doi.org/10.7554/eLife.16039.001 PMID:27351103

Microbial functional diversity alters the structure and sensitivity of oxygen deficient zones

NASA Astrophysics Data System (ADS)

Penn, Justin; Weber, Thomas; Deutsch, Curtis

2016-09-01

Oxygen deficient zones (ODZs) below the ocean surface regulate marine productivity by removing bioavailable nitrogen (N). A complex microbial community mediates N loss, but the interplay of its diverse metabolisms is poorly understood. We present an ecosystem model of the North Pacific ODZ that reproduces observed chemical distributions yet predicts different ODZ structure, rates, and climatic sensitivity compared to traditional geochemical models. An emergent lower O2 limit for aerobic nitrification lies below the upper O2 threshold for anaerobic denitrification, creating a zone of microbial coexistence that causes a larger ODZ but slower total rates of N loss. The O2-dependent competition for the intermediate nitrite produces gradients in its oxidation versus reduction, anammox versus heterotrophic denitrification, and the net ecological stoichiometry of N loss. The latter effect implies that an externally driven ODZ expansion should favor communities that more efficiently remove N, increasing the sensitivity of the N cycle to climate change.

Developmental biology of gut-probiotic interaction

PubMed Central

Patel, Ravi Mangal

2010-01-01

While our current knowledge of probiotic interaction in the developing gut remains poorly understood, emerging science is providing greater biological insight into their mechanism of action and therapeutic potential for human disease. Given their beneficial effects, probiotics remain promising agents in neonatal gastrointestinal disorders. Probiotics may restore or supply essential bacterial strains needed for gut maturation and homeostasis, particularly in hosts where this process has been disrupted. Here we highlight the unique characteristics of developing intestinal epithelia with a focus on gut development and colonization as well as the inflammatory propensity of immature epithelia. Additionally, we review potential mechanisms of beneficial probiotic interaction with immature intestinal epithelia including immunomodulation, upregulation of cytoprotective genes, prevention and regulation of apoptosis and maintenance of barrier function. Improved knowledge of gut-probiotic interaction in developing epithelia will allow for a better understanding of how probiotics exert their beneficial effects and help guide their therapeutic use. PMID:21327024

Current challenges in organic photovoltaic solar energy conversion.

PubMed

Schlenker, Cody W; Thompson, Mark E

2012-01-01

Over the last 10 years, significant interest in utilizing conjugated organic molecules for solid-state solar to electric conversion has produced rapid improvement in device efficiencies. Organic photovoltaic (OPV) devices are attractive for their compatibility with low-cost processing techniques and thin-film applicability to flexible and conformal applications. However, many of the processes that lead to power losses in these systems still remain poorly understood, posing a significant challenge for the future efficiency improvements required to make these devices an attractive solar technology. While semiconductor band models have been employed to describe OPV operation, a more appropriate molecular picture of the pertinent processes is beginning to emerge. This chapter presents mechanisms of OPV device operation, based on the bound molecular nature of the involved transient species. With the intention to underscore the importance of considering both thermodynamic and kinetic factors, recent progress in elucidating molecular characteristics that dictate photovoltage losses in heterojunction organic photovoltaics is also discussed.

Paleo-tribology: development of wear measurement techniques and a three-dimensional model revealing how grinding dentitions self-wear to enable functionality

NASA Astrophysics Data System (ADS)

Erickson, Gregory M.; Sidebottom, Mark A.; Curry, John F.; Kay, David Ian; Kuhn-Hendricks, Stephen; Norell, Mark A.; Sawyer, W. Gregory; Krick, Brandon A.

2016-06-01

In most mammals and a rare few reptilian lineages the evolution of precise dental occlusion led to the capacity to form functional chewing surfaces due to pressures generated while feeding. The complex dental architectures of such teeth and the biomechanics of their self-wearing nature are poorly understood. Our research team composed of paleontologists, evolutionary biologists, and engineers have developed a protocol to: (1) determine the histological make-up of grinding dentitions in extant and fossil taxa; (2) ascertain wear-relevant material properties of the tissues; (3) determine how those properties relate to inter-tissue-biomechanics leading the dental functionality using a three-dimensional Archard’s wear model developed specifically for dental applications; (4) analyze those data in phylogenetic contexts to infer evolutionary patterns as they relate to feeding. Finally we discuss industrial applications that are emerging from our paleontologically-inspired research.

The role of aquaporin-5 in cancer cell migration: A potential active participant.

PubMed

Jensen, Helene H; Login, Frédéric H; Koffman, Jennifer S; Kwon, Tae-Hwan; Nejsum, Lene N

2016-10-01

Emerging data identifies the water channel aquaporin-5 as a major player in multiple cancers. Over-expression of aquaporin-5 has been associated with increased metastasis and poor prognosis, suggesting that aquaporin-5 may enhance cancer cell migration. This review aims to highlight the current knowledge and hypothesis regarding downstream signaling partners of aquaporin-5 in relation to cancer cell migration. The molecular mechanisms that link aquaporin-5 to cell migration are not completely understood. Aquaporin-5 may promote cell movement by increasing water uptake into the front of the cell allowing local swelling. Aquaporin-5 may also activate extracellular-regulated kinases, increasing proliferation and potentially stimulating the migration machinery. Thus, further studies are warranted to identify the underlying mechanisms and signaling pathways. This will reveal whether aquaporin-5 and downstream effectors could be targets for developing new cancer therapeutics. Copyright © 2016 Elsevier Ltd. All rights reserved.

Enhanced heterogeneous ice nucleation by special surface geometry

PubMed Central

Bi, Yuanfei; Cao, Boxiao; Li, Tianshu

2017-01-01

The freezing of water typically proceeds through impurity-mediated heterogeneous nucleation. Although non-planar geometry generically exists on the surfaces of ice nucleation centres, its role in nucleation remains poorly understood. Here we show that an atomically sharp, concave wedge can further promote ice nucleation with special wedge geometries. Our molecular analysis shows that significant enhancements of ice nucleation can emerge both when the geometry of a wedge matches the ice lattice and when such lattice match does not exist. In particular, a 45° wedge is found to greatly enhance ice nucleation by facilitating the formation of special topological defects that consequently catalyse the growth of regular ice. Our study not only highlights the active role of defects in nucleation but also suggests that the traditional concept of lattice match between a nucleation centre and crystalline lattice should be extended to include a broader match with metastable, non-crystalline structural motifs. PMID:28513603

Enhanced heterogeneous ice nucleation by special surface geometry.

PubMed

Bi, Yuanfei; Cao, Boxiao; Li, Tianshu

2017-05-17

The freezing of water typically proceeds through impurity-mediated heterogeneous nucleation. Although non-planar geometry generically exists on the surfaces of ice nucleation centres, its role in nucleation remains poorly understood. Here we show that an atomically sharp, concave wedge can further promote ice nucleation with special wedge geometries. Our molecular analysis shows that significant enhancements of ice nucleation can emerge both when the geometry of a wedge matches the ice lattice and when such lattice match does not exist. In particular, a 45° wedge is found to greatly enhance ice nucleation by facilitating the formation of special topological defects that consequently catalyse the growth of regular ice. Our study not only highlights the active role of defects in nucleation but also suggests that the traditional concept of lattice match between a nucleation centre and crystalline lattice should be extended to include a broader match with metastable, non-crystalline structural motifs.

The multiple subfunctions of attention: differential developmental gateways to literacy and numeracy.

PubMed

Steele, Ann; Karmiloff-Smith, Annette; Cornish, Kim; Scerif, Gaia

2012-11-01

Attention is construed as multicomponential, but the roles of its distinct subfunctions in shaping the broader developing cognitive landscape are poorly understood. The current study assessed 3- to 6-year-olds (N=83) to: (a) trace developmental trajectories of attentional processes and their structure in early childhood and (b) measure the impact of distinct attention subfunctions on concurrent and longitudinal abilities related to literacy and numeracy. Distinct trajectories across attention measures revealed the emergence of 2 attentional factors, encompassing "executive" and "sustained-selective" processes. Executive attention predicted concurrent abilities across domains at Time 1, whereas sustained-selective attention predicted basic numeracy 1 year later. These concurrent and longitudinal constraints cast a broader light on the unfolding relations between domain-general and domain-specific processes over early childhood. © 2012 The Authors. Child Development © 2012 Society for Research in Child Development, Inc.

Epigenetics of sleep and chronobiology.

PubMed

Qureshi, Irfan A; Mehler, Mark F

2014-03-01

The circadian clock choreographs fundamental biological rhythms. This system is comprised of the master circadian pacemaker in the suprachiasmatic nucleus and associated pacemakers in other tissues that coordinate complex physiological processes and behaviors, such as sleep, feeding, and metabolism. The molecular circuitry that underlies these clocks and orchestrates circadian gene expression has been the focus of intensive investigation, and it is becoming clear that epigenetic factors are highly integrated into these networks. In this review, we draw attention to the fundamental roles played by epigenetic mechanisms in transcriptional and post-transcriptional regulation within the circadian clock system. We also highlight how alterations in epigenetic factors and mechanisms are being linked with sleep-wake disorders. These observations provide important insights into the pathogenesis and potential treatment of these disorders and implicate epigenetic deregulation in the significant but poorly understood interconnections now emerging between circadian processes and neurodegeneration, metabolic diseases, cancer, and aging.

The gains and pains of being a cancer support group leader: a qualitative survey of rewards and challenges.

PubMed

Butow, Phyllis; Beeney, Linda; Juraskova, Ilona; Ussher, Jane; Zordan, Rachel

2009-01-01

Rewards derived from leading a cancer support group are poorly understood yet may be crucial to offset the challenges and difficulties of this role. This study sought to obtain the views of a representative sample of Australian cancer support group leaders (CSGLs) concerning the perceived rewards and challenges of their role. All CSGLs identified by the state-based Cancer Councils were invited to participate by postal questionnaire. Qualitative methods were used to analyze responses to open-ended questions concerning rewards and challenges. A total of 300 CSGLs returned the questionnaire (response rate = 66%) with 272 providing qualitative comments. Four parallel themes emerged from the qualitative analysis: (i) Personal, (ii) Relationship, (iii) Group, and (iv) Community rewards and challenges. These were integrated into a model depicting key positive and negative aspects of the CSGL's role, to provide direction for future training and ongoing support of CSGLs.

Recent Advances in Molecular Mechanisms of Abdominal Aortic Aneurysm Formation

PubMed Central

Annambhotla, Suman; Bourgeois, Sebastian; Wang, Xinwen; Lin, Peter H.; Yao, Qizhi; Chen, Changyi

2010-01-01

Abdominal Aortic Aneurysm (AAA) is an increasingly common clinical condition with fatal implications. It is associated with advanced age, male gender, cigarette smoking, atherosclerosis, hypertension, and genetic predisposition. Although significant evidence has emerged in the last decade, the molecular mechanisms of AAA formation remains poorly understood. Currently, the treatment for AAA remains primarily surgical with the lone innovation of endovascular therapy. With advance in the human genome, understanding precisely which molecules and genes mediate AAA development and blocking their activity at the molecular level could lead to important new discoveries and therapies. This review summarizes recent updates in molecular mechanisms of AAA formation including animal models, autoimmune components, infection, key molecules and cytokines, mechanical forces, genetics and pharmacotherapy. This review will be helpful to those who want to recognize the newest endeavors within the field and identify possible lines of investigation in AAA. PMID:18259804

Methodological Issues in the Collection, Analysis, and Reporting of Granular Data in Asian American Populations: Historical Challenges and Potential Solutions

PubMed Central

Islam, Nadia Shilpi; Khan, Suhaila; Kwon, Simona; Jang, Deeana; Ro, Marguerite; Trinh-Shevrin, Chau

2011-01-01

There are close to 15 million Asian Americans living in the United States, and they represent the fastest growing populations in the country. By the year 2050, there will be an estimated 33.4 million Asian Americans living in the country. However, their health needs remain poorly understood and there is a critical lack of data disaggregated by Asian American ethnic subgroups, primary language, and geography. This paper examines methodological issues, challenges, and potential solutions to addressing the collection, analysis, and reporting of disaggregated (or, granular) data on Asian Americans. The article explores emerging efforts to increase granular data through the use of innovative study design and analysis techniques. Concerted efforts to implement these techniques will be critical to the future development of sound research, health programs, and policy efforts targeting this and other minority populations. PMID:21099084

Epigenetic regulator RBP2 is critical for breast cancer progression and metastasis

PubMed Central

Cao, Jian; Liu, Zongzhi; Cheung, William K.C.; Zhao, Minghui; Chen, Sophia Y.; Chan, Siew Wee; Booth, Carmen J.; Nguyen, Don X.; Yan, Qin

2014-01-01

Summary Metastasis is a major clinical challenge for cancer treatment. Emerging evidence suggests that epigenetic aberrations contribute significantly to tumor formation and progression. However, the drivers and roles of such epigenetic changes in tumor metastasis are still poorly understood. Using bioinformatic analysis of human breast cancer gene expression datasets, we identified histone demethylase RBP2 as a putative mediator of metastatic progression. By using both human breast cancer cells and genetically engineered mice, we demonstrated that RBP2 is critical for breast cancer metastasis to the lung in multiple in vivo models. Mechanistically, RBP2 promotes metastasis as a pleiotropic positive regulator of many metastasis genes. In addition, RBP2 loss suppresses tumor formation in the MMTV-neu transgenic mice. These results suggest that therapeutically targeting RBP2 is a potential strategy to inhibit tumor progression and metastasis. PMID:24582965

From Discovery to Function: The Expanding Roles of Long NonCoding RNAs in Physiology and Disease

PubMed Central

Sun, Miao

2015-01-01

Long noncoding RNAs (lncRNAs) are a relatively poorly understood class of RNAs with little or no coding capacity transcribed from a set of incompletely annotated genes. They have received considerable attention in the past few years and are emerging as potentially important players in biological regulation. Here we discuss the evolving understanding of this new class of molecular regulators that has emerged from ongoing research, which continues to expand our databases of annotated lncRNAs and provide new insights into their physical properties, molecular mechanisms of action, and biological functions. We outline the current strategies and approaches that have been employed to identify and characterize lncRNAs, which have been instrumental in revealing their multifaceted roles ranging from cis- to trans-regulation of gene expression and from epigenetic modulation in the nucleus to posttranscriptional control in the cytoplasm. In addition, we highlight the molecular and biological functions of some of the best characterized lncRNAs in physiology and disease, especially those relevant to endocrinology, reproduction, metabolism, immunology, neurobiology, muscle biology, and cancer. Finally, we discuss the tremendous diagnostic and therapeutic potential of lncRNAs in cancer and other diseases. PMID:25426780

Cholangiocarcinoma—controversies and challenges

PubMed Central

Patel, Tushar

2013-01-01

Cholangiocarcinomas are a diverse group of tumors that are presumed to originate from the biliary tract epithelium either within the liver or the biliary tract. These cancers are often difficult to diagnose, their pathogenesis is poorly understood, and their dismal prognosis has resulted in a nihilistic approach to their management. The two major clinical phenotypes are intrahepatic, mass-forming tumors and large ductal tumors. Among the ductal cancers, lesions at the liver hilum are most prevalent. The risk factors, clinical presentation, natural history and management of these two types of cholangiocarcinoma are distinct. Efforts to improve outcomes for patients with these diseases are affected by several challenges to effective management. For example, designations based on anatomical characteristics have been inconsistently applied, which has confounded analysis of epidemiological trends and assessment of risk factors. The evaluation of therapeutic options, particularly systemic therapies, has been limited by a lack of appreciation of the different phenotypes. Controversies exist regarding the appropriate workup and choice of management approach. However, new and emerging tools for improved diagnosis, expanded indications for surgical approaches, an emerging role for locoregional and intrabiliary therapies and improved systemic therapies provide optimism and hope for improved outcomes in the future. PMID:21460876

Patient Characteristics by Type of Hypersexuality Referral: A Quantitative Chart Review of 115 Consecutive Male Cases.

PubMed

Sutton, Katherine S; Stratton, Natalie; Pytyck, Jennifer; Kolla, Nathan J; Cantor, James M

2015-01-01

Hypersexuality remains an increasingly common but poorly understood patient complaint. Despite diversity in clinical presentations of patients referred for hypersexuality, the literature has maintained treatment approaches that are assumed to apply to the entire phenomenon. This approach has proven ineffective, despite its application over several decades. The present study used quantitative methods to examine demographic, mental health, and sexological correlates of common clinical subtypes of hypersexuality referrals. Findings support the existence of subtypes, each with distinct clusters of features. Paraphilic hypersexuals reported greater numbers of sexual partners, more substance abuse, initiation to sexual activity at an earlier age, and novelty as a driving force behind their sexual behavior. Avoidant masturbators reported greater levels of anxiety, delayed ejaculation, and use of sex as an avoidance strategy. Chronic adulterers reported premature ejaculation and later onset of puberty. Designated patients were less likely to report substance abuse, employment, or finance problems. Although quantitative, this article nonetheless presents a descriptive study in which the underlying typology emerged from features most salient in routine sexological assessment. Future studies might apply purely empirical statistical techniques, such as cluster analyses, to ascertain to what extent similar typologies emerge when examined prospectively.

Bioactivation of drugs in the skin: relationship to cutaneous adverse drug reactions.

PubMed

Sharma, Amy M; Uetrecht, Jack

2014-02-01

Drug-induced skin rashes are poorly understood idiosyncratic reactions, and current methods cannot predict their occurrence. Most idiosyncratic drug reactions are thought to be caused by chemically reactive metabolites, and the skin is a frequent site of idiosyncratic reactions; however, the skin has a very limited capacity to metabolize drugs. To balance this, the skin represents a protective barrier with a very active immune response against pathogens and other types of skin injury. Therefore its response to reactive metabolites is quite different from that of the liver. The purpose of this review is to integrate emerging findings into proposed mechanisms of drug and carcinogen metabolism in the skin that are likely responsible for rashes and other immune responses of the skin. Current evidence suggests the skin possesses significant sulfotransferase and flavin monooxygenases activities, but very low cytochromes P450 activity. However, there are skin-specific P450s that are not present in the liver. The manner in which the skin responds to neoantigens through local antigen presentation and innate immune sensing is reviewed with a focus on insights gained from the contact hypersensitivity (CHS) field. The roles of keratinocytes and Langerhans cells, and the emerging function of NOD-like receptors, are highlighted.

Charting the expansion of strategic exploratory behavior during adolescence.

PubMed

Somerville, Leah H; Sasse, Stephanie F; Garrad, Megan C; Drysdale, Andrew T; Abi Akar, Nadine; Insel, Catherine; Wilson, Robert C

2017-02-01

Although models of exploratory decision making implicate a suite of strategies that guide the pursuit of information, the developmental emergence of these strategies remains poorly understood. This study takes an interdisciplinary perspective, merging computational decision making and developmental approaches to characterize age-related shifts in exploratory strategy from adolescence to young adulthood. Participants were 149 12-28-year-olds who completed a computational explore-exploit paradigm that manipulated reward value, information value, and decision horizon (i.e., the utility that information holds for future choices). Strategic directed exploration, defined as information seeking selective for long time horizons, emerged during adolescence and maintained its level through early adulthood. This age difference was partially driven by adolescents valuing immediate reward over new information. Strategic random exploration, defined as stochastic choice behavior selective for long time horizons, was invoked at comparable levels over the age range, and predicted individual differences in attitudes toward risk taking in daily life within the adolescent portion of the sample. Collectively, these findings reveal an expansion of the diversity of strategic exploration over development, implicate distinct mechanisms for directed and random exploratory strategies, and suggest novel mechanisms for adolescent-typical shifts in decision making. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

The Role of Evolutionary Intermediates in the Host Adaptation of Canine Parvovirus

PubMed Central

Stucker, Karla M.; Pagan, Israel; Cifuente, Javier O.; Kaelber, Jason T.; Lillie, Tyler D.; Hafenstein, Susan; Holmes, Edward C.

2012-01-01

The adaptation of viruses to new hosts is a poorly understood process likely involving a variety of viral structures and functions that allow efficient replication and spread. Canine parvovirus (CPV) emerged in the late 1970s as a host-range variant of a virus related to feline panleukopenia virus (FPV). Within a few years of its emergence in dogs, there was a worldwide replacement of the initial virus strain (CPV type 2) by a variant (CPV type 2a) characterized by four amino acid differences in the capsid protein. However, the evolutionary processes that underlie the acquisition of these four mutations, as well as their effects on viral fitness, both singly and in combination, are still uncertain. Using a comprehensive experimental analysis of multiple intermediate mutational combinations, we show that these four capsid mutations act in concert to alter antigenicity, cell receptor binding, and relative in vitro growth in feline cells. Hence, host adaptation involved complex interactions among both surface-exposed and buried capsid mutations that together altered cell infection and immune escape properties of the viruses. Notably, most intermediate viral genotypes containing different combinations of the four key amino acids possessed markedly lower fitness than the wild-type viruses. PMID:22114336

A novel multistep mechanism for initial lymphangiogenesis in mouse embryos based on ultramicroscopy

PubMed Central

Hägerling, René; Pollmann, Cathrin; Andreas, Martin; Schmidt, Christian; Nurmi, Harri; Adams, Ralf H; Alitalo, Kari; Andresen, Volker; Schulte-Merker, Stefan; Kiefer, Friedemann

2013-01-01

During mammalian development, a subpopulation of endothelial cells in the cardinal vein (CV) expresses lymphatic-specific genes and subsequently develops into the first lymphatic structures, collectively termed as lymph sacs. Budding, sprouting and ballooning of lymphatic endothelial cells (LECs) have been proposed to underlie the emergence of LECs from the CV, but the exact mechanisms of lymph vessel formation remain poorly understood. Applying selective plane illumination-based ultramicroscopy to entire wholemount-immunostained mouse embryos, we visualized the complete developing vascular system with cellular resolution. Here, we report emergence of the earliest detectable LECs as strings of loosely connected cells between the CV and superficial venous plexus. Subsequent aggregation of LECs resulted in formation of two distinct, previously unidentified lymphatic structures, the dorsal peripheral longitudinal lymphatic vessel (PLLV) and the ventral primordial thoracic duct (pTD), which at later stages formed a direct contact with the CV. Providing new insights into their function, we found vascular endothelial growth factor C (VEGF-C) and the matrix component CCBE1 indispensable for LEC budding and migration. Altogether, we present a significantly more detailed view and novel model of early lymphatic development. PMID:23299940

Interplay of differential cell mechanical properties, motility, and proliferation in emergent collective behavior of cell co-cultures

NASA Astrophysics Data System (ADS)

Sutter, Leo; Kolbman, Dan; Wu, Mingming; Ma, Minglin; Das, Moumita

The biophysics of cell co-cultures, i.e. binary systems of cell populations, is of great interest in many biological processes including formation of embryos, and tumor progression. During these processes, different types of cells with different physical properties are mixed with each other, with important consequences for cell-cell interaction, aggregation, and migration. The role of the differences in their physical properties in their collective behavior remains poorly understood. Furthermore, until recently most theoretical studies of collective cell migration have focused on two dimensional systems. Under physiological conditions, however, cells often have to navigate three dimensional and confined micro-environments. We study a confined, three-dimensional binary system of interacting, active, and deformable particles with different physical properties such as deformability, motility, adhesion, and division rates using Langevin Dynamics simulations. Our findings may provide insights into how the differences in and interplay between cell mechanical properties, division, and motility influence emergent collective behavior such as cell aggregation and segregation experimentally observed in co-cultures of breast cancer cells and healthy breast epithelial cells. This work was partially supported by a Cottrell College Science Award.

Insights into next developments in advanced gastric cancer.

PubMed

Obermannová, Radka; Lordick, Florian

2016-07-01

The purpose of the review is to delineate novel approaches for biology-based treatment in advanced gastric cancer. We reviewed the latest translational and clinical research articles and congress presentations. A new molecular classification of gastric cancer based on histology, genetic and proteomic alterations has evolved. It provides a roadmap for development of new drugs and combinations and for patient stratification. Anti-HER2 treatment, which is an effective strategy in metastatic gastric cancer, is now also being studied in the perioperative setting. However, resistance mechanisms in advanced disease are poorly understood and optimal patient selection remains challenging. Targeting angiogenesis is an emerging concept in the management of advanced gastric cancer, and ramucirumab has prolonged survival in the second line either as a monotherapy or in combination with paclitaxel. Biomarkers for selecting patients who benefit from ramucirumab are still lacking. Immune checkpoint blockade and inhibition of cancer stemness targets are other emerging directions for the medical treatment of gastric cancer. Large-scale international studies are ongoing. Promising biology-based treatment strategies are evolving. But tumor heterogeneity which is an inherent feature of gastric cancer challenges the development of molecularly targeted and personalized treatment strategies.

The status of tularemia in Europe in a one-health context: a review.

PubMed

Hestvik, G; Warns-Petit, E; Smith, L A; Fox, N J; Uhlhorn, H; Artois, M; Hannant, D; Hutchings, M R; Mattsson, R; Yon, L; Gavier-Widen, D

2015-07-01

The bacterium Francisella tularensis causes the vector-borne zoonotic disease tularemia, and may infect a wide range of hosts including invertebrates, mammals and birds. Transmission to humans occurs through contact with infected animals or contaminated environments, or through arthropod vectors. Tularemia has a broad geographical distribution, and there is evidence which suggests local emergence or re-emergence of this disease in Europe. This review was developed to provide an update on the geographical distribution of F. tularensis in humans, wildlife, domestic animals and vector species, to identify potential public health hazards, and to characterize the epidemiology of tularemia in Europe. Information was collated on cases in humans, domestic animals and wildlife, and on reports of detection of the bacterium in arthropod vectors, from 38 European countries for the period 1992-2012. Multiple international databases on human and animal health were consulted, as well as published reports in the literature. Tularemia is a disease of complex epidemiology that is challenging to understand and therefore to control. Many aspects of this disease remain poorly understood. Better understanding is needed of the epidemiological role of animal hosts, potential vectors, mechanisms of maintenance in the different ecosystems, and routes of transmission of the disease.

From discovery to function: the expanding roles of long noncoding RNAs in physiology and disease.

PubMed

Sun, Miao; Kraus, W Lee

2015-02-01

Long noncoding RNAs (lncRNAs) are a relatively poorly understood class of RNAs with little or no coding capacity transcribed from a set of incompletely annotated genes. They have received considerable attention in the past few years and are emerging as potentially important players in biological regulation. Here we discuss the evolving understanding of this new class of molecular regulators that has emerged from ongoing research, which continues to expand our databases of annotated lncRNAs and provide new insights into their physical properties, molecular mechanisms of action, and biological functions. We outline the current strategies and approaches that have been employed to identify and characterize lncRNAs, which have been instrumental in revealing their multifaceted roles ranging from cis- to trans-regulation of gene expression and from epigenetic modulation in the nucleus to posttranscriptional control in the cytoplasm. In addition, we highlight the molecular and biological functions of some of the best characterized lncRNAs in physiology and disease, especially those relevant to endocrinology, reproduction, metabolism, immunology, neurobiology, muscle biology, and cancer. Finally, we discuss the tremendous diagnostic and therapeutic potential of lncRNAs in cancer and other diseases.

Pathogenic human viruses in coastal waters

USGS Publications Warehouse

Griffin, Dale W.; Donaldson, Kim A.; Paul, J.H.; Rose, Joan B.

2003-01-01

This review addresses both historical and recent investigations into viral contamination of marine waters. With the relatively recent emergence of molecular biology-based assays, a number of investigations have shown that pathogenic viruses are prevalent in marine waters being impacted by sewage. Research has shown that this group of fecal-oral viral pathogens (enteroviruses, hepatitis A viruses, Norwalk viruses, reoviruses, adenoviruses, rotaviruses, etc.) can cause a broad range of asymptomatic to severe gastrointestinal, respiratory, and eye, nose, ear, and skin infections in people exposed through recreational use of the water. The viruses and the nucleic acid signature survive for an extended period in the marine environment. One of the primary concerns of public health officials is the relationship between the presence of pathogens and the recreational risk to human health in polluted marine environments. While a number of studies have attempted to address this issue, the relationship is still poorly understood. A contributing factor to our lack of progress in the field has been the lack of sensitive methods to detect the broad range of both bacterial and viral pathogens. The application of new and advanced molecular methods will continue to contribute to our current state of knowledge in this emerging and

A Longitudinal Examination of the Persistence of Late Emerging Reading Disabilities.

PubMed

Etmanskie, Jill M; Partanen, Marita; Siegel, Linda S

2016-01-01

There are some children who encounter unexpected reading difficulties in the fourth grade. This phenomenon has been described as late emerging reading disabilities (LERD). Using Grade 4 as a starting point, this study examined the reading development of 964 children between kindergarten and Grade 7. The results showed that 72.0% of children had typical reading performance in Grade 4, whereas there was 0.7% with poor word reading, 12.6% with poor reading comprehension, 2.5% with poor word reading and comprehension, and 12.2% with borderline performance. We also showed that there were similar proportions of children who had early versus late emerging reading difficulties; however, most of the late emerging poor readers recovered by Grade 7. Furthermore, our study showed that poor comprehenders showed poorer performance than typical readers on word reading, pseudoword decoding, and spelling between Grade 1 and Grade 7 and poorer performance on a working memory task in kindergarten. Overall, this study showed that most children recover from late emerging reading problems and that working memory may be an early indicator for reading comprehension difficulties. © Hammill Institute on Disabilities 2014.

Bioaccumulation of human pharmaceuticals in fish across habitats of a tidally influenced urban bayou.

PubMed

Du, Bowen; Haddad, Samuel P; Luek, Andreas; Scott, W Casan; Saari, Gavin N; Burket, S Rebekah; Breed, Christopher S; Kelly, Martin; Broach, Linda; Rasmussen, Joseph B; Chambliss, C Kevin; Brooks, Bryan W

2016-04-01

Though pharmaceuticals and other contaminants of emerging concern are increasingly observed in inland water bodies, the occurrence and bioaccumulation of pharmaceuticals in estuaries and coastal ecosystems are poorly understood. In the present study, bioaccumulation of select pharmaceuticals and other contaminants of emerging concern was examined in fish from Buffalo Bayou, a tidally influenced urban ecosystem that receives effluent from a major (∼200 million gallons per day) municipal wastewater treatment plant in Houston, Texas, USA. Using isotope dilution liquid chromatography-tandem mass spectrometry, various target analytes were observed in effluent, surface water, and multiple fish species. The trophic position of each species was determined using stable isotope analysis. Fish tissue levels of diphenhydramine, which represented the only pharmaceutical detected in all fish species, did not significantly differ between freshwater and marine fish predominantly inhabiting benthic habitats; however, saltwater fish with pelagic habitat preferences significantly accumulated diphenhydramine to the highest levels observed in the present study. Consistent with previous observations from an effluent-dependent freshwater river, diphenhydramine did not display trophic magnification, which suggests site-specific, pH-influenced inhalational uptake to a greater extent than dietary exposure in this tidally influenced urban ecosystem. The findings highlight the importance of understanding differential bioaccumulation and risks of ionizable contaminants of emerging concern in habitats of urbanizing coastal systems. © 2015 SETAC.

Morphoelastic control of gastro-intestinal organogenesis: Theoretical predictions and numerical insights

NASA Astrophysics Data System (ADS)

Balbi, V.; Kuhl, E.; Ciarletta, P.

2015-05-01

With nine meters in length, the gastrointestinal tract is not only our longest, but also our structurally most diverse organ. During embryonic development, it evolves as a bilayered tube with an inner endodermal lining and an outer mesodermal layer. Its inner surface displays a wide variety of morphological patterns, which are closely correlated to digestive function. However, the evolution of these intestinal patterns remains poorly understood. Here we show that geometric and mechanical factors can explain intestinal pattern formation. Using the nonlinear field theories of mechanics, we model surface morphogenesis as the instability problem of constrained differential growth. To allow for internal and external expansion, we model the gastrointestinal tract with homogeneous Neumann boundary conditions. To establish estimates for the folding pattern at the onset of folding, we perform a linear stability analysis supplemented by the perturbation theory. To predict pattern evolution in the post-buckling regime, we perform a series of nonlinear finite element simulations. Our model explains why longitudinal folds emerge in the esophagus with a thick and stiff outer layer, whereas circumferential folds emerge in the jejunum with a thinner and softer outer layer. In intermediate regions like the feline esophagus, longitudinal and circumferential folds emerge simultaneously. Our model could serve as a valuable tool to explain and predict alterations in esophageal morphology as a result of developmental disorders or certain digestive pathologies including food allergies.

Prevalence and Nature of Late-Emerging Poor Readers

ERIC Educational Resources Information Center

Catts, Hugh W.; Compton, Donald; Tomblin, J. Bruce; Bridges, Mindy Sittner

2012-01-01

Some children demonstrate adequate or better reading achievement in early school grades but fall significantly behind their peers in later grades. These children are often referred to as late-emerging poor readers. In this study, we investigated the prevalence and heterogeneity of these poor readers. We also examined the early language and…

Isotopic signals of summer denitrification in a northern hardwood forested catchment

Treesearch

Sarah K. Wexler; Christine L. Goodale; Kevin J. McGuire; Scott W. Bailey; Peter M. Groffman

2014-01-01

Despite decades of measurements, the nitrogen balance of temperate forest catchments remains poorly understood. Atmospheric nitrogen deposition often greatly exceeds streamwater nitrogen losses; the fate of the remaining nitrogen is highly uncertain. Gaseous losses of nitrogen to denitrification are especially poorly documented and are often ignored. Here, we provide...

Punishment and Welfare: Paternal Incarceration and Families' Receipt of Public Assistance

ERIC Educational Resources Information Center

Sugie, Naomi F.

2012-01-01

The United States criminal justice and welfare systems are two important government institutions in the lives of the poor. Despite many theoretical discussions about their relationship, their operation at the level of offenders and families remains poorly understood. This paper utilizes Fragile Families and Child Wellbeing data to examine how…

Geographic Diffusion and Implementation of Acute Care Surgery: An Uneven Solution to the National Emergency General Surgery Crisis.

PubMed

Khubchandani, Jasmine A; Ingraham, Angela M; Daniel, Vijaya T; Ayturk, Didem; Kiefe, Catarina I; Santry, Heena P

2018-02-01

Owing to lack of adequate emergency care infrastructure and decline in general surgery workforce, the United States faces a crisis in access to emergency general surgery (EGS) care. Acute care surgery (ACS), an organized system of trauma, general surgery, and critical care, is a proposed solution; however, ACS diffusion remains poorly understood. To investigate geographic diffusion of ACS models of care and characterize the communities in which ACS implementation is lagging. A national survey on EGS practices was developed, tested, and administered at all 2811 US acute care hospitals providing EGS to adults between August 2015 and October 2015. Surgeons responsible for EGS coverage at these hospitals were approached. If these surgeons failed to respond to the initial survey implementation, secondary surgeons or chief medical officers at hospitals with only 1 general surgeon were approached. Survey responses on ACS implementation were linked with geocoded hospital data and national census data to determine geographic diffusion of and access to ACS. We measured the distribution of hospitals with ACS models of care vs those without over time (diffusion) and by US counties characterized by sociodemographic characteristics of county residents (access). Survey response rate was 60% (n = 1690); 272 responding hospitals had implemented ACS by 2015, steadily increasing from 34 in 2001 to 125 in 2010. Acute care surgery implementation has not been uniform. Rural regions have limited ACS access, with hospitals in counties with greater than the 75th percentile population having 5.4 times higher odds (95% CI, 1.66-7.35) of implementing ACS than hospitals in counties with less than 25th percentile population. Communities with greater percentages of adults without a college degree also have limited ACS access (OR, 3.43; 95% CI, 1.81-6.48). However, incorporating EGS into ACS models may be a potential equalizer for poor, black, and Hispanic communities. Understanding and addressing gaps in ACS implementation across communities will be crucial to ensuring health equity for US residents experiencing general surgery emergencies.

Population demography of alpine butterflies: Boloria pales and Boloria napaea (Lepidoptera: Nymphalidae) and their specific adaptations to high mountain environments

NASA Astrophysics Data System (ADS)

Ehl, Stefan; Ebertshäuser, Marlene; Gros, Patrick; Schmitt, Thomas

2017-11-01

High mountain ecosystems are extreme habitats, and adaptation strategies to this ecosystem are still poorly understood in most groups. To unravel such strategies, we performed a MRR study in the Hohe Tauern National Park (Salzburg, Austria) with two nymphalid butterfly species, Boloria pales and B. napaea. We analysed their population structure over one flight period by studying the development of population size and wing wear. B. pales had more individuals and a higher survival probability than B. napaea; the sensitivity to extreme weather conditions or other external influences was higher in B. napaea. We only observed proterandry in B. pales. Imagines of both species survived under snow for at least some days. Additionally, we observed a kind of risk-spreading, in that individuals of both species, and especially B. pales, have regularly emerged throughout the flight period. This emergence pattern divided the population's age structure into three phases: an initial phase with decreasing wing quality (emergence > mortality), followed by an equilibrium phase with mostly constant average wing condition (emergence = mortality) and a final ageing phase with strongly deteriorating wing condition (mortality » emergence). Consequently, neither species would likely become extinct because of particularly unsuitable weather conditions during a single flight period. The observed differences between the two species suggest a better regional adaptation of B. pales, which is restricted to high mountain systems of Europe. In contrast, the arctic-alpine B. napaea might be best adapted to conditions in the Arctic and not the more southern high mountain systems. However, this needs to be examined during future research in the Arctic.

[Mechanisms of viral emergence and interspecies transmission: the exemple of simian foamy viruses in Central Africa].

PubMed

Gessain, Antoine

2013-12-01

A large proportion of viral pathogens that have emerged during the last decades in humans are considered to have originated from various animal species. This is well exemplified by several recent epidemics such as those of Nipah, Severe Acute Respiratory Syndrome, Avian flu, Ebola, Monkeypox, and Hantaviruses. After the initial interspecies transmission per se, the viruses can disseminate into the human population through various and distinct mechanisms. Some of them are well characterized and understood, thus allowing a certain level of risk control and prevention. Surprisingly and in contrast, the initial steps that lead to the emergence of several viruses, and of their associated diseases, remain still poorly understood. Epidemiological field studies conducted in certain specific high-risk populations are thus necessary to obtain new insights into the early events of this emergence process. Human infections by simian viruses represent increasing public health concerns. Indeed, by virtue of their genetic andphysiological similarities, non-human primates (NHPs) are considered to be likely the sources of viruses that can infect humans and thus may pose a significant threat to human population. This is well illustrated by retroviruses, which have the ability to cross species, adapt to a new host and sometimes spread within these new species. Sequence comparison and phylogenetic studies have thus clearly showed that the emergence of human immunodeficiency virus type 1 (HIV-1) and HIV-2 in humans have resulted from several independent interspecies transmissions of different SIV types from Chimpanzees and African monkeys (including sooty mangabeys), respectively, probably during the first part of the last century. The situation for Human T cell Lymphotropic virus type 1 (HTLV-1) is, for certain aspects, quite comparable. Indeed, the origin of most HTLV-1 subtypes appears to be linked to interspecies transmission between STLV-1-infected monkeys and humans, followed by variable periods of evolution in the human host. In this review, after an introduction on emerging viruses, we will briefly present the results of a large epidemiological study performed in groups of Bantus and Pygmies living in villages and settlements located in the rain forest of the South region of Cameroon. These populations are living nearby the habitats of several monkeys and apes, often naturally infected by different retroviruses including SIV, STLV and simianfoamy virus. Most of the persons included in this study were hunters of such NHPs, thus at high risk of contact with infected body fluids (blood, saliva,...) during hunting activities. After reviewing the current available data on the discovery, cross-species transmission from monkeys and apes to humans of the simian foamy retroviruses, we will report the results of our study. Such infection is a unique natural model to study the different mechanisms of restriction of retroviral emergence in Humans.

Syphilis: Re-emergence of an old foe

PubMed Central

Stamm, Lola V.

2016-01-01

Syphilis is caused by infection with Treponema pallidum subsp. pallidum, a not-yet-cultivable spiral-shaped bacterium that is usually transmitted by sexual contact with an infected partner or by an infected pregnant woman to her fetus. There is no vaccine to prevent syphilis. Diagnosis and treatment of infected individuals and their contacts is key to syphilis control programs that also include sex education and promotion of condom use to prevent infection. Untreated syphilis can progress through four stages: primary (chancre, regional lymphadenopathy), secondary (disseminated skin eruptions, generalized lymphadenopathy), latent (decreased re-occurrence of secondary stage manifestations, absence of symptoms), and tertiary (gummas, cardiovascular syphilis and late neurological symptoms). The primary and secondary stages are the most infectious. WHO estimates that each year 11 million new cases of syphilis occur globally among adults aged 15-49 years. Syphilis has re-emerged in several regions including North America, Western Europe, China and Australia. Host-associated factors that drive the re-emergence and spread of syphilis include high-risk sexual activity, migration and travel, and economic and social changes that limit access to health care. Early, uncomplicated syphilis is curable with a single intramuscular injection of benzathine penicillin G (BPG), the first line drug for all stages of syphilis. Emergence of macrolide-resistant T. pallidum has essentially precluded the empirical use of azithromycin as a second-line drug for treatment of syphilis. Virulence attributes of T. pallidum are poorly understood. Genomic and proteomic studies have provided some new information concerning how this spirochete may evade host defense mechanisms to persist for long periods in the host. PMID:28357375

Informing the design of clinical decision support services for evaluation of children with minor blunt head trauma in the emergency department: a sociotechnical analysis.

PubMed

Sheehan, Barbara; Nigrovic, Lise E; Dayan, Peter S; Kuppermann, Nathan; Ballard, Dustin W; Alessandrini, Evaline; Bajaj, Lalit; Goldberg, Howard; Hoffman, Jeffrey; Offerman, Steven R; Mark, Dustin G; Swietlik, Marguerite; Tham, Eric; Tzimenatos, Leah; Vinson, David R; Jones, Grant S; Bakken, Suzanne

2013-10-01

Integration of clinical decision support services (CDSS) into electronic health records (EHRs) may be integral to widespread dissemination and use of clinical prediction rules in the emergency department (ED). However, the best way to design such services to maximize their usefulness in such a complex setting is poorly understood. We conducted a multi-site cross-sectional qualitative study whose aim was to describe the sociotechnical environment in the ED to inform the design of a CDSS intervention to implement the Pediatric Emergency Care Applied Research Network (PECARN) clinical prediction rules for children with minor blunt head trauma. Informed by a sociotechnical model consisting of eight dimensions, we conducted focus groups, individual interviews and workflow observations in 11 EDs, of which 5 were located in academic medical centers and 6 were in community hospitals. A total of 126 ED clinicians, information technology specialists, and administrators participated. We clustered data into 19 categories of sociotechnical factors through a process of thematic analysis and subsequently organized the categories into a sociotechnical matrix consisting of three high-level sociotechnical dimensions (workflow and communication, organizational factors, human factors) and three themes (interdisciplinary assessment processes, clinical practices related to prediction rules, EHR as a decision support tool). Design challenges that emerged from the analysis included the need to use structured data fields to support data capture and re-use while maintaining efficient care processes, supporting interdisciplinary communication, and facilitating family-clinician interaction for decision-making. Copyright © 2013 Elsevier Inc. All rights reserved.

Emergence of KRAS mutations and acquired resistance to anti-EGFR therapy in colorectal cancer.

PubMed

Misale, Sandra; Yaeger, Rona; Hobor, Sebastijan; Scala, Elisa; Janakiraman, Manickam; Liska, David; Valtorta, Emanuele; Schiavo, Roberta; Buscarino, Michela; Siravegna, Giulia; Bencardino, Katia; Cercek, Andrea; Chen, Chin-Tung; Veronese, Silvio; Zanon, Carlo; Sartore-Bianchi, Andrea; Gambacorta, Marcello; Gallicchio, Margherita; Vakiani, Efsevia; Boscaro, Valentina; Medico, Enzo; Weiser, Martin; Siena, Salvatore; Di Nicolantonio, Federica; Solit, David; Bardelli, Alberto

2012-06-28

A main limitation of therapies that selectively target kinase signalling pathways is the emergence of secondary drug resistance. Cetuximab, a monoclonal antibody that binds the extracellular domain of epidermal growth factor receptor (EGFR), is effective in a subset of KRAS wild-type metastatic colorectal cancers. After an initial response, secondary resistance invariably ensues, thereby limiting the clinical benefit of this drug. The molecular bases of secondary resistance to cetuximab in colorectal cancer are poorly understood. Here we show that molecular alterations (in most instances point mutations) of KRAS are causally associated with the onset of acquired resistance to anti-EGFR treatment in colorectal cancers. Expression of mutant KRAS under the control of its endogenous gene promoter was sufficient to confer cetuximab resistance, but resistant cells remained sensitive to combinatorial inhibition of EGFR and mitogen-activated protein-kinase kinase (MEK). Analysis of metastases from patients who developed resistance to cetuximab or panitumumab showed the emergence of KRAS amplification in one sample and acquisition of secondary KRAS mutations in 60% (6 out of 10) of the cases. KRAS mutant alleles were detectable in the blood of cetuximab-treated patients as early as 10 months before radiographic documentation of disease progression. In summary, the results identify KRAS mutations as frequent drivers of acquired resistance to cetuximab in colorectal cancers, indicate that the emergence of KRAS mutant clones can be detected non-invasively months before radiographic progression and suggest early initiation of a MEK inhibitor as a rational strategy for delaying or reversing drug resistance.

Seed Regeneration Potential of Canopy Gaps at Early Formation Stage in Temperate Secondary Forests, Northeast China

PubMed Central

Yan, Qiao-Ling; Zhu, Jiao-Jun; Yu, Li-Zhong

2012-01-01

Promoting the seed regeneration potential of secondary forests undergoing gap disturbances is an important approach for achieving forest restoration and sustainable management. Seedling recruitment from seed banks strongly determines the seed regeneration potential, but the process is poorly understood in the gaps of secondary forests. The objectives of the present study were to evaluate the effects of gap size, seed availability, and environmental conditions on the seed regeneration potential in temperate secondary forests. It was found that gap formation could favor the invasion of more varieties of species in seed banks, but it also could speed up the turnover rate of seed banks leading to lower seed densities. Seeds of the dominant species, Fraxinus rhynchophylla, were transient in soil and there was a minor and discontinuous contribution of the seed bank to its seedling emergence. For Quercus mongolica, emerging seedling number was positively correlated with seed density in gaps (R = 0.32, P<0.01), especially in medium and small gaps (<500 m2). Furthermore, under canopies, there was a positive correlation between seedling number and seed density of Acer mono (R = 0.43, P<0.01). Gap formation could promote seedling emergence of two gap-dependent species (i.e., Q. mongolica and A. mono), but the contribution of seed banks to seedlings was below 10% after gap creation. Soil moisture and temperature were the restrictive factors controlling the seedling emergence from seeds in gaps and under canopies, respectively. Thus, the regeneration potential from seed banks is limited after gap formation. PMID:22745771

Evolution of a sediment wave in an experimental channel

Treesearch

Thomas E. Lisle; James E. Pizzuto; Hiroshi Ikeda; Fujiko Iseya; Yoshinori Kodama

1997-01-01

Abstract - The routing of bed material through channels is poorly understood. We approach the problem by observing and modeling the fate of a low-amplitude sediment wave of poorly sorted sand that we introduced into an experimental channel transporting sediment identical to that of the introduced wave. The wave essentially dispersed upstream and downstream without...

Independent Learning--What We Do When You're Not There

ERIC Educational Resources Information Center

Hockings, Christine; Thomas, Liz; Ottaway, Jim; Jones, Rob

2018-01-01

Independent learning is one of the cornerstones of UK higher education yet it is poorly understood by students and is seen by politicians as a poor substitute for face to face teaching. This paper explores students' understandings, approaches and experiences of independent learning and how they may become more effective independent learners. This…

The role of bedrock groundwater in rainfall-runoff response at hillslope and catchment scales

Treesearch

C. Gabrielli; J.J. McDonnell; W.T. Jarvis

2012-01-01

Bedrock groundwater dynamics in headwater catchments are poorly understood and poorly characterized. Direct hydrometric measurements have been limited due to the logistical challenges associated with drilling through hard rock in steep, remote and often roadless terrain. We used a new portable bedrock drilling system to explore bedrock groundwater dynamics aimed at...

Asian and Pacific Islander American Poverty: The Working Poor and the Jobless Poor.

ERIC Educational Resources Information Center

Toji, Dean S.; Johnson, James H.

1992-01-01

Assesses the incidence of Asian-American and Pacific Islander-American poverty, and offers a theoretical explanation for its existence. It is argued that poverty of Americans of Asian and Pacific Island descent is best understood in the context of the linkage of labor migration and U.S. labor market segmentation. (SLD)

Collaborative Educational Leadership: The Emergence of Human Interactional Sense-Making Process as a Complex System

ERIC Educational Resources Information Center

Jäppinen, Aini-Kristiina

2014-01-01

The article aims at explicating the emergence of human interactional sense-making process within educational leadership as a complex system. The kind of leadership is understood as a holistic entity called collaborative leadership. There, sense-making emerges across interdependent domains, called attributes of collaborative leadership. The…

Self-Definition as Resistance: Understanding Identities among LGBTQ Emerging Adults

ERIC Educational Resources Information Center

Wagaman, M. Alex

2016-01-01

Scholars have questioned the relevance of existing identity categories and labels for lesbian, gay, bisexual, transgender, and queer (LGBTQ) youth and emerging adults. Little is understood, however, about the ways in which LGBTQ emerging adults perceive their own identities and self-define the aspects of themselves that are most relevant to who…

Capacitive charge storage at an electrified interface investigated via direct first-principles simulations

NASA Astrophysics Data System (ADS)

Radin, Maxwell D.; Ogitsu, Tadashi; Biener, Juergen; Otani, Minoru; Wood, Brandon C.

2015-03-01

Understanding the impact of interfacial electric fields on electronic structure is crucial to improving the performance of materials in applications based on charged interfaces. Supercapacitors store energy directly in the strong interfacial field between a solid electrode and a liquid electrolyte; however, the complex interplay between the two is often poorly understood, particularly for emerging low-dimensional electrode materials that possess unconventional electronic structure. Typical descriptions tend to neglect the specific electrode-electrolyte interaction, approximating the intrinsic "quantum capacitance" of the electrode in terms of a fixed electronic density of states. Instead, we introduce a more accurate first-principles approach for directly simulating charge storage in model capacitors using the effective screening medium method, which implicitly accounts for the presence of the interfacial electric field. Applying this approach to graphene supercapacitor electrodes, we find that results differ significantly from the predictions of fixed-band models, leading to improved consistency with experimentally reported capacitive behavior. The differences are traced to two key factors: the inhomogeneous distribution of stored charge due to poor electronic screening and interfacial contributions from the specific interaction with the electrolyte. Our results are used to revise the conventional definition of quantum capacitance and to provide general strategies for improving electrochemical charge storage, particularly in graphene and similar low-dimensional materials.

Emotional and cognitive social processes are impaired in Parkinson's disease and are related to behavioral disorders.

PubMed

Narme, Pauline; Mouras, Harold; Roussel, Martine; Duru, Cécile; Krystkowiak, Pierre; Godefroy, Olivier

2013-03-01

Parkinson's disease (PD) is associated with behavioral disorders that can affect social functioning but are poorly understood. Since emotional and cognitive social processes are known to be crucial in social relationships, impairment of these processes may account for the emergence of behavioral disorders. We used a systematic battery of tests to assess emotional processes and social cognition in PD patients and relate our findings to conventional neuropsychological data (especially behavioral disorders). Twenty-three PD patients and 46 controls (matched for age and educational level) were included in the study and underwent neuropsychological testing, including an assessment of the behavioral and cognitive components of executive function. Emotional and cognitive social processes were assessed with the Interpersonal Reactivity Index caregiver-administered questionnaire (as a measure of empathy), a facial emotion recognition task and two theory of mind (ToM) tasks. When compared with controls, PD patients showed low levels of empathy (p = .006), impaired facial emotion recognition (which persisted after correction for perceptual abilities) (p = .001), poor performance in a second-order ToM task (p = .008) that assessed both cognitive (p = .004) and affective (p = .03) inferences and, lastly, frequent dysexecutive behavioral disorders (in over 40% of the patients). Overall, impaired emotional and cognitive social functioning was observed in 17% of patients and was related to certain cognitive dysexecutive disorders. In terms of behavioral dysexecutive disorders, social behavior disorders were related to impaired emotional and cognitive social functioning (p = .04) but were independent of cognitive impairments. Emotional and cognitive social processes were found to be impaired in Parkinson's disease. This impairment may account for the emergence of social behavioral disorders. PsycINFO Database Record (c) 2013 APA, all rights reserved.

Geomorphological and cryostratigraphical analyses of the Zackenberg Valley, NE Greenland and significance of Holocene alluvial fans

NASA Astrophysics Data System (ADS)

Cable, Stefanie; Christiansen, Hanne H.; Westergaard-Nielsen, Andreas; Kroon, Aart; Elberling, Bo

2018-02-01

In High Arctic northern Greenland, future responses to climatic changes are poorly understood on a landscape scale. Here, we present a study of the geomorphology and cryostratigraphy in the Zackenberg Valley in NE Greenland (74°N) containing a geomorphological map and a simplified geocryological map, combined with analyses of 13 permafrost cores and two exposures. Cores from a solifluction sheet, alluvial fans, and an emerged delta were studied with regards to cryostructures, ice and total carbon contents, grain size distribution, and pore water electrical conductivity; and the samples were AMS 14C dated. The near-surface permafrost on slopes and alluvial fans is ice rich, as opposed to the ice-poor epigenetic permafrost in the emerged delta. Ground ice and carbon distribution are closely linked to sediment transport processes, which largely depend on lithology and topography. Holocene alluvial fans on the lowermost hillslopes, covering 12% of the study area, represent paleoenvironmental archives. During the contrasting climates of the Holocene, the alluvial fans continued to aggrade - through the warmer early Holocene Optimum, the colder late Holocene, and the following climate warming - and by 0.45 mm a- 1, on average. This is caused by three factors: sedimentation, ground ice aggradation, and vegetation growth and is reflected by AMS 14C dating and continuously alternating cryostructures. Highly variable sedimentation rates in space and time at the alluvial fans have been detected. This is also reflected by alternating lenticular and microlenticular cryostructures indicating syngenetic permafrost aggradation during sedimentation with suspended and organic-matrix cryostructures indicating quasi-syngenetic permafrost aggradation in response to vegetation growth in periods with reduced or no sedimentation. Over time, this causes organic matter to become buried, indicating that alluvial fans represent effective carbon sinks that have previously been overlooked.

Tail regeneration and other phenomena of wound healing and tissue restoration in lizards.

PubMed

Jacyniak, Kathy; McDonald, Rebecca P; Vickaryous, Matthew K

2017-08-15

Wound healing is a fundamental evolutionary adaptation with two possible outcomes: scar formation or reparative regeneration. Scars participate in re-forming the barrier with the external environment and restoring homeostasis to injured tissues, but are well understood to represent dysfunctional replacements. In contrast, reparative regeneration is a tissue-specific program that near-perfectly replicates that which was lost or damaged. Although regeneration is best known from salamanders (including newts and axolotls) and zebrafish, it is unexpectedly widespread among vertebrates. For example, mice and humans can replace their digit tips, while many lizards can spontaneously regenerate almost their entire tail. Whereas the phenomenon of lizard tail regeneration has long been recognized, many details of this process remain poorly understood. All of this is beginning to change. This Review provides a comparative perspective on mechanisms of wound healing and regeneration, with a focus on lizards as an emerging model. Not only are lizards able to regrow cartilage and the spinal cord following tail loss, some species can also regenerate tissues after full-thickness skin wounds to the body, transections of the optic nerve and even lesions to parts of the brain. Current investigations are advancing our understanding of the biological requirements for successful tissue and organ repair, with obvious implications for biomedical sciences and regenerative medicine. © 2017. Published by The Company of Biologists Ltd.

What does productivity really mean? Towards an integrative paradigm in the search for biodiversity-productivity relationships

Treesearch

Liangjun Hu; Qinfeng Guo

2013-01-01

How species diversity relates to productivity remains a major debate. To date, however, the underlying mechanisms that regulate the ecological processes involved are still poorly understood. Three major issues persist in early efforts at resolution. First, in the context that productivity drives species diversity, how the pathways operate is poorly-explained. Second,...

Low serum omega-3 and omega-6 polyunsaturated fatty acids and other metabolites are associated with poor linear growth in young children from rural Malawi

USDA-ARS?s Scientific Manuscript database

Stunting affects ~25% of children <5 y of age and is associated with impaired cognitive and motor development and increased morbidity and mortality. The pathogenesis of stunting is poorly understood. The purpose of this study was to identify altered metabolic pathways associated with child stunting...

Feyerabend on politics, education, and scientific culture.

PubMed

Kidd, Ian James

2016-06-01

The purpose of this paper is to offer a sympathetic reconstruction of the political thought of Paul Feyerabend. Using a critical discussion of the idea of the 'free society' it is suggested that his political thought is best understood in terms of three thematic concerns-liberation, hegemony, and the authority of science-and that the political significance of those claims become clear when they are considered in the context of his educational views. It emerges that Feyerabend is best understood as calling for the grounding of cognitive and cultural authorities-like the sciences-in informed deliberation, rather than the uncritical embrace of prevailing convictions. It therefore emerges that a free society is best understood as one of epistemically responsible citizenship rather than epistemically anarchistic relativism of the 'anything goes' sort-a striking anticipation of current debates about philosophy of science in society. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effect of Environmental Factors on Germination and Emergence of Invasive Rumex confertus in Central Europe

PubMed Central

Kołodziejek, Jeremi; Patykowski, Jacek

2015-01-01

Rumex confertus is a biennial species native to Eastern Europe and Asia, where it thrives on meadow-steppes and glades in forest-steppe. This species has increased its range rapidly within central Europe, yet its biology is not well understood, which has led to poorly timed management. Effects of temperature, light, sodium chloride (NaCl), hydrogen ion concentration (pH), potassium nitrate (KNO3), and polyethylene glycol 6000 on seed germination were examined. Seedling emergence was examined for seeds sown at different depths in sand-filled pots. Seeds of R. confertus were nondormant at maturity. The germination percentage and rate of germination were significantly higher in light than in darkness. Secondary dormancy was induced in these seeds by 12 weeks of dark incubation at 4°C. The seeds of R. confertus undergo a seasonal dormancy cycle with deep dormancy in winter and early spring and a low level of dormancy in early autumn. Germination decreased as soil salinity increased. NO3 − increased the percentage and rate of germination in the studied species. Decrease in seedling emergence from the seeds buried at >0.5 cm may be due to deficiency of light. From our experiments, we conclude that the weed R. confertus normally becomes established in vegetation gaps or due to disturbance of the uppermost soil layer during the growing season through the germination of seeds originating from a long-lived seed bank. PMID:26229977

Diagnosing Geospatial Uncertainty Visualization Challenges in Seasonal Temperature and Precipitation Forecasts

NASA Astrophysics Data System (ADS)

Speciale, A.; Kenney, M. A.; Gerst, M.; Baer, A. E.; DeWitt, D.; Gottschalk, J.; Handel, S.

2017-12-01

The uncertainty of future weather and climate conditions is important for many decisions made in communities and economic sectors. One tool that decision-makers use in gauging this uncertainty is forecasts, especially maps (or visualizations) of probabilistic forecast results. However, visualizing geospatial uncertainty is challenging because including probability introduces an extra variable to represent and probability is often poorly understood by users. Using focus group and survey methods, this study seeks to understand the barriers to using probabilistic temperature and precipitation visualizations for specific decisions in the agriculture, energy, emergency management, and water resource sectors. Preliminary results shown here focus on findings of emergency manager needs. Our experimental design uses National Oceanic and Atmospheric Administration (NOAA's) Climate Prediction Center (CPC) climate outlooks, which produce probabilistic temperature and precipitation forecast visualizations at the 6-10 day, 8-14 day, 3-4 week, and 1 and 3 month timeframes. Users were asked to complete questions related to how they use weather information, how uncertainty is represented, and design elements (e.g., color, contour lines) of the visualizations. Preliminary results from the emergency management sector indicate there is significant confusion on how "normal" weather is defined, boundaries between probability ranges, and meaning of the contour lines. After a complete understandability diagnosis is made using results from all sectors, we will collaborate with CPC to suggest modifications to the climate outlook visualizations. These modifications will then be retested in similar focus groups and web-based surveys to confirm they better meet the needs of users.

Mechanisms of pathogenesis of emerging adenoviruses.

PubMed

Cook, James; Radke, Jay

2017-01-01

Periodic outbreaks of human adenovirus infections can cause severe illness in people with no known predisposing conditions. The reasons for this increased viral pathogenicity are uncertain. Adenoviruses are constantly undergoing mutation during circulation in the human population, but related phenotypic changes of the viruses are rarely detected because of the infrequency of such outbreaks and the limited biological studies of the emergent strains. Mutations and genetic recombinations have been identified in these new strains. However, the linkage between these genetic changes and increased pathogenicity is poorly understood. It has been observed recently that differences in virus-induced immunopathogenesis can be associated with altered expression of non-mutant viral genes associated with changes in viral modulation of the host innate immune response. Initial small animal studies indicate that these changes in viral gene expression can be associated with enhanced immunopathogenesis in vivo . Available evidence suggests the hypothesis that there is a critical threshold of expression of certain viral genes that determines both the sustainability of viral transmission in the human population and the enhancement of immunopathogenesis. Studies of this possibility will require extension of the analysis of outbreak viral strains from a sequencing-based focus to biological studies of relationships between viral gene expression and pathogenic responses. Advances in this area will require increased coordination among public health organizations, diagnostic microbiology laboratories, and research laboratories to identify, catalog, and systematically study differences between prototype and emergent viral strains that explain the increased pathogenicity that can occur during clinical outbreaks.

Digestive tract absorption of polychlorinated dibenzo-p-dioxins, dibenzofurans, and biphenyls in a nursing infant

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

McLachlan, M.S.

The digestive tract absorption of environmental contaminants is an important but poorly understood parameter in contaminant is an important but poorly understood parameter in contaminant risk assessments. The net absorption of polychlorinated dibenzo-p-dioxins, dibenzofurans, and biphenyls in a nursing infant was measured under natural conditions over 12 days. The levels of the substances in the mother's milk were typical for Germany. It was found that for almost all congeners over 90% of the ingested compound was absorbed. This indicates that the common assumption of 100% absorption in nursing infants is reasonable. No firm conclusions could be drawn regarding the absorptionmore » of Cl7- and Cl8DD/F due to high blank levels in the cotton diapers used.« less

Poorly Understood Aspects of Striated Muscle Contraction

PubMed Central

Månsson, Alf

2015-01-01

Muscle contraction results from cyclic interactions between the contractile proteins myosin and actin, driven by the turnover of adenosine triphosphate (ATP). Despite intense studies, several molecular events in the contraction process are poorly understood, including the relationship between force-generation and phosphate-release in the ATP-turnover. Different aspects of the force-generating transition are reflected in the changes in tension development by muscle cells, myofibrils and single molecules upon changes in temperature, altered phosphate concentration, or length perturbations. It has been notoriously difficult to explain all these events within a given theoretical framework and to unequivocally correlate observed events with the atomic structures of the myosin motor. Other incompletely understood issues include the role of the two heads of myosin II and structural changes in the actin filaments as well as the importance of the three-dimensional order. We here review these issues in relation to controversies regarding basic physiological properties of striated muscle. We also briefly consider actomyosin mutation effects in cardiac and skeletal muscle function and the possibility to treat these defects by drugs. PMID:25961006

Poorly understood aspects of striated muscle contraction.

PubMed

Månsson, Alf; Rassier, Dilson; Tsiavaliaris, Georgios

2015-01-01

Muscle contraction results from cyclic interactions between the contractile proteins myosin and actin, driven by the turnover of adenosine triphosphate (ATP). Despite intense studies, several molecular events in the contraction process are poorly understood, including the relationship between force-generation and phosphate-release in the ATP-turnover. Different aspects of the force-generating transition are reflected in the changes in tension development by muscle cells, myofibrils and single molecules upon changes in temperature, altered phosphate concentration, or length perturbations. It has been notoriously difficult to explain all these events within a given theoretical framework and to unequivocally correlate observed events with the atomic structures of the myosin motor. Other incompletely understood issues include the role of the two heads of myosin II and structural changes in the actin filaments as well as the importance of the three-dimensional order. We here review these issues in relation to controversies regarding basic physiological properties of striated muscle. We also briefly consider actomyosin mutation effects in cardiac and skeletal muscle function and the possibility to treat these defects by drugs.

Systematic drug screening reveals specific vulnerabilities and co-resistance patterns in endocrine-resistant breast cancer.

PubMed

Kangaspeska, Sara; Hultsch, Susanne; Jaiswal, Alok; Edgren, Henrik; Mpindi, John-Patrick; Eldfors, Samuli; Brück, Oscar; Aittokallio, Tero; Kallioniemi, Olli

2016-07-04

The estrogen receptor (ER) inhibitor tamoxifen reduces breast cancer mortality by 31 % and has served as the standard treatment for ER-positive breast cancers for decades. However, 50 % of advanced ER-positive cancers display de novo resistance to tamoxifen, and acquired resistance evolves in 40 % of patients who initially respond. Mechanisms underlying resistance development remain poorly understood and new therapeutic opportunities are urgently needed. Here, we report the generation and characterization of seven tamoxifen-resistant breast cancer cell lines from four parental strains. Using high throughput drug sensitivity and resistance testing (DSRT) with 279 approved and investigational oncology drugs, exome-sequencing and network analysis, we for the first time, systematically determine the drug response profiles specific to tamoxifen resistance. We discovered emerging vulnerabilities towards specific drugs, such as ERK1/2-, proteasome- and BCL-family inhibitors as the cells became tamoxifen-resistant. Co-resistance to other drugs such as the survivin inhibitor YM155 and the chemotherapeutic agent paclitaxel also occurred. This study indicates that multiple molecular mechanisms dictate endocrine resistance, resulting in unexpected vulnerabilities to initially ineffective drugs, as well as in emerging co-resistances. Thus, combatting drug-resistant tumors will require patient-tailored strategies in order to identify new drug vulnerabilities, and to understand the associated co-resistance patterns.

The acute salivary ghrelin response to a psychosocial stress is enhanced in symptomatic patients with bulimia nervosa: a pilot study.

PubMed

Monteleone, Palmiero; Tortorella, Alfonso; Scognamiglio, Pasquale; Serino, Ismene; Monteleone, Alessio Maria; Maj, Mario

2012-01-01

Stress is a precipitating factor for both binge eating and bulimia nervosa (BN); however, the biological mechanisms through which it may trigger binge eating are poorly understood. There is evidence that the adrenal hormone cortisol and the gastric peptide ghrelin might be involved in stress-induced food ingestion. We hypothesized that symptomatic patients with BN might disclose deranged responses of ghrelin and/or cortisol to stressors and that this could be related to their binge-eating behaviour. Here we investigated salivary cortisol and ghrelin responses to the Trier Social Stress Test (TSST) in 10 women with acute BN and 10 age-matched healthy females. Eating-related psychopathology and behaviours were assessed by self-report measures. No significant differences emerged between bulimic patients and healthy controls in the pre-stress salivary levels of both cortisol and ghrelin. The BN patients displayed normal cortisol but enhanced ghrelin responses to TSST. No significant correlations emerged between stress-induced salivary hormone changes and self-report measures of binge eating. To our knowledge, this is the first study showing deranged salivary ghrelin reactivity to a psychosocial stressor in symptomatic patients with BN. The extent to which this could contribute to the binge-eating behaviour of BN subjects awaits clarification. Copyright © 2012 S. Karger AG, Basel.

Dynamic allocation and transfer of non-structural carbohydrates, a possible mechanism for the explosive growth of Moso bamboo (Phyllostachys heterocycla)

PubMed Central

Song, Xinzhang; Peng, Changhui; Zhou, Guomo; Gu, Honghao; Li, Quan; Zhang, Chao

2016-01-01

Moso bamboo can rapidly complete its growth in both height and diameter within only 35–40 days after shoot emergence. However, the underlying mechanism for this “explosive growth” remains poorly understood. We investigated the dynamics of non-structural carbohydrates (NSCs) in shoots and attached mature bamboos over a 20-month period. The results showed that Moso bamboos rapidly completed their height and diameter growth within 38 days. At the same time, attached mature bamboos transferred almost all the NSCs of their leaves, branches, and especially trunks and rhizomes to the “explosively growing” shoots via underground rhizomes for the structural growth and metabolism of shoots. Approximately 4 months after shoot emergence, this transfer stopped when the leaves of the young bamboos could independently provide enough photoassimilates to meet the carbon demands of the young bamboos. During this period, the NSC content of the leaves, branches, trunks and rhizomes of mature bamboos declined by 1.5, 23, 28 and 5 fold, respectively. The trunk contributed the most NSCs to the shoots. Our findings provide new insight and a possible rational mechanism explaining the “explosive growth” of Moso bamboo and shed new light on understanding the role of NSCs in the rapid growth of Moso bamboo. PMID:27181522

Arenavirus budding resulting from viral-protein-associated cell membrane curvature

PubMed Central

Schley, David; Whittaker, Robert J.; Neuman, Benjamin W.

2013-01-01

Viral replication occurs within cells, with release (and onward infection) primarily achieved through two alternative mechanisms: lysis, in which virions emerge as the infected cell dies and bursts open; or budding, in which virions emerge gradually from a still living cell by appropriating a small part of the cell membrane. Virus budding is a poorly understood process that challenges current models of vesicle formation. Here, a plausible mechanism for arenavirus budding is presented, building on recent evidence that viral proteins embed in the inner lipid layer of the cell membrane. Experimental results confirm that viral protein is associated with increased membrane curvature, whereas a mathematical model is used to show that localized increases in curvature alone are sufficient to generate viral buds. The magnitude of the protein-induced curvature is calculated from the size of the amphipathic region hypothetically removed from the inner membrane as a result of translation, with a change in membrane stiffness estimated from observed differences in virion deformation as a result of protein depletion. Numerical results are based on experimental data and estimates for three arenaviruses, but the mechanisms described are more broadly applicable. The hypothesized mechanism is shown to be sufficient to generate spontaneous budding that matches well both qualitatively and quantitatively with experimental observations. PMID:23864502

Water-seeking behavior in worm-infected crickets and reversibility of parasitic manipulation

PubMed Central

Ponton, Fleur; Lefèvre, Thierry; Guerin, Patrick M.; Lebarbenchon, Camille; Duneau, David; Biron, David G.; Thomas, Frédéric

2011-01-01

One of the most fascinating examples of parasite-induced host manipulation is that of hairworms, first, because they induce a spectacular “suicide” water-seeking behavior in their terrestrial insect hosts and, second, because the emergence of the parasite is not lethal per se for the host that can live several months following parasite release. The mechanisms hairworms use to increase the encounter rate between their host and water remain, however, poorly understood. Considering the selective landscape in which nematomorph manipulation has evolved as well as previously obtained proteomics data, we predicted that crickets harboring mature hairworms would display a modified behavioral response to light. Since following parasite emergence in water, the cricket host and parasitic worm do not interact physiologically anymore, we also predicted that the host would recover from the modified behaviors. We examined the effect of hairworm infection on different behavioral responses of the host when stimulated by light to record responses from uninfected, infected, and ex-infected crickets. We showed that hairworm infection fundamentally modifies cricket behavior by inducing directed responses to light, a condition from which they mostly recover once the parasite is released. This study supports the idea that host manipulation by parasites is subtle, complex, and multidimensional. PMID:22476265

Providing Value to New Health Technology: The Early Contribution of Entrepreneurs, Investors, and Regulatory Agencies

PubMed Central

Lehoux, Pascale; Miller, Fiona A.; Daudelin, Geneviève; Denis, Jean-Louis

2017-01-01

Background: New technologies constitute an important cost-driver in healthcare, but the dynamics that lead to their emergence remains poorly understood from a health policy standpoint. The goal of this paper is to clarify how entrepreneurs, investors, and regulatory agencies influence the value of emerging health technologies. Methods: Our 5-year qualitative research program examined the processes through which new health technologies were envisioned, financed, developed and commercialized by entrepreneurial clinical teams operating in Quebec’s (Canada) publicly funded healthcare system. Results: Entrepreneurs have a direct influence over a new technology’s value proposition, but investors actively transform this value. Investors support a technology that can find a market, no matter its intrinsic value for clinical practice or healthcare systems. Regulatory agencies reinforce the "double" value of a new technology—as a health intervention and as an economic commodity—and provide economic worth to the venture that is bringing the technology to market. Conclusion: Policy-oriented initiatives such as early health technology assessment (HTA) and coverage with evidence may provide technology developers with useful input regarding the decisions they make at an early stage. But to foster technologies that bring more value to healthcare systems, policy-makers must actively support the consideration of health policy issues in innovation policy. PMID:28949463

Resistance of Echovirus 11 to ClO2 Is Associated with Enhanced Host Receptor Use, Altered Entry Routes, and High Fitness

PubMed Central

2017-01-01

Waterborne viruses can exhibit resistance to common water disinfectants, yet the mechanisms that allow them to tolerate disinfection are poorly understood. Here, we generated echovirus 11 (E11) with resistance to chlorine dioxide (ClO2) by experimental evolution, and we assessed the associated genotypic and phenotypic traits. ClO2 resistance emerged after E11 populations were repeatedly reduced (either by ClO2-exposure or by dilution) and then regrown in cell culture. The resistance was linked to an improved capacity of E11 to bind to its host cells, which was further attributed to two potential causes: first, the resistant E11 populations possessed mutations that caused amino acid substitutions from ClO2-labile to ClO2-stable residues in the viral proteins, which likely increased the chemical stability of the capsid toward ClO2. Second, resistant E11 mutants exhibited the capacity to utilize alternative cell receptors for host binding. Interestingly, the emergence of ClO2 resistance resulted in an enhanced replicative fitness compared to the less resistant starting population. Overall this study contributes to a better understanding of the mechanism underlying disinfection resistance in waterborne viruses, and processes that drive resistance development. PMID:28837336

Implementation strategies in pediatric neurocritical care.

PubMed

Markham, Christopher; Proctor, Enola K; Pineda, Jose A

2017-06-01

Brain-directed critical care for children is a relatively new area of subspecialization in pediatric critical care. Pediatric neurocritical care teams combine the expertise of neurology, neurosurgery, and critical care medicine. The positive impact of delivering specialized care to pediatric patients with acute neurological illness is becoming more apparent, but the optimum way to implement and sustain the delivery of this is complicated and poorly understood. We aim to provide emerging evidence supporting that effective implementation of pediatric neurocritical care pathways can improve patient survival and outcomes. We also provide an overview of the most effective strategies across the field of implementation science that can facilitate deployment of neurocritical care pathways in the pediatric ICU. Implementation strategies can broadly be grouped according to six categories: planning, educating, restructuring, financing, managing quality, and attending to the policy context. Using a combination of these strategies in the last decade, several institutions have improved patient morbidity and mortality. Although much work remains to be done, emerging evidence supports that implementation of evidence-based care pathways for critically ill children with two common neurological diagnoses - status epilepticus and traumatic brain injury - improves outcomes. Pediatric and neonatal neurocritical care programs that support evidence-based care can be effectively structured using appropriately sequenced implementation strategies to improve outcomes across a variety of patient populations and in a variety of healthcare settings.

Role of hormones and neurosteroids in epileptogenesis

PubMed Central

Reddy, Doodipala Samba

2013-01-01

This article describes the emerging evidence of hormonal influence on epileptogenesis, which is a process whereby a brain becomes progressively epileptic due to an initial precipitating event of diverse origin such as brain injury, stroke, infection, or prolonged seizures. The molecular mechanisms underlying the development of epilepsy are poorly understood. Neuroinflammation and neurodegeneration appear to trigger epileptogenesis. There is an intense search for drugs that truly prevent the development of epilepsy in people at risk. Hormones play an important role in children and adults with epilepsy. Corticosteroids, progesterone, estrogens, and neurosteroids have been shown to affect seizure activity in animal models and in clinical studies. However, the impact of hormones on epileptogenesis has not been investigated widely. There is emerging new evidence that progesterone, neurosteroids, and endogenous hormones may play a role in regulating the epileptogenesis. Corticosterone has excitatory effects and triggers epileptogenesis in animal models. Progesterone has disease-modifying activity in epileptogenic models. The antiepileptogenic effect of progesterone has been attributed to its conversion to neurosteroids, which binds to GABA-A receptors and enhances phasic and tonic inhibition in the brain. Neurosteroids are robust anticonvulsants. There is pilot evidence that neurosteroids may have antiepileptogenic properties. Future studies may generate new insight on the disease-modifying potential of hormonal agents and neurosteroids in epileptogenesis. PMID:23914154

Dynamic allocation and transfer of non-structural carbohydrates, a possible mechanism for the explosive growth of Moso bamboo (Phyllostachys heterocycla)

NASA Astrophysics Data System (ADS)

Song, Xinzhang; Peng, Changhui; Zhou, Guomo; Gu, Honghao; Li, Quan; Zhang, Chao

2016-05-01

Moso bamboo can rapidly complete its growth in both height and diameter within only 35-40 days after shoot emergence. However, the underlying mechanism for this “explosive growth” remains poorly understood. We investigated the dynamics of non-structural carbohydrates (NSCs) in shoots and attached mature bamboos over a 20-month period. The results showed that Moso bamboos rapidly completed their height and diameter growth within 38 days. At the same time, attached mature bamboos transferred almost all the NSCs of their leaves, branches, and especially trunks and rhizomes to the “explosively growing” shoots via underground rhizomes for the structural growth and metabolism of shoots. Approximately 4 months after shoot emergence, this transfer stopped when the leaves of the young bamboos could independently provide enough photoassimilates to meet the carbon demands of the young bamboos. During this period, the NSC content of the leaves, branches, trunks and rhizomes of mature bamboos declined by 1.5, 23, 28 and 5 fold, respectively. The trunk contributed the most NSCs to the shoots. Our findings provide new insight and a possible rational mechanism explaining the “explosive growth” of Moso bamboo and shed new light on understanding the role of NSCs in the rapid growth of Moso bamboo.

From metabolism to ecology: cross-feeding interactions shape the balance between polymicrobial conflict and mutualism

PubMed Central

Estrela, Sylvie; Trisos, Christopher H.; Brown, Sam P.

2012-01-01

Polymicrobial interactions are widespread in nature, and play a major role in maintaining human health and ecosystems. Whenever one organism uses metabolites produced by another organism as energy or nutrient sources, this is called cross-feeding. The ecological outcomes of cross-feeding interactions are poorly understood and potentially diverse: mutualism, competition, exploitation or commensalism. A major reason for this uncertainty is the lack of theoretical approaches linking microbial metabolism to microbial ecology. To address this issue, we explore the dynamics of a one-way interspecific cross-feeding interaction, in which food can be traded for a service (detoxification). Our results show that diverse ecological interactions (competition, mutualism, exploitation) can emerge from this simple cross-feeding interaction, and can be predicted by the metabolic, demographic and environmental parameters that govern the balance of the costs and benefits of association. In particular, our model predicts stronger mutualism for intermediate by-product toxicity because the resource-service exchange is constrained to the service being neither too vital (high toxicity impairs resource provision) nor dispensable (low toxicity reduces need for service). These results support the idea that bridging microbial ecology and metabolism is a critical step towards a better understanding of the factors governing the emergence and dynamics of polymicrobial interactions. PMID:23070318

Habitat selection by breeding waterbirds at ponds with size-structured fish populations

NASA Astrophysics Data System (ADS)

Kloskowski, Janusz; Nieoczym, Marek; Polak, Marcin; Pitucha, Piotr

2010-07-01

Fish may significantly affect habitat use by birds, either as their prey or as competitors. Fish communities are often distinctly size-structured, but the consequences for waterbird assemblages remain poorly understood. We examined the effects of size structure of common carp ( Cyprinus carpio) cohorts together with other biotic and abiotic pond characteristics on the distribution of breeding waterbirds in a seminatural system of monocultured ponds, where three fish age classes were separately stocked. Fish age corresponded to a distinct fish size gradient. Fish age and total biomass, macroinvertebrate and amphibian abundance, and emergent vegetation best explained the differences in bird density between ponds. Abundance of animal prey other than fish (aquatic macroinvertebrates and larval amphibians) decreased with increasing carp age in the ponds. Densities of ducks and smaller grebes were strongly negatively associated with fish age/size gradient. The largest of the grebes, the piscivorous great crested grebe ( Podiceps cristatus), was the only species that preferred ponds with medium-sized fish and was positively associated with total fish biomass. Habitat selection by bitterns and most rallids was instead strongly influenced by the relative amount of emergent vegetation cover in the ponds. Our results show that fish size structure may be an important cue for breeding habitat choice and a factor affording an opportunity for niche diversification in avian communities.

Linking Early Environmental Exposures to Adult Diseases

MedlinePlus

... diseases. Given that many disorders arise during fetal development from disruptions in the dynamic but still poorly understood interplay of genes, environment and nutrition, prevention may have to occur decades ...

An inexpensive and portable drill rig for bedrock groundwater studies in headwater catchments

Treesearch

C. Gabrielli; J.J. McDonnell

2011-01-01

Bedrock groundwater dynamics in headwater catchments are poorly understood and poorly characterized. Here, we present an inexpensive and portable bedrock drilling system designed for use in remote locations. Our system is capable of drilling bedrock wells up to 11 m deep and 38 mm in diameter in a wide range of bedrock types. The drill consists of a lawn mower engine...

Researchers Realize Major Breakthrough in Understanding Endometriosis

MedlinePlus

... a rarely studied and poorly understood disease that affects many, many women.” Health Terms: Women's Health RELATED LINKS RSS LISTSERV YOUTUBE FACEBOOK TWITTER GOOGLE+ NIH...T URNING D ISCOVERY I ...

Bacterial spore inactivation induced by cold plasma.

PubMed

Liao, Xinyu; Muhammad, Aliyu Idris; Chen, Shiguo; Hu, Yaqin; Ye, Xingqian; Liu, Donghong; Ding, Tian

2018-04-05

Cold plasma has emerged as a non-thermal technology for microbial inactivation in the food industry over the last decade. Spore-forming microorganisms pose challenges for microbiological safety and for the prevention of food spoilage. Inactivation of spores induced by cold plasma has been reported by several studies. However, the exact mechanism of spore deactivation by cold plasma is poorly understood; therefore, it is difficult to control this process and to optimize cold plasma processing for efficient spore inactivation. In this review, we summarize the factors that affect the resistance of spores to cold plasma, including processing parameters, environmental elements, and spore properties. We then describe possible inactivation targets in spore cells (e.g., outer structure, DNA, and metabolic proteins) that associated with inactivation by cold plasma according to previous studies. Kinetic models of the sporicidal activity of cold plasma have also been described here. A better understanding of the interaction between spores and cold plasma is essential for the development and optimization of cold plasma technology in food the industry.

Trait hostility and hostile interpretation biases in daily smokers: associations with reasons for smoking, motivation to quit, and early smoking lapse.

PubMed

Cougle, Jesse R; Hawkins, Kirsten A; Macatee, Richard J; Zvolensky, Michael J; Sarawgi, Shivali

2014-09-01

Hostility has emerged as an important predictor of smoking cessation difficulties, though the mechanisms underlying the hostility and smoking relationship are poorly understood. Further, research has yet to explore relations between hostile interpretation biases and different aspects of smoking behavior. In the present study, current daily smokers (N = 106) were administered measures of smoking characteristics, smoking motivation, reasons for quitting, hostility, and hostile interpretation bias. Neither trait hostility nor hostile interpretation bias were uniquely associated with motivation to quit, reasons for quitting, nicotine dependence, or problematic symptoms following past cessation attempts. However, hostility and hostile interpretation biases were uniquely associated with different reasons for smoking. Additionally, greater hostile interpretation bias (but not hostility) was uniquely associated with early relapse following past cessation attempts. The current findings add uniquely to the growing, but still relatively small, literature on hostility and smoking and implicate hostile interpretation bias as a potential treatment target in smoking cessation interventions.

Social dysfunction after pediatric traumatic brain injury: a translational perspective

PubMed Central

Ryan, Nicholas P.; Catroppa, Cathy; Godfrey, Celia; Noble-Haeusslein, Linda J.; Shultz, Sandy R.; O'Brien, Terence J.; Anderson, Vicki; Semple, Bridgette D.

2016-01-01

Social dysfunction is common after traumatic brain injury (TBI), contributing to reduced quality of life for survivors. Factors which influence the emergence, development or persistence of social deficits after injury remain poorly understood, particularly in the context of ongoing brain maturation during childhood. Aberrant social interactions have recently been modeled in adult and juvenile rodents after experimental TBI, providing an opportunity to gain new insights into the underlying neurobiology of these behaviors. Here, we review our current understanding of social dysfunction in both humans and rodent models of TBI, with a focus on brain injuries acquired during early development. Modulators of social outcomes are discussed, including injury-related and environmental risk and resilience factors. Disruption of social brain network connectivity and aberrant neuroendocrine function are identified as potential mechanisms of social impairments after pediatric TBI. Throughout, we highlight the overlap and disparities between outcome measures and findings from clinical and experimental approaches, and explore the translational potential of future research to prevent or ameliorate social dysfunction after childhood TBI. PMID:26949224

Parkinson’s disease dementia: a neural networks perspective

PubMed Central

Jahanshahi, Marjan; Foltynie, Thomas

2015-01-01

In the long-term, with progression of the illness, Parkinson’s disease dementia affects up to 90% of patients with Parkinson’s disease. With increasing life expectancy in western countries, Parkinson’s disease dementia is set to become even more prevalent in the future. However, current treatments only give modest symptomatic benefit at best. New treatments are slow in development because unlike the pathological processes underlying the motor deficits of Parkinson’s disease, the neural mechanisms underlying the dementing process and its associated cognitive deficits are still poorly understood. Recent insights from neuroscience research have begun to unravel the heterogeneous involvement of several distinct neural networks underlying the cognitive deficits in Parkinson’s disease dementia, and their modulation by both dopaminergic and non-dopaminergic transmitter systems in the brain. In this review we collate emerging evidence regarding these distinct brain networks to give a novel perspective on the pathological mechanisms underlying Parkinson’s disease dementia, and discuss how this may offer new therapeutic opportunities. PMID:25888551

Epigenome confrontation triggers immediate reprogramming of DNA methylation and transposon silencing in Arabidopsis thaliana F1 epihybrids

PubMed Central

Rigal, Mélanie; Becker, Claude; Pélissier, Thierry; Pogorelcnik, Romain; Devos, Jane; Ikeda, Yoko; Weigel, Detlef; Mathieu, Olivier

2016-01-01

Genes and transposons can exist in variable DNA methylation states, with potentially differential transcription. How these epialleles emerge is poorly understood. Here, we show that crossing an Arabidopsis thaliana plant with a hypomethylated genome and a normally methylated WT individual results, already in the F1 generation, in widespread changes in DNA methylation and transcription patterns. Novel nonparental and heritable epialleles arise at many genic loci, including a locus that itself controls DNA methylation patterns, but with most of the changes affecting pericentromeric transposons. Although a subset of transposons show immediate resilencing, a large number display decreased DNA methylation, which is associated with de novo or enhanced transcriptional activation and can translate into transposon mobilization in the progeny. Our findings reveal that the combination of distinct epigenomes can be viewed as an epigenomic shock, which is characterized by a round of epigenetic variation creating novel patterns of gene and TE regulation. PMID:27001853

Trust your gut: galvanizing nutritional interest in intestinal cholesterol metabolism for protection against cardiovascular diseases.

PubMed

Wegner, Casey J; Kim, Bohkyung; Lee, Jiyoung

2013-01-16

Recent studies have demonstrated that the intestine is a key target organ for overall health and longevity. Complementing these studies is the discovery of the trans-intestinal cholesterol efflux pathway and the emerging role of the intestine in reverse cholesterol transport. The surfacing dynamics of the regulation of cholesterol metabolism in the intestine provides an attractive platform for intestine-specific nutritional intervention strategies to lower blood cholesterol levels for protection against cardiovascular diseases. Notably, there is mounting evidence that stimulation of pathways associated with calorie restriction may have a large effect on the regulation of cholesterol removal by the intestine. However, intestinal energy metabolism, specifically the idiosyncrasies surrounding intestinal responses to energy deprivation, is poorly understood. The goal of this paper is to review recent insights into cholesterol regulation by the intestine and to discuss the potential for positive regulation of intestine-driven cholesterol removal through the nutritional induction of pathways associated with calorie restriction.

Trust Your Gut: Galvanizing Nutritional Interest in Intestinal Cholesterol Metabolism for Protection against Cardiovascular Diseases

PubMed Central

Wegner, Casey J.; Kim, Bohkyung; Lee, Jiyoung

2013-01-01

Recent studies have demonstrated that the intestine is a key target organ for overall health and longevity. Complementing these studies is the discovery of the trans-intestinal cholesterol efflux pathway and the emerging role of the intestine in reverse cholesterol transport. The surfacing dynamics of the regulation of cholesterol metabolism in the intestine provides an attractive platform for intestine-specific nutritional intervention strategies to lower blood cholesterol levels for protection against cardiovascular diseases. Notably, there is mounting evidence that stimulation of pathways associated with calorie restriction may have a large effect on the regulation of cholesterol removal by the intestine. However, intestinal energy metabolism, specifically the idiosyncrasies surrounding intestinal responses to energy deprivation, is poorly understood. The goal of this paper is to review recent insights into cholesterol regulation by the intestine and to discuss the potential for positive regulation of intestine-driven cholesterol removal through the nutritional induction of pathways associated with calorie restriction. PMID:23325147

Eotaxin-3 and a uniquely conserved gene-expression profile in eosinophilic esophagitis

PubMed Central

Blanchard, Carine; Wang, Ning; Stringer, Keith F.; Mishra, Anil; Fulkerson, Patricia C.; Abonia, J. Pablo; Jameson, Sean C.; Kirby, Cassie; Konikoff, Michael R.; Collins, Margaret H.; Cohen, Mitchell B.; Akers, Rachel; Hogan, Simon P.; Assa’ad, Amal H.; Putnam, Philip E.; Aronow, Bruce J.; Rothenberg, Marc E.

2006-01-01

Eosinophilic esophagitis (EE) is an emerging disorder with a poorly understood pathogenesis. In order to define disease mechanisms, we took an empirical approach analyzing esophageal tissue by a genome-wide microarray expression analysis. EE patients had a striking transcript signature involving 1% of the human genome that was remarkably conserved across sex, age, and allergic status and was distinct from that associated with non-EE chronic esophagitis. Notably, the gene encoding the eosinophil-specific chemoattractant eotaxin-3 (also known as CCL26) was the most highly induced gene in EE patients compared with its expression level in healthy individuals. Esophageal eotaxin-3 mRNA and protein levels strongly correlated with tissue eosinophilia and mastocytosis. Furthermore, a single-nucleotide polymorphism in the human eotaxin-3 gene was associated with disease susceptibility. Finally, mice deficient in the eotaxin receptor (also known as CCR3) were protected from experimental EE. These results implicate eotaxin-3 as a critical effector molecule for EE and provide insight into disease pathogenesis. PMID:16453027

Bayesian modeling of flexible cognitive control

PubMed Central

Jiang, Jiefeng; Heller, Katherine; Egner, Tobias

2014-01-01

“Cognitive control” describes endogenous guidance of behavior in situations where routine stimulus-response associations are suboptimal for achieving a desired goal. The computational and neural mechanisms underlying this capacity remain poorly understood. We examine recent advances stemming from the application of a Bayesian learner perspective that provides optimal prediction for control processes. In reviewing the application of Bayesian models to cognitive control, we note that an important limitation in current models is a lack of a plausible mechanism for the flexible adjustment of control over conflict levels changing at varying temporal scales. We then show that flexible cognitive control can be achieved by a Bayesian model with a volatility-driven learning mechanism that modulates dynamically the relative dependence on recent and remote experiences in its prediction of future control demand. We conclude that the emergent Bayesian perspective on computational mechanisms of cognitive control holds considerable promise, especially if future studies can identify neural substrates of the variables encoded by these models, and determine the nature (Bayesian or otherwise) of their neural implementation. PMID:24929218

Intestinal Volvulus in Idiopathic Steatorrhea

PubMed Central

Warner, H. A.; Kinnear, D. G.; Cameron, D. G.

1963-01-01

Volvulus of the intestine has recently been observed in three patients with idiopathic steatorrhea in relapse. Two patients gave a history of intermittent abdominal pain, distension and obstipation. Radiographic studies during these attacks revealed obstruction at the level of the sigmoid colon. Reduction under proctoscopic control was achieved in one instance, spontaneous resolution occurring in the other. The third patient presented as a surgical emergency and underwent operative reduction of a small intestinal volvulus. Persistence of diarrhea and weight loss postoperatively led to further investigation and a diagnosis of idiopathic steatorrhea. In all cases, treatment resulted in clinical remission with a coincident disappearance of obstructive intestinal symptoms. The pathogenesis of volvulus in sprue is poorly understood. Atonicity and dilatation of the bowel and stretching of the mesentery likely represent important factors. The symptoms of recurrent abdominal pain and distension in idiopathic steatorrhea necessitate an increased awareness of intestinal volvulus as a complication of this disease. ImagesFig. 1Fig. 2Fig. 3Figs. 4 and 5Fig. 6 PMID:13998948

Midbrain adaptation may set the stage for the perception of musical beat

PubMed Central

2017-01-01

The ability to spontaneously feel a beat in music is a phenomenon widely believed to be unique to humans. Though beat perception involves the coordinated engagement of sensory, motor and cognitive processes in humans, the contribution of low-level auditory processing to the activation of these networks in a beat-specific manner is poorly understood. Here, we present evidence from a rodent model that midbrain preprocessing of sounds may already be shaping where the beat is ultimately felt. For the tested set of musical rhythms, on-beat sounds on average evoked higher firing rates than off-beat sounds, and this difference was a defining feature of the set of beat interpretations most commonly perceived by human listeners over others. Basic firing rate adaptation provided a sufficient explanation for these results. Our findings suggest that midbrain adaptation, by encoding the temporal context of sounds, creates points of neural emphasis that may influence the perceptual emergence of a beat. PMID:29118141

Hantaviruses induce cell type- and viral species-specific host microRNA expression signatures

PubMed Central

Shin, Ok Sarah; Kumar, Mukesh; Yanagihara, Richard; Song, Jin-Won

2014-01-01

The mechanisms of hantavirus-induced modulation of host cellular immunity remain poorly understood. Recently, microRNAs (miRNAs) have emerged as a class of essential regulators of host immune response genes. To ascertain if differential host miRNA expression toward representative hantavirus species correlated with immune response genes, miRNA expression profiles were analyzed in human endothelial cells, macrophages and epithelial cells infected with pathogenic and nonpathogenic rodent- and shrew-borne hantaviruses. Distinct miRNA expression profiles were observed in a cell type- and viral species-specific pattern. A subset of miRNAs, including miR-151-5p and miR-1973, were differentially expressed between Hantaan virus and Prospect Hill virus. Pathway analyses confirmed that the targets of selected miRNAs were associated with inflammatory responses and innate immune receptor-mediated signaling pathways. Our data suggest that differential immune responses following hantavirus infection may be regulated in part by cellular miRNA through dysregulation of genes critical to the inflammatory process. PMID:24074584

The evolution of distributed sensing and collective computation in animal populations

PubMed Central

Hein, Andrew M; Rosenthal, Sara Brin; Hagstrom, George I; Berdahl, Andrew; Torney, Colin J; Couzin, Iain D

2015-01-01

Many animal groups exhibit rapid, coordinated collective motion. Yet, the evolutionary forces that cause such collective responses to evolve are poorly understood. Here, we develop analytical methods and evolutionary simulations based on experimental data from schooling fish. We use these methods to investigate how populations evolve within unpredictable, time-varying resource environments. We show that populations evolve toward a distinctive regime in behavioral phenotype space, where small responses of individuals to local environmental cues cause spontaneous changes in the collective state of groups. These changes resemble phase transitions in physical systems. Through these transitions, individuals evolve the emergent capacity to sense and respond to resource gradients (i.e. individuals perceive gradients via social interactions, rather than sensing gradients directly), and to allocate themselves among distinct, distant resource patches. Our results yield new insight into how natural selection, acting on selfish individuals, results in the highly effective collective responses evident in nature. DOI: http://dx.doi.org/10.7554/eLife.10955.001 PMID:26652003

Resveratrol serves as a protein-substrate interaction stabilizer in human SIRT1 activation

NASA Astrophysics Data System (ADS)

Hou, Xuben; Rooklin, David; Fang, Hao; Zhang, Yingkai

2016-11-01

Resveratrol is a natural compound found in red wine that has been suggested to exert its potential health benefit through the activation of SIRT1, a crucial member of the mammalian NAD+-dependent deacetylases. SIRT1 has emerged as an attractive therapeutic target for many aging related diseases, however, how its activity can only be activated toward some specific substrates by resveratrol has been poorly understood. Herein, by employing extensive molecular dynamics simulations as well as fragment-centric topographical mapping of binding interfaces, we have clarified current controversies in the literature and elucidated that resveratrol plays an important activation role by stabilizing SIRT1/peptide interactions in a substrate-specific manner. This new mechanism highlights the importance of the N-terminal domain in substrate recognition, explains the activity restoration role of resveratrol toward some “loose-binding” substrates of SIRT1, and has significant implications for the rational design of new substrate-specific SIRT1 modulators.

Gender, Contraceptives and Individual Metabolic Predisposition Shape a Healthy Plasma Lipidome.

PubMed

Sales, Susanne; Graessler, Juergen; Ciucci, Sara; Al-Atrib, Rania; Vihervaara, Terhi; Schuhmann, Kai; Kauhanen, Dimple; Sysi-Aho, Marko; Bornstein, Stefan R; Bickle, Marc; Cannistraci, Carlo V; Ekroos, Kim; Shevchenko, Andrej

2016-06-14

Lipidomics of human blood plasma is an emerging biomarker discovery approach that compares lipid profiles under pathological and physiologically normal conditions, but how a healthy lipidome varies within the population is poorly understood. By quantifying 281 molecular species from 27 major lipid classes in the plasma of 71 healthy young Caucasians whose 35 clinical blood test and anthropometric indices matched the medical norm, we provided a comprehensive, expandable and clinically relevant resource of reference molar concentrations of individual lipids. We established that gender is a major lipidomic factor, whose impact is strongly enhanced by hormonal contraceptives and mediated by sex hormone-binding globulin. In lipidomics epidemiological studies should avoid mixed-gender cohorts and females taking hormonal contraceptives should be considered as a separate sub-cohort. Within a gender-restricted cohort lipidomics revealed a compositional signature that indicates the predisposition towards an early development of metabolic syndrome in ca. 25% of healthy male individuals suggesting a healthy plasma lipidome as resource for early biomarker discovery.

Oceanic barnacles act as foundation species on plastic debris: implications for marine dispersal.

PubMed

Gil, Michael A; Pfaller, Joseph B

2016-01-27

Plastic has emerged as an abundant, stable substratum for oceanic dispersal of organisms via rafting. However, the ecological mechanisms underlying community diversity on plastic debris remain poorly understood. On a cruise from California to Hawai'i, we surveyed plastic debris, some likely originating from the 2011 Tōhoku tsunami, to examine the relationship between rafting community diversity and both habitat area and stalked barnacle (Lepas spp.) abundance. For sessile taxa richness, we observed an interaction in which the positive effect of debris area weakened the negative effect of barnacle cover. In contrast, for mobile taxa richness, including cohabiting species from opposite sides of the Pacific Ocean, barnacle abundance had a positive effect that was strongest at smaller debris sizes. These findings suggest that barnacles, through interactions with habitat area, have trait-dependent effects on other species, serving as both foundation species and competitors, mediating the diversity and dispersal potential of marine organisms on plastic debris.

Distinct myocardial lineages break atrial symmetry during cardiogenesis in zebrafish

PubMed Central

Stone, Oliver; Arnaout, Rima; Guenther, Stefan; Ahuja, Suchit; Uribe, Verónica; Vanhollebeke, Benoit; Stainier, Didier YR

2018-01-01

The ultimate formation of a four-chambered heart allowing the separation of the pulmonary and systemic circuits was key for the evolutionary success of tetrapods. Complex processes of cell diversification and tissue morphogenesis allow the left and right cardiac compartments to become distinct but remain poorly understood. Here, we describe an unexpected laterality in the single zebrafish atrium analogous to that of the two atria in amniotes, including mammals. This laterality appears to derive from an embryonic antero-posterior asymmetry revealed by the expression of the transcription factor gene meis2b. In adult zebrafish hearts, meis2b expression is restricted to the left side of the atrium where it controls the expression of pitx2c, a regulator of left atrial identity in mammals. Altogether, our studies suggest that the multi-chambered atrium in amniotes arose from a molecular blueprint present before the evolutionary emergence of cardiac septation and provide insights into the establishment of atrial asymmetry. PMID:29762122

Basal-like Breast Cancers: From Pathology to Biology and Back Again.

PubMed

Gusterson, Barry; Eaves, Connie J

2018-06-05

Human breast cancers referred to as "basal-like" are of interest because they lack effective therapies and their biology is poorly understood. The term basal-like derives from studies demonstrating tumor gene expression profiles that include some transcripts characteristic of the basal cells of the normal adult human mammary gland and others associated with a subset of normal luminal cells. Elucidating the mechanisms responsible for the profiles of basal-like tumors is an active area of investigation. More refined molecular analysis of patients' samples and genetic strategies to produce breast cancers de novo from defined populations of normal mouse mammary cells have served as complementary approaches to identify relevant pathway alterations. However, both also have limitations. Here, we review some of the underlying reasons, including the unifying concept that some normal luminal cells have both luminal and basal features, as well as some emerging new avenues of investigation. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Mechanisms and Early Detections of Multidecadal Oxygen Changes in the Interior Subpolar North Atlantic

NASA Astrophysics Data System (ADS)

Tjiputra, J. F.; Goris, N.; Lauvset, S. K.; Heinze, C.; Olsen, A.; Schwinger, J.; Steinfeldt, R.

2018-05-01

The oxygen response in the subpolar North Atlantic (SPNA) to future climate change is poorly understood. We investigate the multidecadal variability in interior oxygen and its association with the subpolar gyre index (a gyre strength proxy) for models and data. During positive phases, persistent strong Labrador Sea (LS) lateral and vertical mixing entrains oxygen-rich water into the interior southern SPNA and vice versa during negative phases. This is indicated by the observed anomalously fresh, cold, and low apparent oxygen utilization, resembling LS water mass during positive phases. We use this relationship to benchmark Earth system models. Under a high CO2 future, the best performing models project a steady decline in SPNA oxygen, driven partly by lower solubility and increases in apparent oxygen utilization. The deoxygenation depends on the sensitivity of the LS mixing to warming. The time of emergence of interior oxygen is projected to be decades earlier than that of temperature and salinity.

African American Women's Breastfeeding Experiences: Cultural, Personal, and Political Voices.

PubMed

Spencer, Becky; Wambach, Karen; Domain, Elaine Williams

2015-07-01

The low rate of breastfeeding among African American women in the United States is a poorly understood, persistent disparity. Our purpose in this study was to gain an understanding of how African American women experience breastfeeding in the context of their day-to-day lives. The Sequential-Consensual Qualitative Design (SCQD), a 3-stage qualitative methodology aimed at exploring the cultural, personal, and political context of phenomena, was used to explore the experiences of African American women who felt successful with breastfeeding. An integration of qualitative content analysis and Black feminist theory was used to analyze the data. Themes that emerged from Stage-2 data analysis included self-determination, spirituality and breastfeeding, and empowerment. In Stage 3 of the study, participant recommendations regarding breastfeeding promotion and support initiatives for African American breastfeeding were categorized into three themes, including engaging spheres of influence, sparking breastfeeding activism, and addressing images of the sexual breast vs. the nurturing breast. © The Author(s) 2014.

What makes you tic? Translational approaches to study the role of stress and contextual triggers in Tourette syndrome

PubMed Central

Godar, Sean C; Bortolato, Marco

2016-01-01

Tourette syndrome (TS) is a neurodevelopmental condition characterized by multiple, recurring motor and phonic tics. Rich empirical evidence shows that the severity of tics and associated manifestations is increased by several stressors and contextual triggers; however, the neurobiological mechanisms responsible for symptom exacerbation in TS remain poorly understood. This conceptual gap partially reflects the high phenotypic variability in tics, as well as the existing difficulties in operationalizing and standardizing stress and its effects in a clinical setting. Animal models of TS may be highly informative tools to overcome some of these limitations; these experimental preparations have already provided critical insights on key aspects of TS pathophysiology, and may prove useful to identify the neurochemical alterations induced by different stressful contingencies. In particular, emerging knowledge on the role of contextual triggers in animal models of TS may inform the development of novel pharmacological interventions to reduce tic fluctuations in this disorder. PMID:27939782

ΔNp63 promotes stem cell activity in mammary gland development and basal-like breast cancer by enhancing Fzd7 expression and Wnt signaling

PubMed Central

Chakrabarti, Rumela; Wei, Yong; Hwang, Julie; Hang, Xiang; Blanco, Mario Andres; Choudhury, Abrar; Tiede, Benjamin; Romano, Rose-Anne; DeCoste, Christina; Mercatali, Laura; Ibrahim, Toni; Amadori, Dino; Kannan, Nagarajan; Eaves, Connie J; Sinha, Satrajit; Kang, Yibin

2014-01-01

Emerging evidence suggests that cancer is populated and maintained by tumor initiating cells (TICs) with stem-like properties similar to that of adult tissue stem cells. Despite recent advances, the molecular regulatory mechanisms that may be shared between normal and malignant stem cells remain poorly understood. Here we show that the ΔNp63 isoform of the Trp63 transcription factor promotes normal mammary stem cell (MaSC) activity by increasing the expression of the Wnt receptor Fzd7, thereby enhancing Wnt signaling. Importantly, Fzd7-dependent enhancement of Wnt signaling by ΔNp63 also governs tumor initiating activity of the basal subtype of breast cancer. These findings establish ΔNp63 as a key regulator of stem cells in both normal and malignant mammary tissues and provide direct evidence that breast cancer TICs and normal MaSCs share common regulatory mechanisms. PMID:25241036

Influence of ENSO on Gulf Stream cyclogenesis and the North Atlantic storm track

NASA Astrophysics Data System (ADS)

Li, C.; Schemm, S.; Ciasto, L.; Kvamsto, N. G.

2015-12-01

There is emerging evidence that climate in the North Atlantic-European sector is sensitive to vacillations of tropical Pacific sea surface temperatures, in particular, the central Pacific flavour of the El Nino Southern Oscillation (ENSO) and concomitant trends in atmospheric heating. The frequency of central Pacific ENSOs appears to have increased over the last decades and some studies suggest it may continue increasing in the future, but the precise mechanisms by which these events affect the North Atlantic synoptic scale circulation are poorly understood. Here, we show that central Pacific ENSOs influence where midlatitude cyclogenesis occurs over the Gulf Stream, producing more cyclogenesis in the jet exit region rather than in the climatologically preferred jet entrance region. The cyclones forming over the Gulf Stream in central Pacific ENSO seasons tend to veer north, penetrating deeper into the Arctic rather than into continental Europe. The shift in cyclogenesis is linked to changes in the large scale circulation, namely, the upper-level trough formed in the lee of the Rocky Mountains.

Acyl-CoA synthetase 3 promotes lipid droplet biogenesis in ER microdomains

PubMed Central

Kassan, Adam; Herms, Albert; Fernández-Vidal, Andrea; Bosch, Marta; Schieber, Nicole L.; Reddy, Babu J.N.; Fajardo, Alba; Gelabert-Baldrich, Mariona; Tebar, Francesc; Enrich, Carlos; Gross, Steven P.

2013-01-01

Control of lipid droplet (LD) nucleation and copy number are critical, yet poorly understood, processes. We use model peptides that shift from the endoplasmic reticulum (ER) to LDs in response to fatty acids to characterize the initial steps of LD formation occurring in lipid-starved cells. Initially, arriving lipids are rapidly packed in LDs that are resistant to starvation (pre-LDs). Pre-LDs are restricted ER microdomains with a stable core of neutral lipids. Subsequently, a first round of “emerging” LDs is nucleated, providing additional lipid storage capacity. Finally, in proportion to lipid concentration, new rounds of LDs progressively assemble. Confocal microscopy and electron tomography suggest that emerging LDs are nucleated in a limited number of ER microdomains after a synchronized stepwise process of protein gathering, lipid packaging, and recognition by Plin3 and Plin2. A comparative analysis demonstrates that the acyl-CoA synthetase 3 is recruited early to the assembly sites, where it is required for efficient LD nucleation and lipid storage. PMID:24368806

Probing Leader Cells in Endothelial Collective Migration by Plasma Lithography Geometric Confinement

PubMed Central

Yang, Yongliang; Jamilpour, Nima; Yao, Baoyin; Dean, Zachary S.; Riahi, Reza; Wong, Pak Kin

2016-01-01

When blood vessels are injured, leader cells emerge in the endothelium to heal the wound and restore the vasculature integrity. The characteristics of leader cells during endothelial collective migration under diverse physiological conditions, however, are poorly understood. Here we investigate the regulation and function of endothelial leader cells by plasma lithography geometric confinement generated. Endothelial leader cells display an aggressive phenotype, connect to follower cells via peripheral actin cables and discontinuous adherens junctions, and lead migrating clusters near the leading edge. Time-lapse microscopy, immunostaining, and particle image velocimetry reveal that the density of leader cells and the speed of migrating clusters are tightly regulated in a wide range of geometric patterns. By challenging the cells with converging, diverging and competing patterns, we show that the density of leader cells correlates with the size and coherence of the migrating clusters. Collectively, our data provide evidence that leader cells control endothelial collective migration by regualting the migrating clusters. PMID:26936382

A Catalytic Mechanism for Cysteine N-Terminal Nucleophile Hydrolases, as Revealed by Free Energy Simulations

PubMed Central

Lodola, Alessio; Branduardi, Davide; De Vivo, Marco; Capoferri, Luigi; Mor, Marco; Piomelli, Daniele; Cavalli, Andrea

2012-01-01

The N-terminal nucleophile (Ntn) hydrolases are a superfamily of enzymes specialized in the hydrolytic cleavage of amide bonds. Even though several members of this family are emerging as innovative drug targets for cancer, inflammation, and pain, the processes through which they catalyze amide hydrolysis remains poorly understood. In particular, the catalytic reactions of cysteine Ntn-hydrolases have never been investigated from a mechanistic point of view. In the present study, we used free energy simulations in the quantum mechanics/molecular mechanics framework to determine the reaction mechanism of amide hydrolysis catalyzed by the prototypical cysteine Ntn-hydrolase, conjugated bile acid hydrolase (CBAH). The computational analyses, which were confirmed in water and using different CBAH mutants, revealed the existence of a chair-like transition state, which might be one of the specific features of the catalytic cycle of Ntn-hydrolases. Our results offer new insights on Ntn-mediated hydrolysis and suggest possible strategies for the creation of therapeutically useful inhibitors. PMID:22389698

Representing Sex in the Brain, One Module at a Time

PubMed Central

Yang, Cindy F.; Shah, Nirao M.

2014-01-01

Summary Sexually dimorphic behaviors, qualitative or quantitative differences in behaviors between the sexes, result from the activity of a sexually differentiated nervous system. Sensory cues and sex hormones control the entire repertoire of sexually dimorphic behaviors, including those commonly thought to be charged with emotion such as courtship and aggression. Recent studies show that these over-arching control mechanisms regulate distinct genes and neurons that in turn specify the display of such behaviors in a modular manner. How such modular control is transformed into cohesive internal states that correspond to sexually dimorphic behavior is poorly understood. We summarize current understanding of the neural circuit control of sexually dimorphic behaviors from several perspectives, including how neural circuits in general, and sexually dimorphic neurons in particular, can generate sex differences in behavior, and how molecular mechanisms and evolutionary constraints shape these behaviors. We propose that emergent themes such as the modular genetic and neural control of dimorphic behavior are broadly applicable to the neural control of other behaviors. PMID:24742456

Long Noncoding RNAs as a Key Player in Hepatocellular Carcinoma

PubMed Central

Mehra, Mrigaya; Chauhan, Ranjit

2017-01-01

Hepatocellular carcinoma (HCC) is a major malignancy in the liver and has emerged as one of the main cancers in the world with a high mortality rate. However, the molecular mechanisms of HCC are still poorly understood. Long noncoding RNAs (lncRNAs) have recently come to the forefront as functional non–protein-coding RNAs that are involved in a variety of cellular processes ranging from maintaining the structural integrity of chromosomes to gene expression regulation in a spatiotemporal manner. Many recent studies have reported the involvement of lncRNAs in HCC which has led to a better understanding of the underlying molecular mechanisms operating in HCC. Long noncoding RNAs have been shown to regulate development and progression of HCC, and thus, lncRNAs have both diagnostic and therapeutic potentials. In this review, we present an overview of the lncRNAs involved in different stages of HCC and their potential in clinical applications which have been studied so far. PMID:29147078

A novel perivascular cell population in the zebrafish brain

PubMed Central

Galanternik, Marina Venero; Castranova, Daniel; Gore, Aniket V; Blewett, Nathan H; Jung, Hyun Min; Stratman, Amber N; Kirby, Martha R; Iben, James; Miller, Mayumi F; Kawakami, Koichi; Maraia, Richard J; Weinstein, Brant M

2017-01-01

The blood-brain barrier is essential for the proper homeostasis and function of the CNS, but its mechanism of function is poorly understood. Perivascular cells surrounding brain blood vessels are thought to be important for blood-brain barrier establishment, but their roles are not well defined. Here, we describe a novel perivascular cell population closely associated with blood vessels on the zebrafish brain. Based on similarities in their morphology, location, and scavenger behavior, these cells appear to be the zebrafish equivalent of cells variably characterized as Fluorescent Granular Perithelial cells (FGPs), perivascular macrophages, or ‘Mato Cells’ in mammals. Despite their macrophage-like morphology and perivascular location, zebrafish FGPs appear molecularly most similar to lymphatic endothelium, and our imaging studies suggest that these cells emerge by differentiation from endothelium of the optic choroidal vascular plexus. Our findings provide the first report of a perivascular cell population in the brain derived from vascular endothelium. DOI: http://dx.doi.org/10.7554/eLife.24369.001 PMID:28395729

Relationship between HIV stigma and self-isolation among people living with HIV in Tennessee.

PubMed

Audet, Carolyn M; McGowan, Catherine C; Wallston, Kenneth A; Kipp, Aaron M

2013-01-01

HIV stigma is a contributing factor to poor patient outcomes. Although HIV stigma has been documented, its impact on patient well-being in the southern US is not well understood. Thirty-two adults participated in cognitive interviews after completing the Berger HIV or the Van Rie stigma scale. Participant responses were probed to ensure the scales accurately measured stigma and to assess the impact stigma had on behavior. Three main themes emerged regarding HIV stigma: (1) negative attitudes, fear of contagion, and misperceptions about transmission; (2) acts of discrimination by families, friends, health care providers, and within the workplace; and (3) participants' use of self-isolation as a coping mechanism. Overwhelming reluctance to disclose a person's HIV status made identifying enacted stigma with a quantitative scale difficult. Fear of discrimination resulted in participants isolating themselves from friends or experiences to avoid disclosure. Participant unwillingness to disclose their HIV status to friends and family could lead to an underestimation of enacted HIV stigma in quantitative scales.

Kibra and Merlin Activate the Hippo Pathway Spatially Distinct from and Independent of Expanded.

PubMed

Su, Ting; Ludwig, Michael Z; Xu, Jiajie; Fehon, Richard G

2017-03-13

The Hippo pathway is emerging as a key evolutionarily conserved signaling mechanism that controls organ size. Three membrane-associated proteins, Kibra, Merlin, and Expanded, regulate pathway activity, but the precise molecular mechanism by which they function is still poorly understood. Here we provide evidence that Merlin and Kibra activate Hippo signaling in parallel to Expanded at a spatially distinct cellular domain, the medial apical cortex. Merlin and Kibra together recruit the adapter protein Salvador, which in turn recruits the core kinase Hippo. In addition, we show that Crumbs has a dual effect on Hippo signaling. Crumbs promotes the ability of Expanded to activate the pathway but also sequesters Kibra to downregulate Hippo signaling. Together, our findings elucidate the mechanism of Hippo pathway activation by Merlin and Kibra, identify a subcellular domain for Hippo pathway regulation, and demonstrate differential activity of upstream regulators in different subcellular domains. Copyright © 2017 Elsevier Inc. All rights reserved.

Interleukin-17B Antagonizes Interleukin-25-Mediated Mucosal Inflammation.

PubMed

Reynolds, Joseph M; Lee, Young-Hee; Shi, Yun; Wang, Xiaohu; Angkasekwinai, Pornpimon; Nallaparaju, Kalyan C; Flaherty, Stephanie; Chang, Seon Hee; Watarai, Hiroshi; Dong, Chen

2015-04-21

The interleukin-17 (IL-17) family of cytokines has emerged as a critical player in inflammatory diseases. Among them, IL-25 has been shown to be important in allergic inflammation and protection against parasitic infection. Here we have demonstrated that IL-17B, a poorly understood cytokine, functions to inhibit IL-25-driven inflammation. IL-17B and IL-25, both binding to the interleukin-17 receptor B (IL-17RB), were upregulated in their expression after acute colonic inflammation. Individual inhibition of these cytokines revealed opposing functions in colon inflammation: IL-25 was pathogenic but IL-17B was protective. Similarly opposing phenotypes were observed in Citrobacter rodentium infection and allergic asthma. Moreover, IL-25 was found to promote IL-6 production from colon epithelial cells, which was inhibited by IL-17B. Therefore, our data demonstrate that IL-17B is an anti-inflammatory cytokine in the IL-17 family. Copyright © 2015 Elsevier Inc. All rights reserved.

Reciprocal relations between body satisfaction and self-esteem: A large 13-year prospective study of adolescents.

PubMed

Wichstrøm, Lars; von Soest, Tilmann

2016-02-01

Previous research has demonstrated that body satisfaction and self-esteem are highly correlated in adolescence, but reasons are poorly understood. We tested three explanations: (i) the two constructs are actually one; (ii) the correlation is explained by a third factor; (iii) there are prospective relationships between body satisfaction and self-esteem. A population based sample of Norwegian adolescents (n = 3251) was examined four times over a 13-year period. Confirmatory factor analysis showed that body satisfaction and self-esteem were separate constructs and the correlation between them was not attenuated when adjusting for 3rd variables. Autoregressive cross-lagged analysis showed reciprocal relations between body satisfaction and self-esteem. The prospective relationship between body satisfaction during adolescence and self-esteem in late adolescence and emerging adulthood was stronger than at later stages. Copyright © 2015 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

Parkinson's disease dementia: a neural networks perspective.

PubMed

Gratwicke, James; Jahanshahi, Marjan; Foltynie, Thomas

2015-06-01

In the long-term, with progression of the illness, Parkinson's disease dementia affects up to 90% of patients with Parkinson's disease. With increasing life expectancy in western countries, Parkinson's disease dementia is set to become even more prevalent in the future. However, current treatments only give modest symptomatic benefit at best. New treatments are slow in development because unlike the pathological processes underlying the motor deficits of Parkinson's disease, the neural mechanisms underlying the dementing process and its associated cognitive deficits are still poorly understood. Recent insights from neuroscience research have begun to unravel the heterogeneous involvement of several distinct neural networks underlying the cognitive deficits in Parkinson's disease dementia, and their modulation by both dopaminergic and non-dopaminergic transmitter systems in the brain. In this review we collate emerging evidence regarding these distinct brain networks to give a novel perspective on the pathological mechanisms underlying Parkinson's disease dementia, and discuss how this may offer new therapeutic opportunities. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain.

Multicellular contractility contributes to the emergence of mesothelioma nodules

NASA Astrophysics Data System (ADS)

Czirok, Andras

Malignant pleural mesothelioma (MPM) nodules arise from the mesothelial lining of the pleural cavity by a poorly understood mechanism. We demonstrate that macroscopic multicellular aggregates, reminiscent of the MPM nodules found in patients, develop when MPM cell lines are cultured at high cell densities for several weeks. Surprisingly, the nodule-like aggregates do not arise by excessive local cell proliferation, but by myosin II-driven cell contractility. Contractile nodules contain prominent actin cables that can span several cells. Several features of the in vitro MPM nodule development can be explained by a computational model that assumes uniform and steady intercellular contractile forces within a monolayer of cells, and a mechanical load-dependent lifetime of cell-cell contacts. The model behaves as a self-tensioned Maxwell fluid and exhibits an instability that leads to pattern formation. Altogether, our findings suggest that inhibition of the actomyosin system may provide a hitherto not utilized therapeutic approach to affect MPM growth. NIH R01-GM102801.

Emerging Roles for the Lysosome in Lipid Metabolism.

PubMed

Thelen, Ashley M; Zoncu, Roberto

2017-11-01

Precise regulation of lipid biosynthesis, transport, and storage is key to the homeostasis of cells and organisms. Cells rely on a sophisticated but poorly understood network of vesicular and nonvesicular transport mechanisms to ensure efficient delivery of lipids to target organelles. The lysosome stands at the crossroads of this network due to its ability to process and sort exogenous and endogenous lipids. The lipid-sorting function of the lysosome is intimately connected to its recently discovered role as a metabolic command-and-control center, which relays multiple nutrient cues to the master growth regulator, mechanistic target of rapamycin complex (mTORC)1 kinase. In turn, mTORC1 potently drives anabolic processes, including de novo lipid synthesis, while inhibiting lipid catabolism. Here, we describe the dual role of the lysosome in lipid transport and biogenesis, and we discuss how integration of these two processes may play important roles both in normal physiology and in disease. Copyright © 2017 Elsevier Ltd. All rights reserved.

Flocking Transition in Confluent Tissues

NASA Astrophysics Data System (ADS)

Paoluzzi, Matteo; Giavazzi, Fabio; Macchi, Marta; Scita, Giorgio; Cerbino, Roberto; Manning, Lisa; Marchetti, Cristina

The emerging of collective migration in biological tissues plays a pivotal role in embryonic morphogenesis, wound healing and cancer invasion. While many aspects of single cell movements are well established, the mechanisms leading to coherent displacements of cohesive cell groups are still poorly understood. Some of us recently proposed a Self-Propelled Voronoi (SPV) model of dense tissues that combines self-propelled particle models and vertex models of confluent cell layers and exhibits a liquid-solid transition as a function of cell shape and cell motility. We now examine the role of cell polarization on collective cell dynamics by introducing an orientation mechanism that aligns cell polarization with local cell motility. The model predicts a density-independent flocking transition tuned by the strength of the aligning interaction, with both solid and liquid flocking states existing in different regions of parameter space. MP and MCM were supported by the Simons Foundation Targeted Grant in the Mathematical Modeling of Living Systems Number: 342354 and by the Syracuse Soft Matter Program.

Efficacy and safety of fidaxomicin compared with oral vancomycin for the treatment of adults with Clostridium difficile-associated diarrhea: data from the OPT-80-003 and OPT-80-004 studies.

PubMed

Chen, Luke F; Anderson, Deverick J

2012-06-01

Clostridium difficile is emerging as one of the most important and devastating pathogens affecting hospitalized populations around the world. The incidence of C. difficile infection is increasing and disease severity is worsening. Thus, an effective alternative to metronidazole and oral vancomycin is urgently needed. Two Phase III trials, OPT-80-003 and OPT-80-004, showed that oral fidaxomicin for 10 days was noninferior compared with treatment with oral vancomycin among adult patients with toxin-positive C. difficile-associated diarrhea (CDAD). Furthermore, fidaxomicin was associated with a lower rate of recurrence of CDAD within 4 weeks of completion of therapy. The safety and tolerability of fidaxomicin was consistent with earlier studies and established that fidaxomicin is an efficacious and well-tolerated treatment option for CDAD. Despite these potential advantages, the cost-effectiveness of this expensive agent remains poorly understood.

Probing Leader Cells in Endothelial Collective Migration by Plasma Lithography Geometric Confinement.

PubMed

Yang, Yongliang; Jamilpour, Nima; Yao, Baoyin; Dean, Zachary S; Riahi, Reza; Wong, Pak Kin

2016-03-03

When blood vessels are injured, leader cells emerge in the endothelium to heal the wound and restore the vasculature integrity. The characteristics of leader cells during endothelial collective migration under diverse physiological conditions, however, are poorly understood. Here we investigate the regulation and function of endothelial leader cells by plasma lithography geometric confinement generated. Endothelial leader cells display an aggressive phenotype, connect to follower cells via peripheral actin cables and discontinuous adherens junctions, and lead migrating clusters near the leading edge. Time-lapse microscopy, immunostaining, and particle image velocimetry reveal that the density of leader cells and the speed of migrating clusters are tightly regulated in a wide range of geometric patterns. By challenging the cells with converging, diverging and competing patterns, we show that the density of leader cells correlates with the size and coherence of the migrating clusters. Collectively, our data provide evidence that leader cells control endothelial collective migration by regualting the migrating clusters.

Antidepressant effects of ketamine and the roles of AMPA glutamate receptors and other mechanisms beyond NMDA receptor antagonism.

PubMed

Aleksandrova, Lily R; Phillips, Anthony G; Wang, Yu Tian

2017-06-01

The molecular mechanisms underlying major depressive disorder remain poorly understood, and current antidepressant treatments have many shortcomings. The recent discovery that a single intravenous infusion of ketamine at a subanesthetic dose had robust, rapid and sustained antidepressant effects in individuals with treatment-resistant depression inspired tremendous interest in investigating the molecular mechanisms mediating ketamine's clinical efficacy as well as increased efforts to identify new targets for antidepressant action. We review the clinical utility of ketamine and recent insights into its mechanism of action as an antidepressant, including the roles of N -methyl-D-aspartate receptor inhibition, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor upregulation, activation of downstream synaptogenic signalling pathways and the production of an active ketamine metabolite, hydroxynorketamine. Emerging knowledge of the molecular mechanisms underlying both ketamine's positive therapeutic and detrimental side effects will aid the development of a new generation of much-needed superior antidepressant agents.

Alternatives to animal testing in basic and preclinical research of atopic dermatitis.

PubMed

Löwa, Anna; Jevtić, Marijana; Gorreja, Frida; Hedtrich, Sarah

2018-05-01

Atopic dermatitis (AD) is a chronic inflammatory skin disease of increasing prevalence, especially in industrialized countries. Roughly 25% of the children and 1%-3% of adults are affected. Although significant progress has been made in the understanding of the pathogenesis of AD, many aspects remain poorly understood. Moreover, there is a pressing need for improved therapeutic options. Studies to elucidate the pathophysiological pathways of AD and to identify novel therapeutic targets over the last few decades have been conducted almost exclusively in animal models. However, in vitro approaches such as 3D skin disease models have recently emerged due to an increasing awareness of distinct interspecies-related differences that hamper the effective translation of results from animal models to humans. In addition, there is growing political and social pressure to develop alternatives to animal models according to the 3Rs principle (reduction, refinement and replacement of animal models). © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Flow induced migration in polymer melts – Theory and simulation

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

Dorgan, John Robert, E-mail: jdorgan@mines.edu; Rorrer, Nicholas Andrew, E-mail: nrorrer@mines.edu

2015-04-28

Flow induced migration, whereby polymer melts are fractionated by molecular weight across a flow field, represents a significant complication in the processing of polymer melts. Despite its long history, such phenomena remain relatively poorly understood. Here a simple analytical theory is presented which predicts the phenomena based on well-established principles of non-equilibrium thermodynamics. It is unambiguously shown that for purely viscous materials, a gradient in shear rate is needed to drive migration; for purely viscometric flows no migration is expected. Molecular scale simulations of flow migration effects in dense polymer melts are also presented. In shear flow the melts exhibitmore » similar behavior as the quiescent case; a constant shear rate across the gap does not induce chain length based migration. In comparison, parabolic flow causes profound migration for both unentangled and entangled melts. These findings are consistent with the analytical theory. The picture that emerges is consistent with flow induced migration mechanisms predominating over competing chain degradation mechanisms.« less

Midbrain adaptation may set the stage for the perception of musical beat.

PubMed

Rajendran, Vani G; Harper, Nicol S; Garcia-Lazaro, Jose A; Lesica, Nicholas A; Schnupp, Jan W H

2017-11-15

The ability to spontaneously feel a beat in music is a phenomenon widely believed to be unique to humans. Though beat perception involves the coordinated engagement of sensory, motor and cognitive processes in humans, the contribution of low-level auditory processing to the activation of these networks in a beat-specific manner is poorly understood. Here, we present evidence from a rodent model that midbrain preprocessing of sounds may already be shaping where the beat is ultimately felt. For the tested set of musical rhythms, on-beat sounds on average evoked higher firing rates than off-beat sounds, and this difference was a defining feature of the set of beat interpretations most commonly perceived by human listeners over others. Basic firing rate adaptation provided a sufficient explanation for these results. Our findings suggest that midbrain adaptation, by encoding the temporal context of sounds, creates points of neural emphasis that may influence the perceptual emergence of a beat. © 2017 The Authors.

What influences urban Indian secondary school students' food consumption? - A qualitative study.

PubMed

Rathi, Neha; Riddell, Lynn; Worsley, Anthony

2016-10-01

Indian adolescents' over reliance on foods such as nutrient-poor snacks, sugar-sweetened beverages and take-away foods puts them at significant risk of obesity and several diet-related chronic diseases. Therefore, the factors that influence their dietary behaviours need to be better understood in order to develop effective nutrition promotion strategies. The purpose of this qualitative inquiry was to investigate adolescents', parents', teachers', and school principals' perceptions of the main influences on adolescent eating behaviours. Fifteen adolescents aged 14-15 years, 15 parents, 12 teachers and 10 principals from 10 private English-speaking schools in Kolkata, India, participated in semi-structured interviews. The digitally-recorded conversations were transcribed verbatim and analysed thematically. The 52 interviews revealed a number of factors that may influence adolescents' eating habits including parent and peer influences, home and school food environments, and the mass media. Emerging evidence suggests that future health and nutrition promotion interventions need to target the different influences on Indian teenagers' food consumption. Copyright © 2016. Published by Elsevier Ltd.

Targeted Degradation of CTCF Decouples Local Insulation of Chromosome Domains from Genomic Compartmentalization.

PubMed

Nora, Elphège P; Goloborodko, Anton; Valton, Anne-Laure; Gibcus, Johan H; Uebersohn, Alec; Abdennur, Nezar; Dekker, Job; Mirny, Leonid A; Bruneau, Benoit G

2017-05-18

The molecular mechanisms underlying folding of mammalian chromosomes remain poorly understood. The transcription factor CTCF is a candidate regulator of chromosomal structure. Using the auxin-inducible degron system in mouse embryonic stem cells, we show that CTCF is absolutely and dose-dependently required for looping between CTCF target sites and insulation of topologically associating domains (TADs). Restoring CTCF reinstates proper architecture on altered chromosomes, indicating a powerful instructive function for CTCF in chromatin folding. CTCF remains essential for TAD organization in non-dividing cells. Surprisingly, active and inactive genome compartments remain properly segregated upon CTCF depletion, revealing that compartmentalization of mammalian chromosomes emerges independently of proper insulation of TADs. Furthermore, our data support that CTCF mediates transcriptional insulator function through enhancer blocking but not as a direct barrier to heterochromatin spreading. Beyond defining the functions of CTCF in chromosome folding, these results provide new fundamental insights into the rules governing mammalian genome organization. Copyright © 2017 Elsevier Inc. All rights reserved.

Targeted degradation of CTCF decouples local insulation of chromosome domains from genomic compartmentalization

PubMed Central

Nora, Elphège P.; Goloborodko, Anton; Valton, Anne-Laure; Gibcus, Johan H.; Uebersohn, Alec; Abdennur, Nezar; Dekker, Job; Mirny, Leonid A.; Bruneau, Benoit G.

2017-01-01

Summary The molecular mechanisms underlying folding of mammalian chromosomes remain poorly understood. The transcription factor CTCF is a candidate regulator of chromosomal structure. Using the auxin-inducible degron system in mouse embryonic stem cells, we show that CTCF is absolutely and dose-dependently required for looping between CTCF target sites and insulation of topologically associating domains (TADs). Restoring CTCF reinstates proper architecture on altered chromosomes, indicating a powerful instructive function for CTCF in chromatin folding. CTCF remains essential for TAD organization in non-dividing cells. Surprisingly, active and inactive genome compartments remain properly segregated upon CTCF depletion, revealing that compartmentalization of mammalian chromosomes emerges independently of proper insulation of TADs. Further, our data support that CTCF mediates transcriptional insulator function through enhancer-blocking but not as a direct barrier to heterochromatin spreading. Beyond defining the functions of CTCF in chromosome folding these results provide new fundamental insights into the rules governing mammalian genome organization. PMID:28525758

A mitogen-activated protein kinase regulates male gametogenesis and transmission of the malaria parasite Plasmodium berghei

PubMed Central

Rangarajan, Radha; Bei, Amy K; Jethwaney, Deepa; Maldonado, Priscilla; Dorin, Dominique; Sultan, Ali A; Doerig, Christian

2005-01-01

Differentiation of malaria parasites into sexual forms (gametocytes) in the vertebrate host and their subsequent development into gametes in the mosquito vector are crucial steps in the completion of the parasite's life cycle and transmission of the disease. The molecular mechanisms that regulate the sexual cycle are poorly understood. Although several signal transduction pathways have been implicated, a clear understanding of the pathways involved has yet to emerge. Here, we show that a Plasmodium berghei homologue of Plasmodium falciparum mitogen-activated kinase-2 (Pfmap-2), a gametocyte-specific mitogen-activated protein kinase (MAPK), is required for male gamete formation. Parasites lacking Pbmap-2 are competent for gametocytogenesis, but exflagellation of male gametocytes, the process that leads to male gamete formation, is almost entirely abolished in mutant parasites. Consistent with this result, transmission of mutant parasites to mosquitoes is grossly impaired. This finding identifies a crucial role for a MAPK pathway in malaria transmission. PMID:15864297

Selection on hemagglutinin imposes a bottleneck during mammalian transmission of reassortant H5N1 influenza viruses

PubMed Central

Wilker, Peter R.; Dinis, Jorge M.; Starrett, Gabriel; Imai, Masaki; Hatta, Masato; Nelson, Chase W.; O’Connor, David H.; Hughes, Austin L.; Neumann, Gabriele; Kawaoka, Yoshihiro; Friedrich, Thomas C.

2013-01-01

The emergence of human-transmissible H5N1 avian influenza viruses poses a major pandemic threat. H5N1 viruses are thought to be highly genetically diverse both among and within hosts, but the effects of this diversity on viral replication and transmission are poorly understood. Here we use deep sequencing to investigate the impact of within-host viral variation on adaptation and transmission of H5N1 viruses in ferrets. We show that although within-host genetic diversity in hemagglutinin (HA) increases during replication in inoculated ferrets, HA diversity is dramatically reduced upon respiratory droplet transmission, where infection is established by only 1–2 distinct HA segments from a diverse source virus population in transmitting animals. Moreover, minor HA variants present in as little as 5.9% of viruses within the source animal become dominant in ferrets infected via respiratory droplets. These findings demonstrate that selective pressures acting during influenza virus transmission among mammals impose a significant bottleneck. PMID:24149915

mRNA export in the apicomplexan parasite Toxoplasma gondii: emerging divergent components of a crucial pathway.

PubMed

Ávila, Andréa Rodrigues; Cabezas-Cruz, Alexjandro; Gissot, Mathieu

2018-01-25

Control of gene expression is crucial for parasite survival and is the result of a series of processes that are regulated to permit fine-tuning of gene expression in response to biological changes during the life-cycle of apicomplexan parasites. Control of mRNA nuclear export is a key process in eukaryotic cells but is poorly understood in apicomplexan parasites. Here, we review recent knowledge regarding this process with an emphasis on T. gondii. We describe the presence of divergent orthologs and discuss structural and functional differences in export factors between apicomplexans and other eukaryotic lineages. Undoubtedly, the use of the CRISPR/Cas9 system in high throughput screenings associated with the discovery of mRNA nuclear export complexes by proteomic analysis will contribute to identify these divergent factors. Ligand-based or structure-based strategies may be applied to investigate the potential use of these proteins as targets for new antiprotozoal agents.

Shape Transformations of Epithelial Shells

PubMed Central

Misra, Mahim; Audoly, Basile; Kevrekidis, Ioannis G.; Shvartsman, Stanislav Y.

2016-01-01

Regulated deformations of epithelial sheets are frequently foreshadowed by patterning of their mechanical properties. The connection between patterns of cell properties and the emerging tissue deformations is studied in multiple experimental systems, but the general principles remain poorly understood. For instance, it is in general unclear what determines the direction in which the patterned sheet is going to bend and whether the resulting shape transformation will be discontinuous or smooth. Here these questions are explored computationally, using vertex models of epithelial shells assembled from prismlike cells. In response to rings and patches of apical cell contractility, model epithelia smoothly deform into invaginated or evaginated shapes similar to those observed in embryos and tissue organoids. Most of the observed effects can be captured by a simpler model with polygonal cells, modified to include the effects of the apicobasal polarity and natural curvature of epithelia. Our models can be readily extended to include the effects of multiple constraints and used to describe a wide range of morphogenetic processes. PMID:27074691

Automated analysis of long-term grooming behavior in Drosophila using a k-nearest neighbors classifier

PubMed Central

Allen, Victoria W; Shirasu-Hiza, Mimi

2018-01-01

Despite being pervasive, the control of programmed grooming is poorly understood. We addressed this gap by developing a high-throughput platform that allows long-term detection of grooming in Drosophila melanogaster. In our method, a k-nearest neighbors algorithm automatically classifies fly behavior and finds grooming events with over 90% accuracy in diverse genotypes. Our data show that flies spend ~13% of their waking time grooming, driven largely by two major internal programs. One of these programs regulates the timing of grooming and involves the core circadian clock components cycle, clock, and period. The second program regulates the duration of grooming and, while dependent on cycle and clock, appears to be independent of period. This emerging dual control model in which one program controls timing and another controls duration, resembles the two-process regulatory model of sleep. Together, our quantitative approach presents the opportunity for further dissection of mechanisms controlling long-term grooming in Drosophila. PMID:29485401

Aerobiology Over Antarctica – A New Initiative for Atmospheric Ecology

PubMed Central

Pearce, David A.; Alekhina, Irina A.; Terauds, Aleks; Wilmotte, Annick; Quesada, Antonio; Edwards, Arwyn; Dommergue, Aurelien; Sattler, Birgit; Adams, Byron J.; Magalhães, Catarina; Chu, Wan-Loy; Lau, Maggie C. Y.; Cary, Craig; Smith, David J.; Wall, Diana H.; Eguren, Gabriela; Matcher, Gwynneth; Bradley, James A.; de Vera, Jean-Pierre; Elster, Josef; Hughes, Kevin A.; Cuthbertson, Lewis; Benning, Liane G.; Gunde-Cimerman, Nina; Convey, Peter; Hong, Soon Gyu; Pointing, Steve B.; Pellizari, Vivian H.; Vincent, Warwick F.

2016-01-01

The role of aerial dispersal in shaping patterns of biodiversity remains poorly understood, mainly due to a lack of coordinated efforts in gathering data at appropriate temporal and spatial scales. It has been long known that the rate of dispersal to an ecosystem can significantly influence ecosystem dynamics, and that aerial transport has been identified as an important source of biological input to remote locations. With the considerable effort devoted in recent decades to understanding atmospheric circulation in the south-polar region, a unique opportunity has emerged to investigate the atmospheric ecology of Antarctica, from regional to continental scales. This concept note identifies key questions in Antarctic microbial biogeography and the need for standardized sampling and analysis protocols to address such questions. A consortium of polar aerobiologists is established to bring together researchers with a common interest in the airborne dispersion of microbes and other propagules in the Antarctic, with opportunities for comparative studies in the Arctic. PMID:26909068

Long noncoding RNA AB074169 inhibits cell proliferation via modulation of KHSRP-mediated p21 expression in papillary thyroid carcinoma.

PubMed

Gou, Qiheng; Gao, Linbo; Nie, Xinwen; Pu, Wenchen; Zhu, Jingqiang; Wang, Yichao; Liu, Xuesha; Tan, Shuangyan; Zhou, Jian-Kang; Gong, Yanqiu; He, Juan; Wu, Ke; Xie, Yuxin; Zhao, Wanjun; Dai, Lunzhi; Liu, Lunxu; Xiang, Rong; Wei, Yu-Quan; Zhang, Lin; Peng, Yong

2018-05-07

Long noncoding RNAs (lncRNAs) are emerging as a novel class of regulators in gene expression associated with tumorigenesis. However, the role of lncRNAs in papillary thyroid carcinoma (PTC) is poorly understood. Here we conducted global lncRNA profiling and identified lncRNA AB074169 (lncAB) as significantly downregulated in PTC. Decreased expression of lncAB in PTC was caused by CpG hypermethylation within its gene promoter. Functional studies showed that lncAB overexpression led to cell cycle arrest and tumor growth inhibition in vitro and in vivo, whereas lncAB knockdown promoted cell proliferation. Mechanistic analyses revealed that lncAB bound KH-type splicing regulatory protein (KHSRP) and also decreased expression of KHSRP, thus increasing CDKN1a (p21) expression and decreasing CDK2 expression to repress cell proliferation. Taken together, these findings demonstrate that lncAB functions as a tumor suppressor during PTC tumorigenesis. Copyright ©2018, American Association for Cancer Research.

Uptake and Accumulation of Nephrotoxic and Carcinogenic Aristolochic Acids in Food Crops Grown in Aristolochia clematitis-Contaminated Soil and Water.

PubMed

Li, Weiwei; Hu, Qin; Chan, Wan

2016-01-13

Emerging evidence has suggested aristolochic acids (AAs) are linked to the development of Balkan endemic nephropathy (BEN), a chronic renal disease affecting numerous farmers living in the Balkan peninsula. However, the pathway by which AAs enter the human food chain and cause kidney disease remains poorly understood. Using our previously developed analytical method with high sensitivity and selectivity (Chan, W.; Lee, K. C.; Liu, N.; Cai, Z. J. Chromatogr. A 2007, 1164, 113-119), we quantified AAs in lettuce, tomato, and spring onion grown in AA-contaminated soil and culture medium. Our study revealed that AAs were being taken up from the soil and bioaccumulated in food crops in a time- and dose-dependent manner. To the best of our knowledge, this study is the first to identify one of the possible pathways by which AAs enter our food chain to cause chronic food poisoning. Results also demonstrated that AAs were resistant to the microbial activity of the soil/water.

Resveratrol serves as a protein-substrate interaction stabilizer in human SIRT1 activation.

PubMed

Hou, Xuben; Rooklin, David; Fang, Hao; Zhang, Yingkai

2016-11-30

Resveratrol is a natural compound found in red wine that has been suggested to exert its potential health benefit through the activation of SIRT1, a crucial member of the mammalian NAD + -dependent deacetylases. SIRT1 has emerged as an attractive therapeutic target for many aging related diseases, however, how its activity can only be activated toward some specific substrates by resveratrol has been poorly understood. Herein, by employing extensive molecular dynamics simulations as well as fragment-centric topographical mapping of binding interfaces, we have clarified current controversies in the literature and elucidated that resveratrol plays an important activation role by stabilizing SIRT1/peptide interactions in a substrate-specific manner. This new mechanism highlights the importance of the N-terminal domain in substrate recognition, explains the activity restoration role of resveratrol toward some "loose-binding" substrates of SIRT1, and has significant implications for the rational design of new substrate-specific SIRT1 modulators.

Oceanic barnacles act as foundation species on plastic debris: implications for marine dispersal

PubMed Central

Gil, Michael A.; Pfaller, Joseph B.

2016-01-01

Plastic has emerged as an abundant, stable substratum for oceanic dispersal of organisms via rafting. However, the ecological mechanisms underlying community diversity on plastic debris remain poorly understood. On a cruise from California to Hawai’i, we surveyed plastic debris, some likely originating from the 2011 Tōhoku tsunami, to examine the relationship between rafting community diversity and both habitat area and stalked barnacle (Lepas spp.) abundance. For sessile taxa richness, we observed an interaction in which the positive effect of debris area weakened the negative effect of barnacle cover. In contrast, for mobile taxa richness, including cohabiting species from opposite sides of the Pacific Ocean, barnacle abundance had a positive effect that was strongest at smaller debris sizes. These findings suggest that barnacles, through interactions with habitat area, have trait-dependent effects on other species, serving as both foundation species and competitors, mediating the diversity and dispersal potential of marine organisms on plastic debris. PMID:26813348

Inflammation and wound healing: The role of the macrophage

PubMed Central

Koh, Timothy J.; DiPietro, Luisa Ann

2013-01-01

The macrophage is a prominent inflammatory cell in wounds, but its role in healing remains incompletely understood. Macrophages have been described to have many functions in wounds, including host defense, the promotion and resolution of inflammation, the removal of apoptotic cells, and the support of cell proliferation and tissue restoration following injury. Recent studies suggest that macrophages exist in several different phenotypic states within the healing wound, and that the influence of these cells on each stage of repair varies with the specific phenotypes. While the macrophage is beneficial to the repair of normally healing wounds, this pleotropic cell type may promote excessive inflammation and/or fibrosis in certain circumstances. Emerging evidence suggests that macrophage dysfunction is a component of the pathogenesis of non-healing and poorly healing wounds. Due to advances in the understanding of this multi-functional cell, the macrophage continues to be an attractive therapeutic target both to reduce fibrosis and scarring, and to improve healing of chronic wounds. PMID:21740602

TRIM E3 ligases in HIV infection: can these intrinsic immunity factors be harnessed for novel vaccines or therapies?

PubMed

Ndung'u, Thumbi

2011-01-01

Tripartite motif-containing (TRIM) E3 ligases are a recently identified family of proteins with potent antiviral activity in mammalian cells. The prototype TRIM E3 ligase, TRIM5α was initially identified as a species-specific antiviral restriction factor but subsequent studies suggest some antiviral activity by several TRIM E3 ligases in human cells. However, the mechanisms of antiviral activity by these proteins and their transcriptional, translational and post-translational regulation are poorly understood. Furthermore, the contribution of TRIM E3 ligases to relative resistance or viral control in vivo is largely unknown. Emerging data from our laboratory and other groups suggests that these proteins may have antiviral activity in vivo and contribute to HIV pathogenesis. Considering the significant difficulties so far encountered in developing an effective HIV vaccine and with the use of antiretroviral therapies, it will be important to further investigate the potential of TRIM E3 ligases as novel prophylactics or therapies.

A method for multiprotein assembly in cells reveals independent action of kinesins in complex

PubMed Central

Norris, Stephen R.; Soppina, Virupakshi; Dizaji, Aslan S.; Schimert, Kristin I.; Sept, David; Cai, Dawen; Sivaramakrishnan, Sivaraj

2014-01-01

Teams of processive molecular motors are critical for intracellular transport and organization, yet coordination between motors remains poorly understood. Here, we develop a system using protein components to generate assemblies of defined spacing and composition inside cells. This system is applicable to studying macromolecular complexes in the context of cell signaling, motility, and intracellular trafficking. We use the system to study the emergent behavior of kinesin motors in teams. We find that two kinesin motors in complex act independently (do not help or hinder each other) and can alternate their activities. For complexes containing a slow kinesin-1 and fast kinesin-3 motor, the slow motor dominates motility in vitro but the fast motor can dominate on certain subpopulations of microtubules in cells. Both motors showed dynamic interactions with the complex, suggesting that motor–cargo linkages are sensitive to forces applied by the motors. We conclude that kinesin motors in complex act independently in a manner regulated by the microtubule track. PMID:25365993

Migration of cells in a social context

PubMed Central

Vedel, Søren; Tay, Savaş; Johnston, Darius M.; Bruus, Henrik; Quake, Stephen R.

2013-01-01

In multicellular organisms and complex ecosystems, cells migrate in a social context. Whereas this is essential for the basic processes of life, the influence of neighboring cells on the individual remains poorly understood. Previous work on isolated cells has observed a stereotypical migratory behavior characterized by short-time directional persistence with long-time random movement. We discovered a much richer dynamic in the social context, with significant variations in directionality, displacement, and speed, which are all modulated by local cell density. We developed a mathematical model based on the experimentally identified “cellular traffic rules” and basic physics that revealed that these emergent behaviors are caused by the interplay of single-cell properties and intercellular interactions, the latter being dominated by a pseudopod formation bias mediated by secreted chemicals and pseudopod collapse following collisions. The model demonstrates how aspects of complex biology can be explained by simple rules of physics and constitutes a rapid test bed for future studies of collective migration of individual cells. PMID:23251032

Migration of cells in a social context.

PubMed

Vedel, Søren; Tay, Savaş; Johnston, Darius M; Bruus, Henrik; Quake, Stephen R

2013-01-02

In multicellular organisms and complex ecosystems, cells migrate in a social context. Whereas this is essential for the basic processes of life, the influence of neighboring cells on the individual remains poorly understood. Previous work on isolated cells has observed a stereotypical migratory behavior characterized by short-time directional persistence with long-time random movement. We discovered a much richer dynamic in the social context, with significant variations in directionality, displacement, and speed, which are all modulated by local cell density. We developed a mathematical model based on the experimentally identified "cellular traffic rules" and basic physics that revealed that these emergent behaviors are caused by the interplay of single-cell properties and intercellular interactions, the latter being dominated by a pseudopod formation bias mediated by secreted chemicals and pseudopod collapse following collisions. The model demonstrates how aspects of complex biology can be explained by simple rules of physics and constitutes a rapid test bed for future studies of collective migration of individual cells.

Structural Basis for NADH/NAD+ Redox Sensing by a Rex Family Repressor

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

McLaughlin, K.J.; Soares, A.; Strain-Damerell, C. M.

2010-05-28

Nicotinamide adenine dinucleotides have emerged as key signals of the cellular redox state. Yet the structural basis for allosteric gene regulation by the ratio of reduced NADH to oxidized NAD{sup +} is poorly understood. A key sensor among Gram-positive bacteria, Rex represses alternative respiratory gene expression until a limited oxygen supply elevates the intracellular NADH:NAD{sup +} ratio. Here we investigate the molecular mechanism for NADH/NAD{sup +} sensing among Rex family members by determining structures of Thermus aquaticus Rex bound to (1) NAD{sup +}, (2) DNA operator, and (3) without ligand. Comparison with the Rex/NADH complex reveals that NADH releases Rexmore » from the DNA site following a 40{sup o} closure between the dimeric subunits. Complementary site-directed mutagenesis experiments implicate highly conserved residues in NAD-responsive DNA-binding activity. These rare views of a redox sensor in action establish a means for slight differences in the nicotinamide charge, pucker, and orientation to signal the redox state of the cell.« less

Paradoxical Vocal Cord Motion in Pediatric Patients.

PubMed

Palla, John; Friedman, Aaron D

2016-05-01

Paradoxical vocal cord motion (PVCM), also termed vocal cord dysfunction, is a poorly understood disorder of episodic dyspnea characterized by inappropriate vocal cord adduction during inspiration and potentially during expiration. It can coexist or be confused with asthma, so appropriate diagnosis is key to optimizing treatment success. Although many patients with PVCM may have underlying psychologic issues, there is emerging evidence to suggest that this entity is not psychogenic in every patient. Both laryngeal irritants and exercise have been identified as additional contributing factors in PVCM. Diagnosis of PVCM requires awake laryngoscopic confirmation. However, many patients do not exhibit signs of PVCM during this examination, despite provocation during testing. Therefore, clinical history remains key in determining which patients should proceed with behavioral therapy under the guidance of a speech pathologist. In addition, treatment may include limiting patient exposure to potential sources of laryngeal irritation. Refractory patients may benefit from psychologic assessment and treatment. [Pediatr Ann. 2016;45(5):e184-e188.]. Copyright 2016, SLACK Incorporated.

Specification of Drosophila Corpora Cardiaca Neuroendocrine Cells from Mesoderm Is Regulated by Notch Signaling

PubMed Central

Park, Sangbin; Bustamante, Erika L.; Antonova, Julie; McLean, Graeme W.; Kim, Seung K.

2011-01-01

Drosophila neuroendocrine cells comprising the corpora cardiaca (CC) are essential for systemic glucose regulation and represent functional orthologues of vertebrate pancreatic α-cells. Although Drosophila CC cells have been regarded as developmental orthologues of pituitary gland, the genetic regulation of CC development is poorly understood. From a genetic screen, we identified multiple novel regulators of CC development, including Notch signaling factors. Our studies demonstrate that the disruption of Notch signaling can lead to the expansion of CC cells. Live imaging demonstrates localized emergence of extra precursor cells as the basis of CC expansion in Notch mutants. Contrary to a recent report, we unexpectedly found that CC cells originate from head mesoderm. We show that Tinman expression in head mesoderm is regulated by Notch signaling and that the combination of Daughterless and Tinman is sufficient for ectopic CC specification in mesoderm. Understanding the cellular, genetic, signaling, and transcriptional basis of CC cell specification and expansion should accelerate discovery of molecular mechanisms regulating ontogeny of organs that control metabolism. PMID:21901108

Is Chytridiomycosis an Emerging Infectious Disease in Asia?

PubMed Central

Swei, Andrea; Rowley, Jodi J. L.; Rödder, Dennis; Diesmos, Mae L. L.; Diesmos, Arvin C.; Briggs, Cheryl J.; Brown, Rafe; Cao, Trung Tien; Cheng, Tina L.; Chong, Rebecca A.; Han, Ben; Hero, Jean-Marc; Hoang, Huy Duc; Kusrini, Mirza D.; Le, Duong Thi Thuy; McGuire, Jimmy A.; Meegaskumbura, Madhava; Min, Mi-Sook; Mulcahy, Daniel G.; Neang, Thy; Phimmachak, Somphouthone; Rao, Ding-Qi; Reeder, Natalie M.; Schoville, Sean D.; Sivongxay, Niane; Srei, Narin; Stöck, Matthias; Stuart, Bryan L.; Torres, Lilia S.; Tran, Dao Thi Anh; Tunstall, Tate S.; Vieites, David; Vredenburg, Vance T.

2011-01-01

The disease chytridiomycosis, caused by the fungus Batrachochytrium dendrobatidis (Bd), has caused dramatic amphibian population declines and extinctions in Australia, Central and North America, and Europe. Bd is associated with >200 species extinctions of amphibians, but not all species that become infected are susceptible to the disease. Specifically, Bd has rapidly emerged in some areas of the world, such as in Australia, USA, and throughout Central and South America, causing population and species collapse. The mechanism behind the rapid global emergence of the disease is poorly understood, in part due to an incomplete picture of the global distribution of Bd. At present, there is a considerable amount of geographic bias in survey effort for Bd, with Asia being the most neglected continent. To date, Bd surveys have been published for few Asian countries, and infected amphibians have been reported only from Indonesia, South Korea, China and Japan. Thus far, there have been no substantiated reports of enigmatic or suspected disease-caused population declines of the kind that has been attributed to Bd in other areas. In order to gain a more detailed picture of the distribution of Bd in Asia, we undertook a widespread, opportunistic survey of over 3,000 amphibians for Bd throughout Asia and adjoining Papua New Guinea. Survey sites spanned 15 countries, approximately 36° latitude, 111° longitude, and over 2000 m in elevation. Bd prevalence was very low throughout our survey area (2.35% overall) and infected animals were not clumped as would be expected in epizootic events. This suggests that Bd is either newly emerging in Asia, endemic at low prevalence, or that some other ecological factor is preventing Bd from fully invading Asian amphibians. The current observed pattern in Asia differs from that in many other parts of the world. PMID:21887238

Feeling understood: a melody of human becoming.

PubMed

Jonas-Simpson, C M

2001-07-01

This phenomenological-hermeneutic study centered on the phenomenon of feeling understood, which was conceptualized by the researcher as a melody of human becoming significant to quality of life. For the first time the Parse research method was used with music as part of the dialogical engagement. The study was conducted with 10 women living with an enduring health situation who volunteered to be in tape-recorded dialogue with the researcher to discuss feeling understood and to create a musical expression of this phenomenon. The finding of this study, which is the structure of the lived experience of feeling understood, surfaced from the dialogues and musical expressions: Feeling understood is an unburdening quietude with triumphant bliss arising with the attentive reverence of nurturing engagements, while fortifying integrity emerges amid potential disregard.

Using the Co-Production of Knowledge for Developing Realistic Natural Disaster Scenarios for Small-to-Medium Scale Emergency Management Exercises

NASA Astrophysics Data System (ADS)

Robinson, T.; Wilson, T. M.; Davies, T. R.; Orchiston, C.; Thompson, J.

2014-12-01

Disaster scenarios for Emergency Management (EM) exercises are a widely-used and effective tool for communicating hazard information to policy makers, EM personnel, lifelines operators and communities in general. It is crucial that the scenarios are as realistic as possible. Major disasters however, contain a series of cascading consequences, both environmental and social, which are difficult to model. Consequently, only recently have large-scale exercises included such processes; incorporating these in small- and medium-scale scenarios has yet to be attempted. This study details work undertaken in a recent medium-scale earthquake exercise in New Zealand to introduce such cascading processes into the disaster scenario. Given limited time, data, and funding, we show that the co-production of knowledge between natural disaster scientists, EM personnel, and governance and lifelines organisations can yield detailed, realistic scenarios. Using the co-production process, scenario development was able to identify where the pre-exercise state of knowledge was insufficient. This enabled a focussed research response driven by end-user needs. This found that in general, seismic hazard (ground shaking) and its likely impacts were well known and understood by all parties. However, subsequent landsliding and associated effects were poorly known and understood and their potential impacts unconsidered. Scenario development therefore focussed primarily on understanding these processes and their potential effects. This resulted in cascading hazards being included in a medium-scale NZ exercise for the first time. Further, all participants were able to focus on the potential impacts on their specific sectors, increasing the level of knowledge of cascading processes across all parties. Using group based discussions throughout the design process allowed a detailed scenario to be created, fostered stronger inter-disciplinary relationships, and identified areas for further research. Consequently, further detailed research has begun specifically into the impacts from secondary effects in an effort to further increase resilience to future events.

76 FR 61379 - Final Recovery Plan, Bexar County Karst Invertebrates

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-04

... 200, Austin, TX (512-490-0057 ext. 223). FOR FURTHER INFORMATION CONTACT: Adam Zerrenner, at the above... poorly understood, recovery is also dependant on incorporating research findings into adaptive management...

Fine-scale landscape genetics of the American badger (Taxidea taxus): disentangling landscape effects and sampling artifacts in a poorly understood species

PubMed Central

Kierepka, E M; Latch, E K

2016-01-01

Landscape genetics is a powerful tool for conservation because it identifies landscape features that are important for maintaining genetic connectivity between populations within heterogeneous landscapes. However, using landscape genetics in poorly understood species presents a number of challenges, namely, limited life history information for the focal population and spatially biased sampling. Both obstacles can reduce power in statistics, particularly in individual-based studies. In this study, we genotyped 233 American badgers in Wisconsin at 12 microsatellite loci to identify alternative statistical approaches that can be applied to poorly understood species in an individual-based framework. Badgers are protected in Wisconsin owing to an overall lack in life history information, so our study utilized partial redundancy analysis (RDA) and spatially lagged regressions to quantify how three landscape factors (Wisconsin River, Ecoregions and land cover) impacted gene flow. We also performed simulations to quantify errors created by spatially biased sampling. Statistical analyses first found that geographic distance was an important influence on gene flow, mainly driven by fine-scale positive spatial autocorrelations. After controlling for geographic distance, both RDA and regressions found that Wisconsin River and Agriculture were correlated with genetic differentiation. However, only Agriculture had an acceptable type I error rate (3–5%) to be considered biologically relevant. Collectively, this study highlights the benefits of combining robust statistics and error assessment via simulations and provides a method for hypothesis testing in individual-based landscape genetics. PMID:26243136

Dental Emergencies: Management Strategies That Improve Outcomes [Digest].

PubMed

Pedigo, Ryan Anthony; Zaurova, Milana

2017-06-22

Points & Pearls is a digest of Emergency Medicine Practice . Acute dental emergencies are a common chief complaint presenting to emergency departments, and they are increasing substantially in frequency. The diagnosis and management of dental emergencies is a core competency of the emergency clinician, and proper therapeutic strategies can significantly improve cosmetic and functional outcomes for patients. This issue provides a systematic review of the literature on common acute traumatic and atraumatic dental emergencies with a focus on the historical and physical examination findings that must be understood to identify life-threatening infections, relieve pain, salvage natural teeth, and communicate with specialists in the further management of patients after emergency treatment.

Biodiversity and ecosystem function in species-poor communities: community structure and leaf litter breakdown in a Pacific island stream

Treesearch

Jonathan P. Benstead; James G. March; Catherine M. Pringle; Katherine C. Ewel; John W. Short

2009-01-01

Pacific island stream communities are species-poor because of the effects of extreme geographic isolation on colonization rates of taxa common to continental regions. The effects of such low species richness on stream ecosystem function are not well understood. Here, we provide data on community structure and leaf litter breakdown rate in a virtually pristine stream on...

Theoretical properties of Omega-loops in the convective zone of the Sun. 1: Emerging bipolar magnetic regions

NASA Technical Reports Server (NTRS)

Parker, E. N.

1994-01-01

It is proposed that the observed 500 G intensity of the magnetic fields emerging through the surface of the Sun can be understood from the Bernoulli effect in the upwelling Omega-loops of magnetic field. It is also proposed that the inferred 10(exp 5) G azimuthal flux bundles below the base of the convective zone can be understood as a consequence of the large-scale buoyancy associated with the upwelling fluid in and around the rising Omega-loop. The process fits in naturally with the Babcock-Leighton form of the solar alpha-omega-dynamo. The emerging Omega-loop implies the coherence of the upwelling all the way from the bottom of the convective zone, enhancing the convective heat transport to account for the observed variation of the solar irradiance by about two parts in 10(exp 3).

The public's belief about biology.

PubMed

Wolpert, L

2007-02-01

This short review is concerned with a topic that has been neglected and is still very poorly understood: what the general public think and believe about biology (including health and medicine, and bioethics), and, in particular, about biotechnology.

A Production Function Approach to Regional Environmental-Economic Assessments

EPA Science Inventory

Numerous difficulties await those creating regional-scale environmental assessments, from data having inconsistent spatial or temporal scales to poorly understood environmental processes and indicators. Including socioeconomic variables further complicates the situation. In place...

Significance of the E3 ubiquitin protein UBR5 as an oncogene and a prognostic biomarker in colorectal cancer

PubMed Central

Xu, Xiaowen; Zhu, Yan; Guo, Aizhen; Shen, Xian; Cao, Fuao; Chang, Wenjun

2017-01-01

The E3 ubiquitin protein UBR5 has been implicated in the regulation of multiple biological functions and has recently emerged as a key regulator of the ubiquitin-proteasome system (UPS) in cancer. However, the clinical significance and biological function of UBR5 in colorectal cancer (CRC) are poorly understood. In this study, we compared the expression pattern of UBR5 between CRC and adjacent normal tissues and found that UBR5 expression was frequently elevated in CRC, possibly through chromosomal gains. Using three CRC patient cohorts, we found that patients with high UBR5 mRNA levels, UBR5 gene amplification, or high nuclear UBR5 protein levels had poor prognoses. Multivariate analysis showed that the alterations in UBR5 were independent predictors of CRC prognosis with the TNM stage as a confounding factor. Furthermore, knockdown of UBR5 prevented the proliferation, colony formation, migration, and invasion of CRC cells in cell culture models. An in vivo animal model further confirmed that UBR5 knockdown reduced the growth of CRC tumors. In conclusion, our study is the first to systematically investigate the clinical and biological significance of UBR5 and to conclude that an elevated UBR5 level plays an oncogenic role and may be a potential prognostic marker in CRC. PMID:29296225

High Expression of FAM83B Predicts Poor Prognosis in Patients with Pancreatic Ductal Adenocarcinoma and Correlates with Cell Cycle and Cell Proliferation

PubMed Central

Shen, Chao-qin; Yan, Ting-Ting; Liu, Wei; Zhu, Xiao-qiang; Tian, Xiang-long; Fu, Xue-liang; Hua, Rong; Zhang, Jun-feng; Huo, Yan-miao; Liu, De-jun; Yang, Jian-yu; Sun, Yong-Wei; Fang, Jing-Yuan; Chen, Hao-Yan; Hong, Jie

2017-01-01

FAM83B (family with sequence similarity 83, member B) seems to emerge as a new class of players involved in the development of a variety of malignant tumors. Yet the molecular mechanisms are not well understood. The present study is intended to investigate the expression and function of FAM83B in pancreatic ductal adenocarcinoma (PDAC). In this study, we found that the expression of FAM83B was significantly increased both in PDAC cell lines and PDAC tumor tissues. FAM83B expression was positively related with advanced clinical stage and poor vital status. Higher FAM83B expression predicted shorter overall survival in PDAC patients, regardless of lymphatic metastasis status and histological differentiation. Actually, FAM83B may act as an independent prognostic indicator as well. What's more, down-regulation of FAM83B in PDAC cells contributed to G0/G1 phase arrest and inhibition of cell proliferation. Finally, a subcutaneous xenograft model indicated that knockdown of FAM83B significantly reduced the tumor volume in vivo. Our findings have provided supporting evidence for the potential molecular biomarker role of FAM83B in PDAC. It's of great interest and broad significance to target FAM83B in PDAC, which may conduce to develop a meaningful and effective strategy in the diagnosis and treatment of PDAC. PMID:29158787

Health‐related beliefs and experiences of Gypsies and Travellers: a qualitative study

PubMed Central

Van Cleemput, Patrice; Parry, Glenys; Thomas, Kate; Peters, Jean; Cooper, Cindy

2007-01-01

Objective To illuminate findings of the survey of the health status of Gypsies and Travellers by exploring their health‐related beliefs and experiences. Design Qualitative study of a purposive subsample from in‐depth interviews using framework analysis. Setting The homes or alternative community settings of the participants in five geographically dispersed study locations in England. Participants 27 Gypsies and Travellers with an experience of ill health, purposively sampled from a larger population participating in an epidemiological survey of health status. Results The experience of poor health and daily encounters of ill health among extended family members were normalised and accepted. Four major themes emerged relating to health beliefs and the effect of lifestyle on health for these respondents: the travelling way; low expectations of health; self‐reliance and staying in control; fatalism and fear of death. These themes dominated accounts of health experience and were relevant to the experience. These themes add richness to the health status data and inform our understanding. Conclusions Among Gypsies and Travellers, coherent cultural beliefs and attitudes underpin health‐related behaviour, and health experiences must be understood in this context. In this group, ill health is seen as normal, an inevitable consequence of adverse social experiences, and is stoically and fatalistically accepted. The provision of effective healthcare and improvement of poor health in Gypsies and Travellers will require multi‐agency awareness of these issues. PMID:17325396

Capacitive charge storage at an electrified interface investigated via direct first-principles simulations [Direct Simulation of Capacitive Charging of Graphene and Implications for Supercapacitor Design

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

Radin, Maxwell D.; Ogitsu, Tadashi; Biener, Juergen

Understanding the impact of interfacial electric fields on electronic structure is crucial to improving the performance of materials in applications based on charged interfaces. Supercapacitors store energy directly in the strong interfacial field between a solid electrode and a liquid electrolyte; however, the complex interplay between the two is often poorly understood, particularly for emerging low-dimensional electrode materials that possess unconventional electronic structure. Typical descriptions tend to neglect the specific electrode-electrolyte interaction, approximating the intrinsic “quantum capacitance” of the electrode in terms of a fixed electronic density of states. Instead, we introduce a more accurate first-principles approach for directly simulatingmore » charge storage in model capacitors using the effective screening medium method, which implicitly accounts for the presence of the interfacial electric field. Applying this approach to graphene supercapacitor electrodes, we find that results differ significantly from the predictions of fixed-band models, leading to improved consistency with experimentally reported capacitive behavior. The differences are traced to two key factors: the inhomogeneous distribution of stored charge due to poor electronic screening and interfacial contributions from the specific interaction with the electrolyte. Lastly, our results are used to revise the conventional definition of quantum capacitance and to provide general strategies for improving electrochemical charge storage, particularly in graphene and similar low-dimensional materials.« less

Capacitive charge storage at an electrified interface investigated via direct first-principles simulations [Direct Simulation of Capacitive Charging of Graphene and Implications for Supercapacitor Design

DOE PAGES

Radin, Maxwell D.; Ogitsu, Tadashi; Biener, Juergen; ...

2015-03-11

Understanding the impact of interfacial electric fields on electronic structure is crucial to improving the performance of materials in applications based on charged interfaces. Supercapacitors store energy directly in the strong interfacial field between a solid electrode and a liquid electrolyte; however, the complex interplay between the two is often poorly understood, particularly for emerging low-dimensional electrode materials that possess unconventional electronic structure. Typical descriptions tend to neglect the specific electrode-electrolyte interaction, approximating the intrinsic “quantum capacitance” of the electrode in terms of a fixed electronic density of states. Instead, we introduce a more accurate first-principles approach for directly simulatingmore » charge storage in model capacitors using the effective screening medium method, which implicitly accounts for the presence of the interfacial electric field. Applying this approach to graphene supercapacitor electrodes, we find that results differ significantly from the predictions of fixed-band models, leading to improved consistency with experimentally reported capacitive behavior. The differences are traced to two key factors: the inhomogeneous distribution of stored charge due to poor electronic screening and interfacial contributions from the specific interaction with the electrolyte. Lastly, our results are used to revise the conventional definition of quantum capacitance and to provide general strategies for improving electrochemical charge storage, particularly in graphene and similar low-dimensional materials.« less

Blaming the helpers: the marginalization of teachers and parents of the urban poor.

PubMed

Farber, B A; Azar, S T

1999-10-01

The nature and origins of the current tendency toward disparaging parents and teachers of the urban poor are examined. It is suggested that the influence of parents and teachers must be understood in the context of multiple intervening variables. Several explanations are offered for the phenomenon of blame, including the fact that women constitute the great majority of teachers and are often the primary agents of parenting.

Sequence type 1 group B Streptococcus, an emerging cause of invasive disease in adults, evolves by small genetic changes

PubMed Central

Flores, Anthony R.; Galloway-Peña, Jessica; Sahasrabhojane, Pranoti; Saldaña, Miguel; Yao, Hui; Su, Xiaoping; Ajami, Nadim J.; Holder, Michael E.; Petrosino, Joseph F.; Thompson, Erika; Margarit Y Ros, Immaculada; Rosini, Roberto; Grandi, Guido; Horstmann, Nicola; Teatero, Sarah; McGeer, Allison; Fittipaldi, Nahuel; Rappuoli, Rino; Baker, Carol J.; Shelburne, Samuel A.

2015-01-01

The molecular mechanisms underlying pathogen emergence in humans is a critical but poorly understood area of microbiologic investigation. Serotype V group B Streptococcus (GBS) was first isolated from humans in 1975, and rates of invasive serotype V GBS disease significantly increased starting in the early 1990s. We found that 210 of 229 serotype V GBS strains (92%) isolated from the bloodstream of nonpregnant adults in the United States and Canada between 1992 and 2013 were multilocus sequence type (ST) 1. Elucidation of the complete genome of a 1992 ST-1 strain revealed that this strain had the highest homology with a GBS strain causing cow mastitis and that the 1992 ST-1 strain differed from serotype V strains isolated in the late 1970s by acquisition of cell surface proteins and antimicrobial resistance determinants. Whole-genome comparison of 202 invasive ST-1 strains detected significant recombination in only eight strains. The remaining 194 strains differed by an average of 97 SNPs. Phylogenetic analysis revealed a temporally dependent mode of genetic diversification consistent with the emergence in the 1990s of ST-1 GBS as major agents of human disease. Thirty-one loci were identified as being under positive selective pressure, and mutations at loci encoding polysaccharide capsule production proteins, regulators of pilus expression, and two-component gene regulatory systems were shown to affect the bacterial phenotype. These data reveal that phenotypic diversity among ST-1 GBS is mainly driven by small genetic changes rather than extensive recombination, thereby extending knowledge into how pathogens adapt to humans. PMID:25941374

A Virtual Week study of prospective memory function in autism spectrum disorders.

PubMed

Henry, Julie D; Terrett, Gill; Altgassen, Mareike; Raponi-Saunders, Sandra; Ballhausen, Nicola; Schnitzspahn, Katharina M; Rendell, Peter G

2014-11-01

Prospective memory (PM) refers to the implementation of delayed intentions, a cognitive ability that plays a critical role in daily life because of its involvement in goal-directed behavior and consequently the development and maintenance of independence. Emerging evidence indicates that PM may be disrupted in autism spectrum disorders (ASDs), potentially contributing to the functional difficulties that characterize this group. However, the degree, nature, and specificity of ASD-related impairment remains poorly understood. In the current study, children between 8 and 12 years of age who were diagnosed with ASDs (n=30) were compared with typically developing children (n=30) on a child-appropriate version of the Virtual Week board game. This measure provides an opportunity to investigate the different sorts of PM failures that occur. The ASD group showed significant PM impairment on measures of time-based (but not event-based) prospective remembering. However, only a subtle difference emerged between regular and irregular PM tasks, and group differences were consistent across these tasks. Because regular and irregular tasks differentially load retrospective memory, these data imply that the PM difficulties seen in ASDs may primarily reflect a monitoring deficit and not an encoding and memory storage deficit. PM performance was poorer under conditions of high ongoing task absorption, but the magnitude of this effect did not vary as a function of group. In both groups, time-based (but not event-based) PM difficulties were associated with functional outcomes in daily life, but only an inconsistent association with executive control emerged. Copyright © 2014 Elsevier Inc. All rights reserved.

Agricultural chemicals: life changer for mosquito vectors in agricultural landscapes?

PubMed

Kibuthu, Tabitha W; Njenga, Sammy M; Mbugua, Amos K; Muturi, Ephantus J

2016-09-13

Although many mosquito species develop within agricultural landscapes where they are potentially exposed to agricultural chemicals (fertilizers and pesticides), the effects of these chemicals on mosquito biology remain poorly understood. This study investigated the effects of sublethal concentrations of four agricultural chemicals on the life history traits of Anopheles arabiensis and Culex quinquefasciatus mosquitoes. Field and laboratory experiments were conducted to examine how sublethal concentrations of four agricultural chemicals: an insecticide (cypermethrin), a herbicide (glyphosate), and two nitrogenous fertilizers (ammonium sulfate and diammonium phosphate) alter oviposition site selection, emergence rates, development time, adult body size, and longevity of An. arabiensis and Cx. quinquefasciatus. Both mosquito species had preference to oviposit in fertilizer treatments relative to pesticide treatments. Emergence rates for An. arabiensis were significantly higher in the control and ammonium sulfate treatments compared to cypermethrin treatment, while emergence rates for Cx. quinquefasciatus were significantly higher in the diammonium phosphate treatment compared to glyphosate and cypermethrin treatments. For both mosquito species, individuals from the ammonium sulfate and diammonium phosphate treatments took significantly longer time to develop compared to those from cypermethrin and glyphosate treatments. Although not always significant, males and females of both mosquito species tended to be smaller in the ammonium sulfate and diammonium phosphate treatments compared to cypermethrin and glyphosate treatments. There was no significant effect of the agrochemical treatments on the longevity of either mosquito species. These results demonstrate that the widespread use of agricultural chemicals to enhance crop production can have unexpected effects on the spatial distribution and abundance of mosquito vectors of malaria and lymphatic filariasis.

Sequence type 1 group B Streptococcus, an emerging cause of invasive disease in adults, evolves by small genetic changes.

PubMed

Flores, Anthony R; Galloway-Peña, Jessica; Sahasrabhojane, Pranoti; Saldaña, Miguel; Yao, Hui; Su, Xiaoping; Ajami, Nadim J; Holder, Michael E; Petrosino, Joseph F; Thompson, Erika; Margarit Y Ros, Immaculada; Rosini, Roberto; Grandi, Guido; Horstmann, Nicola; Teatero, Sarah; McGeer, Allison; Fittipaldi, Nahuel; Rappuoli, Rino; Baker, Carol J; Shelburne, Samuel A

2015-05-19

The molecular mechanisms underlying pathogen emergence in humans is a critical but poorly understood area of microbiologic investigation. Serotype V group B Streptococcus (GBS) was first isolated from humans in 1975, and rates of invasive serotype V GBS disease significantly increased starting in the early 1990s. We found that 210 of 229 serotype V GBS strains (92%) isolated from the bloodstream of nonpregnant adults in the United States and Canada between 1992 and 2013 were multilocus sequence type (ST) 1. Elucidation of the complete genome of a 1992 ST-1 strain revealed that this strain had the highest homology with a GBS strain causing cow mastitis and that the 1992 ST-1 strain differed from serotype V strains isolated in the late 1970s by acquisition of cell surface proteins and antimicrobial resistance determinants. Whole-genome comparison of 202 invasive ST-1 strains detected significant recombination in only eight strains. The remaining 194 strains differed by an average of 97 SNPs. Phylogenetic analysis revealed a temporally dependent mode of genetic diversification consistent with the emergence in the 1990s of ST-1 GBS as major agents of human disease. Thirty-one loci were identified as being under positive selective pressure, and mutations at loci encoding polysaccharide capsule production proteins, regulators of pilus expression, and two-component gene regulatory systems were shown to affect the bacterial phenotype. These data reveal that phenotypic diversity among ST-1 GBS is mainly driven by small genetic changes rather than extensive recombination, thereby extending knowledge into how pathogens adapt to humans.

Nonreplicative RNA Recombination of an Animal Plus-Strand RNA Virus in the Absence of Efficient Translation of Viral Proteins

PubMed Central

Kleine Büning, Maximiliane; Meyer, Denise; Austermann-Busch, Sophia; Roman-Sosa, Gleyder; Rümenapf, Tillmann

2017-01-01

RNA recombination is a major driving force for the evolution of RNA viruses and is significantly implicated in the adaptation of viruses to new hosts, changes of virulence, as well as in the emergence of new viruses including drug-resistant and escape mutants. However, the molecular details of recombination in animal RNA viruses are only poorly understood. In order to determine whether viral RNA recombination depends on translation of viral proteins, a nonreplicative recombination system was established which is based on cotransfection of cells with synthetic bovine viral diarrhea virus (family Flaviviridae) RNA genome fragments either lacking the internal ribosome entry site required for cap-independent translation or lacking almost the complete polyprotein coding region. The emergence of a number of recombinant viruses demonstrated that IRES-mediated translation of viral proteins is dispensable for efficient recombination and suggests that RNA recombination can occur in the absence of viral proteins. Analyses of 58 independently emerged viruses led to the detection of recombinant genomes with duplications, deletions and insertions in the 5′ terminal region of the open reading frame, leading to enlarged core fusion proteins detectable by Western blot analysis. This demonstrates a remarkable flexibility of the pestivirus core protein. Further experiments with capped and uncapped genome fragments containing a luciferase gene for monitoring the level of protein translation revealed that even a ∼1,000-fold enhancement of translation of viral proteins did not increase the frequency of RNA recombination. Taken together, this study highlights that nonreplicative RNA recombination does not require translation of viral proteins. PMID:28338950

Airway mucus, inflammation and remodeling: emerging links in the pathogenesis of chronic lung diseases.

PubMed

Zhou-Suckow, Zhe; Duerr, Julia; Hagner, Matthias; Agrawal, Raman; Mall, Marcus A

2017-03-01

Airway mucus obstruction is a hallmark of many chronic lung diseases including rare genetic disorders such as cystic fibrosis (CF) and primary ciliary dyskinesia, as well as common lung diseases such as asthma and chronic obstructive pulmonary disease (COPD), which have emerged as a leading cause of morbidity and mortality worldwide. However, the role of excess airway mucus in the in vivo pathogenesis of these diseases remains poorly understood. The generation of mice with airway-specific overexpression of epithelial Na + channels (ENaC), exhibiting airway surface dehydration (mucus hyperconcentration), impaired mucociliary clearance (MCC) and mucus plugging, led to a model of muco-obstructive lung disease that shares key features of CF and COPD. In this review, we summarize recent progress in the understanding of causes of impaired MCC and in vivo consequences of airway mucus obstruction that can be inferred from studies in βENaC-overexpressing mice. These studies confirm that mucus hyperconcentration on airway surfaces plays a critical role in the pathophysiology of impaired MCC, mucus adhesion and airway plugging that cause airflow obstruction and provide a nidus for bacterial infection. In addition, these studies support the emerging concept that excess airway mucus per se, probably via several mechanisms including hypoxic epithelial necrosis, retention of inhaled irritants or allergens, and potential immunomodulatory effects, is a potent trigger of chronic airway inflammation and associated lung damage, even in the absence of bacterial infection. Finally, these studies suggest that improvement of mucus clearance may be a promising therapeutic strategy for a spectrum of muco-obstructive lung diseases.

[Rabies].

PubMed

Nishizono, Akira

2009-02-01

Rabies is a fetal viral encephalitis caused by the rabies virus, that is mainly transmitted through the saliva of infected domestic or wild animals. Rabies remains an important public health issue worldwide due to the prevalence of endemic dog rabies in developing countries. The epidemiological impact is particularly still high in Asian and African countries. In contrast, in the developed countries, including Japan, rabies is a re-emerging disease. The Lyssaviruses (types EBLV and ABL) and rabies virus infections via bats have recently emerged in Europe and the United States. Although the incubation period averages 1-3 months, there is no known treatment once the symptoms of rabies appear. On the basis of clinical manifestations, rabies can be classified into 2 types: furious and paralytic rabies. The former is characterized by the well-known symptoms of hydrophobia, aerophobia, and hypersalivation. However the latter type is likely to be misdiagnosed because of its similarity to Guillian-Barré syndrome and neuropsychiatric illnesses. Therefore, post-exposure treatment (PET) using a tissue-culture vaccine is the only way to prevent the disease. In the case of exposure to severe bites (WHO category III), rabies immunoglobulin (RIG) is essential for PET. Although the mechanism underlying the pathogenesis of rabies remains poorly understood, the recent technique of reverse genetics can be a useful tool for understanding rabies pathogenesis at a genetic level. Japan has been free of rabies for over 50 years because of the proper registration of domestic animals and control over their vaccinations. However, it is necessary to always remember that rabies is still a global burden as a representative of a re-emerging disease.

Factors Associated with Emergency Department Use among the Rural Elderly

ERIC Educational Resources Information Center

Fan, Lin; Shah, Manish N.; Veazie, Peter J.; Friedman, Bruce

2011-01-01

Context: Emergency Department (ED) use among the rural elderly may present a different pattern from the urban elderly, thus requiring different policy initiatives. However, ED use among the rural elderly has seldom been studied and is little understood. Purpose: To characterize factors associated with having any versus no ED use among the rural…

The Avian-Origin PB1 Gene Segment Facilitated Replication and Transmissibility of the H3N2/1968 Pandemic Influenza Virus

PubMed Central

Wendel, Isabel; Rubbenstroth, Dennis; Doedt, Jennifer; Kochs, Georg; Wilhelm, Jochen; Staeheli, Peter; Klenk, Hans-Dieter

2015-01-01

ABSTRACT The H2N2/1957 and H3N2/1968 pandemic influenza viruses emerged via the exchange of genomic RNA segments between human and avian viruses. The avian hemagglutinin (HA) allowed the hybrid viruses to escape preexisting immunity in the human population. Both pandemic viruses further received the PB1 gene segment from the avian parent (Y. Kawaoka, S. Krauss, and R. G. Webster, J Virol 63:4603–4608, 1989), but the biological significance of this observation was not understood. To assess whether the avian-origin PB1 segment provided pandemic viruses with some selective advantage, either on its own or via cooperation with the homologous HA segment, we modeled by reverse genetics the reassortment event that led to the emergence of the H3N2/1968 pandemic virus. Using seasonal H2N2 virus A/California/1/66 (Cal) as a surrogate precursor human virus and pandemic virus A/Hong Kong/1/68 (H3N2) (HK) as a source of avian-derived PB1 and HA gene segments, we generated four reassortant recombinant viruses and compared pairs of viruses which differed solely by the origin of PB1. Replacement of the PB1 segment of Cal by PB1 of HK facilitated viral polymerase activity, replication efficiency in human cells, and contact transmission in guinea pigs. A combination of PB1 and HA segments of HK did not enhance replicative fitness of the reassortant virus compared with the single-gene PB1 reassortant. Our data suggest that the avian PB1 segment of the 1968 pandemic virus served to enhance viral growth and transmissibility, likely by enhancing activity of the viral polymerase complex. IMPORTANCE Despite the high impact of influenza pandemics on human health, some mechanisms underlying the emergence of pandemic influenza viruses still are poorly understood. Thus, it was unclear why both H2N2/1957 and H3N2/1968 reassortant pandemic viruses contained, in addition to the avian HA, the PB1 gene segment of the avian parent. Here, we addressed this long-standing question by modeling the emergence of the H3N2/1968 virus from its putative human and avian precursors. We show that the avian PB1 segment increased activity of the viral polymerase and facilitated viral replication. Our results suggest that in addition to the acquisition of antigenically novel HA (i.e., antigenic shift), enhanced viral polymerase activity is required for the emergence of pandemic influenza viruses from their seasonal human precursors. PMID:25631088

The avian-origin PB1 gene segment facilitated replication and transmissibility of the H3N2/1968 pandemic influenza virus.

PubMed

Wendel, Isabel; Rubbenstroth, Dennis; Doedt, Jennifer; Kochs, Georg; Wilhelm, Jochen; Staeheli, Peter; Klenk, Hans-Dieter; Matrosovich, Mikhail

2015-04-01

The H2N2/1957 and H3N2/1968 pandemic influenza viruses emerged via the exchange of genomic RNA segments between human and avian viruses. The avian hemagglutinin (HA) allowed the hybrid viruses to escape preexisting immunity in the human population. Both pandemic viruses further received the PB1 gene segment from the avian parent (Y. Kawaoka, S. Krauss, and R. G. Webster, J Virol 63:4603-4608, 1989), but the biological significance of this observation was not understood. To assess whether the avian-origin PB1 segment provided pandemic viruses with some selective advantage, either on its own or via cooperation with the homologous HA segment, we modeled by reverse genetics the reassortment event that led to the emergence of the H3N2/1968 pandemic virus. Using seasonal H2N2 virus A/California/1/66 (Cal) as a surrogate precursor human virus and pandemic virus A/Hong Kong/1/68 (H3N2) (HK) as a source of avian-derived PB1 and HA gene segments, we generated four reassortant recombinant viruses and compared pairs of viruses which differed solely by the origin of PB1. Replacement of the PB1 segment of Cal by PB1 of HK facilitated viral polymerase activity, replication efficiency in human cells, and contact transmission in guinea pigs. A combination of PB1 and HA segments of HK did not enhance replicative fitness of the reassortant virus compared with the single-gene PB1 reassortant. Our data suggest that the avian PB1 segment of the 1968 pandemic virus served to enhance viral growth and transmissibility, likely by enhancing activity of the viral polymerase complex. Despite the high impact of influenza pandemics on human health, some mechanisms underlying the emergence of pandemic influenza viruses still are poorly understood. Thus, it was unclear why both H2N2/1957 and H3N2/1968 reassortant pandemic viruses contained, in addition to the avian HA, the PB1 gene segment of the avian parent. Here, we addressed this long-standing question by modeling the emergence of the H3N2/1968 virus from its putative human and avian precursors. We show that the avian PB1 segment increased activity of the viral polymerase and facilitated viral replication. Our results suggest that in addition to the acquisition of antigenically novel HA (i.e., antigenic shift), enhanced viral polymerase activity is required for the emergence of pandemic influenza viruses from their seasonal human precursors. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

PHYTOASSESSMENT OF ESTUARINE SEDIMENTS

EPA Science Inventory

Most sediment quality assessments and quality guidelines are based on the laboratory response of single animal species and benthic animal community composition. The role of plants in this hazard assessment process is poorly understood despite the fact that plant-dominated habitat...

FACTORS INFLUENCING LIGHT-INDUCED MORTALITY OF ENTEROCOCCI IN SEDIMENT SUSPENSIONS

EPA Science Inventory

Contamination of recreational waters by pathogenic microorganisms occurs through complex, poorly understood interactions involving variable microbial sources, hydrodynamic transport, arid microbial fate processes. Fecal indicator bacteria such as enterococci have been used to ass...

Plantation management intensity affects belowground carbon and nitrogen storage in northern California

Treesearch

K. J. McFarlane; S. H. Schoenholtz; R. F. Powers

2009-01-01

Belowground C and N storage is important in maintaining forestproductivity and to CO2 sequestration. How these pools respondto management is poorly understood. We investigated effectsof repeated applications of complete fertilizer and competing...

Predictive Models of Liver Cancer

EPA Science Inventory

Predictive models of chemical-induced liver cancer face the challenge of bridging causative molecular mechanisms to adverse clinical outcomes. The latent sequence of intervening events from chemical insult to toxicity are poorly understood because they span multiple levels of bio...

Moving toward New Horizons for Marketing Education: Designing a Marketing Training for the Poor in Developing and Emerging Markets

ERIC Educational Resources Information Center

Teklehaimanot, Mebrahtu L.; Ingenbleek, Paul T. M.; Tessema, Workneh K.; van Trijp, Hans C. M.

2017-01-01

In recent years, marketing education has broadened to poor people in developing and emerging countries. In this article, the authors use four empirical studies that apply well-established training design procedures to design a marketing training program for Ethiopian pastoralists. Because pastoralists operate in extremely remote, traditional, and…

What Can Plasticity Contribute to Insect Responses to Climate Change?

PubMed

Sgrò, Carla M; Terblanche, John S; Hoffmann, Ary A

2016-01-01

Plastic responses figure prominently in discussions on insect adaptation to climate change. Here we review the different types of plastic responses and whether they contribute much to adaptation. Under climate change, plastic responses involving diapause are often critical for population persistence, but key diapause responses under dry and hot conditions remain poorly understood. Climate variability can impose large fitness costs on insects showing diapause and other life cycle responses, threatening population persistence. In response to stressful climatic conditions, insects also undergo ontogenetic changes including hardening and acclimation. Environmental conditions experienced across developmental stages or by prior generations can influence hardening and acclimation, although evidence for the latter remains weak. Costs and constraints influence patterns of plasticity across insect clades, but they are poorly understood within field contexts. Plastic responses and their evolution should be considered when predicting vulnerability to climate change-but meaningful empirical data lag behind theory.

Activity-Induced Remodeling of Olfactory Bulb Microcircuits Revealed by Monosynaptic Tracing

PubMed Central

Arenkiel, Benjamin R.; Hasegawa, Hiroshi; Yi, Jason J.; Larsen, Rylan S.; Wallace, Michael L.; Philpot, Benjamin D.; Wang, Fan; Ehlers, Michael D.

2011-01-01

The continued addition of new neurons to mature olfactory circuits represents a remarkable mode of cellular and structural brain plasticity. However, the anatomical configuration of newly established circuits, the types and numbers of neurons that form new synaptic connections, and the effect of sensory experience on synaptic connectivity in the olfactory bulb remain poorly understood. Using in vivo electroporation and monosynaptic tracing, we show that postnatal-born granule cells form synaptic connections with centrifugal inputs and mitral/tufted cells in the mouse olfactory bulb. In addition, newly born granule cells receive extensive input from local inhibitory short axon cells, a poorly understood cell population. The connectivity of short axon cells shows clustered organization, and their synaptic input onto newborn granule cells dramatically and selectively expands with odor stimulation. Our findings suggest that sensory experience promotes the synaptic integration of new neurons into cell type-specific olfactory circuits. PMID:22216277

The Multifactorial Epidemiology of Blackwater Fever.

PubMed

Shanks, G Dennis

2017-12-01

Blackwater fever is a massive hemolytic event usually occurring in the context of repeated falciparum malaria infections and intermittent quinine use. Its etiology is poorly understood, and it is rarely seen today. Historical epidemiological observations from the 20th century demonstrated variable patterns in prisoners in Andaman Islands, refugees in Macedonia, canal workers in Panama, expatriates in Rhodesia, and Second World War soldiers. Rates of blackwater fever per 1,000 malaria cases varied over two orders of magnitude. Islands, such as the Andaman Islands and New Guinea, had lower blackwater fever rates than continental areas. During the Second World War, blackwater fever rates in British soldiers in West Africa and Australian soldiers in New Guinea differed by a factor of 40 despite similar treatment regimens and falciparum malaria transmission risks. Blackwater fever is a complex interaction between host erythrocyte, falciparum malaria, and antimalarial drugs which remains poorly understood.

Communicating in the "gray zone": perceptions about emergency physician hospitalist handoffs and patient safety.

PubMed

Apker, Julie; Mallak, Larry A; Gibson, Scott C

2007-10-01

To identify the perceptions of emergency physicians (EPs) and hospitalists regarding interservice handoff communication as patients are transferred from the emergency department to the inpatient setting. Investigators conducted individual interviews with 12 physicians (six EPs and six hospitalists). Data evaluation consisted of using the steps of constant comparative, thematic analysis. Physicians perceived handoff communication as a gray zone characterized by ambiguity about patients' conditions and treatment. Two major themes emerged regarding the handoff gray zone. The first theme, poor communication practices and conflicting communication expectations, presented barriers that exacerbated physicians' information ambiguity. Specifically, handoffs consisting of insufficient information, incomplete data, omissions, and faulty information flow exacerbated gray zone problems and may negatively affect patient outcomes. EPs and hospitalists had different expectations about handoffs, and those expectations influenced their interactions in ways that may result in communication breakdowns. The second theme illustrated how poor handoff communication contributes to boarding-related patient safety threats for boarders and emergency department patients alike. Those interviewed talked about the systemic failures that lead to patient boarding and how poor handoffs exacerbated system flaws. Handoffs between EPs and hospitalists both reflect and contribute to the ambiguity inherent in emergency medicine. Poor handoffs, consisting of faulty communication behaviors and conflicting expectations for information, contribute to patient boarding conditions that can pose safety threats. Pragmatic conclusions are drawn regarding physician-physician communication in patient transfers, and recommendations are offered for medical education.

Leaves of field-grown mastic trees suffer oxidative stress at the two extremes of their lifespan.

PubMed

Juvany, Marta; Müller, Maren; Munné-Bosch, Sergi

2012-08-01

Leaf senescence is a complex phenomenon occurring in all plant species, but it is still poorly understood in plants grown in Mediterranean field conditions and well-adapted to harsh climatic conditions. To better understand the physiological processes underlying leaf senescence in mastic trees (Pistacia lentiscus L.), we evaluated leaf growth, water and N content, photosystem II (PSII) photochemistry, lipid peroxidation and levels of photosynthetic pigments, antioxidants, abscisic acid, and salicylic acid and jasmonic acid during the complete leaf lifespan, from early expansion to late senescence in relation to natural climatic conditions in the field. While mature leaves suffered from water and N deficit during late spring and summer, both young (emerging) and old (senescing) leaves were most sensitive to photo-oxidative stress, as indicated by reductions in the F(v)/F(m) ratio and enhanced lipid peroxidation during late autumn and winter. Reductions in the F(v)/F(m) ratio were associated with low α-tocopherol (vitamin E) levels, while very old, senescing leaves additionally showed severe anthocyanin losses. We have concluded that both young (emerging) and old (senescing) leaves suffer oxidative stress in mastic trees, which may be linked in part to suboptimal temperatures during late autumn and winter as well as to low vitamin E levels. © 2012 Institute of Botany, Chinese Academy of Sciences.

The Roles of p53 in Mitochondrial Dynamics and Cancer Metabolism: The Pendulum between Survival and Death in Breast Cancer?

PubMed

Moulder, David E; Hatoum, Diana; Tay, Enoch; Lin, Yiguang; McGowan, Eileen M

2018-06-08

Cancer research has been heavily geared towards genomic events in the development and progression of cancer. In contrast, metabolic regulation, such as aberrant metabolism in cancer, is poorly understood. Alteration in cellular metabolism was once regarded simply as a consequence of cancer rather than as playing a primary role in cancer promotion and maintenance. Resurgence of cancer metabolism research has identified critical metabolic reprogramming events within biosynthetic and bioenergetic pathways needed to fulfill the requirements of cancer cell growth and maintenance. The tumor suppressor protein p53 is emerging as a key regulator of metabolic processes and metabolic reprogramming in cancer cells—balancing the pendulum between cell death and survival. This review provides an overview of the classical and emerging non-classical tumor suppressor roles of p53 in regulating mitochondrial dynamics: mitochondrial engagement in cell death processes in the prevention of cancer. On the other hand, we discuss p53 as a key metabolic switch in cellular function and survival. The focus is then on the conceivable roles of p53 in breast cancer metabolism. Understanding the metabolic functions of p53 within breast cancer metabolism will, in due course, reveal critical metabolic hotspots that cancers advantageously re-engineer for sustenance. Illustration of these events will pave the way for finding novel therapeutics that target cancer metabolism and serve to overcome the breast cancer burden.

Joint Attention and Brain Functional Connectivity in Infants and Toddlers.

PubMed

Eggebrecht, Adam T; Elison, Jed T; Feczko, Eric; Todorov, Alexandre; Wolff, Jason J; Kandala, Sridhar; Adams, Chloe M; Snyder, Abraham Z; Lewis, John D; Estes, Annette M; Zwaigenbaum, Lonnie; Botteron, Kelly N; McKinstry, Robert C; Constantino, John N; Evans, Alan; Hazlett, Heather C; Dager, Stephen; Paterson, Sarah J; Schultz, Robert T; Styner, Martin A; Gerig, Guido; Das, Samir; Kostopoulos, Penelope; Schlaggar, Bradley L; Petersen, Steven E; Piven, Joseph; Pruett, John R

2017-03-01

Initiating joint attention (IJA), the behavioral instigation of coordinated focus of 2 people on an object, emerges over the first 2 years of life and supports social-communicative functioning related to the healthy development of aspects of language, empathy, and theory of mind. Deficits in IJA provide strong early indicators for autism spectrum disorder, and therapies targeting joint attention have shown tremendous promise. However, the brain systems underlying IJA in early childhood are poorly understood, due in part to significant methodological challenges in imaging localized brain function that supports social behaviors during the first 2 years of life. Herein, we show that the functional organization of the brain is intimately related to the emergence of IJA using functional connectivity magnetic resonance imaging and dimensional behavioral assessments in a large semilongitudinal cohort of infants and toddlers. In particular, though functional connections spanning the brain are involved in IJA, the strongest brain-behavior associations cluster within connections between a small subset of functional brain networks; namely between the visual network and dorsal attention network and between the visual network and posterior cingulate aspects of the default mode network. These observations mark the earliest known description of how functional brain systems underlie a burgeoning fundamental social behavior, may help improve the design of targeted therapies for neurodevelopmental disorders, and, more generally, elucidate physiological mechanisms essential to healthy social behavior development. © The Author 2017. Published by Oxford University Press.

Host phylogeny determines viral persistence and replication in novel hosts.

PubMed

Longdon, Ben; Hadfield, Jarrod D; Webster, Claire L; Obbard, Darren J; Jiggins, Francis M

2011-09-01

Pathogens switching to new hosts can result in the emergence of new infectious diseases, and determining which species are likely to be sources of such host shifts is essential to understanding disease threats to both humans and wildlife. However, the factors that determine whether a pathogen can infect a novel host are poorly understood. We have examined the ability of three host-specific RNA-viruses (Drosophila sigma viruses from the family Rhabdoviridae) to persist and replicate in 51 different species of Drosophilidae. Using a novel analytical approach we found that the host phylogeny could explain most of the variation in viral replication and persistence between different host species. This effect is partly driven by viruses reaching a higher titre in those novel hosts most closely related to the original host. However, there is also a strong effect of host phylogeny that is independent of the distance from the original host, with viral titres being similar in groups of related hosts. Most of this effect could be explained by variation in general susceptibility to all three sigma viruses, as there is a strong phylogenetic correlation in the titres of the three viruses. These results suggest that the source of new emerging diseases may often be predictable from the host phylogeny, but that the effect may be more complex than simply causing most host shifts to occur between closely related hosts.

Direct Conjugation of Emerging Contaminants in Arabidopsis: Indication for an Overlooked Risk in Plants?

PubMed

Fu, Qiuguo; Zhang, Jianbo; Borchardt, Dan; Schlenk, Daniel; Gan, Jay

2017-06-06

Agricultural use of treated wastewater, biosolids, and animal wastes introduces a multitude of contaminants of emerging concerns (CECs) into the soil-plant system. The potential for food crops to accumulate CECs depends largely on their metabolism in plants, which at present is poorly understood. Here, we evaluated the metabolism of naproxen and ibuprofen, two of the most-used human drugs from the Profen family, in Arabidopsis thaliana cells and the Arabidopsis plant. The complementary use of high-resolution mass spectrometry and 14 C labeling allowed the characterization of both free and conjugated metabolites, as well as nonextractable residues. Naproxen and ibuprofen, in their parent form, were conjugated quickly and directly with glutamic acid and glutamine, and further with peptides, in A. thaliana cells. For example, after 120 h, the metabolites of naproxen accounted for >90% of the extractable chemical mass, while the intact parent itself was negligible. The structures of glutamate and glutamine conjugates were confirmed using synthesized standards and further verified in whole plants. Amino acid conjugates may easily deconjugate, releasing the parent molecule. This finding highlights the possibility that the bioactivity of such CECs may be effectively preserved through direct conjugation, a previously overlooked risk. Many other CECs are also carboxylic acids, such as the profens. Therefore, direct conjugation may be a common route for plant metabolism of these CECs, making it imperative to consider conjugates when assessing their risks.

Making sense of landscape change: Long-term perceptions among local residents following river restoration

NASA Astrophysics Data System (ADS)

Westling, Emma L.; Surridge, Ben W. J.; Sharp, Liz; Lerner, David N.

2014-11-01

Efforts to restore rivers are increasingly concerned with the social implications of landscape change. However, the fundamental issue of how people make sense of local riverine environments in the context of restoration remains poorly understood. Our research examined influences on perception among local residents 14 years after a restoration scheme on the River Dearne in the north of England. Human-landscape relationships emerging from semi-structured interviews with 16 local residents were analysed using an interpretive research framework. Nine recurring factors influenced perception among local residents: scenic beauty; the condition of riparian vegetation and of river channel morphology; opportunities to observe flora and fauna; cleanliness of the riverine environment; access available to the river; connections between the river and the surrounding landscape; disturbance and change in the familiarity of the landscape following restoration. These factors were not solely related to tangible outcomes of the restoration scheme, but were also influenced by history, memories, traditions and practices associated with the river. Critically, these factors also interacted rather than operating in isolation and two idealised perceptual frameworks were developed to map these interactions. Our research contributes to theoretical understanding of the relationships between humans and landscape change, whilst also considering how restoration practice may better reflect these relationships. The importance of a social dimension to the template of possibilities for restoring any given river emerges, underpinning place-based design and implementation of river restoration schemes.

Joint Attention and Brain Functional Connectivity in Infants and Toddlers

PubMed Central

Eggebrecht, Adam T.; Elison, Jed T.; Feczko, Eric; Todorov, Alexandre; Wolff, Jason J.; Kandala, Sridhar; Adams, Chloe M.; Snyder, Abraham Z.; Lewis, John D.; Estes, Annette M.; Zwaigenbaum, Lonnie; Botteron, Kelly N.; McKinstry, Robert C.; Constantino, John N.; Evans, Alan; Hazlett, Heather C.; Dager, Stephen; Paterson, Sarah J.; Schultz, Robert T.; Styner, Martin A.; Gerig, Guido; Das, Samir; Kostopoulos, Penelope; Schlaggar, Bradley L.; Petersen, Steven E.; Piven, Joseph; Pruett, John R.

2017-01-01

Abstract Initiating joint attention (IJA), the behavioral instigation of coordinated focus of 2 people on an object, emerges over the first 2 years of life and supports social-communicative functioning related to the healthy development of aspects of language, empathy, and theory of mind. Deficits in IJA provide strong early indicators for autism spectrum disorder, and therapies targeting joint attention have shown tremendous promise. However, the brain systems underlying IJA in early childhood are poorly understood, due in part to significant methodological challenges in imaging localized brain function that supports social behaviors during the first 2 years of life. Herein, we show that the functional organization of the brain is intimately related to the emergence of IJA using functional connectivity magnetic resonance imaging and dimensional behavioral assessments in a large semilongitudinal cohort of infants and toddlers. In particular, though functional connections spanning the brain are involved in IJA, the strongest brain-behavior associations cluster within connections between a small subset of functional brain networks; namely between the visual network and dorsal attention network and between the visual network and posterior cingulate aspects of the default mode network. These observations mark the earliest known description of how functional brain systems underlie a burgeoning fundamental social behavior, may help improve the design of targeted therapies for neurodevelopmental disorders, and, more generally, elucidate physiological mechanisms essential to healthy social behavior development. PMID:28062515

Evaluating health policy capacity: Learning from international and Australian experience

PubMed Central

Gleeson, Deborah H; Legge, David G; O'Neill, Deirdre

2009-01-01

Background The health sector in Australia faces major challenges that include an ageing population, spiralling health care costs, continuing poor Aboriginal health, and emerging threats to public health. At the same time, the environment for policy-making is becoming increasingly complex. In this context, strong policy capacity – broadly understood as the capacity of government to make "intelligent choices" between policy options – is essential if governments and societies are to address the continuing and emerging problems effectively. Results This paper explores the question: "What are the factors that contribute to policy capacity in the health sector?" In the absence of health sector-specific research on this topic, a review of Australian and international public sector policy capacity research was undertaken. Studies from the United Kingdom, Canada, New Zealand and Australia were analysed to identify common themes in the research findings. This paper discusses these policy capacity studies in relation to context, models and methods for policy capacity research, elements of policy capacity and recommendations for building capacity. Conclusion Based on this analysis, the paper discusses the organisational and individual factors that are likely to contribute to health policy capacity, highlights the need for further research in the health sector and points to some of the conceptual and methodological issues that need to be taken into consideration in such research. PMID:19245704

GABA and Gap Junctions in the Development of Synchronized Activity in Human Pluripotent Stem Cell-Derived Neural Networks

PubMed Central

Mäkinen, Meeri Eeva-Liisa; Ylä-Outinen, Laura; Narkilahti, Susanna

2018-01-01

The electrical activity of the brain arises from single neurons communicating with each other. However, how single neurons interact during early development to give rise to neural network activity remains poorly understood. We studied the emergence of synchronous neural activity in human pluripotent stem cell (hPSC)-derived neural networks simultaneously on a single-neuron level and network level. The contribution of gamma-aminobutyric acid (GABA) and gap junctions to the development of synchronous activity in hPSC-derived neural networks was studied with GABA agonist and antagonist and by blocking gap junctional communication, respectively. We characterized the dynamics of the network-wide synchrony in hPSC-derived neural networks with high spatial resolution (calcium imaging) and temporal resolution microelectrode array (MEA). We found that the emergence of synchrony correlates with a decrease in very strong GABA excitation. However, the synchronous network was found to consist of a heterogeneous mixture of synchronously active cells with variable responses to GABA, GABA agonists and gap junction blockers. Furthermore, we show how single-cell distributions give rise to the network effect of GABA, GABA agonists and gap junction blockers. Finally, based on our observations, we suggest that the earliest form of synchronous neuronal activity depends on gap junctions and a decrease in GABA induced depolarization but not on GABAA mediated signaling. PMID:29559893

The influence of underwater turbulence on optical phase measurements

NASA Astrophysics Data System (ADS)

Redding, Brandon; Davis, Allen; Kirkendall, Clay; Dandridge, Anthony

2016-05-01

Emerging underwater optical imaging and sensing applications rely on phase-sensitive detection to provide added functionality and improved sensitivity. However, underwater turbulence introduces spatio-temporal variations in the refractive index of water which can degrade the performance of these systems. Although the influence of turbulence on traditional, non-interferometric imaging has been investigated, its influence on the optical phase remains poorly understood. Nonetheless, a thorough understanding of the spatio-temporal dynamics of the optical phase of light passing through underwater turbulence are crucial to the design of phase-sensitive imaging and sensing systems. To address this concern, we combined underwater imaging with high speed holography to provide a calibrated characterization of the effects of turbulence on the optical phase. By measuring the modulation transfer function of an underwater imaging system, we were able to calibrate varying levels of optical turbulence intensity using the Simple Underwater Imaging Model (SUIM). We then used high speed holography to measure the temporal dynamics of the optical phase of light passing through varying levels of turbulence. Using this method, we measured the variance in the amplitude and phase of the beam, the temporal correlation of the optical phase, and recorded the turbulence induced phase noise as a function of frequency. By bench marking the effects of varying levels of turbulence on the optical phase, this work provides a basis to evaluate the real-world potential of emerging underwater interferometric sensing modalities.

Hormone Distribution and Transcriptome Profiles in Bamboo Shoots Provide Insights on Bamboo Stem Emergence and Growth.

PubMed

Gamuyao, Rico; Nagai, Keisuke; Ayano, Madoka; Mori, Yoshinao; Minami, Anzu; Kojima, Mikiko; Suzuki, Takamasa; Sakakibara, Hitoshi; Higashiyama, Tetsuya; Ashikari, Motoyuki; Reuscher, Stefan

2017-04-01

Growth and development are tightly co-ordinated events in the lifetime of living organisms. In temperate bamboo plants, spring is the season when environmental conditions are suitable for the emergence of new shoots. Previous studies demonstrated that bamboo plants undergo an energy-consuming 'fast stem growth' phase. However, the events during the initiation of stem elongation in bamboo are poorly understood. To understand the onset of bamboo stem growth, we performed hormone and transcriptome profiling of tissue regions in newly elongating shoots of the Moso bamboo Phyllostachys edulis. The growth hormones auxins, cytokinins and gibberellins accumulated in the shoot apex, while the stress hormones ABA, salicylic acid (SA) and jasmonic acid (JA) are predominantly found in the lower part of the stem. The mature basal part of the stem showed enrichment of transcripts associated with cell wall metabolism and biosynthesis of phenylpropanoid metabolites, such as lignin. In the young upper stem region, expression of cell formation- and DNA synthesis-related genes was enriched. Moreover, the apical region showed enhanced expression of genes involved in meristem maintenance, leaf differentiation and development, abaxial/adaxial polarity and flowering. Our findings integrate the spatial regulation of hormones and transcriptome programs during the initiation of bamboo stem growth. © The Author 2017. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Pediatric pulmonary arterial hypertension and hyperthyroidism: a potentially fatal combination.

PubMed

Trapp, Christine M; Elder, Robert W; Gerken, Adrienne T; Sopher, Aviva B; Lerner, Shulamit; Aranoff, Gaya S; Rosenzweig, Erika B

2012-07-01

Patients with pulmonary arterial hypertension (PAH) who develop hyperthyroidism are at risk for acute cardiopulmonary decompensation and death. We present a series of eight idiopathic PAH/heritable PAH pediatric patients who developed hyperthyroidism between 1999 and 2011. Institutional Review Board approval was obtained; informed consent was waived due to the retrospective nature of the series. All eight patients were receiving iv epoprostenol; five of the eight patients presented with acute cardiopulmonary decompensation in the setting of hyperthyroidism. In the remaining three patients, hyperthyroidism was detected during routine screening of thyroid function tests. The one patient who underwent emergency thyroidectomy was the only survivor of those who presented in cardiopulmonary decline. Aggressive treatment of the hyperthyroid state, including emergency total thyroidectomy and escalation of targeted PAH therapy and β-blockade when warranted, may prove lifesaving in these patients. Prompt thyroidectomy or radioactive iodine ablation should be considered for clinically stable PAH patients with early and/or mild hyperthyroidism to avoid potentially life-threatening cardiopulmonary decompensation. Although the association between hyperthyroidism and PAH remains poorly understood, the potential impact of hyperthyroidism on the cardiopulmonary status of PAH patients must not be ignored. Hyperthyroidism must be identified early in this patient population to optimize intervention before acute decompensation. Thyroid function tests should be checked routinely in patients with PAH, particularly those on iv epoprostenol, and urgently in patients with acute decompensation or symptoms of hyperthyroidism.

Host Phylogeny Determines Viral Persistence and Replication in Novel Hosts

PubMed Central

Longdon, Ben; Hadfield, Jarrod D.; Webster, Claire L.

2011-01-01

Pathogens switching to new hosts can result in the emergence of new infectious diseases, and determining which species are likely to be sources of such host shifts is essential to understanding disease threats to both humans and wildlife. However, the factors that determine whether a pathogen can infect a novel host are poorly understood. We have examined the ability of three host-specific RNA-viruses (Drosophila sigma viruses from the family Rhabdoviridae) to persist and replicate in 51 different species of Drosophilidae. Using a novel analytical approach we found that the host phylogeny could explain most of the variation in viral replication and persistence between different host species. This effect is partly driven by viruses reaching a higher titre in those novel hosts most closely related to the original host. However, there is also a strong effect of host phylogeny that is independent of the distance from the original host, with viral titres being similar in groups of related hosts. Most of this effect could be explained by variation in general susceptibility to all three sigma viruses, as there is a strong phylogenetic correlation in the titres of the three viruses. These results suggest that the source of new emerging diseases may often be predictable from the host phylogeny, but that the effect may be more complex than simply causing most host shifts to occur between closely related hosts. PMID:21966271

Tracking contaminant flux from aquatic to terrestrial food webs

EPA Science Inventory

Aquatic insects provide a critical energy subsidy to riparian food webs, yet their role as vectors of contaminants to terrestrial ecosystems is poorly understood. We investigated aquatic resource utilization and contaminant exposure among riparian invertivores (spiders and herpt...

Asthma and Respiratory Allergic Disease

EPA Science Inventory

The pathogenesis of non-communicable diseases such as allergy is complex and poorly understood. The causes of chronic allergic diseases including asthma involve to a large extent, immunomodulation of the adaptive and particularly the innate immune systems and are markedly influen...

A Production Function Approach to Regional Environmental Economic Assessments

EPA Science Inventory

Regional-scale environmental assessments require integrating many available types of data having inconsistent spatial or temporal scales. Moreover, the relationships among the environmental variables in the assessment tend to be poorly understood, a situation made even more compl...

AtCHX13 is a plasma membrane K(+) transporter

USDA-ARS?s Scientific Manuscript database

Potassium (K+) homeostasis is essential for diverse cellular processes, although how various cation transporters collaborate to maintain a suitable K(+) required for growth and development is poorly understood. The Arabidopsis ("Arabidopsis thaliana") genome contains numerous cation:proton antiporte...

AtCHX13 is a plasma membrane K+ transporter

USDA-ARS?s Scientific Manuscript database

Potassium (K+) homeostasis is essential for diverse cellular processes, although how various cation transporters collaborate to maintain a suitable K+ required for growth and development is poorly understood. The Arabidopsis (Arabidopsis thaliana) genome contains numerous cation:proton antiporters (...

The 2011 National Wetland Condition Assessment

EPA Science Inventory

The ecological condition of wetland resources across the conterminous United States is poorly understood. To address this issue, the U.S. Environmental Protection Agency (USEPA), in collaboration with states, tribes, and other federal partners, is conducting the first-ever Natio...

Impacts of Human Activity on the Microbial Communities of Devon Island, Canadian High Arctic

NASA Astrophysics Data System (ADS)

Bywaters, K. B.; Burton, A. S.; Wallace, S. L.; Glass, B. J.

2016-09-01

The impacts of human activities on microbial communities in arctic environments are poorly understood. This project compares the distribution of microbes at the HMP Mars analog site prior to and after human settlement.

AN IMPROVED METHOD FOR DETECTING VIRUSES IN WATER

EPA Science Inventory

Enteroviruses are important etiological agents of waterborne disease and are responsible for outbreaks of gastroenteritis. However, the prevalence and occurrence of these pathogens in raw drinking water sources is poorly understood. This is primarily due to the limited methods ...

The mechanisms of intrarenal hemodynamic changes following acute arterial occlusion.

DOT National Transportation Integrated Search

1963-10-01

The hemodynamic response of the kidney to acute arterial occlusion is poorly understood. The purpose of the present study was to determine intrarenal hemodynamic changes in intact and isolated kidneys following arterial occlusion. : The relative role...

Prediction of Membership in Rehabilitation Counseling Professional Associations

ERIC Educational Resources Information Center

Phillips, Brian N.; Leahy, Michael J.

2012-01-01

Declining membership is a concerning yet poorly understood issue affecting professional associations across disciplines (Bauman, 2008). Rehabilitation counseling association membership is in decline even while number of certified rehabilitation counselors continues to increase (Leahy, 2009). Factors influencing rehabilitation counseling…

The prevalence and causes of autistic spectrum disorders.

PubMed

Hainsworth, Terry

Autism and autistic spectrum disorders are still relatively poorly understood. This article outlines the results of new research into the prevalence of autism and into the causes of the condition and highlights implications for nurses from the findings.

Familiarity and Aptness in Metaphor Comprehension.

PubMed

Damerall, Alison Whiteford; Kellogg, Ronald T

2016-01-01

The career of metaphor hypothesis suggests that novel metaphors are understood through a search for shared features between the topic and vehicle, but with repeated exposure, the figurative meaning is understood directly as a new category is established. The categorization hypothesis argues that instead good or apt metaphors are understood through a categorization process, whether or not they are familiar. Only poor metaphors ever invoke a literal comparison. In Experiment 1, with aptness equated, we found that high familiarity speeded comprehension time over low-familiarity metaphors. In Experiment 2a, providing a literal prime failed to facilitate interpretation of low-familiarity metaphors, contrary to the career of metaphor hypothesis. In Experiment 2b, with familiarity equated, high- and low-aptness metaphors did not differ, contrary to the categorization hypothesis.

Loneliness in psychosis: a systematic review.

PubMed

Lim, Michelle H; Gleeson, John F M; Alvarez-Jimenez, Mario; Penn, David L

2018-03-01

The aim of the review is to understand the relationships between loneliness and related psychological and social factors in individuals with psychosis. Loneliness is poorly understood in people with psychosis. Given the myriad of social challenges facing individuals with psychosis, these findings can inform psychosocial interventions that specifically target loneliness in this vulnerable group. We adhered to the PRISMA guidelines and systematically reviewed empirical studies that measured loneliness either as a main outcome or as an associated variable in individuals with psychosis. A total of ten studies examining loneliness in people diagnosed with a psychotic disorder were examined. Heterogeneity in the assessment of loneliness was found, and there were contradictory findings on the relationship between loneliness and psychotic symptomatology. In individuals with psychosis, loneliness may be influenced by psychological and social factors such as increased depression, psychosis, and anxiety, poor social support, poor quality of life, more severe internalised stigma and perceived discrimination, and low self-esteem. The relationship between loneliness and psychosis remains poorly understood due to a lack of rigorous studies. Although having strong social relationships is crucial to facilitate recovery from serious mental illness, psychosocial interventions that specifically target loneliness in individuals with psychosis are lacking and sorely needed. Interventions targeting loneliness in those with psychosis will also need to account for additional barriers associated with psychosis (e.g., social skill deficits, impoverished social networks, and negative symptoms).

Providing skilled birth attendants and emergency obstetric care to the poor through partnership with private sector obstetricians in Gujarat, India.

PubMed

Singh, Amarjit; Mavalankar, Dileep V; Bhat, Ramesh; Desai, Ajesh; Patel, S R; Singh, Prabal V; Singh, Neelu

2009-12-01

India has the world's largest number of maternal deaths estimated at 117,000 per year. Past efforts to provide skilled birth attendants and emergency obstetric care in rural areas have not succeeded because obstetricians are not willing to be posted in government hospitals at subdistrict level. We have documented an innovative public-private partnership scheme between the Government of Gujarat, in India, and private obstetricians practising in rural areas to provide delivery care to poor women. In April 2007, the majority of poor women delivered their babies at home without skilled care. More than 800 obstetricians joined the scheme and more than 176,000 poor women delivered in private facilities. We estimate that the coverage of deliveries among poor women under the scheme increased from 27% to 53% between April and October 2007. The programme is considered very successful and shows that these types of social health insurance programmes can be managed by the state health department without help from any insurance company or international donor. At least in some areas of India, it is possible to develop large-scale partnerships with the private sector to provide skilled birth attendants and emergency obstetric care to poor women at a relatively small cost. Poor women will take up the benefit of skilled delivery care rapidly, if they do not have to pay for it.

Literature Discussions as Mangles of Practice: Sociological Theories of Emergence and/in Dialogic Learning Events

ERIC Educational Resources Information Center

Kamberelis, George; McGinley, William; Welker, Alyson

2015-01-01

In this report, we argue that some of the most productive and edifying kinds of literature discussions among certain ages/grade levels may be best understood as "mangles of practice" (Pickering, 1995). Mangles of practice involve the coalescence of planned and contingent forces, and they produce emergent or self-organizing…

Continuous-variable quantum key distribution protocols over noisy channels.

PubMed

García-Patrón, Raúl; Cerf, Nicolas J

2009-04-03

A continuous-variable quantum key distribution protocol based on squeezed states and heterodyne detection is introduced and shown to attain higher secret key rates over a noisy line than any other one-way Gaussian protocol. This increased resistance to channel noise can be understood as resulting from purposely adding noise to the signal that is converted into the secret key. This notion of noise-enhanced tolerance to noise also provides a better physical insight into the poorly understood discrepancies between the previously defined families of Gaussian protocols.

Geochemical Legacies and the Future Health of Cities: An Analysis of two Neurotoxins in Urban Soils

NASA Astrophysics Data System (ADS)

Filippelli, G. M.; Risch, M.

2015-12-01

The past and future of cities are inextricably linked, a linkage that can be seen clearly in the long-term impacts of urban geochemical legacies. As loci of population as well as the means of employment and industry to support these populations, cities have a long history of co-locating contaminating practices and people, sometimes with negative implications for human health. Working at the intersection between geochemical processes, communities, and human health is critical to grapple with environmental legacies and to support healthy, sustainable, and growing urban populations. An emerging area of environmental health research is to understand the impacts of chronic exposures and exposure mixtures—these impacts are very poorly studied, yet have materialized as perhaps the greatest threat to large-scale population health. Acute exposure to lead (Pb), a powerful neurotoxin to which children are particularly susceptible, has largely been eliminated in the U.S. and other countries through policy-based restrictions on leaded gasoline and lead-based paints. But these legacy Pb sources are still around in the form of surface soil Pb contamination, a common problem in cities and one that has only recently emerged as a pernicious and widespread chronic exposure mechanism in cities. Some urban soils are also contaminated with another neurotoxin, mercury (Hg), although very little work has been done to understand human exposures to low levels of this element in soils. The most documented human exposure to Hg is through fish consumption, so eating fish caught in urban areas presents risks for above average dietary Hg exposure. The potential double impact of chronic exposure to these two neurotoxins is pronounced in cities. Many aspects of the dose-response curves for individual elements and mixtures are poorly understood, especially at lower levels, leaving unanswered several interesting and provocative questions about environmental impacts on neurological and developmental disorders.

Predictive Models of Nanotoxicity: Relationship of Physicochemical Properties to Particle Movement Through Biological Barriers

EPA Science Inventory

Understanding the linkage between the physicochemical (PC) properties of nanoparticles (NP) and their activation of biological systems is poorly understood, yet fundamental to predicting nanotoxicity, idenitifying mode of actions and developing appropriate and effective regul...

Physiological benefits of nectar-feeding by a predatory beetle

USDA-ARS?s Scientific Manuscript database

Extrafloral nectar is an important food source for many animals, including predatory lady beetles (Coleoptera: Coccinellidae), although the physiological benefits of nectar consumption are poorly understood for most consumers. Under laboratory conditions, we confined new females of Coleomegilla macu...

Fructose, high fructose corn syrup, sucrose, and non-alcoholic liver disease

USDA-ARS?s Scientific Manuscript database

Nonalcoholic fatty liver disease (NAFLD), formerly called nonalcoholic steatohepatitis, is characterized by hepatic steatosis and abnormal triglyceride accumulation in liver cells. Its etiology, pathophysiology, and pathogenesis are still poorly understood. Some have suggested that the increased in...

Salary, Performance, and Superintendent Turnover

ERIC Educational Resources Information Center

Grissom, Jason A.; Mitani, Hajime

2016-01-01

Purpose: Superintendent retention is an important goal for many school districts, yet the factors contributing to superintendent turnover are poorly understood. Most prior quantitative studies of superintendent turnover have relied on small, cross-sectional samples, limiting the evidence base. Utilizing longitudinal administrative records from…

New perspectives on microbial community distortion after whole-genome amplification

EPA Science Inventory

Whole-genome amplification (WGA) has become an important tool to explore the genomic information of microorganisms in an environmental sample with limited biomass, however potential selective biases during the amplification processes are poorly understood. Here, we describe the e...

Ankle ligament injuries.

PubMed

Abbassian, Ali; Thomas, Rhidian

2008-06-01

Ankle ligament injuries in the presence or in the absence of fractures are common. They often present a diagnostic challenge, and their management is poorly understood and subject to debate. This article reviews and discusses the current literature on the management and diagnosis of these injuries.

Accurately Characterizing the Importance of Wave-Particle Interactions in Radiation Belt Dynamics: The Pitfalls of Statistical Wave Representations

NASA Technical Reports Server (NTRS)

Murphy, Kyle R.; Mann, Ian R.; Rae, I. Jonathan; Sibeck, David G.; Watt, Clare E. J.

2016-01-01

Wave-particle interactions play a crucial role in energetic particle dynamics in the Earths radiation belts. However, the relative importance of different wave modes in these dynamics is poorly understood. Typically, this is assessed during geomagnetic storms using statistically averaged empirical wave models as a function of geomagnetic activity in advanced radiation belt simulations. However, statistical averages poorly characterize extreme events such as geomagnetic storms in that storm-time ultralow frequency wave power is typically larger than that derived over a solar cycle and Kp is a poor proxy for storm-time wave power.

An integrative model of the impairments in insight in schizophrenia: emerging research on causal factors and treatments.

PubMed

Vohs, Jenifer L; George, Sunita; Leonhardt, Bethany L; Lysaker, Paul H

2016-10-01

Poor insight, or unawareness of some major aspect of mental illness, is a major barrier to wellness when it interferes with persons seeking out treatment or forming their own understanding of the challenges they face. One barrier to addressing impaired insight is the absence of a comprehensive model of how poor insight develops. To explore this issue we review how poor insight is the result of multiple phenomena which interfere with the construction of narrative accounts of psychiatric challenges, rather than a single social or biological cause. Expert commentary: We propose an integrative model of poor insight in schizophrenia which involves the interaction of symptoms, deficits in neurocognition, social cognition, metacognition, and stigma. Emerging treatments for poor insight including therapies which focus on the development of metacognition are discussed.

Perfectionism related to self-reported insomnia severity, but not when controlled for stress and emotion regulation.

PubMed

Brand, Serge; Kirov, Roumen; Kalak, Nadeem; Gerber, Markus; Pühse, Uwe; Lemola, Sakari; Correll, Christoph U; Cortese, Samuele; Meyer, Till; Holsboer-Trachsler, Edith

2015-01-01

Perfectionism is understood as a set of personality traits such as unrealistically high and rigid standards for performance, fear of failure, and excessive self-criticism. Previous studies showed a direct association between increased perfectionism and poor sleep, though without taking into account possible mediating factors. Here, we tested the hypothesis that perfectionism was directly associated with poor sleep, and that this association collapsed, if mediating factors such as stress and poor emotion regulation were taken into account. Three hundred and forty six young adult students (M=23.87 years) completed questionnaires relating to perfectionism traits, sleep, and psychological functioning such as stress perception, coping with stress, emotion regulation, and mental toughness. Perfectionism was directly associated with poor sleep and poor psychological functioning. When stress, poor coping, and poor emotion regulation were entered in the equation, perfectionism traits no longer contributed substantively to the explanation of poor sleep. Though perfectionism traits seem associated with poor sleep, the direct role of such traits seemed small, when mediating factors such as stress perception and emotion regulation were taken into account.

Perfectionism related to self-reported insomnia severity, but not when controlled for stress and emotion regulation

PubMed Central

Brand, Serge; Kirov, Roumen; Kalak, Nadeem; Gerber, Markus; Pühse, Uwe; Lemola, Sakari; Correll, Christoph U; Cortese, Samuele; Meyer, Till; Holsboer-Trachsler, Edith

2015-01-01

Background Perfectionism is understood as a set of personality traits such as unrealistically high and rigid standards for performance, fear of failure, and excessive self-criticism. Previous studies showed a direct association between increased perfectionism and poor sleep, though without taking into account possible mediating factors. Here, we tested the hypothesis that perfectionism was directly associated with poor sleep, and that this association collapsed, if mediating factors such as stress and poor emotion regulation were taken into account. Methods Three hundred and forty six young adult students (M=23.87 years) completed questionnaires relating to perfectionism traits, sleep, and psychological functioning such as stress perception, coping with stress, emotion regulation, and mental toughness. Results Perfectionism was directly associated with poor sleep and poor psychological functioning. When stress, poor coping, and poor emotion regulation were entered in the equation, perfectionism traits no longer contributed substantively to the explanation of poor sleep. Conclusion Though perfectionism traits seem associated with poor sleep, the direct role of such traits seemed small, when mediating factors such as stress perception and emotion regulation were taken into account. PMID:25678791

Mineral potential for incompatible element deposits hosted in pegmatites, alkaline rocks, and carbonatites in the Islamic Republic of Mauritania (phase V, deliverable 87): Chapter Q in Second projet de renforcement institutionnel du secteur minier de la République Islamique de Mauritanie (PRISM-II)

USGS Publications Warehouse

Taylor, Cliff D.; Giles, Stuart A.

2015-01-01

USGS review of PRISM-I data suggests that there is abundant documentation of the Bou Naga alkaline complex and to a lesser degree, the Guelb er Richat carbonatite complex, but that all other occurrences of U, Th, REE, and associated elements are poorly described, and poorly understood (Taylor, 2007)

Atherosclerosis associated with pericardial effusion in a central bearded dragon (Pogona vitticeps).

PubMed

Schilliger, Lionel; Lemberger, Karin; Chai, Norin; Bourgeois, Aude; Charpentier, Maud

2010-09-01

Atherosclerosis is a common disease in pet birds, particularly in psittacines, and is frequently found when performing postmortem examinations on adult and old dogs, in which it is mainly associated with endocrine diseases, such as hypothyroidism and diabetes mellitus. However, atherosclerosis is poorly documented in reptiles and consequently poorly understood. In the current case report, atherosclerosis and pericardial effusion were diagnosed in a 2-year-old male central bearded dragon (Pogona vitticeps) based on ultrasound visualization, necropsy, and histologic examination.

Disease emergence and resurgence—the wildlife-human connection

USGS Publications Warehouse

Friend, Milton; Hurley, James W.; Nol, Pauline; Wesenberg, Katherine

2006-01-01

In 2000, the Global Outbreak Alert and Response Network (GOARN) was organized as a global disease watchdog group to coordinate disease outbreak information and health crisis response. The World Health Organization (WHO) is the headquarters for this network. Understandably, the primary focus for WHO is human health. However, diseases such as the H5N1 avian influenza epizootic in Asian bird populations demonstrate the need for integrating knowledge about disease emergence in animals and in humans.Aside from human disease concerns, H5N1 avian influenza has major economic consequences for the poultry industry worldwide. Many other emerging diseases, such as severe acute respiratory syndrome (SARS), monkeypox, Ebola fever, and West Nile fever, also have an important wildlife component. Despite these wildlife associations, the true integration of the wildlife component in approaches towards disease emergence remains elusive. This separation between wildlife and other species’ interests is counterproductive because the emergence of zoonotic viruses and other pathogens maintained by wildlife reservoir hosts is poorly understood.This book is about the wildlife component of emerging diseases. It is intended to enhance the reader’s awareness of the role of wildlife in disease emergence. By doing so, perhaps a more holistic approach to disease prevention and control will emerge for the benefit of human, domestic animal, and free-ranging wildlife populations alike. The perspectives offered are influenced by more than four decades of my experiences as a wildlife disease practitioner. Although wildlife are victims to many of the same disease agents affecting humans and domestic animals, many aspects of disease in free-ranging wildlife require different approaches than those commonly applied to address disease in humans or domestic animals. Nevertheless, the broader community of disease investigators and health care professionals has largely pursued a separatist approach for human, domestic animal, and wildlife rather than embracing the periodically proposed concept of “one medicine.” We especially need to embrace this concept as the human population increases because there will be more contact, direct and indirect, among humans, domestic animals, and wildlife. An “Ecology for a Crowded Planet” will be an even more pressing concern, and that includes increasing our understanding of disease ecology, especially that of the zoonoses.

Mechanistic insights into the role of mTOR signaling in neuronal differentiation.

PubMed

Bateman, Joseph M

2015-01-01

Temporal control of neuronal differentiation is critical to produce a complete and fully functional nervous system. Loss of the precise temporal control of neuronal cell fate can lead to defects in cognitive development and to disorders such as epilepsy and autism. Mechanistic target of rapamycin (mTOR) is a large serine/threonine kinase that acts as a crucial sensor of cellular homeostasis. mTOR signaling has recently emerged as a key regulator of neurogenesis. However, the mechanism by which mTOR regulates neurogenesis is poorly understood. In constrast to other functions of the pathway, 'neurogenic mTOR pathway factors' have not previously been identified. We have very recently used Drosophila as a model system to identify the gene unkempt as the first component of the mTOR pathway regulating neuronal differentiation. Our study demonstrates that specific adaptor proteins exist that channel mTOR signaling toward the regulation of neuronal cell fate. In this Commentary we discuss the role of mTOR signaling in neurogenesis and the significance of these findings in advancing our understanding of the mechanism by which mTOR signaling controls neuronal differentiation.

Child Dopamine Transporter Genotype and Parenting: Evidence for Evocative Gene-Environment Correlations

PubMed Central

Hayden, Elizabeth P.; Hanna, Brigitte; Sheikh, Haroon I.; Laptook, Rebecca S.; Kim, Jiyon; Singh, Shiva M.; Klein, Daniel N.

2017-01-01

The dopamine transporter (DAT1) gene is implicated in psychopathology risk. While the processes by which this gene exerts its effects on risk are poorly understood, a small body of research suggests that DAT1 influences early emerging negative emotionality (NE), a marker of children’s psychopathology risk. As child NE evokes negative parenting practices, the DAT1 may also play a role in gene-environment correlations. To test this model, children (N = 365) were genotyped for DAT1 and participated in standardized parent-child interaction tasks with their primary caregiver. The DAT1 9-repeat variant was associated with child negative affect expressed toward the parent during parent-child interactions, and parents of children with a 9-repeat allele exhibited more hostility and lower guidance/engagement than parents of children without a 9-repeat allele. These gene-environment associations were partially mediated by child negative affect toward the parent. Findings implicate a specific polymorphism in eliciting negative parenting, suggesting that evocative associations play a role in elevating children’s risk for emotional trajectories toward psychopathology risk. PMID:23398760

Metabolic Reprogramming and Oncogenesis: One Hallmark, Many Organelles.

PubMed

Costa, A S H; Frezza, C

2017-01-01

The process of tumorigenesis can be described by a series of molecular features, among which alteration of cellular metabolism has recently emerged. This metabolic rewiring fulfills the energy and biosynthetic demands of fast proliferating cancer cells and amplifies their metabolic repertoire to survive and proliferate in the poorly oxygenated and nutrient-deprived tumor microenvironment. During the last decade, the complex reprogramming of cancer cell metabolism has been widely investigated, revealing cancer-specific metabolic alterations. These include dysregulation of glucose and glutamine metabolism, alterations of lipid synthesis and oxidation, and a complex rewiring of mitochondrial function. However, mitochondria are not the only metabolically active organelles within the cell, and other organelles, including lysosomes, peroxisomes, and endoplasmic reticulum, harbor components of the metabolic network. Of note, dysregulation of the function of these organelles is increasingly recognized in cancer cells. However, to what extent these organelles contribute to the metabolic reprogramming of cancer is not fully understood. In this review, we describe the main metabolic functions of these organelles and provide insights into how they communicate to orchestrate a coordinated metabolic reprogramming during transformation. © 2017 Elsevier Inc. All rights reserved.

A landscape-based reconnaissance survey of estrogenic activity in streams of the upper Potomac, upper James, and Shenandoah Rivers, USA.

PubMed

Young, John; Iwanowicz, Luke; Sperry, Adam; Blazer, Vicki

2014-09-01

Endocrine-disrupting compounds (EDCs) are becoming of increasing concern in waterways of the USA and worldwide. What remains poorly understood, however, is how prevalent these emerging contaminants are in the environment and what methods are best able to determine landscape sources of EDCs. We describe the development of a spatially structured sampling design and a reconnaissance survey of estrogenic activity along gradients of land use within sub-watersheds. We present this example as a useful approach for state and federal agencies with an interest in identifying locations potentially impacted by EDCs that warrant more intensive, focused research. Our study confirms the importance of agricultural activities on levels of a measured estrogenic equivalent (E2Eq) and also highlights the importance of other potential sources of E2Eq in areas where intensive agriculture is not the dominant land use. Through application of readily available geographic information system (GIS) data, coupled with spatial statistical analysis, we demonstrate the correlation of specific land use types to levels of estrogenic activity across a large area in a consistent and unbiased manner.

Another look at the legal and ethical consequences of pharmacological memory dampening: the case of sexual assault.

PubMed

Chandler, Jennifer A; Mogyoros, Alexandra; Rubio, Tristana Martin; Racine, Eric

2013-01-01

Research on the use of propranolol as a pharmacological memory dampening treatment for post-traumatic stress disorder is continuing and justifies a second look at the legal and ethical issues raised in the past. We summarize the general ethical and legal issues raised in the literature so far, and we select two for in-depth reconsideration. We address the concern that a traumatized witness may be less effective in a prosecution emerging from the traumatic event after memory dampening treatment. We analyze this issue in relation to sexual assault, where the suggestion that corroborating evidence may remedy any memory defects is less likely to be helpful. We also consider the clinical ethical question about a physician's obligation to discuss potential legal consequences of memory dampening treatment. We conclude that this latter question reflects a general problem related to novel medical treatments where the broader socio-legal consequences may be poorly understood, and suggest that issues of this sort could usefully be addressed through the promulgation of practice guidelines. © 2013 American Society of Law, Medicine & Ethics, Inc.

MiR-285 targets P450 (CYP6N23) to regulate pyrethroid resistance in Culex pipiens pallens.

PubMed

Tian, Mengmeng; Liu, Bingqian; Hu, Hongxia; Li, Xixi; Guo, Qin; Zou, Feifei; Liu, Xianmiao; Hu, Mengxue; Guo, Juxin; Ma, Lei; Zhou, Dan; Sun, Yan; Shen, Bo; Zhu, Changliang

2016-12-01

MicroRNAs play critical roles in post-transcriptional regulation of gene expression, which participate in the modulation of almost all of the cellular processes. Although emerging evidence indicates that microRNAs are related with antineoplastic drugs resistance, whether microRNAs are responsible for insecticide resistance in mosquitos is poorly understood. In this paper, we found that miR-285 was significantly upregulated in the deltamethrin-resistant strain of Culex pipiens pallens, and overexpression miR-285 through microinjection increased mosquito survival rate against deltamethrin treatement. Using bioinformatic software, quantitative reverse transcription PCR, luciferase reporter assay and microinjection approaches, we conformed that CYP6N23 was the target of miR-285. Lower expression of CYP6N23 was observed in the deltamethrin-resistant strain. While, mosquito mortality rate was decreased after downregulating expression of CYP6N23 by dsRNA against CYP6N23 or miR-285 mimic microinjection. These findings revealed that miR-285 could target CYP6N23 to regulate pyrethroid resistance, providing new insights into mosquito insecticide resistance surveillance and control.

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

Micro-CT X-ray imaging exposes structured diffusion barriers within biofilms.

PubMed

Keren-Paz, Alona; Brumfeld, Vlad; Oppenheimer-Shaanan, Yaara; Kolodkin-Gal, Ilana

2018-01-01

In nature, bacteria predominantly exist as highly structured biofilms, which are held together by extracellular polymeric substance and protect their residents from environmental insults, such as antibiotics. The mechanisms supporting this phenotypic resistance are poorly understood. Recently, we identified a new mechanism maintaining biofilms - an active production of calcite minerals. In this work, a high-resolution and robust µCT technique is used to study the mineralized areas within intact bacterial biofilms. µCT is a vital tool for visualizing bacterial communities that can provide insights into the relationship between bacterial biofilm structure and function. Our results imply that dense and structured calcium carbonate lamina forms a diffusion barrier sheltering the inner cell mass of the biofilm colony. Therefore, µCT can be employed in clinical settings to predict the permeability of the biofilms. It is demonstrated that chemical interference with urease, a key enzyme in biomineralization, inhibits the assembly of complex bacterial structures, prevents the formation of mineral diffusion barriers and increases biofilm permeability. Therefore, biomineralization enzymes emerge as novel therapeutic targets for highly resistant infections.

Electrosensory Midbrain Neurons Display Feature Invariant Responses to Natural Communication Stimuli.

PubMed

Aumentado-Armstrong, Tristan; Metzen, Michael G; Sproule, Michael K J; Chacron, Maurice J

2015-10-01

Neurons that respond selectively but in an invariant manner to a given feature of natural stimuli have been observed across species and systems. Such responses emerge in higher brain areas, thereby suggesting that they occur by integrating afferent input. However, the mechanisms by which such integration occurs are poorly understood. Here we show that midbrain electrosensory neurons can respond selectively and in an invariant manner to heterogeneity in behaviorally relevant stimulus waveforms. Such invariant responses were not seen in hindbrain electrosensory neurons providing afferent input to these midbrain neurons, suggesting that response invariance results from nonlinear integration of such input. To test this hypothesis, we built a model based on the Hodgkin-Huxley formalism that received realistic afferent input. We found that multiple combinations of parameter values could give rise to invariant responses matching those seen experimentally. Our model thus shows that there are multiple solutions towards achieving invariant responses and reveals how subthreshold membrane conductances help promote robust and invariant firing in response to heterogeneous stimulus waveforms associated with behaviorally relevant stimuli. We discuss the implications of our findings for the electrosensory and other systems.

Structural Basis of Vta1 Function in the Multivesicular Body Sorting Pathway

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

Xiao, Junyu; Xia, Hengchuan; Zhou, Jiahai

The MVB pathway plays essential roles in several eukaryotic cellular processes. Proper function of the MVB pathway requires reversible membrane association of the ESCRTs, a process catalyzed by Vps4 ATPase. Vta1 regulates the Vps4 activity, but its mechanism of action was poorly understood. We report the high-resolution crystal structures of the Did2- and Vps60-binding N-terminal domain and the Vps4-binding C-terminal domain of S. cerevisiae Vta1. The C-terminal domain also mediates Vta1 dimerization and both subunits are required for its function as a Vps4 regulator. Emerging from our analysis is a mechanism of regulation by Vta1 in which the C-terminal domainmore » stabilizes the ATP-dependent double ring assembly of Vps4. In addition, the MIT motif-containing N-terminal domain, projected by a long disordered linker, allows contact between the Vps4 disassembly machinery and the accessory ESCRT-III proteins. This provides an additional level of regulation and coordination for ESCRT-III assembly and disassembly.« less

Is the risk of cardiovascular disease altered with anti-inflammatory therapies? Insights from rheumatoid arthritis

PubMed Central

Kraakman, Michael J; Dragoljevic, Dragana; Kammoun, Helene L; Murphy, Andrew J

2016-01-01

Cardiovascular disease (CVD) remains the leading cause of mortality worldwide. Atherosclerosis is the most common form of CVD, which is complex and multifactorial with an elevated risk observed in people with either metabolic or inflammatory diseases. Accumulating evidence now links obesity with a state of chronic low-grade inflammation and has renewed our understanding of this condition and its associated comorbidities. An emerging theme linking disease states with atherosclerosis is the increased production of myeloid cells, which can initiate and exacerbate atherogenesis. Although anti-inflammatory drug treatments exist and have been successfully used to treat inflammatory conditions such as rheumatoid arthritis (RA), a commonly observed side effect is dyslipidemia, inadvertently, a major risk factor for the development of atherosclerosis. The mechanisms leading to dyslipidemia associated with anti-inflammatory drug use and whether CVD risk is actually increased by this dyslipidemia are of great therapeutic importance and currently remain poorly understood. Here we review recent data providing links between inflammation, hematopoiesis, dyslipidemia and CVD risk in the context of anti-inflammatory drug use. PMID:27350883

A Synergistic Antiobesity Effect by a Combination of Capsinoids and Cold Temperature Through Promoting Beige Adipocyte Biogenesis

PubMed Central

Ohyama, Kana; Nogusa, Yoshihito; Shinoda, Kosaku; Suzuki, Katsuya

2016-01-01

Beige adipocytes emerge postnatally within the white adipose tissue in response to certain environmental cues, such as chronic cold exposure. Because of its highly recruitable nature and relevance to adult humans, beige adipocytes have gained much attention as an attractive cellular target for antiobesity therapy. However, molecular circuits that preferentially promote beige adipocyte biogenesis remain poorly understood. We report that a combination of mild cold exposure at 17°C and capsinoids, a nonpungent analog of capsaicin, synergistically and preferentially promotes beige adipocyte biogenesis and ameliorates diet-induced obesity. Gain- and loss-of-function studies show that the combination of capsinoids and cold exposure synergistically promotes beige adipocyte development through the β2-adrenoceptor signaling pathway. This synergistic effect on beige adipocyte biogenesis occurs through an increased half-life of PRDM16, a dominant transcriptional regulator of brown/beige adipocyte development. We document a previously unappreciated molecular circuit that controls beige adipocyte biogenesis and suggest a plausible approach to increase whole-body energy expenditure by combining dietary components and environmental cues. PMID:26936964

Consumption of freshwater bivalves by muskrats in the Green River, Kentucky

USGS Publications Warehouse

Hersey, Kimberly Asmus; Clark, Joseph D.; Layzer, James B.

2013-01-01

Muskrats (Ondatra zibethicus) are known to prey on freshwater bivalves (mussels and clams) and can negatively impact imperiled mussel species. However, factors that influence muskrat predation on bivalves are poorly understood. We evaluated the feeding ecology of muskrats in the Green River, Kentucky, by using stable isotope analysis of muskrat hair samples and by monitoring bivalve shell deposition at muskrat middens. Bayesian mixing-model analysis of stable isotope δ15N and δ13C ratios revealed that the median muskrat biomass derived from bivalves was 51.4% (5th and 95th percentiles were 39.1 to 63.4%, respectively), a much higher dietary proportion than previously reported. Shell depositions by muskrats at middens decreased with the availability of seasonal emergent vegetation, suggesting that the consumption of animal matter is in response to a scarcity of plant foods, perhaps exacerbated by the altered flow regimes on the Green River. Our results add to the growing body of evidence that muskrats have the potential to impact mussel population growth and recovery in some environments.

LIN28 phosphorylation by MAPK/ERK couples signaling to the post-transcriptional control of pluripotency

PubMed Central

Tsanov, Kaloyan M.; Pearson, Daniel S.; Wu, Zhaoting; Han, Areum; Triboulet, Robinson; Seligson, Marc T.; Powers, John T.; Osborne, Jihan K.; Kane, Susan; Gygi, Steven P.; Gregory, Richard I.; Daley, George Q.

2016-01-01

Signaling and post-transcriptional gene control are both critical for the regulation of pluripotency1,2, yet how they are integrated to influence cell identity remains poorly understood. LIN28 (also known as LIN28A), a highly conserved RNA-binding protein (RBP), has emerged as a central post-transcriptional regulator of cell fate through blockade of let-7 microRNA (miRNA) biogenesis and direct modulation of mRNA translation3. Here we show that LIN28 is phosphorylated by MAPK/ERK in pluripotent stem cells (PSCs), which increases its levels via post-translational stabilization. LIN28 phosphorylation had little impact on let-7 but enhanced LIN28’s effect on its direct mRNA targets, revealing a mechanism that uncouples LIN28’s let-7-dependent and independent activities. We have linked this mechanism to the induction of pluripotency by somatic cell reprogramming and the transition from naïve to primed pluripotency. Collectively, our findings indicate that MAPK/ERK directly impacts LIN28, defining an axis that connects signaling, post-transcriptional gene control, and cell fate regulation. PMID:27992407

Suppression of RND3 activity by AES downregulation promotes cancer cell proliferation and invasion.

PubMed

Xia, Hongwei; Li, Mingxing; Chen, Liang; Leng, Weibing; Yuan, Dandan; Pang, Xiaohui; Chen, Liu; Li, Ronghui; Tang, Qiulin; Bi, Feng

2013-05-01

Amino-terminal enhancer of split (AES) is a member of the Groucho/TLE family. Although it has no DNA-binding site, AES can regulate transcriptional activity by interacting with transcriptional factors. Emerging evidence indicates that AES may play an important role in tumor metastasis, but the molecular mechanism is still poorly understood. In this study, we found that knockdown of AES by RNA interference (RNAi) downregulated RND3 expression at the mRNA and protein levels in MDA-MB-231 and HepG2, two cancer cell lines. Furthermore, luciferase assays showed that overexpression of AES significantly enhanced RND3 promoter activity. Moreover, inhibition of AES both in MDA-MB-231 and HepG2 cells by RNAi significantly promoted cell proliferation, cell cycle progression and invasion, consistent with the effects of RNAi-mediated RND3 knockdown in these cells. For the first time, data are presented showing that alteration of the malignant behavior of cancer cells by AES is related to RND3 regulation, and these findings also provide new insights into the mechanism of AES action in regulating tumor malignancy.

Sensing Exocytosis and Triggering Endocytosis at Synapses: Synaptic Vesicle Exocytosis–Endocytosis Coupling

PubMed Central

Lou, Xuelin

2018-01-01

The intact synaptic structure is critical for information processing in neural circuits. During synaptic transmission, rapid vesicle exocytosis increases the size of never terminals and endocytosis counteracts the increase. Accumulating evidence suggests that SV exocytosis and endocytosis are tightly connected in time and space during SV recycling, and this process is essential for synaptic function and structural stability. Research in the past has illustrated the molecular details of synaptic vesicle (SV) exocytosis and endocytosis; however, the mechanisms that timely connect these two fundamental events are poorly understood at central synapses. Here we discuss recent progress in SV recycling and summarize several emerging mechanisms by which synapses can “sense” the occurrence of exocytosis and timely initiate compensatory endocytosis. They include Ca2+ sensing, SV proteins sensing, and local membrane stress sensing. In addition, the spatial organization of endocytic zones adjacent to active zones provides a structural basis for efficient coupling between SV exocytosis and endocytosis. Through linking different endocytosis pathways with SV fusion, these mechanisms ensure necessary plasticity and robustness of nerve terminals to meet diverse physiological needs. PMID:29593500

Ecology and conservation biology of avian malaria.

PubMed

Lapointe, Dennis A; Atkinson, Carter T; Samuel, Michael D

2012-02-01

Avian malaria is a worldwide mosquito-borne disease caused by Plasmodium parasites. These parasites occur in many avian species but primarily affect passerine birds that have not evolved with the parasite. Host pathogenicity, fitness, and population impacts are poorly understood. In contrast to continental species, introduced avian malaria poses a substantial threat to naive birds on Hawaii, the Galapagos, and other archipelagoes. In Hawaii, transmission is maintained by susceptible native birds, competence and abundance of mosquitoes, and a disease reservoir of chronically infected native birds. Although vector habitat and avian communities determine the geographic distribution of disease, climate drives transmission patterns ranging from continuous high infection in warm lowland forests, seasonal infection in midelevation forests, and disease-free refugia in cool high-elevation forests. Global warming is expected to increase the occurrence, distribution, and intensity of avian malaria across this elevational gradient and threaten high-elevation refugia, which is the key to survival of many susceptible Hawaiian birds. Increased temperatures may have already increased global avian malaria prevalence and contributed to an emergence of disease in New Zealand. © 2012 New York Academy of Sciences.

Identification of genetic factors that modify motor performance and body weight using Collaborative Cross mice

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

Mao, Jian -Hua; Langley, Sasha A.; Huang, Yurong

Evidence has emerged that suggests a link between motor deficits, obesity and many neurological disorders. However, the contributing genetic risk factors are poorly understood. Here we used the Collaborative Cross (CC), a large panel of newly inbred mice that captures 90% of the known variation among laboratory mice, to identify the genetic loci controlling rotarod performance and its relationship with body weight in a cohort of 365 mice across 16 CC strains. Body weight and rotarod performance varied widely across CC strains and were significantly negatively correlated. Genetic linkage analysis identified 14 loci that were associated with body weight. However,more » 45 loci affected rotarod performance, seven of which were also associated with body weight, suggesting a strong link at the genetic level. As a result, we show that genes identified in this study overlap significantly with those related to neurological disorders and obesity found in human GWA studies. In conclusion, our results provide a genetic framework for studies of the connection between body weight, the central nervous system and behavior.« less

Genetic diversity in the interference selection limit.

PubMed

Good, Benjamin H; Walczak, Aleksandra M; Neher, Richard A; Desai, Michael M

2014-03-01

Pervasive natural selection can strongly influence observed patterns of genetic variation, but these effects remain poorly understood when multiple selected variants segregate in nearby regions of the genome. Classical population genetics fails to account for interference between linked mutations, which grows increasingly severe as the density of selected polymorphisms increases. Here, we describe a simple limit that emerges when interference is common, in which the fitness effects of individual mutations play a relatively minor role. Instead, similar to models of quantitative genetics, molecular evolution is determined by the variance in fitness within the population, defined over an effectively asexual segment of the genome (a "linkage block"). We exploit this insensitivity in a new "coarse-grained" coalescent framework, which approximates the effects of many weakly selected mutations with a smaller number of strongly selected mutations that create the same variance in fitness. This approximation generates accurate and efficient predictions for silent site variability when interference is common. However, these results suggest that there is reduced power to resolve individual selection pressures when interference is sufficiently widespread, since a broad range of parameters possess nearly identical patterns of silent site variability.

Effects of energy development on wetland plants and macroinvertebrate communities in Prairie Pothole Region wetlands

USGS Publications Warehouse

Preston, Todd M.; Ray, Andrew M.

2016-01-01

Energy production in the Williston Basin, USA, results in the coproduction of highly saline, sodium chloride-dominated water (brine). The Prairie Pothole Region (PPR) overlies the northeastern portion of the Williston Basin. Although PPR wetlands span a range of salinity, the dominant salt is sodium sulfate, and salinities are much lower than brine. Introduction of brine to wetlands can result in pronounced water-quality changes; however, the ecological effects of such contamination are poorly understood. We examined the effects of brine contamination on primary productivity, emergent macrophyte tissue chemistry, and invertebrate communities from 10 wetlands in the PPR. Based on a recognized Contamination Index (CI) used to identify brine contamination in the PPR, water-quality samples indicated that six wetlands were uncontaminated while four were contaminated. Across this gradient, we observed a significant decrease in above-ground biomass and a significant increase in tissue chloride concentrations of hardstem bulrush (Schoenoplectus acutus) with increased CI values. Additionally, a significant decrease in macroinvertebrate taxonomic richness with increased CI values was observed. These findings provide needed insight on the biological effects of brine contamination on PPR wetlands.

Emerging therapeutic targets in myeloproliferative neoplasms and peripheral T-cell leukemia and lymphomas

PubMed Central

Orlova, Anna; Wingelhofer, Bettina; Neubauer, Heidi A.; Maurer, Barbara; Berger-Becvar, Angelika; Keserű, György Miklós; Gunning, Patrick T.; Valent, Peter; Moriggl, Richard

2018-01-01

ABSTRACT Introduction: Hematopoietic neoplasms are often driven by gain-of-function mutations of the JAK-STAT pathway together with mutations in chromatin remodeling and DNA damage control pathways. The interconnection between the JAK-STAT pathway, epigenetic regulation or DNA damage control is still poorly understood in cancer cell biology. Areas covered: Here, we focus on a broader description of mutational insights into myeloproliferative neoplasms and peripheral T-cell leukemia and lymphomas, since sequencing efforts have identified similar combinations of driver mutations in these diseases covering different lineages. We summarize how these pathways might be interconnected in normal or cancer cells, which have lost differentiation capacity and drive oncogene transcription. Expert opinion: Due to similarities in driver mutations including epigenetic enzymes, JAK-STAT pathway activation and mutated checkpoint control through TP53, we hypothesize that similar therapeutic approaches could be of benefit in these diseases. We give an overview of how driver mutations in these malignancies contribute to hematopoietic cancer initiation or progression, and how these pathways can be targeted with currently available tools. PMID:29148847

Memory, forgetting, and economic crisis: drug use and social fragmentation in an Argentine shantytown.

PubMed

Epele, Maria E

2010-03-01

Closely linked to the increase in psychotropic pill consumption, forgetting and remembering emerged from devastated social scenarios as a new local idiom among poor youth in the late 1990s and the new millennium. Drawing on ethnographic fieldwork carried out during the years of the deepest economic crisis in Argentina (2001-03), I argue that psychotropic pill consumption is associated with not only deteriorating economic conditions but also changes in the quality and price of cocaine, and in the scarcity and subsequent change of status of medications during the economic breakdown. Taking into account developments in the field of memory studies, I examine the relationship among political economy, social memory work, and changing drug-use practices. Regarding memory as a social practice, I argue that the growth of psychotropic pill consumption in the late 1990s can be understood through the interplay of Paul Ricoeur's notions regarding different kinds and levels of forgetting. By analyzing changing survival strategies, social network dismantlement, changing mortality patterns, and abusive police repression, I discuss how social fragmentation engendered by structural reforms has modified social memory work.

Human Genomic Signatures of Brain Oscillations During Memory Encoding.

PubMed

Berto, Stefano; Wang, Guang-Zhong; Germi, James; Lega, Bradley C; Konopka, Genevieve

2018-05-01

Memory encoding is an essential step for all learning. However, the genetic and molecular mechanisms underlying human memory encoding remain poorly understood, and how this molecular framework permits the emergence of specific patterns of brain oscillations observed during mnemonic processing is unknown. Here, we directly compare intracranial electroencephalography recordings from the neocortex in individuals performing an episodic memory task with human gene expression from the same areas. We identify genes correlated with oscillatory memory effects across 6 frequency bands. These genes are enriched for autism-related genes and have preferential expression in neurons, in particular genes encoding synaptic proteins and ion channels, supporting the idea that the genes regulating voltage gradients are involved in the modulation of oscillatory patterns during successful memory encoding across brain areas. Memory-related genes are distinct from those correlated with other forms of cognitive processing and resting state fMRI. These data are the first to identify correlations between gene expression and active human brain states as well as provide a molecular window into memory encoding oscillations in the human brain.

A theoretical perspective to inform assessment and treatment strategies for animal hoarders.

PubMed

Patronek, Gary J; Nathanson, Jane N

2009-04-01

Animal hoarding is a poorly understood, maladaptive, destructive behavior whose etiology and pathology are only beginning to emerge. We compare and contrast animal hoarding to the compulsive hoarding of objects and proceed to draw upon attachment theory, the literature of personality disorder and trauma, and our own clinical experience to propose a developmental trajectory. Throughout life, there is a persistent struggle to form a functional attachment style and achieve positive social integration. For some people, particularly those affected by a dysfunctional primary attachment experience in childhood, a protective, comforting relationship with animals may form an indelible imprint. In adulthood, when human attachment has been chronically problematic, compulsive caregiving of animals can become the primary means of maintaining or building a sense of self. Improving assessment and treatment of animal hoarders requires attention to contributing psychosocial conditions, while taking into account the centrality of the animals to the hoarder's identity, self-esteem and sense of control. It is our hope that the information presented will provide a basis upon which clinicians can focus their own counseling style, assessment, and methods of treatment.

Mechanism of West Nile Virus Neuroinvasion: A Critical Appraisal

PubMed Central

Suen, Willy W.; Prow, Natalie A.; Hall, Roy A.; Bielefeldt-Ohmann, Helle

2014-01-01

West Nile virus (WNV) is an important emerging neurotropic virus, responsible for increasingly severe encephalitis outbreaks in humans and horses worldwide. However, the mechanism by which the virus gains entry to the brain (neuroinvasion) remains poorly understood. Hypotheses of hematogenous and transneural entry have been proposed for WNV neuroinvasion, which revolve mainly around the concepts of blood-brain barrier (BBB) disruption and retrograde axonal transport, respectively. However, an over‑representation of in vitro studies without adequate in vivo validation continues to obscure our understanding of the mechanism(s). Furthermore, WNV infection in the current rodent models does not generate a similar viremia and character of CNS infection, as seen in the common target hosts, humans and horses. These differences ultimately question the applicability of rodent models for pathogenesis investigations. Finally, the role of several barriers against CNS insults, such as the blood-cerebrospinal fluid (CSF), the CSF-brain and the blood-spinal cord barriers, remain largely unexplored, highlighting the infancy of this field. In this review, a systematic and critical appraisal of the current evidence relevant to the possible mechanism(s) of WNV neuroinvasion is conducted. PMID:25046180

How will ocean acidification affect Baltic sea ecosystems? an assessment of plausible impacts on key functional groups.

PubMed

Havenhand, Jonathan N

2012-09-01

Increasing partial pressure of atmospheric CO₂ is causing ocean pH to fall-a process known as 'ocean acidification'. Scenario modeling suggests that ocean acidification in the Baltic Sea may cause a ≤ 3 times increase in acidity (reduction of 0.2-0.4 pH units) by the year 2100. The responses of most Baltic Sea organisms to ocean acidification are poorly understood. Available data suggest that most species and ecologically important groups in the Baltic Sea food web (phytoplankton, zooplankton, macrozoobenthos, cod and sprat) will be robust to the expected changes in pH. These conclusions come from (mostly) single-species and single-factor studies. Determining the emergent effects of ocean acidification on the ecosystem from such studies is problematic, yet very few studies have used multiple stressors and/or multiple trophic levels. There is an urgent need for more data from Baltic Sea populations, particularly from environmentally diverse regions and from controlled mesocosm experiments. In the absence of such information it is difficult to envision the likely effects of future ocean acidification on Baltic Sea species and ecosystems.

A landscape-based reconnaissance survey of estrogenicactivity in streams of the upper Potomac, upper James,and Shenandoah Rivers, USA

USGS Publications Warehouse

Young, John A.; Iwanowicz, Luke R.; Sperry, Adam J.; Blazer, Vicki

2014-01-01

Endocrine-disrupting compounds (EDCs) are becoming of increasing concern in waterways of the USA and worldwide. What remains poorly understood, however, is how prevalent these emerging contaminants are in the environment and what methods are best able to determine landscape sources of EDCs. We describe the development of a spatially structured sampling design and a reconnaissance survey of estrogenic activity along gradients of land use within sub-watersheds.We present this example as a useful approach for state and federal agencies with an interest in identifying locations potentially impacted by EDCs that warrant more intensive, focused research. Our study confirms the importance of agricultural activities on levels of a measured estrogenic equivalent (E2Eq) and also highlights the importance of other potential sources of E2Eq in areas where intensive agriculture is not the dominant land use. Through application of readily available geographic information system (GIS) data, coupled with spatial statistical analysis, we demonstrate the correlation of specific land use types to levels of estrogenic activity across a large area in a consistent and unbiased manner.

Ecology and conservation biology of avian malaria

USGS Publications Warehouse

LaPointe, Dennis A.; Atkinson, Carter T.; Samuel, Michael D.

2012-01-01

Avian malaria is a worldwide mosquito-borne disease caused by Plasmodium parasites. These parasites occur in many avian species but primarily affect passerine birds that have not evolved with the parasite. Host pathogenicity, fitness, and population impacts are poorly understood. In contrast to continental species, introduced avian malaria poses a substantial threat to naive birds on Hawaii, the Galapagos, and other archipelagoes. In Hawaii, transmission is maintained by susceptible native birds, competence and abundance of mosquitoes, and a disease reservoir of chronically infected native birds. Although vector habitat and avian communities determine the geographic distribution of disease, climate drives transmission patterns ranging from continuous high infection in warm lowland forests, seasonal infection in midelevation forests, and disease-free refugia in cool high-elevation forests. Global warming is expected to increase the occurrence, distribution, and intensity of avian malaria across this elevational gradient and threaten high-elevation refugia, which is the key to survival of many susceptible Hawaiian birds. Increased temperatures may have already increased global avian malaria prevalence and contributed to an emergence of disease in New Zealand.

Making Fat Work*

PubMed Central

Sargis, Robert M.; Brady, Matthew J.

2014-01-01

The burgeoning obesity and metabolic disease epidemics in the developed world are exerting a terrible toll on society, yet the precise mechanisms responsible for the emergence of these dramatic trends over a relatively short period of time remain poorly understood. Philip A. Wood’s book How Fat Works provides important insights into cellular lipid metabolism, as well as discussing some of the important external contributors to the development of human obesity. The foundation provided by this book allows for the exploration of how body fat has gone from hero during the millennia when starvation was the paramount nutritional risk to its current role as villain in our period of caloric excess. With the incredible personal and societal costs brought about by excess body weight, a comprehensive understanding of the mechanisms responsible for obesity is fundamentally necessary if we are to reverse these dire trends. Here, we delve deeper into some of the forces contributing to the obesity epidemic and discuss some individual measures as well as public policy decisions that may help reverse weight trends, while specifically focusing on the growing problem of pediatric obesity. PMID:21037416

Identification of genetic factors that modify motor performance and body weight using Collaborative Cross mice

DOE PAGES

Mao, Jian -Hua; Langley, Sasha A.; Huang, Yurong; ...

2015-11-09

Evidence has emerged that suggests a link between motor deficits, obesity and many neurological disorders. However, the contributing genetic risk factors are poorly understood. Here we used the Collaborative Cross (CC), a large panel of newly inbred mice that captures 90% of the known variation among laboratory mice, to identify the genetic loci controlling rotarod performance and its relationship with body weight in a cohort of 365 mice across 16 CC strains. Body weight and rotarod performance varied widely across CC strains and were significantly negatively correlated. Genetic linkage analysis identified 14 loci that were associated with body weight. However,more » 45 loci affected rotarod performance, seven of which were also associated with body weight, suggesting a strong link at the genetic level. As a result, we show that genes identified in this study overlap significantly with those related to neurological disorders and obesity found in human GWA studies. In conclusion, our results provide a genetic framework for studies of the connection between body weight, the central nervous system and behavior.« less

Social learning in humans and other animals

PubMed Central

Gariépy, Jean-François; Watson, Karli K.; Du, Emily; Xie, Diana L.; Erb, Joshua; Amasino, Dianna; Platt, Michael L.

2014-01-01

Decisions made by individuals can be influenced by what others think and do. Social learning includes a wide array of behaviors such as imitation, observational learning of novel foraging techniques, peer or parental influences on individual preferences, as well as outright teaching. These processes are believed to underlie an important part of cultural variation among human populations and may also explain intraspecific variation in behavior between geographically distinct populations of animals. Recent neurobiological studies have begun to uncover the neural basis of social learning. Here we review experimental evidence from the past few decades showing that social learning is a widespread set of skills present in multiple animal species. In mammals, the temporoparietal junction, the dorsomedial, and dorsolateral prefrontal cortex, as well as the anterior cingulate gyrus, appear to play critical roles in social learning. Birds, fish, and insects also learn from others, but the underlying neural mechanisms remain poorly understood. We discuss the evolutionary implications of these findings and highlight the importance of emerging animal models that permit precise modification of neural circuit function for elucidating the neural basis of social learning. PMID:24765063

Lipid Gymnastics: Tethers and Fingers in membrane

NASA Astrophysics Data System (ADS)

Tayebi, Lobat; Miller, Gregory; Parikh, Atul

2009-03-01

A significant body of evidence now links local mesoscopic structure (e.g., shape and composition) of the cell membrane with its function; the mechanisms by which cellular membranes adopt the specific shapes remain poorly understood. Among all the different structures adopted by cellular membranes, the tubular shape is one of the most surprising one. While their formation is typically attributed to the reorganization of membrane cytoskeleton, many exceptions exist. We report the instantaneous formation of tubular membrane mesophases following the hydration under specific thermal conditions. The shapes emerge in a bimodal way where we have two distinct diameter ranges for tubes, ˜20μm and ˜1μm, namely fat fingers and narrow tethers. We study the roughening of hydrated drops of 3 lipids in 3 different spontaneous curvatures at various temp. and ionic strength to figure out the dominant effect in selection of tethers and fingers. Dynamics of the tubes are of particular interest where we observe four distinct steps of birth, coiling, uncoiling and retraction with different lifetime on different thermal condition. These dynamics appear to reflect interplay between membrane elasticity, surface adhesion, and thermal or hydrodynamic gradient.

Structural basis of Vta1 function in the multi-vesicular body sorting pathway

PubMed Central

Xiao, Junyu; Xia, Hengchuan; Zhou, Jiahai; Azmi, Ishara; Davies, Brian A.; Katzmann, David J.; Xu, Zhaohui

2009-01-01

Summary The MVB pathway plays essential roles in several eukaryotic cellular processes. Proper function of the MVB pathway requires reversible membrane association of the ESCRTs, a process catalyzed by Vps4 ATPase. Vta1 regulates the Vps4 activity but its mechanism of action was poorly understood. We report the high-resolution crystal structures of the Did2- and Vps60-binding N-terminal domain and the Vps4-binding C-terminal domain of S. cerevisiae Vta1. The C-terminal domain also mediates Vta1 dimerization and both subunits are required for its function as a Vps4 regulator. Emerging from our analysis is a mechanism of regulation by Vta1 in which the C-terminal domain stabilizes the ATP-dependent double ring assembly of Vps4. In addition, the MIT motif containing N-terminal domain, projected by a long disordered linker, allows contact between the Vps4 disassembly machinery and the accessory ESCRT-III proteins. This provides an additional level of regulation and coordination for ESCRT-III assembly and disassembly. PMID:18194651

Airway epithelial repair in health and disease: Orchestrator or simply a player?

PubMed

Iosifidis, Thomas; Garratt, Luke W; Coombe, Deirdre R; Knight, Darryl A; Stick, Stephen M; Kicic, Anthony

2016-04-01

Epithelial cells represent the most important surface of contact in the body and form the first line of defence of the body to external environment. Consequently, epithelia have numerous roles in order to maintain a homeostatic defence barrier. Although the epithelium has been extensively studied over several decades, it remains the focus of new research, indicating a lack of understanding that continues to exist around these cells in specific disease settings. Importantly, evidence is emerging that airway epithelial cells in particular have varied complex functions rather than simple passive roles. One area of current interest is its role following injury. In particular, the epithelial-specific cellular mechanisms regulating their migration during wound repair remain poorly understood and remain an area that requires much needed investigation. A better understanding of the physiological, cellular and molecular wound repair mechanisms could assist in elucidating pathological processes that contribute to airway epithelial pathology. This review attempts to highlight migration-specific and cell-extracellular matrix (ECM) aspects of repair used by epithelial cells under normal and disease settings, in the context of human airways. © 2016 Asian Pacific Society of Respirology.

Relationship between HIV Stigma and Self-Isolation among People Living with HIV in Tennessee

PubMed Central

Audet, Carolyn M.; McGowan, Catherine C.; Wallston, Kenneth A.; Kipp, Aaron M.

2013-01-01

Introduction HIV stigma is a contributing factor to poor patient outcomes. Although HIV stigma has been documented, its impact on patient well-being in the southern US is not well understood. Methods Thirty-two adults participated in cognitive interviews after completing the Berger HIV or the Van Rie stigma scale. Participant responses were probed to ensure the scales accurately measured stigma and to assess the impact stigma had on behavior. Results Three main themes emerged regarding HIV stigma: (1) negative attitudes, fear of contagion, and misperceptions about transmission; (2) acts of discrimination by families, friends, health care providers, and within the workplace; and (3) participants’ use of self-isolation as a coping mechanism. Overwhelming reluctance to disclose a person’s HIV status made identifying enacted stigma with a quantitative scale difficult. Discussion Fear of discrimination resulted in participants isolating themselves from friends or experiences to avoid disclosure. Participant unwillingness to disclose their HIV status to friends and family could lead to an underestimation of enacted HIV stigma in quantitative scales. PMID:23950897

USING MOLECULAR PROBES TO STUDY INTERFACIAL REDOX REACTION AT FE-BEARING SMECTITES

EPA Science Inventory

The interfacial electron transfer of clay-water systems has a wide range of significance in geochemical and biogeochernical environments. However the mechanism of interfacial electron transport is poorly understood. The electron transfer mechanism at the solid-water interfaces of...

Larval fish distribution in the St. Louis River estuary

EPA Science Inventory

Our objective was to determine what study design, environmental, and habitat variables contribute to the distribution and abundance of larval fish in the St. Louis River estuary. Larval fish habitat associations are poorly understood in Great Lakes coastal wetlands, yet critical ...

Post-traumatic unilateral plantar hyperhidrosis.

PubMed

Eren, Y; Yavasoglu, N G; Comoglu, S S

2016-02-01

Localized unilateral hyperhidrosis is rare and poorly understood, sometimes stemming from trauma. Feet, quite vulnerable to trauma are affected by disease-mediated plantar hyperhidrosis, usually bilaterally. This report describes partial hyperhidrosis developing post-traumatically on the left plantar region of a 52-year-old male.

Predator-prey interaction reveals local effects of high-altitude insect migration

USDA-ARS?s Scientific Manuscript database

High-altitude nocturnal insect migrations represent significant pulses of resources, yet are difficult to study and poorly understood. Predator-prey interactions, specifically migratory moth consumption by high-flying bats, potentially reveal flows of migratory insects across a landscape. In North...

Assessing Effects of Pesticides on the Bee Immune System

EPA Science Inventory

Populations of some managed and wild pollinators are in decline as a result of multiple interacting factors including parasites, disease, poor nutrition and pesticides. The role that diminished immunity plays in these declines is not understood. The U.S. Environmental Protection ...

DISSECTING COLONY DEVELOPMENT OF NEUROSPORA CRASSA USING mRNA PROFILING AND COMPARTATIVE GENOMICS APPROACHES

USDA-ARS?s Scientific Manuscript database

Colony development, which includes hyphal extension, branching, anastomosis and asexual sporulation are fundamental aspects of the lifecycle of filamentous fungi; genetic mechanisms underlying these phenomena are poorly understood. We conducted transcriptional profiling during colony development of...

USEPA RESEARCH ON FISH - HABITAT RELATIONSHIPS IN GREAT LAKES COASTAL MARSHES

EPA Science Inventory

Despite numerous studies documenting fish use of particular habitat elements, the role of habitat mosaics in supporting wetland fishes is poorly understood. USEPA's Mid-Continent Ecology Division has initiated research to identify relationships of fish and habitat in coastal mars...

A Cellular Game of Telephone: Trans Tissue Reprogramming of Responses to Toxic Stimuli

EPA Science Inventory

Exposure to air pollution is a leading cause of cardiopulmonary morbidity and mortality; however, while these effects outside the lung have been associated with aberrant oxidative stress and inflammation, the underlying molecular mechanisms are poorly understood. We hypothesized ...

Cellular Plasticity in the Diabetic Myocardium

DTIC Science & Technology

2017-09-01

demonstrated that obese diabetic db/db mice in a C57Bl6J background exhibit cardiac remodeling, associated with modest ventricular dilation...HFpEF, the cellular basis for fibrotic remodeling of the ventricle is poorly understood. Metabolic diseases (such as obesity and diabetes) are

Reduce Confusion about Diffusion.

ERIC Educational Resources Information Center

Hebrank, Mary R.

1997-01-01

Presents activities that allow students to explore the fundamental but poorly understood concept of diffusion by appealing to their kinesthetic senses first, then challenging their analytical skills as they try to deduce the mathematical principle involved. Presents a computer simulation of diffusion and discusses diffusion's limitations and…

INTERNATIONAL CHILDHOOD CANCER COHORT CONSORTIUM (Journal Article)

EPA Science Inventory

Childhood cancers are rare conditions whose etiology is poorly understood. There is evidence that for some, the causal pathway may commence in utero or during peri-conception. One traditional epidemiologic approach to the study of rare diseases is the use of a retrospective cas...

A Multilevel Investigation of Neighborhood Effects on Parental Warmth

ERIC Educational Resources Information Center

Tendulkar, Shalini A.; Buka, Stephen; Dunn, Erin C.; Subramanian, S. V.; Koenen, Karestan C.

2010-01-01

Although researchers recognize that social contexts shape parenting behaviors, the relationship between neighborhood environment and parenting remains poorly understood. To address this gap, we investigated the associations between compositional and contextual (structural, social, and safety) characteristics of neighborhoods and parental warmth.…

Origins of Brain Tumor Macrophages.

PubMed

De Palma, Michele

2016-12-12

The ontogeny of brain-tumor-associated macrophages is poorly understood. New findings indicate that both resident microglia and blood-derived monocytes generate the pool of macrophages that infiltrate brain tumors of either primary or metastatic origin. Copyright © 2016 Elsevier Inc. All rights reserved.

Pollinator guilds respond differently to urban habitat fragmentation in a oak-savannah ecosystem

USDA-ARS?s Scientific Manuscript database

Habitat fragmentation is widely thought to threaten biodiversity. However, response of pollinators to habitat fragmentation is still poorly understood, as pollinator communities are notoriously spatially variable. We investigated pollinator community structure in a highly fragmented oak-savannah ec...

Effects of ecosystem development on benthic secondary production in restored and created mangrove habitats

EPA Science Inventory

Wetland creation, enhancement, and restoration activities are commonly implemented to compensate for wetland loss or degradation. However, functional equivalence in restored and created wetland habitats is often poorly understood. In estuarine habitats, changes in habitat qualit...

Ozone-Induced Metabolic Impairment is Attenuated in Adrenalectomized Wistar Kyoto Rats

EPA Science Inventory

Rationale: Air pollutants have been linked to increased incidence of metabolic syndrome however the mechanisms are poorly understood. We have recently shown that ozone exposure induces significant hyperglycemia together with elevated serum leptin and epinephrine in the Wistar Ky...

THE INTERACTION OF VAPOUR PHASE ORGANIC COMPOUNDS WITH INDOOR SINKS

EPA Science Inventory

The interaction of indoor air pollutants with interior surfaces (i.e., sinks) is a well known, but poorly understood, phenomenon. Studies have shown that re-emissions of adsorbed organic vapours can contribute to elevated concentrations of organics in indoor environments. Researc...

Preschool Executive Functioning Abilities Predict Early Mathematics Achievement

ERIC Educational Resources Information Center

Clark, Caron A. C.; Pritchard, Verena E.; Woodward, Lianne J.

2010-01-01

Impairments in executive function have been documented in school-age children with mathematical learning difficulties. However, the utility and specificity of preschool executive function abilities in predicting later mathematical achievement are poorly understood. This study examined linkages between children's developing executive function…

HYDRAULIC REDISTRIBUTION IN THE PACIFIC NORTHWEST: TWEAKING THE SYSTEM

EPA Science Inventory

Hydraulic redistribution (HR) has recently been documented in Pacific Northwest forests, but the controls governing this process and its importance to shallow-rooted species are poorly understood. Our objective in this study was to manipulate the soil-root system to tease apart ...

REVIEW OF QUANTITATIVE STANDARDS AND GUIDELINES FOR FUNGI IN INDOOR AIR

EPA Science Inventory

Exposure to fungal aerosols clearly causes human disease. However, methods for assessing exposure remain poorly understood, and guidelines for interpreting data are often contradictory. The purposes of this paper are to review and compare existing guidelines for indoor airborne...

Emerging Occupational Patterns in Australia in the Era of Globalisation and Rapid Technological Change: Implications for Education and Training.

ERIC Educational Resources Information Center

Maglen, Leo; Shah, Chandra

The effects of globalization and rapid technological change on emerging occupational patterns in Australia need to be understood in order to understand their implications for the effects on education and vocational training. Building on the classification scheme introduced by Robert Reich in his 1992 book, the Work of Nations, Australian…

Parent and Health Care Provider Perspectives Related to Disclosure of Autism Spectrum Disorder in Pediatric Emergency Departments

ERIC Educational Resources Information Center

Muskat, Barbara; Greenblatt, Andrea; Nicholas, David B.; Ratnapalan, Savithiri; Cohen-Silver, Justine; Newton, Amanda S.; Craig, William R.; Kilmer, Christopher; Zwaigenbaum, Lonnie

2016-01-01

Children and youth with autism spectrum disorder presenting in emergency departments face potential cognitive, sensory, and behavioral challenges, and it is crucial for providers to be aware of their unique needs. However, disclosure of a child's autism spectrum disorder can be complex for parental caregivers and is not well understood. This…

Dealing with Emergence, Diversity and Multiplicity of Grammar and Interaction: The Japanese Clause-Ending Form TE

ERIC Educational Resources Information Center

Hashimoto, Yuria

2011-01-01

Grammar in natural interaction is an emergent, dynamic and adaptive system that is consistently subject to change. It is understood as a collection of open multiple subsystems, each of which is activated as the language users recurrently participate in a particular linguistic, interactional and social activity. When a certain linguistic form or…

Age of First Use as a Predictor of Current Alcohol and Marijuana Use among College-Bound Emerging Adults

ERIC Educational Resources Information Center

Bergen-Cico, Dessa K.; Lape, Megan E.

2013-01-01

Background: Alcohol and marijuana are the most commonly used psychoactive substances; however, the sequencing and relationship between age of first use and continued current problematic use among college-bound emerging adults is not well understood. Methods: This is a cross-sectional study of current and historical alcohol and marijuana use among…

Providing skilled birth attendants and emergency obstetric care to the poor through partnership with private sector obstetricians in Gujarat, India

PubMed Central

Singh, Amarjit; Bhat, Ramesh; Desai, Ajesh; Patel, SR; Singh, Prabal V; Singh, Neelu

2009-01-01

Abstract Problem India has the world’s largest number of maternal deaths estimated at 117 000 per year. Past efforts to provide skilled birth attendants and emergency obstetric care in rural areas have not succeeded because obstetricians are not willing to be posted in government hospitals at subdistrict level. Approach We have documented an innovative public–private partnership scheme between the Government of Gujarat, in India, and private obstetricians practising in rural areas to provide delivery care to poor women. Local setting In April 2007, the majority of poor women delivered their babies at home without skilled care. Relevant changes More than 800 obstetricians joined the scheme and more than 176 000 poor women delivered in private facilities. We estimate that the coverage of deliveries among poor women under the scheme increased from 27% to 53% between April and October 2007. The programme is considered very successful and shows that these types of social health insurance programmes can be managed by the state health department without help from any insurance company or international donor. Lessons learned At least in some areas of India, it is possible to develop large-scale partnerships with the private sector to provide skilled birth attendants and emergency obstetric care to poor women at a relatively small cost. Poor women will take up the benefit of skilled delivery care rapidly, if they do not have to pay for it. PMID:20454488

Dynamic stroma reorganization drives blood vessel dysmorphia during glioma growth.

PubMed

Mathivet, Thomas; Bouleti, Claire; Van Woensel, Matthias; Stanchi, Fabio; Verschuere, Tina; Phng, Li-Kun; Dejaegher, Joost; Balcer, Marly; Matsumoto, Ken; Georgieva, Petya B; Belmans, Jochen; Sciot, Raf; Stockmann, Christian; Mazzone, Massimiliano; De Vleeschouwer, Steven; Gerhardt, Holger

2017-12-01

Glioma growth and progression are characterized by abundant development of blood vessels that are highly aberrant and poorly functional, with detrimental consequences for drug delivery efficacy. The mechanisms driving this vessel dysmorphia during tumor progression are poorly understood. Using longitudinal intravital imaging in a mouse glioma model, we identify that dynamic sprouting and functional morphogenesis of a highly branched vessel network characterize the initial tumor growth, dramatically changing to vessel expansion, leakage, and loss of branching complexity in the later stages. This vascular phenotype transition was accompanied by recruitment of predominantly pro-inflammatory M1-like macrophages in the early stages, followed by in situ repolarization to M2-like macrophages, which produced VEGF-A and relocate to perivascular areas. A similar enrichment and perivascular accumulation of M2 versus M1 macrophages correlated with vessel dilation and malignancy in human glioma samples of different WHO malignancy grade. Targeting macrophages using anti-CSF1 treatment restored normal blood vessel patterning and function. Combination treatment with chemotherapy showed survival benefit, suggesting that targeting macrophages as the key driver of blood vessel dysmorphia in glioma progression presents opportunities to improve efficacy of chemotherapeutic agents. We propose that vessel dysfunction is not simply a general feature of tumor vessel formation, but rather an emergent property resulting from a dynamic and functional reorganization of the tumor stroma and its angiogenic influences. © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

Impact of sleep quality on amygdala reactivity, negative affect, and perceived stress.

PubMed

Prather, Aric A; Bogdan, Ryan; Hariri, Ahmad R

2013-05-01

Research demonstrates a negative impact of sleep disturbance on mood and affect; however, the biological mechanisms mediating these links are poorly understood. Amygdala reactivity to negative stimuli has emerged as one potential pathway. Here, we investigate the influence of self-reported sleep quality on associations between threat-related amygdala reactivity and measures of negative affect and perceived stress. Analyses on data from 299 participants (125 men, 50.5% white, mean [standard deviation] age = 19.6 [1.3] years) who completed the Duke Neurogenetics Study were conducted. Participants completed several self-report measures of negative affect and perceived stress. Threat-related (i.e., angry and fearful facial expressions) amygdala reactivity was assayed using blood oxygen level-dependent functional magnetic resonance imaging. Global sleep quality was assessed using the Pittsburgh Sleep Quality Index. Amygdala reactivity to fearful facial expressions predicted greater depressive symptoms and higher perceived stress in poor (β values = 0.18-1.86, p values < .05) but not good sleepers (β values = -0.13 to -0.01, p values > .05). In sex-specific analyses, men reporting poorer global sleep quality showed a significant association between amygdala reactivity and levels of depression and perceived stress (β values = 0.29-0.44, p values < .05). In contrast, no significant associations were observed in men reporting good global sleep quality or in women, irrespective of sleep quality. This study provides novel evidence that self-reported sleep quality moderates the relationships between amygdala reactivity, negative affect, and perceived stress, particularly among men.

Immigration, employment relations, and health: Developing a research agenda.

PubMed

Benach, Joan; Muntaner, Carles; Chung, Haejoo; Benavides, Fernando G

2010-04-01

International migration has emerged as a global issue that has transformed the lives of hundreds of millions of persons. Migrant workers contribute to the economic growth of high-income countries often serving as the labour force performing dangerous, dirty and degrading work that nationals are reluctant to perform. Critical examination of the scientific and "grey" literatures on immigration, employment relations and health. Both lay and scientific literatures indicate that public health researchers should be concerned about the health consequences of migration processes. Migrant workers are more represented in dangerous industries and in hazardous jobs, occupations and tasks. They are often hired as labourers in precarious jobs with poverty wages and experience more serious abuse and exploitation at the workplace. Also, analyses document migrant workers' problems of social exclusion, lack of health and safety training, fear of reprisals for demanding better working conditions, linguistic and cultural barriers that minimize the effectiveness of training, incomplete OHS surveillance of foreign workers and difficulty accessing care and compensation when injured. Therefore migrant status can be an important source of occupational health inequalities. Available evidence shows that the employment conditions and associated work organization of most migrant workers are dangerous to their health. The overall impact of immigration on population health, however, still is poorly understood and many mechanisms, pathways and overall health impact are poorly documented. Current limitations highlight the need to engage in explicit analytical, intervention and policy research. (c) 2009 Wiley-Liss, Inc.

Do Slow and Steady Residents Win the Race? Modeling the Effects of Peak and Overall Resident Productivity in the Emergency Department.

PubMed

Joseph, Joshua W; Novack, Victor; Wong, Matthew L; Nathanson, Larry A; Sanchez, Leon D

2017-08-01

Emergency medicine residents need to be staffed in a way that balances operational needs with their educational experience. Key to developing an optimal schedule is knowing a resident's expected productivity, a poorly understood metric. We sought to measure how a resident's busiest (peak) workload affects their overall productivity for the shift. We conducted a retrospective, observational study of resident productivity at an urban, tertiary care center with a 3-year Accreditation Council for Graduate Medical Education-approved emergency medicine training program, with 55,000 visits annually. We abstracted resident productivity data from a database of patient assignments from July 1, 2010 to June 20, 2015, utilizing a generalized estimation equation method to evaluate physician shifts. Our primary outcome measure was the total number of patients seen by a resident over a shift. The secondary outcome was the number of patients seen excluding those in the peak hour. A total of 14,361 shifts were evaluated. Multivariate analysis showed that the total number of patients seen was significantly associated with the number of patients seen during the peak hour, level of training, the timing of the shift, but most prominently, lower variance in patients seen per hour (coefficient of variation < 0.10). A resident's peak productivity can be a strong predictor of their overall productivity, but the substantial negative effect of variability favors a steadier pace. This suggests that resident staffing and patient assignments should generally be oriented toward a more consistent workload, an effect that should be further investigated with attending physicians. Copyright © 2017 Elsevier Inc. All rights reserved.

Substituent Effects on the Self-Assembly/Coassembly and Hydrogelation of Phenylalanine Derivatives.

PubMed

Liyanage, Wathsala; Nilsson, Bradley L

2016-01-26

Supramolecular hydrogels derived from the self-assembly of organic molecules have been exploited for applications ranging from drug delivery to tissue engineering. The relationship between the structure of the assembly motif and the emergent properties of the resulting materials is often poorly understood, impeding rational approaches for the creation of next-generation materials. Aromatic π-π interactions play a significant role in the self-assembly of many supramolecular hydrogelators, but the exact nature of these interactions lacks definition. Conventional models that describe π-π interactions rely on quadrupolar electrostatic interactions between neighboring aryl groups in the π-system. However, recent experimental and computational studies reveal the potential importance of local dipolar interactions between elements of neighboring aromatic rings in stabilizing π-π interactions. Herein, we examine the nature of π-π interactions in the self- and coassembly of Fmoc-Phe-derived hydrogelators by systematically varying the electron-donating or electron-withdrawing nature of the side chain benzyl substituents and correlating these effects to the emergent assembly and gelation properties of the systems. These studies indicate a significant role for stabilizing dipolar interactions between neighboring benzyl groups in the assembled materials. Additional evidence for specific dipolar interactions is provided by high-resolution crystal structures obtained from dynamic transition of gel fibrils to crystals for several of the self-assembled/coassembled Fmoc-Phe derivatives. In addition to electronic effects, steric properties also have a significant effect on the interaction between neighboring benzyl groups in these assembled systems. These findings provide significant insight into the structure-function relationship for Fmoc-Phe-derived hydrogelators and give cues for the design of next-generation materials with desired emergent properties.

Nonreplicative RNA Recombination of an Animal Plus-Strand RNA Virus in the Absence of Efficient Translation of Viral Proteins.

PubMed

Kleine Büning, Maximiliane; Meyer, Denise; Austermann-Busch, Sophia; Roman-Sosa, Gleyder; Rümenapf, Tillmann; Becher, Paul

2017-04-01

RNA recombination is a major driving force for the evolution of RNA viruses and is significantly implicated in the adaptation of viruses to new hosts, changes of virulence, as well as in the emergence of new viruses including drug-resistant and escape mutants. However, the molecular details of recombination in animal RNA viruses are only poorly understood. In order to determine whether viral RNA recombination depends on translation of viral proteins, a nonreplicative recombination system was established which is based on cotransfection of cells with synthetic bovine viral diarrhea virus (family Flaviviridae) RNA genome fragments either lacking the internal ribosome entry site required for cap-independent translation or lacking almost the complete polyprotein coding region. The emergence of a number of recombinant viruses demonstrated that IRES-mediated translation of viral proteins is dispensable for efficient recombination and suggests that RNA recombination can occur in the absence of viral proteins. Analyses of 58 independently emerged viruses led to the detection of recombinant genomes with duplications, deletions and insertions in the 5' terminal region of the open reading frame, leading to enlarged core fusion proteins detectable by Western blot analysis. This demonstrates a remarkable flexibility of the pestivirus core protein. Further experiments with capped and uncapped genome fragments containing a luciferase gene for monitoring the level of protein translation revealed that even a ∼1,000-fold enhancement of translation of viral proteins did not increase the frequency of RNA recombination. Taken together, this study highlights that nonreplicative RNA recombination does not require translation of viral proteins. © The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Comparison of emergency medical services systems across Pan-Asian countries: a Web-based survey.

PubMed

Shin, Sang Do; Ong, Marcus Eng Hock; Tanaka, Hideharu; Ma, Matthew Huei-Ming; Nishiuchi, Tatsuya; Alsakaf, Omer; Karim, Sarah Abdul; Khunkhlai, Nalinas; Lin, Chih-Hao; Song, Kyoung Jun; Ryoo, Hyun Wook; Ryu, Hyun Ho; Tham, Lai Peng; Cone, David C

2012-01-01

There are great variations in out-of-hospital cardiac arrest (OHCA) survival outcomes among different countries and different emergency medical services (EMS) systems. The impact of different systems and their contribution to enhanced survival are poorly understood. This paper compares the EMS systems of several Asian sites making up the Pan-Asian Resuscitation Outcomes Study (PAROS) network. Some preliminary cardiac arrest outcomes are also reported. This is a cross-sectional descriptive survey study addressing population demographics, service levels, provider characteristics, system operations, budget and finance, medical direction (leadership), and oversight. Most of the systems are single-tiered. Fire-based EMS systems are predominant. Bangkok and Kuala Lumpur have hospital-based systems. Service level is relatively low, from basic to intermediate in most of the communities. Korea, Japan, Singapore, and Bangkok have intermediate emergency medical technician (EMT) service levels, while Taiwan and Dubai have paramedic service levels. Medical direction and oversight have not been systemically established, except in some communities. Systems are mostly dependent on public funding. We found variations in available resources in terms of ambulances and providers. The number of ambulances is 0.3 to 3.2 per 100,000 population, and most ambulances are basic life support (BLS) vehicles. The number of human resources ranges from 4.0 per 100,000 population in Singapore to 55.7 per 100,000 population in Taipei. Average response times vary between 5.1 minutes (Tainan) and 22.5 minutes (Kuala Lumpur). We found substantial variation in 11 communities across the PAROS EMS systems. This study will provide the foundation for understanding subsequent studies arising from the PAROS effort.

Testing Spatial Correlation of Subduction Interplate Coupling and Forearc Morpho-Tectonics

NASA Technical Reports Server (NTRS)

Goldfinger, Chris; Meigs, Andrew; Meigs, Andrew; Kaye, Grant D.; VanLaningham, Sam

2005-01-01

Subduction zones that are capable of generating great (Mw greater than 8) earthquakes appear to have a common assemblage of forearc morphologic elements. Although details vary, each have (from the trench landward), an accretionary prism, outer arc high, outer forearc basin, an inner forean: basin, and volcanic arc. This pattern is common in spite of great variation in forearc architecture. Because interseismic strain is known to be associated with a locked seismogenic plate interface, we infer that this common forearc morphology is related, in an unknown way, to the process of interseismic Strain accumulation and release in great earthquakes. To date, however, no clear relationship between the subduction process and the common elements of upper plate form has emerged. Whereas certain elements of the system, i.e. the outer arc high, are reasonably well- understood in a structural context, there is little understanding of the structural or topographic evolution of the other key elements like the inner arc and inner forearc basin, particularly with respect to the coupled zone of earthquake generation. This project developed a model of the seismologic, topographic, and uplift/denudation linkages between forearc topography and the subduction system by: 1) comparing geophysical, geodetic, and topographic data from subduction margins that generate large earthquakes; 2) using existing GPS, seismicity, and other data to model the relationship between seismic cycles involving a locked interface and upper-plate topographic development; and 3) using new GPS data and a range-scale topographic, uplift, and denudation analysis of the presently aseismic Cascadia margin to constrain topographic/plate coupling relationships at this poorly understood margin.

Viruses and neurodegeneration

PubMed Central

2013-01-01

Neurodegenerative diseases (NDs) are chronic degenerative diseases of the central nervous system (CNS), which affect 37 million people worldwide. As the lifespan increases, the NDs are the fourth leading cause of death in the developed countries and becoming increasingly prevalent in developing countries. Despite considerable research, the underlying mechanisms remain poorly understood. Although the large majority of studies do not show support for the involvement of pathogenic aetiology in classical NDs, a number of emerging studies show support for possible association of viruses with classical neurodegenerative diseases in humans. Space does not permit for extensive details to be discussed here on non-viral-induced neurodegenerative diseases in humans, as they are well described in literature. Viruses induce alterations and degenerations of neurons both directly and indirectly. Their ability to attack the host immune system, regions of nervous tissue implies that they can interfere with the same pathways involved in classical NDs in humans. Supporting this, many similarities between classical NDs and virus-mediated neurodegeneration (non-classical) have been shown at the anatomic, sub-cellular, genomic and proteomic levels suggesting that viruses can explain neurodegenerative disorders mechanistically. The main objective of this review is to provide readers a detailed snapshot of similarities viral and non-viral neurodegenerative diseases share, so that mechanistic pathways of neurodegeneration in human NDs can be clearly understood. Viruses can guide us to unveil these pathways in human NDs. This will further stimulate the birth of new concepts in the biological research, which is needed for gaining deeper insights into the treatment of human NDs and delineate mechanisms underlying neurodegeneration. PMID:23724961

IN-STREAM AND WATERSHED PREDICTORS OF GENETIC DIVERSITY, EFFECTIVE POPULATION SIZE AND IMMIGRATION ACROSS RIVER-STREAM NETWORKS

EPA Science Inventory

The influence of spatial processes on population dynamics within river-stream networks is poorly understood. Utilizing spatially explicit analyses of temporal genetic variance, we examined whether persistence of Central Stonerollers (Campostoma anomalum) reflects differences in h...

Worldwide patterns of ancestry, divergence, and admixture in domesticated cattle

USDA-ARS?s Scientific Manuscript database

The domestication and development of cattle has considerably impacted human societies, but the histories of cattle breeds have been poorly understood especially for African, Asian, and American breeds. Using genotypes from 43,043 autosomal single nucleotide polymorphism markers scored in 1,543 anima...

WWW: The Scientific Method

ERIC Educational Resources Information Center

Blystone, Robert V.; Blodgett, Kevin

2006-01-01

The scientific method is the principal methodology by which biological knowledge is gained and disseminated. As fundamental as the scientific method may be, its historical development is poorly understood, its definition is variable, and its deployment is uneven. Scientific progress may occur without the strictures imposed by the formal…

From Movements to Actions: Two Mechanisms for Learning Action Sequences

ERIC Educational Resources Information Center

Endress, Ansgar D.; Wood, Justin N.

2011-01-01

When other individuals move, we interpret their movements as discrete, hierarchically-organized, goal-directed actions. However, the mechanisms that integrate visible movement features into actions are poorly understood. Here, we consider two sequence learning mechanisms--transitional probability-based (TP) and position-based encoding…

Accumulation of the Antibiotic Phenazine-1-Carboxylic Acid in the Rhizosphere of Dryland Cereals

USDA-ARS?s Scientific Manuscript database

Natural antibiotics are thought to function in the defense, fitness, competitiveness, biocontrol activity, communication and gene regulation of microorganisms. However, the scale and quantitative aspects of antibiotic production in natural settings are poorly understood. We addressed these fundament...

Size matters: The contribution of mega-infauna to the food webs and ecosystem services of an Oregon estuary - ESA

EPA Science Inventory

Background/Questions/Methods Large-bodied invertebrates (bivalves, polychaetes, burrowing shrimps) are common to infaunal communities of NE Pacific estuaries, but their contribution to estuarine community structure, function and ecosystem services is poorly understood because ...

Olfactory disruption: towards controlling important insect vectors of disease

USDA-ARS?s Scientific Manuscript database

Chemical repellents are used to decrease contacts between insect disease vectors and their hosts, thus reducing the probability of disease transmission. The molecular mechanisms by which repellents have their effects are poorly understood and remain a controversial topic. Here we present recent re...

Environmental enteric dysfunction is associated with carnitine deficiency and altered fatty acid oxidation

USDA-ARS?s Scientific Manuscript database

Environmental enteric dysfunction (EED), a condition characterized by small intestine inflammation and abnormal gut permeability, is widespread in children in developing countries and a major cause of growth failure. The pathophysiology of EED remains poorly understood. We measured serum metabolite...

LOCAL VS. REGIONAL EFFECTS ON FISH DIVERSITY AS MEDIATED BY STREAMFLOW DISTURBANCE REGIME

EPA Science Inventory

abstract

The interplay of local and regional processes on fish diversity is poorly understood, especially related to patterns of streamflow disturbance regime. Articulation of the relationship between flow disturbance patterns and river fishes across local to regional scal...

Disruption of the circadian clock within the cardiomyocyte influences mycardial contractile function, metabolism, and gene expression

USDA-ARS?s Scientific Manuscript database

Virtually every mammalian cell, including cardiomyocytes, possesses an intrinsic circadian clock. The role of this transcriptionally based molecular mechanism in cardiovascular biology is poorly understood. We hypothesized that the circadian clock within the cardiomyocyte influences diurnal variatio...

The role of methionine metabolism in inflammatory bowel disease

USDA-ARS?s Scientific Manuscript database

Methionine (Met) cycle activity is critical for normal cell functions. Met metabolites S-adenosylmethionine (SAM) and methylthioadenosine (MTA) are anti-inflammatory, yet their role in inflammatory bowel disease (IBD) is poorly understood. We hypothesize that active IBD leads to changes in Met metab...

Molecular basis for the thermostability of Newcastle disease virus

USDA-ARS?s Scientific Manuscript database

Thermostable Newcastle disease virus (NDV) vaccines have been used widely to protect village chickens against Newcastle disease, due to their decreased dependence on cold chain for transport and storage. However, the genetic basis underlying the NDV thermostability is poorly understood. In this stud...

Development and preliminary validation of the Parenting around SNAcking Questionnaire (P-SNAQ)

USDA-ARS?s Scientific Manuscript database

Snacking makes significant contributions to children's dietary intake but is poorly understood from a parenting perspective. This research was designed to develop and evaluate the psychometrics of a theoretically grounded, empirically-informed measure of snack parenting. The Parenting around SNAckin...

Do boll weevils really diapause?

USDA-ARS?s Scientific Manuscript database

Boll weevil, Anthonomus grandis grandis Boheman, diapause has been poorly understood since the term was first used 50 yrs ago to describe the pest’s winter dormancy in temperate regions. This literature-based study found that low temperature and changes in photoperiod are the boll weevil diapause-i...

Effects of exurban development on trophic interactions in a desert landscape

USDA-ARS?s Scientific Manuscript database

Context Mechanisms of ecosystem change in urbanizing landscapes are poorly understood, especially in exurban areas featuring residential or commercial development set in a matrix of modified and natural vegetation. We asked how development altered trophic interactions and ecosystem processes in the ...

Light absorption of secondary organic aerosol: Composition and contribution of nitro-aromatic compounds

EPA Science Inventory

Secondary organic aerosol (SOA) might affect the atmospheric radiation balance through absorbing light at shorter visible and UV wavelengths. However, the composition and optical properties of light-absorbing SOA is poorly understood. In this work, SOA filter samples were collect...

Reproductive responses of northern goshawks to variable prey populations

Treesearch

Susan R. Salafsky; Richard T. Reynolds; Barry R. Noon; John A. Wiens

2007-01-01

Developing comprehensive conservation strategies requires knowledge of factors influencing population growth and persistence. Although variable prey resources are often associated with fluctuations in raptor demographic parameters, the mechanisms of food limitation are poorly understood, especially for a generalist predator like the northern goshawk (Accipiter...

The dark side of suibsidies: quantifying contaminant exposure to riparian predators via stream insects

EPA Science Inventory

Aquatic insects provide a critical nutrient subsidy to riparian food webs, yet their role as vectors of contaminants to terrestrial ecosystems is poorly understood. We investigated relationships between aquatic (resource utilization) and contaminant exposure for a riparian invert...

The geography of spatial synchrony

Treesearch

Jonathan A. Walter; Lawrence W. Sheppard; Thomas L. Anderson; Jude H. Kastens; Ottar N. Bjørnstad; Andrew M. Liebhold; Daniel C. Reuman; Bernd Blasius

2017-01-01

Spatial synchrony, defined as correlated temporal fluctuations among populations, is a fundamental feature of population dynamics, but many aspects of synchrony remain poorly understood. Few studies have examined detailed geographical patterns of synchrony; instead most focus on how synchrony declines with increasing linear distance between locations, making the...

Relations between Alcohol, Violence and Victimization in Adolescence

ERIC Educational Resources Information Center

Shepherd, J. P.; Sutherland, I.; Newcombe, R. G.

2006-01-01

Background: Compared to links between alcohol and aggression, links between alcohol and vulnerability are poorly understood. Objectives: To determine whether there is a significant relationship between vulnerability to physical violence and alcohol consumption in adolescence independent of a relationship between alcohol consumption and violent…

Heredity Factors in Spatial Visualization.

ERIC Educational Resources Information Center

Vandenberg, S. G.

Spatial visualization is not yet clearly understood. Some researchers have concluded that two factors or abilities are involved, spatial orientation and spatial visualization. Different definitions and different tests have been proposed for these two abilities. Several studies indicate that women generally perform more poorly on spatial tests than…

Ecosystem Development after Mangrove Wetland Creation: Plant-Soil Change across a 20-year Chronosequence

EPA Science Inventory

Mangrove wetland restoration and creation efforts are increasingly proposed as mechanisms to compensate for mangrove wetland loss. However, ecosystem development and functional equivalence in restored and created mangrove wetlands is poorly understood. We compared a 20-yr chrono...

Working Model Hearts

ERIC Educational Resources Information Center

Brock, David

2009-01-01

Despite student interest, the heart is often a poorly understood topic in biology. To help students understand this vital organ's physiology, the author created this investigation activity involving the mammalian heart and its role in the circulatory system. Students design, build, and demonstrate working artificial "hearts" to exhibit what they…

Technology-Enhanced Discovery

ERIC Educational Resources Information Center

Harrow, Chris; Chin, Lillian

2014-01-01

Exploration, innovation, proof: For students, teachers, and others who are curious, keeping an open mind and being ready to investigate unusual or unexpected properties will always lead to learning something new. Technology can further this process, allowing various behaviors to be analyzed that were previously memorized or poorly understood. This…

Multi-scale assessment of human-induced changes to Amazonian instream habitats

EPA Science Inventory

Context: Land use change and forest degradation have myriad effects on tropical ecosystems. Yet their consequences for low-order streams remain very poorly understood, including in the world´s largest freshwater basin, the Amazon.Objectives: Determine the degree to which ph...

Child stunting is associated with low circulating essential amino acids

USDA-ARS?s Scientific Manuscript database

Stunting affects about one-quarter of children under five worldwide. The pathogenesis of stunting is poorly understood. Nutritional interventions have had only modest effects in reducing stunting. We hypothesized that insufficiency in essential amino acids may be limiting the linear growth of childr...

Introduction to the Thematic Minireview Series: Brain glycogen metabolism.

PubMed

Carlson, Gerald M; Dienel, Gerald A; Colbran, Roger J

2018-05-11

The synthesis of glycogen allows for efficient intracellular storage of glucose molecules in a soluble form that can be rapidly released to enter glycolysis in response to energy demand. Intensive studies of glucose and glycogen metabolism, predominantly in skeletal muscle and liver, have produced innumerable insights into the mechanisms of hormone action, resulting in the award of several Nobel Prizes over the last one hundred years. Glycogen is actually present in all cells and tissues, albeit at much lower levels than found in muscle or liver. However, metabolic and physiological roles of glycogen in other tissues are poorly understood. This series of Minireviews summarizes what is known about the enzymes involved in brain glycogen metabolism and studies that have linked glycogen metabolism to multiple brain functions involving metabolic communication between astrocytes and neurons. Recent studies unexpectedly linking some forms of epilepsy to mutations in two poorly understood proteins involved in glycogen metabolism are also reviewed. © 2018 Carlson et al.

Immigrant dairy workers' perceptions of health and safety on the farm in America's Heartland.

PubMed

Liebman, Amy King; Juarez-Carrillo, Patricia Margarita; Reyes, Iris Anne Cruz; Keifer, Matthew Charles

2016-03-01

Dairy farming is dangerous. Yearly, farms grow fewer and larger by employing immigrant workers, who have limited industrial agriculture experience and safety and health training. We examined results of five focus groups with 37 Hispanic, immigrant dairy workers. Analysis followed a grounded theory approach and employed ATLAS.ti. Reported injury experience affirmed the hazardous nature of dairy. Some workers received appropriate worker compensation benefits, whereas others were instructed to deny work-relatedness. Some employers covered medical injury costs out-of-pocket, whereas others did not. Cows were a major injury source. Pressure to work and weather were noted as injury risk factors. Worker compensation was poorly understood, and immigration status and fear of deportation influenced injury and hazard reporting. Injury management practices range from benevolent to threatening. Workers compensation is poorly understood and undocumented status is an occupational hazard. We underscore the need for further research and immigration policy change. © 2015 Wiley Periodicals, Inc.

Direct observation of closed magnetic flux trapped in the high-latitude magnetosphere.

PubMed

Fear, R C; Milan, S E; Maggiolo, R; Fazakerley, A N; Dandouras, I; Mende, S B

2014-12-19

The structure of Earth's magnetosphere is poorly understood when the interplanetary magnetic field is northward. Under this condition, uncharacteristically energetic plasma is observed in the magnetotail lobes, which is not expected in the textbook model of the magnetosphere. Using satellite observations, we show that these lobe plasma signatures occur on high-latitude magnetic field lines that have been closed by the fundamental plasma process of magnetic reconnection. Previously, it has been suggested that closed flux can become trapped in the lobe and that this plasma-trapping process could explain another poorly understood phenomenon: the presence of auroras at extremely high latitudes, called transpolar arcs. Observations of the aurora at the same time as the lobe plasma signatures reveal the presence of a transpolar arc. The excellent correspondence between the transpolar arc and the trapped closed flux at high altitudes provides very strong evidence of the trapping mechanism as the cause of transpolar arcs. Copyright © 2014, American Association for the Advancement of Science.

Sea-level-induced seismicity and submarine landslide occurrence

USGS Publications Warehouse

Brothers, Daniel S.; Luttrell, Karen M.; Chaytor, Jason D.

2013-01-01

The temporal coincidence between rapid late Pleistocene sea-level rise and large-scale slope failures is widely documented. Nevertheless, the physical mechanisms that link these phenomena are poorly understood, particularly along nonglaciated margins. Here we investigate the causal relationships between rapid sea-level rise, flexural stress loading, and increased seismicity rates along passive margins. We find that Coulomb failure stress across fault systems of passive continental margins may have increased more than 1 MPa during rapid late Pleistocene–early Holocene sea-level rise, an amount sufficient to trigger fault reactivation and rupture. These results suggest that sea-level–modulated seismicity may have contributed to a number of poorly understood but widely observed phenomena, including (1) increased frequency of large-scale submarine landslides during rapid, late Pleistocene sea-level rise; (2) emplacement of coarse-grained mass transport deposits on deep-sea fans during the early stages of marine transgression; and (3) the unroofing and release of methane gas sequestered in continental slope sediments.

Inhibiting platelet-derived growth factor beta reduces Ewing's sarcoma growth and metastasis in a novel orthotopic human xenograft model.

PubMed

Wang, Yong Xin; Mandal, Deendayal; Wang, Suizhau; Hughes, Dennis; Pollock, Raphael E; Lev, Dina; Kleinerman, Eugenie; Hayes-Jordan, Andrea

2009-01-01

Despite aggressive therapy, Ewing's sarcoma (ES) patients have a poor five-year overall survival of only 20-40%. Pulmonary metastasis is the most common form of demise in these patients. The pathogenesis of pulmonary metastasis is poorly understood and few orthotopic models exist that allow study of spontaneous pulmonary metastasis in ES. We have developed a novel orthotopic xenograft model in which spontaneous pulmonary metastases develop. While the underlying biology of ES is incompletely understood, in addition to the EWS-FLI-1 mutation, it is known that platelet-derived growth factor receptor beta (PDGFR-beta) is highly expressed in ES. Hypothesizing that PDGFR-beta expression is indicative of a specific role for this receptor protein in ES progression, the effect of PDGFR-beta inhibition on ES growth and metastasis was assessed in this novel orthotopic ES model. Silencing PDGFR-beta reduced spontaneous growth and metastasis in ES. Preclinical therapeutically relevant findings such as these may ultimately lead to new treatment initiatives in ES.

Cortical dendritic activity correlates with spindle-rich oscillations during sleep in rodents.

PubMed

Seibt, Julie; Richard, Clément J; Sigl-Glöckner, Johanna; Takahashi, Naoya; Kaplan, David I; Doron, Guy; de Limoges, Denis; Bocklisch, Christina; Larkum, Matthew E

2017-09-25

How sleep influences brain plasticity is not known. In particular, why certain electroencephalographic (EEG) rhythms are linked to memory consolidation is poorly understood. Calcium activity in dendrites is known to be necessary for structural plasticity changes, but this has never been carefully examined during sleep. Here, we report that calcium activity in populations of neocortical dendrites is increased and synchronised during oscillations in the spindle range in naturally sleeping rodents. Remarkably, the same relationship is not found in cell bodies of the same neurons and throughout the cortical column. Spindles during sleep have been suggested to be important for brain development and plasticity. Our results provide evidence for a physiological link of spindles in the cortex specific to dendrites, the main site of synaptic plasticity.Different stages of sleep, marked by particular electroencephalographic (EEG) signatures, have been linked to memory consolidation, but underlying mechanisms are poorly understood. Here, the authors show that dendritic calcium synchronisation correlates with spindle-rich sleep phases.

Emerging pollutants in wastewater: a review of the literature.

PubMed

Deblonde, Tiphanie; Cossu-Leguille, Carole; Hartemann, Philippe

2011-11-01

For 20 years, many articles report the presence of new compounds, called "emerging compounds", in wastewater and aquatic environments. The US EPA (United States - Environmental Protection Agency) defines emerging pollutants as new chemicals without regulatory status and which impact on environment and human health are poorly understood. The objective of this work was to identify data on emerging pollutants concentrations in wastewater, in influent and effluent from wastewater treatment plants (WWTPs) and to determine the performance of sewage disposal. We collected 44 publications in our database. We sought especially for data on phthalates, Bisphenol A and pharmaceuticals (including drugs for human health and disinfectants). We gathered concentration data and chose 50 pharmaceutical molecules, six phthalates and Bisphenol A. The concentrations measured in the influent ranged from 0.007 to 56.63 μg per liter and the removal rates ranges from 0% (contrast media) to 97% (psychostimulant). Caffeine is the molecule whose concentration in influent was highest among the molecules investigated (in means 56.63 μg per liter) with a removal rate around 97%, leading to a concentration in the effluent that did not exceed 1.77 μg per liter. The concentrations of ofloxacin were the lowest and varied between 0.007 and 2.275 μg per liter in the influent treatment plant and 0.007 and 0.816 μg per liter in the effluent. Among phthalates, DEHP is the most widely used, and quantified by the authors in wastewater, and the rate of removal of phthalates is greater than 90% for most of the studied compounds. The removal rate for antibiotics is about 50% and 71% for Bisphenol A. Analgesics, anti inflammatories and beta-blockers are the most resistant to treatment (30-40% of removal rate). Some pharmaceutical molecules for which we have not collected many data and which concentrations seem high as Tetracycline, Codeine and contrast products deserve further research. Copyright © 2011 Elsevier GmbH. All rights reserved.

Should diagnosis codes from emergency department data be used for case selection for emergency department key performance indicators?

PubMed

Howell, Stuart C; Wills, Rachael A; Johnston, Trisha C

2014-02-01

The aim of the present study was to assess the suitability of emergency department (ED) discharge diagnosis for identifying patient cohorts included in the definitions of key performance indicators (KPIs) that are used to evaluate ED performance. Hospital inpatient episodes of care with a principal diagnosis that corresponded to an ED-defined KPI were extracted from the Queensland Hospital Admitted Patient Data Collection (QHAPDC) for the year 2010-2011. The data were then linked to the corresponding ED patient record and the diagnoses applied in the two settings were compared. The asthma and injury cohorts produced favourable results with respect to matching the QHAPDC principal diagnosis with the ED discharge diagnosis. The results were generally modest when the QHAPDC principal diagnosis was upper respiratory tract infection, poisoning and toxic effects or a mental health diagnosis, and were quite poor for influenza. There is substantial variation in the capture of patient cohorts using discharge diagnosis as recorded on Queensland Hospital Emergency Department data. WHAT IS KNOWN ABOUT THE TOPIC? There are several existing KPIs that are defined according to the diagnosis recorded on ED data collections. However, there have been concerns over the quality of ED diagnosis in Queensland and other jurisdictions, and the value of these data in identifying patient cohorts for the purpose of assessing ED performance remains uncertain. WHAT DOES THIS PAPER ADD? This paper identifies diagnosis codes that are suitable for use in capturing the patient cohorts that are used to evaluate ED performance, as well as those codes that may be of limited value. WHAT ARE THE IMPLICATIONS FOR PRACTITIONERS? The limitations of diagnosis codes within ED data should be understood by those seeking to use these data items for healthcare planning and management or for research into healthcare quality and outcomes.

A missed Fe-S cluster handoff causes a metabolic shakeup.

PubMed

Berteau, Olivier

2018-05-25

The general framework of pathways by which iron-sulfur (Fe-S) clusters are assembled in cells is well-known, but the cellular consequences of disruptions to that framework are not fully understood. Crooks et al. report a novel cellular system that creates an acute Fe-S cluster deficiency, using mutants of ISCU, the main scaffold protein for Fe-S cluster assembly. Surprisingly, the resultant metabolic reprogramming leads to the accumulation of lipid droplets, a situation encountered in many poorly understood pathological conditions, highlighting unanticipated links between Fe-S assembly machinery and human disease. © 2018 Berteau.

Demystifying a Black Box: A Grounded Theory of How Travel Experiences Impact the Jewish Identity Development of Jewish Emerging Adults

ERIC Educational Resources Information Center

Aaron, Scott

2015-01-01

The positive impact on the Jewish Identity Development of Jewish Emerging Adults of both the 10 day trips to Israel popularly known as Birthright trips and the service learning trips commonly known as Alternative Spring Breaks has been well-documented. However, the mechanics of how this positive impact occurs has not been well-understood. This…

The mystery of a supposed massive star exploding in a brightest cluster galaxy

NASA Astrophysics Data System (ADS)

Hosseinzadeh, Griffin

2017-08-01

Most of the diversity of core-collapse supernovae results from late-stage mass loss by their progenitor stars. Supernovae that interact with circumstellar material (CSM) are a particularly good probe of these last stages of stellar evolution. Type Ibn supernovae are a rare and poorly understood class of hydrogen-poor explosions that show signs of interaction with helium-rich CSM. The leading hypothesis is that they are explosions of very massive Wolf-Rayet stars in which the supernova ejecta excites material previously lost by stellar winds. These massive stars have very short lifetimes, and therefore should only found in actively star-forming galaxies. However, PS1-12sk is a Type Ibn supernova found on the outskirts of a giant elliptical galaxy. As this is extraordinary unlikely, we propose to obtain deep UV images of the host environment of PS1-12sk in order to map nearby star formation and/or find a potential unseen star-forming host. If star formation is detected, its amount and location will provide deep insights into the progenitor picture for the poorly-understood Type Ibn class. If star formation is still not detected, these observations would challenge the well-accepted hypothesis that these are core-collapse supernovae at all.

Triage of patients with acute gastrointestinal bleeding for intensive care unit admission based on risk factors for poor outcome.

PubMed

Afessa, B

2000-04-01

This study's aim was to determine the prognostic factors and to develop a triage system for intensive care unit (ICU) admission of patients with gastrointestinal bleeding (GIB). This prospective, observational study included 411 adults consecutively hospitalized for GIB. Each patient's selected clinical findings and laboratory values at presentation were obtained. The Acute Physiology and Chronic Health Evaluation (APACHE) II scores were calculated from the initial findings in the emergency department. Poor outcome was defined as recurrent GIB, emergency surgery, or death. The role of hepatic cirrhosis, APACHE II score, active GIB, end-organ dysfunction, and hypotension in predicting outcome was evaluated. Chi-square, Student's t, Mann-Whitney U, and logistic regression analysis tests were used for statistical comparisons. Poor outcome developed in 81 (20%) patients; 39 died, 23 underwent emergency surgery, and 47 rebled. End-organ dysfunction, active bleeding, hepatic cirrhosis, and high APACHE II scores were independent predictors of poor outcome with odds ratios of 3:1, 3:1, 2:3, and 1:1, respectively. The ICU admission rate was 37%. High APACHE II score, active bleeding, end-organ dysfunction, and hepatic cirrhosis are independent predictors of poor outcome in patients with GIB and can be used in the triage of these patients for ICU admission.

A Physiologically-Based Pharmacokinetic (PBPK) Model With Metabolic Interactions of Chloroform (CHCL3) and Trichloroethylene

EPA Science Inventory

Exposure to mixtures is frequent, but biologic pathways such as metabolic inhibition, are poorly understood. CHCl3 and TCE are model volatiles frequently co-occurring; combined exposure results in less than additive hepatotoxicity. Here, we explore the underlying metabolic inte...

Advanced Pavement Design: Finite Element Modeling for Rigid Pavement Joints, Report II: Model Development

DOT National Transportation Integrated Search

1998-03-01

The contribution of a cement-stabilized base course to the strength of the rigid pavement structure is poorly understood. The objective of this research was to obtain data on the response of the rigid pavement slab-joint-foundation system by conducti...

Integrating Demographic, Clinical,and Environmental Exposure Information to Identify Genomic Biomarkers Associated With Subtypes of Childhood Asthma

EPA Science Inventory

Childhood asthma is a multifactorial disease with a disturbingly high incidence in urbanized areas. The pathogenesis of asthma is poorly understood due to the complex relationship between genetic susceptibility and modulating environmental factors. The Mechanistic Indicators of C...

NITROGEN OUTPUTS FROM FECAL AND URINE DEPOSITION OF SMALL MAMMALS: IMPLICATIONS FOR NITROGEN CYCLING

EPA Science Inventory

The contribution of small mammals to nitrogen cycling is poorly understood, but it could have reverberations back to the producer community by maintaining or perhaps magnifying nitrogen availability. Our objective was to model nitrogen outputs (deposition of feces and urine) of ...